Evidence-Based Reviews

Attending the wrong 12-step meeting can turn off some patients, despite the substance abuse treatment support offered by Alcoholics Anonymous (AA) and similar programs. Because of the stigma associated with alcohol or drug addiction, most patients are ambivalent at best about attending their first 12-step meetings. Feeling “out of place”—the most common turn-off—can transform this ambivalence into adamant resistance.

Simply advising an addicted patient to “call AA” is tantamount to giving a depressed patient a copy of the Physicians’ Desk Reference and telling him or her to pick an antidepressant. Not all 12-step meetings are alike; 50,000 AA meetings are held every week in the United States (Box 1).^1-7 Recognizing the differences between the groups in your area will help you guide your patients to the best match.

In prescribing a 12-step program, consider these six patient factors: socioeconomic status, gender, age, attitude towards spirituality, smoking status, and drug of choice.

Box 1

Socioeconomic status

Matching patients with meetings according to socioeconomic status is not elitist—it’s pragmatic. Patients generally feel most comfortable and relate most readily at meetings where they feel they have something in common with the other members. For example, when a newly recovering middle-class alcoholic visits an AA group that is frequented by homeless and unemployed alcoholics, chances are that he will become more ambivalent about attending meetings. After all, he was never “that bad.”

A good practice is to give your patients an up-to-date 12-step meeting directory (Box 2). Suggest that they identify the meetings where they think they will feel most comfortable, based on the neighborhoods in which they are held.

Patients in early recovery often are terrified of encountering someone they know at a 12-step meeting. One strategy for patients concerned about protecting their anonymity—as many are—is to attend meetings outside their own neighborhoods but still in areas that match their socioeconomic status. Similarly, referring patients to meetings that are “closed to members only” might reduce their concerns about exposure.

Once a patient has connected with a 12-step program, matching by socioeconomic status becomes less important. Many begin to see similarities between themselves and other addicted individuals from all walks of life. In the beginning, however, similarities attract.

Your patient’s gender

Though women were once a small minority in AA and Narcotics Anonymous (NA), today they make up about one-third of AA’s membership and more than 40% of NA.⁸ One factor that may have boosted the number of women attending 12-step programs is the increased availability of women-only meetings.

Most cities have women-only meetings, and they generally will be a good place for your female patients to begin. Evidence indicates that gender-specific treatment enhances treatment outcomes.^9,10 Women-only meetings tend to be smaller than mixed groups, and the senior members are often particularly willing to welcome newcomers.

Although it is severely frowned upon, the phenomenon of AA or NA members attempting to become romantically or sexually involved with a newcomer is common enough that 12-step members have coined a term for it: “13-stepping.” Newly recovering patients are often emotionally vulnerable and at risk of becoming enmeshed in a potentially destructive relationship. Beginning recovery in gender-specific meetings helps to reduce this risk.

Your patient’s age

A 12-step meeting dominated by people with gray, blue, or no hair can quickly put off teens and young adults in early recovery. Though these meetings with older members are likely to include persons who have achieved long-term and healthy recovery (making such meetings ideal territory for finding a sponsor), finding peers of a similar age is also important.

Meetings intended for young people are identified in 12-step meeting directories, but many of these “young peoples’ ” meetings have a preponderance of members older than 30—quite ancient by a 16-year-old’s standards. Conversely, some generic 12-step meetings might have a cadre of teenagers that attend regularly—at least for a while.

In AA and NA, teens and young adults tend to travel in nomadic packs, linger for a few months, then move on. For this reason, having contacts familiar with the characteristics of local meetings can be invaluable as you try to match a younger patient with a 12-step meeting.

Attitude toward spirituality

One of patients’ most common complaints about 12-step meetings is their surprise at how “religious” the programs are. Insiders are quick to point out that 12-step programs are “spiritual” and not “religious,” but the distinction is moot to patients who are uneasy with this aspect of meetings. The talk about “God as I understand Him,” the opening and closing of meetings with prayers, and the generous adoption of Judeo-Christian practices can rub agnostic, atheistic, and otherwise spiritually indifferent patients the wrong way.

To protect your patients from being blind-sided, review with them some of the spiritual practices employed in 12-step programs before they attend their first meeting:

• Meetings begin with reading the Twelve Steps (Box 3) and other 12-step literature; all readings are peppered with spiritually-loaded words such as “God,” “Higher Power,” “prayer,” and “meditation.”
• Meetings end with a prayer in which the group stands and holds hands (in AA) or links their arms in a huddle (NA). [I advise patients who might find this activity intolerable to duck out to the rest room 5 minutes before the meeting ends.]
• Group leaders typically collect donations by passing the basket.

Certain meetings have a particularly heavy spiritual focus and might be appropriately prescribed for patients hungering for spiritual growth. But for patients who have had toxic encounters with religion or otherwise are ill-at-ease with spirituality or religious matters, starting out at one of the more spiritually hardcore 12-step meetings could be overwhelming. While your 12-step contact person is your best guide in these matters, the following points also apply:

• Meetings listed as “11th Step” or “God as I understand Him” meetings will have a strong spiritual focus.
• Meetings held on Sunday mornings often have the express purpose of focusing on spirituality.
• “Step” meetings generally have a more spiritual focus, as 11 of the 12 steps are aimed at eliciting a “spiritual awakening.”
• “Speaker” or “topic discussion” meetings tend to have a less spiritual focus, though this will vary with the meeting chairperson’s preferences.
• “Beginners” meetings, when available, are intended for new members and devote more time to helping the newcomer understand the 12-step approach to spirituality.

Box 2

Box 3

AA’s main text, the so-called “Big Book” (its real title is: Alcoholics Anonymous⁷) has a chapter titled, “We Agnostics.” AA has many long-time members who have found support in the fellowship but never “found God” or a belief in a higher power other than the fellowship itself. These secular 12-step members demonstrate one of the many ironies of AA and NA—that spiritual fellowships can work even for individuals who reject spirituality.

Patients who resist spirituality are advised to “take what you can use” from the fellowship and “leave the rest.” While 12-step members will propose that the newcomer keep an open mind about spirituality, patients should also be assured that a seat is always waiting for them, regardless.

Whether your patient smokes

Most 12-step meetings today are smoke-free, not because of enlightenment within the fellowships but because meetings are usually held in churches, synagogues, and health care facilities where smoking is banned. The perception that attending 12-step meetings can be harmful to your health is out-of-date. Nonetheless, because most meetings have banned smoking, the few in which smoking is allowed are thick with smoke.

In general, 12-step clubhouses are among the holdouts where smoking is allowed during and after meetings. A clubhouse is typically a storefront rented or acquired by AA/NA members where meetings are held around the clock. Given the evidence that quitting smoking may improve overall health,^10,11 patients should be encouraged to begin their involvement in smoke-free fellowships, which are identified in 12-step directories.

Your patient’s drug of choice

As its name implies, AA is intended for persons who desire to stop drinking. In practice, however, much of AA’s membership is addicted to more than one substance, and—in some cases—the drug of choice might not be alcohol.

Narcotics Anonymous—contrary to what its name implies—is for individuals addicted to any drug, not just narcotics. Patients generally should be advised to join the fellowship (AA or NA) that best matches their substance use history. There is, however, at least one exception that might best be illustrated with an example:

After I recommended NA meetings to a middle-class nurse addicted to analgesics, she returned for her next appointment quite angry. She attended three different NA meetings, and “all of the members were either heroin or crack cocaine addicts.” It seemed to her that all of them were on probation or parole. She was very uncomfortable throughout the meetings and upset with my recommendation.

In matching patients with meetings, socioeconomic and cultural factors take precedence over biochemistry. At the neuronal level, a nurse addicted to analgesics has a lot in common with a heroin addict, but her ability to relate to another recovering person—particularly in early recovery—may be limited. Arguing with my patient or countering that other nurses were probably at the meetings she attended would not have eased her reluctance to return to NA or helped our therapeutic alliance.

NA meetings are generally attended by individuals addicted to illicit drugs: amphetamines, crack cocaine, cannabis, and heroin. In larger cities, other 12-step fellowships may focus on specific drugs, such as cocaine, but these are rare. Just as individuals addicted to prescription narcotics are a minority in the treatment population, they are also a minority in NA.

For this reason, our prior recommendation—to match patients to meetings based on socioeconomic status—applies. It’s good policy to recommend that patients addicted to prescription medications try both AA and NA meetings and decide where they feel most comfortable.

The third tradition of AA states, “the only requirement for AA membership is a desire to stop drinking.” Though a purist might suggest that our analgesics-dependent nurse should join NA, her need to connect culturally with similar persons in recovery argues strongly for her to blend in at open AA meetings. A social drinker who never fulfilled the diagnostic criteria for alcohol dependence, she will have a better chance of abstaining from analgesics if she abstains from alcohol as well. For this reason, she should qualify for AA membership because she does, in fact, have “a desire to stop drinking.”

Some professionals addicted to prescription drugs will feel at home in NA meetings, whereas others will react as my patient did. Having access to a 12-step contact person who knows about the demographics of local NA meetings can help you make the best patient/meeting match.

Related resources

• Alcoholics Anonymous. www.alcoholics-anonymous.org
• Narcotics Anonymous. www.na.org
• Alanon-Alateen. www.al-anon.org

Attending the wrong 12-step meeting can turn off some patients, despite the substance abuse treatment support offered by Alcoholics Anonymous (AA) and similar programs. Because of the stigma associated with alcohol or drug addiction, most patients are ambivalent at best about attending their first 12-step meetings. Feeling “out of place”—the most common turn-off—can transform this ambivalence into adamant resistance.

Simply advising an addicted patient to “call AA” is tantamount to giving a depressed patient a copy of the Physicians’ Desk Reference and telling him or her to pick an antidepressant. Not all 12-step meetings are alike; 50,000 AA meetings are held every week in the United States (Box 1).^1-7 Recognizing the differences between the groups in your area will help you guide your patients to the best match.

In prescribing a 12-step program, consider these six patient factors: socioeconomic status, gender, age, attitude towards spirituality, smoking status, and drug of choice.

Box 1

Socioeconomic status

Matching patients with meetings according to socioeconomic status is not elitist—it’s pragmatic. Patients generally feel most comfortable and relate most readily at meetings where they feel they have something in common with the other members. For example, when a newly recovering middle-class alcoholic visits an AA group that is frequented by homeless and unemployed alcoholics, chances are that he will become more ambivalent about attending meetings. After all, he was never “that bad.”

A good practice is to give your patients an up-to-date 12-step meeting directory (Box 2). Suggest that they identify the meetings where they think they will feel most comfortable, based on the neighborhoods in which they are held.

Patients in early recovery often are terrified of encountering someone they know at a 12-step meeting. One strategy for patients concerned about protecting their anonymity—as many are—is to attend meetings outside their own neighborhoods but still in areas that match their socioeconomic status. Similarly, referring patients to meetings that are “closed to members only” might reduce their concerns about exposure.

Once a patient has connected with a 12-step program, matching by socioeconomic status becomes less important. Many begin to see similarities between themselves and other addicted individuals from all walks of life. In the beginning, however, similarities attract.

Your patient’s gender

Though women were once a small minority in AA and Narcotics Anonymous (NA), today they make up about one-third of AA’s membership and more than 40% of NA.⁸ One factor that may have boosted the number of women attending 12-step programs is the increased availability of women-only meetings.

Most cities have women-only meetings, and they generally will be a good place for your female patients to begin. Evidence indicates that gender-specific treatment enhances treatment outcomes.^9,10 Women-only meetings tend to be smaller than mixed groups, and the senior members are often particularly willing to welcome newcomers.

Although it is severely frowned upon, the phenomenon of AA or NA members attempting to become romantically or sexually involved with a newcomer is common enough that 12-step members have coined a term for it: “13-stepping.” Newly recovering patients are often emotionally vulnerable and at risk of becoming enmeshed in a potentially destructive relationship. Beginning recovery in gender-specific meetings helps to reduce this risk.

Your patient’s age

A 12-step meeting dominated by people with gray, blue, or no hair can quickly put off teens and young adults in early recovery. Though these meetings with older members are likely to include persons who have achieved long-term and healthy recovery (making such meetings ideal territory for finding a sponsor), finding peers of a similar age is also important.

Meetings intended for young people are identified in 12-step meeting directories, but many of these “young peoples’ ” meetings have a preponderance of members older than 30—quite ancient by a 16-year-old’s standards. Conversely, some generic 12-step meetings might have a cadre of teenagers that attend regularly—at least for a while.

In AA and NA, teens and young adults tend to travel in nomadic packs, linger for a few months, then move on. For this reason, having contacts familiar with the characteristics of local meetings can be invaluable as you try to match a younger patient with a 12-step meeting.

Attitude toward spirituality

One of patients’ most common complaints about 12-step meetings is their surprise at how “religious” the programs are. Insiders are quick to point out that 12-step programs are “spiritual” and not “religious,” but the distinction is moot to patients who are uneasy with this aspect of meetings. The talk about “God as I understand Him,” the opening and closing of meetings with prayers, and the generous adoption of Judeo-Christian practices can rub agnostic, atheistic, and otherwise spiritually indifferent patients the wrong way.

To protect your patients from being blind-sided, review with them some of the spiritual practices employed in 12-step programs before they attend their first meeting:

• Meetings begin with reading the Twelve Steps (Box 3) and other 12-step literature; all readings are peppered with spiritually-loaded words such as “God,” “Higher Power,” “prayer,” and “meditation.”
• Meetings end with a prayer in which the group stands and holds hands (in AA) or links their arms in a huddle (NA). [I advise patients who might find this activity intolerable to duck out to the rest room 5 minutes before the meeting ends.]
• Group leaders typically collect donations by passing the basket.

Certain meetings have a particularly heavy spiritual focus and might be appropriately prescribed for patients hungering for spiritual growth. But for patients who have had toxic encounters with religion or otherwise are ill-at-ease with spirituality or religious matters, starting out at one of the more spiritually hardcore 12-step meetings could be overwhelming. While your 12-step contact person is your best guide in these matters, the following points also apply:

• Meetings listed as “11th Step” or “God as I understand Him” meetings will have a strong spiritual focus.
• Meetings held on Sunday mornings often have the express purpose of focusing on spirituality.
• “Step” meetings generally have a more spiritual focus, as 11 of the 12 steps are aimed at eliciting a “spiritual awakening.”
• “Speaker” or “topic discussion” meetings tend to have a less spiritual focus, though this will vary with the meeting chairperson’s preferences.
• “Beginners” meetings, when available, are intended for new members and devote more time to helping the newcomer understand the 12-step approach to spirituality.

Box 2

Box 3

AA’s main text, the so-called “Big Book” (its real title is: Alcoholics Anonymous⁷) has a chapter titled, “We Agnostics.” AA has many long-time members who have found support in the fellowship but never “found God” or a belief in a higher power other than the fellowship itself. These secular 12-step members demonstrate one of the many ironies of AA and NA—that spiritual fellowships can work even for individuals who reject spirituality.

Patients who resist spirituality are advised to “take what you can use” from the fellowship and “leave the rest.” While 12-step members will propose that the newcomer keep an open mind about spirituality, patients should also be assured that a seat is always waiting for them, regardless.

Whether your patient smokes

Most 12-step meetings today are smoke-free, not because of enlightenment within the fellowships but because meetings are usually held in churches, synagogues, and health care facilities where smoking is banned. The perception that attending 12-step meetings can be harmful to your health is out-of-date. Nonetheless, because most meetings have banned smoking, the few in which smoking is allowed are thick with smoke.

In general, 12-step clubhouses are among the holdouts where smoking is allowed during and after meetings. A clubhouse is typically a storefront rented or acquired by AA/NA members where meetings are held around the clock. Given the evidence that quitting smoking may improve overall health,^10,11 patients should be encouraged to begin their involvement in smoke-free fellowships, which are identified in 12-step directories.

Your patient’s drug of choice

As its name implies, AA is intended for persons who desire to stop drinking. In practice, however, much of AA’s membership is addicted to more than one substance, and—in some cases—the drug of choice might not be alcohol.

Narcotics Anonymous—contrary to what its name implies—is for individuals addicted to any drug, not just narcotics. Patients generally should be advised to join the fellowship (AA or NA) that best matches their substance use history. There is, however, at least one exception that might best be illustrated with an example:

After I recommended NA meetings to a middle-class nurse addicted to analgesics, she returned for her next appointment quite angry. She attended three different NA meetings, and “all of the members were either heroin or crack cocaine addicts.” It seemed to her that all of them were on probation or parole. She was very uncomfortable throughout the meetings and upset with my recommendation.

In matching patients with meetings, socioeconomic and cultural factors take precedence over biochemistry. At the neuronal level, a nurse addicted to analgesics has a lot in common with a heroin addict, but her ability to relate to another recovering person—particularly in early recovery—may be limited. Arguing with my patient or countering that other nurses were probably at the meetings she attended would not have eased her reluctance to return to NA or helped our therapeutic alliance.

NA meetings are generally attended by individuals addicted to illicit drugs: amphetamines, crack cocaine, cannabis, and heroin. In larger cities, other 12-step fellowships may focus on specific drugs, such as cocaine, but these are rare. Just as individuals addicted to prescription narcotics are a minority in the treatment population, they are also a minority in NA.

For this reason, our prior recommendation—to match patients to meetings based on socioeconomic status—applies. It’s good policy to recommend that patients addicted to prescription medications try both AA and NA meetings and decide where they feel most comfortable.

The third tradition of AA states, “the only requirement for AA membership is a desire to stop drinking.” Though a purist might suggest that our analgesics-dependent nurse should join NA, her need to connect culturally with similar persons in recovery argues strongly for her to blend in at open AA meetings. A social drinker who never fulfilled the diagnostic criteria for alcohol dependence, she will have a better chance of abstaining from analgesics if she abstains from alcohol as well. For this reason, she should qualify for AA membership because she does, in fact, have “a desire to stop drinking.”

Some professionals addicted to prescription drugs will feel at home in NA meetings, whereas others will react as my patient did. Having access to a 12-step contact person who knows about the demographics of local NA meetings can help you make the best patient/meeting match.

Related resources

• Alcoholics Anonymous. www.alcoholics-anonymous.org
• Narcotics Anonymous. www.na.org
• Alanon-Alateen. www.al-anon.org

Attending the wrong 12-step meeting can turn off some patients, despite the substance abuse treatment support offered by Alcoholics Anonymous (AA) and similar programs. Because of the stigma associated with alcohol or drug addiction, most patients are ambivalent at best about attending their first 12-step meetings. Feeling “out of place”—the most common turn-off—can transform this ambivalence into adamant resistance.

Simply advising an addicted patient to “call AA” is tantamount to giving a depressed patient a copy of the Physicians’ Desk Reference and telling him or her to pick an antidepressant. Not all 12-step meetings are alike; 50,000 AA meetings are held every week in the United States (Box 1).^1-7 Recognizing the differences between the groups in your area will help you guide your patients to the best match.

In prescribing a 12-step program, consider these six patient factors: socioeconomic status, gender, age, attitude towards spirituality, smoking status, and drug of choice.

Box 1

Socioeconomic status

Matching patients with meetings according to socioeconomic status is not elitist—it’s pragmatic. Patients generally feel most comfortable and relate most readily at meetings where they feel they have something in common with the other members. For example, when a newly recovering middle-class alcoholic visits an AA group that is frequented by homeless and unemployed alcoholics, chances are that he will become more ambivalent about attending meetings. After all, he was never “that bad.”

A good practice is to give your patients an up-to-date 12-step meeting directory (Box 2). Suggest that they identify the meetings where they think they will feel most comfortable, based on the neighborhoods in which they are held.

Patients in early recovery often are terrified of encountering someone they know at a 12-step meeting. One strategy for patients concerned about protecting their anonymity—as many are—is to attend meetings outside their own neighborhoods but still in areas that match their socioeconomic status. Similarly, referring patients to meetings that are “closed to members only” might reduce their concerns about exposure.

Once a patient has connected with a 12-step program, matching by socioeconomic status becomes less important. Many begin to see similarities between themselves and other addicted individuals from all walks of life. In the beginning, however, similarities attract.

Your patient’s gender

Though women were once a small minority in AA and Narcotics Anonymous (NA), today they make up about one-third of AA’s membership and more than 40% of NA.⁸ One factor that may have boosted the number of women attending 12-step programs is the increased availability of women-only meetings.

Most cities have women-only meetings, and they generally will be a good place for your female patients to begin. Evidence indicates that gender-specific treatment enhances treatment outcomes.^9,10 Women-only meetings tend to be smaller than mixed groups, and the senior members are often particularly willing to welcome newcomers.

Although it is severely frowned upon, the phenomenon of AA or NA members attempting to become romantically or sexually involved with a newcomer is common enough that 12-step members have coined a term for it: “13-stepping.” Newly recovering patients are often emotionally vulnerable and at risk of becoming enmeshed in a potentially destructive relationship. Beginning recovery in gender-specific meetings helps to reduce this risk.

Your patient’s age

A 12-step meeting dominated by people with gray, blue, or no hair can quickly put off teens and young adults in early recovery. Though these meetings with older members are likely to include persons who have achieved long-term and healthy recovery (making such meetings ideal territory for finding a sponsor), finding peers of a similar age is also important.

Meetings intended for young people are identified in 12-step meeting directories, but many of these “young peoples’ ” meetings have a preponderance of members older than 30—quite ancient by a 16-year-old’s standards. Conversely, some generic 12-step meetings might have a cadre of teenagers that attend regularly—at least for a while.

In AA and NA, teens and young adults tend to travel in nomadic packs, linger for a few months, then move on. For this reason, having contacts familiar with the characteristics of local meetings can be invaluable as you try to match a younger patient with a 12-step meeting.

Attitude toward spirituality

One of patients’ most common complaints about 12-step meetings is their surprise at how “religious” the programs are. Insiders are quick to point out that 12-step programs are “spiritual” and not “religious,” but the distinction is moot to patients who are uneasy with this aspect of meetings. The talk about “God as I understand Him,” the opening and closing of meetings with prayers, and the generous adoption of Judeo-Christian practices can rub agnostic, atheistic, and otherwise spiritually indifferent patients the wrong way.

To protect your patients from being blind-sided, review with them some of the spiritual practices employed in 12-step programs before they attend their first meeting:

• Meetings begin with reading the Twelve Steps (Box 3) and other 12-step literature; all readings are peppered with spiritually-loaded words such as “God,” “Higher Power,” “prayer,” and “meditation.”
• Meetings end with a prayer in which the group stands and holds hands (in AA) or links their arms in a huddle (NA). [I advise patients who might find this activity intolerable to duck out to the rest room 5 minutes before the meeting ends.]
• Group leaders typically collect donations by passing the basket.

Certain meetings have a particularly heavy spiritual focus and might be appropriately prescribed for patients hungering for spiritual growth. But for patients who have had toxic encounters with religion or otherwise are ill-at-ease with spirituality or religious matters, starting out at one of the more spiritually hardcore 12-step meetings could be overwhelming. While your 12-step contact person is your best guide in these matters, the following points also apply:

• Meetings listed as “11th Step” or “God as I understand Him” meetings will have a strong spiritual focus.
• Meetings held on Sunday mornings often have the express purpose of focusing on spirituality.
• “Step” meetings generally have a more spiritual focus, as 11 of the 12 steps are aimed at eliciting a “spiritual awakening.”
• “Speaker” or “topic discussion” meetings tend to have a less spiritual focus, though this will vary with the meeting chairperson’s preferences.
• “Beginners” meetings, when available, are intended for new members and devote more time to helping the newcomer understand the 12-step approach to spirituality.

Box 2

Box 3

AA’s main text, the so-called “Big Book” (its real title is: Alcoholics Anonymous⁷) has a chapter titled, “We Agnostics.” AA has many long-time members who have found support in the fellowship but never “found God” or a belief in a higher power other than the fellowship itself. These secular 12-step members demonstrate one of the many ironies of AA and NA—that spiritual fellowships can work even for individuals who reject spirituality.

Patients who resist spirituality are advised to “take what you can use” from the fellowship and “leave the rest.” While 12-step members will propose that the newcomer keep an open mind about spirituality, patients should also be assured that a seat is always waiting for them, regardless.

Whether your patient smokes

Most 12-step meetings today are smoke-free, not because of enlightenment within the fellowships but because meetings are usually held in churches, synagogues, and health care facilities where smoking is banned. The perception that attending 12-step meetings can be harmful to your health is out-of-date. Nonetheless, because most meetings have banned smoking, the few in which smoking is allowed are thick with smoke.

In general, 12-step clubhouses are among the holdouts where smoking is allowed during and after meetings. A clubhouse is typically a storefront rented or acquired by AA/NA members where meetings are held around the clock. Given the evidence that quitting smoking may improve overall health,^10,11 patients should be encouraged to begin their involvement in smoke-free fellowships, which are identified in 12-step directories.

Your patient’s drug of choice

As its name implies, AA is intended for persons who desire to stop drinking. In practice, however, much of AA’s membership is addicted to more than one substance, and—in some cases—the drug of choice might not be alcohol.

Narcotics Anonymous—contrary to what its name implies—is for individuals addicted to any drug, not just narcotics. Patients generally should be advised to join the fellowship (AA or NA) that best matches their substance use history. There is, however, at least one exception that might best be illustrated with an example:

After I recommended NA meetings to a middle-class nurse addicted to analgesics, she returned for her next appointment quite angry. She attended three different NA meetings, and “all of the members were either heroin or crack cocaine addicts.” It seemed to her that all of them were on probation or parole. She was very uncomfortable throughout the meetings and upset with my recommendation.

In matching patients with meetings, socioeconomic and cultural factors take precedence over biochemistry. At the neuronal level, a nurse addicted to analgesics has a lot in common with a heroin addict, but her ability to relate to another recovering person—particularly in early recovery—may be limited. Arguing with my patient or countering that other nurses were probably at the meetings she attended would not have eased her reluctance to return to NA or helped our therapeutic alliance.

NA meetings are generally attended by individuals addicted to illicit drugs: amphetamines, crack cocaine, cannabis, and heroin. In larger cities, other 12-step fellowships may focus on specific drugs, such as cocaine, but these are rare. Just as individuals addicted to prescription narcotics are a minority in the treatment population, they are also a minority in NA.

For this reason, our prior recommendation—to match patients to meetings based on socioeconomic status—applies. It’s good policy to recommend that patients addicted to prescription medications try both AA and NA meetings and decide where they feel most comfortable.

The third tradition of AA states, “the only requirement for AA membership is a desire to stop drinking.” Though a purist might suggest that our analgesics-dependent nurse should join NA, her need to connect culturally with similar persons in recovery argues strongly for her to blend in at open AA meetings. A social drinker who never fulfilled the diagnostic criteria for alcohol dependence, she will have a better chance of abstaining from analgesics if she abstains from alcohol as well. For this reason, she should qualify for AA membership because she does, in fact, have “a desire to stop drinking.”

Some professionals addicted to prescription drugs will feel at home in NA meetings, whereas others will react as my patient did. Having access to a 12-step contact person who knows about the demographics of local NA meetings can help you make the best patient/meeting match.

Related resources

• Alcoholics Anonymous. www.alcoholics-anonymous.org
• Narcotics Anonymous. www.na.org
• Alanon-Alateen. www.al-anon.org

Negative symptoms are the major contributor to low function levels and debilitation in most patients with schizophrenia. Poorly motivated patients cannot function adequately at school or work. Relationships with family and friends decay in the face of unresponsive affect and inattention to social cues. Personal interests yield to the dampening influences of anhedonia, apathy, and inattention.

Yet because active psychosis is the most common cause of hospital admission, a primary goal of treatment—and sometimes the only objective of pharmacologic treatment—is to eliminate or reduce positive symptoms. And although controlling positive symptoms is remarkably effective in reducing hospitalizations, patients’ functional capacity improves only minimally as psychosis abates. Even with optimal antipsychotic treatment, negative symptoms tend to persist.

For psychiatrists, the three major challenges of schizophrenia’s negative symptoms are their modest therapeutic response, pervasiveness, and diminution of patients’ quality of life. To help you manage negative symptoms, we suggest the following approach to their assessment and treatment.

Importance of negative symptoms

Schizophrenia is a heterogeneous disorder characterized by positive, negative, cognitive, and mood symptoms. The relative severity of these four pathologic domains varies from case to case and within the same individual over time. Though related, these domains have distinct underlying mechanisms and are differentially related to functional capacity and quality of life. They also show different patterns of response to treatment. Whereas positive symptoms refer to new psychological experiences outside the range of normal (e.g., delusions, hallucinations, suspiciousness, disorganized thinking), negative symptoms represent loss of normal function.

Negative symptoms include blunting of affect, poverty of speech and thought, apathy, anhedonia, reduced social drive, loss of motivation, lack of social interest, and inattention to social or cognitive input. These symptoms have devastating consequences on patients’ lives, and only modest progress has been made in treating them effectively.

From negative to positive. Early investigators^1,2 considered negative symptoms to represent the fundamental defect of schizophrenia. Over the years, however, the importance of negative symptoms was progressively downplayed. Positive symptoms were increasingly emphasized because:

• positive symptoms have a more dramatic and easily recognized presentation
• negative symptoms are more difficult to reliably define and document
• antipsychotics, which revolutionized schizophrenia treatment, produce their most dramatic improvement in positive symptoms.

Renewed interest. The almost universal presence and relative persistence of negative symptoms, and the fact that they represent the most debilitating and refractory aspect of schizophrenic psychopathology, make them difficult to ignore. Consequently, interest in negative symptoms resurged in the 1980s-90s, with intense efforts to better understand them and treat them more effectively.^3-5

Table

SCHIZOPHRENIA’S NEGATIVE SYMPTOMS: PRIMARY AND SECONDARY COMPONENTS

Negative symptoms are now better (but still incompletely) understood, and their treatment has improved but is still inadequate. Because intense effort yielded only modest success, researchers and clinicians have again begun to pay less attention to negative symptoms and shifted their focus to cognition in schizophrenia. Negative symptoms remain relevant, however, because they constitute the main barrier to a better quality of life for patients with schizophrenia.

Assessment for negative symptoms

The four major clinical subgroups of negative symptoms are affective, communicative, conational, and relational.

Affective. Blunted affect—including deficits in facial expression, eye contact, gestures, and voice pattern—is perhaps the most conspicuous negative symptom. In mild form, gestures may seem artificial or mechanical, and the voice is stilted or lacks normal inflection. Patients with severe blunted affect may appear devoid of facial expression or communicative gestures. They may sit impassively with little spontaneous movement, speak in a monotone, and gaze blankly in no particular direction.

Even when conversation becomes emotional, the patient’s affect does not adjust appropriately to reflect his or her feelings. Nor does the patient display even a basic level of understanding or responsiveness that typically characterize casual human interactions. The ability to experience pleasure (anhedonia) and sense of caring (apathy) are also reduced.

Communicative. The patient’s speech may be reduced in quantity (poverty of speech) and information (poverty of content of speech). In mild forms of impoverished speech (alogia), the patient makes brief, unelaborated statements; in the more severe form, the patient can be virtually mute. Whatever speech is present tends to be vague and overly generalized. Periods of silence may occur, either before the patient answers a question (increased latency) or in the midst of a response (blocking).

Conational. The patient may show a lack of drive or goal-directed behavior (avolition). Personal grooming may be poor. Physical activity may be limited. Patients typically have great difficulty following a work schedule or hospital ward routine. They fail to initiate activities, participate grudgingly, and require frequent direction and encouragement.

Continue to: Relational

Relational. Interest in social activities and relationships is reduced (asociality). Even enjoyable and recreational activities are neglected. Interpersonal relations may be of little interest. Friendships become rare and shallow, with little sharing of intimacy. Contacts with family are neglected. Sexual interest declines. As symptoms progress, patients become increasingly isolated.

Primary and secondary symptoms

Negative symptoms are an intrinsic component of schizophrenic psychopathology, and they can also be caused by secondary factors (Table).^6,7 Distinguishing between primary and secondary causes of negative symptoms can help you select appropriate treatment in specific clinical situations.

Primary symptoms. From a longitudinal perspective, the three major components of primary negative symptoms are:

• premorbid negative symptoms (present prior to psychosis onset and associated with poor premorbid functioning)
• psychotic-phase, nonenduring negative symptoms that fluctuate with positive symptoms around periods of psychotic exacerbation
• deteriorative negative symptoms that intensify following each psychotic exacerbation and reflect a decline from premorbid levels of functioning.

Though little can be done to treat the premorbid component, psychotic-phase negative symptoms improve along with positive symptoms (although more slowly).^8,9 Therefore, the best strategy for managing negative symptoms is to treat positive symptoms more effectively. Although there is no specific treatment for deteriorative negative symptoms, the severity of this component appears to be related to the “toxicity of psychosis” and can be reduced by early, effective antipsychotic treatment.^10,11

Secondary negative symptoms occur in association with (and presumably are caused by) factors such as depression, extrapyramidal symptoms (EPS), and environmental deprivation. Secondary negative symptoms usually respond to treatment of the underlying cause.

Assessment

Symptom severity. Assessing the severity of a patient’s negative symptoms on an ongoing basis is a most important first step towards optimal treatment:

• Our objective is to improve patients’ function and quality of life, and negative symptoms compromise both of these more than any other factor.
• Ongoing assessment can track whether prescribed treatments are improving or worsening a patient’s symptoms.

Tools to assess the severity of negative symptoms include the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS).¹² The Scale for the Assessment of Negative Symptoms (SANS)¹³ measures them exclusively, and others such as the Schedule for the Deficit Syndrome (SDS)¹⁴ attempt to classify them into subgroups.

Discussing these instruments is beyond the scope of this article, but they differ greatly in their approach to assessing negative symptoms. Instead of using cumbersome assessment instruments, however, we recommend that you focus on two to four of a patient’s “target” symptoms or behaviors and note their severity on an ongoing basis.

Contributing factors. Determining the overall contribution of different factors to a patient’s negative symptoms allows us to target treatments. Sorting out these relative factors can be difficult, however. For example:

• In a patient on antipsychotic treatment who is experiencing psychotic symptoms (eg, persecutory delusions), depressive symptoms, and prominent negative symptoms, the clinician can only guess whether the negative symptoms are primary or secondary.
• In a patient who is socially withdrawn and delusional, withdrawal may be secondary to delusions or may represent a primary negative symptom.
• In a patient on typical antipsychotics, a flat affect may be caused by antipsychotic-induced EPS or it may be a primary negative symptom.
• A disorganized patient with schizophrenia and depression is often unable to convey his or her feelings coherently, so that negative symptoms secondary to affective disturbance may often be mistaken as primary.

Even in research settings, the distinction between primary and secondary symptoms is quite unreliable; nevertheless, it is of great clinical importance. Two strategies may be helpful:

• Consider whether symptoms are specific to the presumed etiology, such as guilt and sadness in depression or cogwheeling and tremor in EPS.
• Treat empirically, and monitor whether negative symptoms improve. If they improve with antidepressant treatment, for example, then depression was the presumable cause. If they improve with anticholinergics, they were presumably secondary to EPS.

Treatment

Negative symptoms are generally viewed as treatment-resistant, but evidence suggests that they do respond to pharmacologic and social interventions (Box). Most responsive to treatment are negative symptoms that occur in association with positive symptoms (psychotic-phase) and secondary negative symptoms caused by neuroleptic medication, depression, or lack of stimulation.

The most effective treatment for secondary symptoms is to target the underlying cause. Neuroleptic-induced akinesia may respond to anticholinergic agents, reduction in antipsychotic dose, or a change in antipsychotic. Using one of the newer-generation antipsychotics (clozapine, risperidone, olanzapine, quetiapine, or ziprasidone) may prevent EPS.

Box

Comorbid depression may require adding an antidepressant, or it may respond directly to an antipsychotic. Lack of stimulation is best handled by placing the patient in a more appropriately stimulating (but not overstimulating) and supportive environment. Nonenduring primary or psychotic-phase negative symptoms respond to effective antipsychotic treatment of the positive symptoms.

Atypical antipsychotics. Conventional antipsychotics (e.g., haloperidol, chlorpromazine) clearly offer some benefit in treating negative symptoms, but they have a much greater effect on positive symptoms.¹⁵ Using higher-than-appropriate doses diminishes their effect on negative symptoms and may result in severe EPS.

Two-thirds of the approximately 35 studies comparing conventional and atypical antipsychotics in treating negative symptoms have found atypicals to be significantly more effective (regardless of which atypical was used). In general, atypical antipsychotics improve negative symptoms by about 25%, compared with 10 to 15% improvement with conventional agents.^16,17

Much of the greater benefit with atypicals appears to be related to their at least equivalent ability to improve positive symptoms without causing EPS. Consequently, the key to improved patient outcomes is appropriate dosing of atypical antipsychotics that reduces positive symptoms optimally without EPS and without the need for an anticholinergic (Figure).

Whether the greater improvement with atypical agents implies an improvement in primary versus secondary negative symptoms is academic.¹⁸ From the patient’s perspective, the greater reduction in negative symptoms is meaningful, regardless of why it occurs.

Other medications. Secondary negative symptoms are most effectively treated with medications directed at the primary etiology. For EPS, change the antipsychotic, reduce the dosage, or add an anticholinergic. For depression, try an antidepressant (preferably a selective serotonin reuptake inhibitor). If a likely contributing factor can be identified, then initiate specific treatment.

Figure
ANTIPSYCHOTICS IMPROVE NEGATIVE SYMPTOMS THROUGH THEIR EFFECT ON PSYCHOSIS

Source: Adapted from Tandon et al. J Psychiatric Res. 1993;27:341-347.

Antipsychotics improve negative symptoms through their effect on positive (psychotic) symptoms, but they do not affect secondary components—such as environmental deprivation and depression—or the primary components of deterioration and premorbid symptoms. Typical and atypical antipsychotics have similar effects on positive symptoms, but atypical antipsychotics carry a lower risk of extrapyramidal side effects.

Empiric therapy—trying one agent and then another in an effort to reduce negative symptoms—is appropriate if done systematically and sequentially. Medications that are found not to be helpful should be discontinued. Electroconvulsive therapy is not effective in treating negative symptoms.

Related resources

• Greden JF, Tandon R (eds). Negative schizophrenic symptoms: pathophysiology and clinical implications. Washington, DC: American Psychiatric Press, 1991.
• Keefe RSE, McEvoy JP (eds). Negative symptom and cognitive deficit treatment response in schizophrenia. Washington, DC: American Psychiatric Press, 2001.

Drug brand names

• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Haloperidol • Haldol
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Ziprasidone • Geodon

Negative symptoms are the major contributor to low function levels and debilitation in most patients with schizophrenia. Poorly motivated patients cannot function adequately at school or work. Relationships with family and friends decay in the face of unresponsive affect and inattention to social cues. Personal interests yield to the dampening influences of anhedonia, apathy, and inattention.

Yet because active psychosis is the most common cause of hospital admission, a primary goal of treatment—and sometimes the only objective of pharmacologic treatment—is to eliminate or reduce positive symptoms. And although controlling positive symptoms is remarkably effective in reducing hospitalizations, patients’ functional capacity improves only minimally as psychosis abates. Even with optimal antipsychotic treatment, negative symptoms tend to persist.

For psychiatrists, the three major challenges of schizophrenia’s negative symptoms are their modest therapeutic response, pervasiveness, and diminution of patients’ quality of life. To help you manage negative symptoms, we suggest the following approach to their assessment and treatment.

Importance of negative symptoms

Schizophrenia is a heterogeneous disorder characterized by positive, negative, cognitive, and mood symptoms. The relative severity of these four pathologic domains varies from case to case and within the same individual over time. Though related, these domains have distinct underlying mechanisms and are differentially related to functional capacity and quality of life. They also show different patterns of response to treatment. Whereas positive symptoms refer to new psychological experiences outside the range of normal (e.g., delusions, hallucinations, suspiciousness, disorganized thinking), negative symptoms represent loss of normal function.

Negative symptoms include blunting of affect, poverty of speech and thought, apathy, anhedonia, reduced social drive, loss of motivation, lack of social interest, and inattention to social or cognitive input. These symptoms have devastating consequences on patients’ lives, and only modest progress has been made in treating them effectively.

From negative to positive. Early investigators^1,2 considered negative symptoms to represent the fundamental defect of schizophrenia. Over the years, however, the importance of negative symptoms was progressively downplayed. Positive symptoms were increasingly emphasized because:

• positive symptoms have a more dramatic and easily recognized presentation
• negative symptoms are more difficult to reliably define and document
• antipsychotics, which revolutionized schizophrenia treatment, produce their most dramatic improvement in positive symptoms.

Renewed interest. The almost universal presence and relative persistence of negative symptoms, and the fact that they represent the most debilitating and refractory aspect of schizophrenic psychopathology, make them difficult to ignore. Consequently, interest in negative symptoms resurged in the 1980s-90s, with intense efforts to better understand them and treat them more effectively.^3-5

Table

SCHIZOPHRENIA’S NEGATIVE SYMPTOMS: PRIMARY AND SECONDARY COMPONENTS

Negative symptoms are now better (but still incompletely) understood, and their treatment has improved but is still inadequate. Because intense effort yielded only modest success, researchers and clinicians have again begun to pay less attention to negative symptoms and shifted their focus to cognition in schizophrenia. Negative symptoms remain relevant, however, because they constitute the main barrier to a better quality of life for patients with schizophrenia.

Assessment for negative symptoms

The four major clinical subgroups of negative symptoms are affective, communicative, conational, and relational.

Affective. Blunted affect—including deficits in facial expression, eye contact, gestures, and voice pattern—is perhaps the most conspicuous negative symptom. In mild form, gestures may seem artificial or mechanical, and the voice is stilted or lacks normal inflection. Patients with severe blunted affect may appear devoid of facial expression or communicative gestures. They may sit impassively with little spontaneous movement, speak in a monotone, and gaze blankly in no particular direction.

Even when conversation becomes emotional, the patient’s affect does not adjust appropriately to reflect his or her feelings. Nor does the patient display even a basic level of understanding or responsiveness that typically characterize casual human interactions. The ability to experience pleasure (anhedonia) and sense of caring (apathy) are also reduced.

Communicative. The patient’s speech may be reduced in quantity (poverty of speech) and information (poverty of content of speech). In mild forms of impoverished speech (alogia), the patient makes brief, unelaborated statements; in the more severe form, the patient can be virtually mute. Whatever speech is present tends to be vague and overly generalized. Periods of silence may occur, either before the patient answers a question (increased latency) or in the midst of a response (blocking).

Conational. The patient may show a lack of drive or goal-directed behavior (avolition). Personal grooming may be poor. Physical activity may be limited. Patients typically have great difficulty following a work schedule or hospital ward routine. They fail to initiate activities, participate grudgingly, and require frequent direction and encouragement.

Continue to: Relational

Relational. Interest in social activities and relationships is reduced (asociality). Even enjoyable and recreational activities are neglected. Interpersonal relations may be of little interest. Friendships become rare and shallow, with little sharing of intimacy. Contacts with family are neglected. Sexual interest declines. As symptoms progress, patients become increasingly isolated.

Primary and secondary symptoms

Negative symptoms are an intrinsic component of schizophrenic psychopathology, and they can also be caused by secondary factors (Table).^6,7 Distinguishing between primary and secondary causes of negative symptoms can help you select appropriate treatment in specific clinical situations.

Primary symptoms. From a longitudinal perspective, the three major components of primary negative symptoms are:

• premorbid negative symptoms (present prior to psychosis onset and associated with poor premorbid functioning)
• psychotic-phase, nonenduring negative symptoms that fluctuate with positive symptoms around periods of psychotic exacerbation
• deteriorative negative symptoms that intensify following each psychotic exacerbation and reflect a decline from premorbid levels of functioning.

Though little can be done to treat the premorbid component, psychotic-phase negative symptoms improve along with positive symptoms (although more slowly).^8,9 Therefore, the best strategy for managing negative symptoms is to treat positive symptoms more effectively. Although there is no specific treatment for deteriorative negative symptoms, the severity of this component appears to be related to the “toxicity of psychosis” and can be reduced by early, effective antipsychotic treatment.^10,11

Secondary negative symptoms occur in association with (and presumably are caused by) factors such as depression, extrapyramidal symptoms (EPS), and environmental deprivation. Secondary negative symptoms usually respond to treatment of the underlying cause.

Assessment

Symptom severity. Assessing the severity of a patient’s negative symptoms on an ongoing basis is a most important first step towards optimal treatment:

• Our objective is to improve patients’ function and quality of life, and negative symptoms compromise both of these more than any other factor.
• Ongoing assessment can track whether prescribed treatments are improving or worsening a patient’s symptoms.

Tools to assess the severity of negative symptoms include the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS).¹² The Scale for the Assessment of Negative Symptoms (SANS)¹³ measures them exclusively, and others such as the Schedule for the Deficit Syndrome (SDS)¹⁴ attempt to classify them into subgroups.

Discussing these instruments is beyond the scope of this article, but they differ greatly in their approach to assessing negative symptoms. Instead of using cumbersome assessment instruments, however, we recommend that you focus on two to four of a patient’s “target” symptoms or behaviors and note their severity on an ongoing basis.

Contributing factors. Determining the overall contribution of different factors to a patient’s negative symptoms allows us to target treatments. Sorting out these relative factors can be difficult, however. For example:

• In a patient on antipsychotic treatment who is experiencing psychotic symptoms (eg, persecutory delusions), depressive symptoms, and prominent negative symptoms, the clinician can only guess whether the negative symptoms are primary or secondary.
• In a patient who is socially withdrawn and delusional, withdrawal may be secondary to delusions or may represent a primary negative symptom.
• In a patient on typical antipsychotics, a flat affect may be caused by antipsychotic-induced EPS or it may be a primary negative symptom.
• A disorganized patient with schizophrenia and depression is often unable to convey his or her feelings coherently, so that negative symptoms secondary to affective disturbance may often be mistaken as primary.

Even in research settings, the distinction between primary and secondary symptoms is quite unreliable; nevertheless, it is of great clinical importance. Two strategies may be helpful:

• Consider whether symptoms are specific to the presumed etiology, such as guilt and sadness in depression or cogwheeling and tremor in EPS.
• Treat empirically, and monitor whether negative symptoms improve. If they improve with antidepressant treatment, for example, then depression was the presumable cause. If they improve with anticholinergics, they were presumably secondary to EPS.

Treatment

Negative symptoms are generally viewed as treatment-resistant, but evidence suggests that they do respond to pharmacologic and social interventions (Box). Most responsive to treatment are negative symptoms that occur in association with positive symptoms (psychotic-phase) and secondary negative symptoms caused by neuroleptic medication, depression, or lack of stimulation.

The most effective treatment for secondary symptoms is to target the underlying cause. Neuroleptic-induced akinesia may respond to anticholinergic agents, reduction in antipsychotic dose, or a change in antipsychotic. Using one of the newer-generation antipsychotics (clozapine, risperidone, olanzapine, quetiapine, or ziprasidone) may prevent EPS.

Box

Comorbid depression may require adding an antidepressant, or it may respond directly to an antipsychotic. Lack of stimulation is best handled by placing the patient in a more appropriately stimulating (but not overstimulating) and supportive environment. Nonenduring primary or psychotic-phase negative symptoms respond to effective antipsychotic treatment of the positive symptoms.

Atypical antipsychotics. Conventional antipsychotics (e.g., haloperidol, chlorpromazine) clearly offer some benefit in treating negative symptoms, but they have a much greater effect on positive symptoms.¹⁵ Using higher-than-appropriate doses diminishes their effect on negative symptoms and may result in severe EPS.

Two-thirds of the approximately 35 studies comparing conventional and atypical antipsychotics in treating negative symptoms have found atypicals to be significantly more effective (regardless of which atypical was used). In general, atypical antipsychotics improve negative symptoms by about 25%, compared with 10 to 15% improvement with conventional agents.^16,17

Much of the greater benefit with atypicals appears to be related to their at least equivalent ability to improve positive symptoms without causing EPS. Consequently, the key to improved patient outcomes is appropriate dosing of atypical antipsychotics that reduces positive symptoms optimally without EPS and without the need for an anticholinergic (Figure).

Whether the greater improvement with atypical agents implies an improvement in primary versus secondary negative symptoms is academic.¹⁸ From the patient’s perspective, the greater reduction in negative symptoms is meaningful, regardless of why it occurs.

Other medications. Secondary negative symptoms are most effectively treated with medications directed at the primary etiology. For EPS, change the antipsychotic, reduce the dosage, or add an anticholinergic. For depression, try an antidepressant (preferably a selective serotonin reuptake inhibitor). If a likely contributing factor can be identified, then initiate specific treatment.

Figure
ANTIPSYCHOTICS IMPROVE NEGATIVE SYMPTOMS THROUGH THEIR EFFECT ON PSYCHOSIS

Source: Adapted from Tandon et al. J Psychiatric Res. 1993;27:341-347.

Antipsychotics improve negative symptoms through their effect on positive (psychotic) symptoms, but they do not affect secondary components—such as environmental deprivation and depression—or the primary components of deterioration and premorbid symptoms. Typical and atypical antipsychotics have similar effects on positive symptoms, but atypical antipsychotics carry a lower risk of extrapyramidal side effects.

Empiric therapy—trying one agent and then another in an effort to reduce negative symptoms—is appropriate if done systematically and sequentially. Medications that are found not to be helpful should be discontinued. Electroconvulsive therapy is not effective in treating negative symptoms.

Related resources

• Greden JF, Tandon R (eds). Negative schizophrenic symptoms: pathophysiology and clinical implications. Washington, DC: American Psychiatric Press, 1991.
• Keefe RSE, McEvoy JP (eds). Negative symptom and cognitive deficit treatment response in schizophrenia. Washington, DC: American Psychiatric Press, 2001.

Drug brand names

• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Haloperidol • Haldol
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Ziprasidone • Geodon

Negative symptoms are the major contributor to low function levels and debilitation in most patients with schizophrenia. Poorly motivated patients cannot function adequately at school or work. Relationships with family and friends decay in the face of unresponsive affect and inattention to social cues. Personal interests yield to the dampening influences of anhedonia, apathy, and inattention.

Yet because active psychosis is the most common cause of hospital admission, a primary goal of treatment—and sometimes the only objective of pharmacologic treatment—is to eliminate or reduce positive symptoms. And although controlling positive symptoms is remarkably effective in reducing hospitalizations, patients’ functional capacity improves only minimally as psychosis abates. Even with optimal antipsychotic treatment, negative symptoms tend to persist.

For psychiatrists, the three major challenges of schizophrenia’s negative symptoms are their modest therapeutic response, pervasiveness, and diminution of patients’ quality of life. To help you manage negative symptoms, we suggest the following approach to their assessment and treatment.

Importance of negative symptoms

Schizophrenia is a heterogeneous disorder characterized by positive, negative, cognitive, and mood symptoms. The relative severity of these four pathologic domains varies from case to case and within the same individual over time. Though related, these domains have distinct underlying mechanisms and are differentially related to functional capacity and quality of life. They also show different patterns of response to treatment. Whereas positive symptoms refer to new psychological experiences outside the range of normal (e.g., delusions, hallucinations, suspiciousness, disorganized thinking), negative symptoms represent loss of normal function.

Negative symptoms include blunting of affect, poverty of speech and thought, apathy, anhedonia, reduced social drive, loss of motivation, lack of social interest, and inattention to social or cognitive input. These symptoms have devastating consequences on patients’ lives, and only modest progress has been made in treating them effectively.

From negative to positive. Early investigators^1,2 considered negative symptoms to represent the fundamental defect of schizophrenia. Over the years, however, the importance of negative symptoms was progressively downplayed. Positive symptoms were increasingly emphasized because:

• positive symptoms have a more dramatic and easily recognized presentation
• negative symptoms are more difficult to reliably define and document
• antipsychotics, which revolutionized schizophrenia treatment, produce their most dramatic improvement in positive symptoms.

Renewed interest. The almost universal presence and relative persistence of negative symptoms, and the fact that they represent the most debilitating and refractory aspect of schizophrenic psychopathology, make them difficult to ignore. Consequently, interest in negative symptoms resurged in the 1980s-90s, with intense efforts to better understand them and treat them more effectively.^3-5

Table

SCHIZOPHRENIA’S NEGATIVE SYMPTOMS: PRIMARY AND SECONDARY COMPONENTS

Negative symptoms are now better (but still incompletely) understood, and their treatment has improved but is still inadequate. Because intense effort yielded only modest success, researchers and clinicians have again begun to pay less attention to negative symptoms and shifted their focus to cognition in schizophrenia. Negative symptoms remain relevant, however, because they constitute the main barrier to a better quality of life for patients with schizophrenia.

Assessment for negative symptoms

The four major clinical subgroups of negative symptoms are affective, communicative, conational, and relational.

Affective. Blunted affect—including deficits in facial expression, eye contact, gestures, and voice pattern—is perhaps the most conspicuous negative symptom. In mild form, gestures may seem artificial or mechanical, and the voice is stilted or lacks normal inflection. Patients with severe blunted affect may appear devoid of facial expression or communicative gestures. They may sit impassively with little spontaneous movement, speak in a monotone, and gaze blankly in no particular direction.

Even when conversation becomes emotional, the patient’s affect does not adjust appropriately to reflect his or her feelings. Nor does the patient display even a basic level of understanding or responsiveness that typically characterize casual human interactions. The ability to experience pleasure (anhedonia) and sense of caring (apathy) are also reduced.

Communicative. The patient’s speech may be reduced in quantity (poverty of speech) and information (poverty of content of speech). In mild forms of impoverished speech (alogia), the patient makes brief, unelaborated statements; in the more severe form, the patient can be virtually mute. Whatever speech is present tends to be vague and overly generalized. Periods of silence may occur, either before the patient answers a question (increased latency) or in the midst of a response (blocking).

Conational. The patient may show a lack of drive or goal-directed behavior (avolition). Personal grooming may be poor. Physical activity may be limited. Patients typically have great difficulty following a work schedule or hospital ward routine. They fail to initiate activities, participate grudgingly, and require frequent direction and encouragement.

Continue to: Relational

Relational. Interest in social activities and relationships is reduced (asociality). Even enjoyable and recreational activities are neglected. Interpersonal relations may be of little interest. Friendships become rare and shallow, with little sharing of intimacy. Contacts with family are neglected. Sexual interest declines. As symptoms progress, patients become increasingly isolated.

Primary and secondary symptoms

Negative symptoms are an intrinsic component of schizophrenic psychopathology, and they can also be caused by secondary factors (Table).^6,7 Distinguishing between primary and secondary causes of negative symptoms can help you select appropriate treatment in specific clinical situations.

Primary symptoms. From a longitudinal perspective, the three major components of primary negative symptoms are:

• premorbid negative symptoms (present prior to psychosis onset and associated with poor premorbid functioning)
• psychotic-phase, nonenduring negative symptoms that fluctuate with positive symptoms around periods of psychotic exacerbation
• deteriorative negative symptoms that intensify following each psychotic exacerbation and reflect a decline from premorbid levels of functioning.

Though little can be done to treat the premorbid component, psychotic-phase negative symptoms improve along with positive symptoms (although more slowly).^8,9 Therefore, the best strategy for managing negative symptoms is to treat positive symptoms more effectively. Although there is no specific treatment for deteriorative negative symptoms, the severity of this component appears to be related to the “toxicity of psychosis” and can be reduced by early, effective antipsychotic treatment.^10,11

Secondary negative symptoms occur in association with (and presumably are caused by) factors such as depression, extrapyramidal symptoms (EPS), and environmental deprivation. Secondary negative symptoms usually respond to treatment of the underlying cause.

Assessment

Symptom severity. Assessing the severity of a patient’s negative symptoms on an ongoing basis is a most important first step towards optimal treatment:

• Our objective is to improve patients’ function and quality of life, and negative symptoms compromise both of these more than any other factor.
• Ongoing assessment can track whether prescribed treatments are improving or worsening a patient’s symptoms.

Tools to assess the severity of negative symptoms include the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS).¹² The Scale for the Assessment of Negative Symptoms (SANS)¹³ measures them exclusively, and others such as the Schedule for the Deficit Syndrome (SDS)¹⁴ attempt to classify them into subgroups.

Discussing these instruments is beyond the scope of this article, but they differ greatly in their approach to assessing negative symptoms. Instead of using cumbersome assessment instruments, however, we recommend that you focus on two to four of a patient’s “target” symptoms or behaviors and note their severity on an ongoing basis.

Contributing factors. Determining the overall contribution of different factors to a patient’s negative symptoms allows us to target treatments. Sorting out these relative factors can be difficult, however. For example:

• In a patient on antipsychotic treatment who is experiencing psychotic symptoms (eg, persecutory delusions), depressive symptoms, and prominent negative symptoms, the clinician can only guess whether the negative symptoms are primary or secondary.
• In a patient who is socially withdrawn and delusional, withdrawal may be secondary to delusions or may represent a primary negative symptom.
• In a patient on typical antipsychotics, a flat affect may be caused by antipsychotic-induced EPS or it may be a primary negative symptom.
• A disorganized patient with schizophrenia and depression is often unable to convey his or her feelings coherently, so that negative symptoms secondary to affective disturbance may often be mistaken as primary.

Even in research settings, the distinction between primary and secondary symptoms is quite unreliable; nevertheless, it is of great clinical importance. Two strategies may be helpful:

• Consider whether symptoms are specific to the presumed etiology, such as guilt and sadness in depression or cogwheeling and tremor in EPS.
• Treat empirically, and monitor whether negative symptoms improve. If they improve with antidepressant treatment, for example, then depression was the presumable cause. If they improve with anticholinergics, they were presumably secondary to EPS.

Treatment

Negative symptoms are generally viewed as treatment-resistant, but evidence suggests that they do respond to pharmacologic and social interventions (Box). Most responsive to treatment are negative symptoms that occur in association with positive symptoms (psychotic-phase) and secondary negative symptoms caused by neuroleptic medication, depression, or lack of stimulation.

The most effective treatment for secondary symptoms is to target the underlying cause. Neuroleptic-induced akinesia may respond to anticholinergic agents, reduction in antipsychotic dose, or a change in antipsychotic. Using one of the newer-generation antipsychotics (clozapine, risperidone, olanzapine, quetiapine, or ziprasidone) may prevent EPS.

Box

Comorbid depression may require adding an antidepressant, or it may respond directly to an antipsychotic. Lack of stimulation is best handled by placing the patient in a more appropriately stimulating (but not overstimulating) and supportive environment. Nonenduring primary or psychotic-phase negative symptoms respond to effective antipsychotic treatment of the positive symptoms.

Atypical antipsychotics. Conventional antipsychotics (e.g., haloperidol, chlorpromazine) clearly offer some benefit in treating negative symptoms, but they have a much greater effect on positive symptoms.¹⁵ Using higher-than-appropriate doses diminishes their effect on negative symptoms and may result in severe EPS.

Two-thirds of the approximately 35 studies comparing conventional and atypical antipsychotics in treating negative symptoms have found atypicals to be significantly more effective (regardless of which atypical was used). In general, atypical antipsychotics improve negative symptoms by about 25%, compared with 10 to 15% improvement with conventional agents.^16,17

Much of the greater benefit with atypicals appears to be related to their at least equivalent ability to improve positive symptoms without causing EPS. Consequently, the key to improved patient outcomes is appropriate dosing of atypical antipsychotics that reduces positive symptoms optimally without EPS and without the need for an anticholinergic (Figure).

Whether the greater improvement with atypical agents implies an improvement in primary versus secondary negative symptoms is academic.¹⁸ From the patient’s perspective, the greater reduction in negative symptoms is meaningful, regardless of why it occurs.

Other medications. Secondary negative symptoms are most effectively treated with medications directed at the primary etiology. For EPS, change the antipsychotic, reduce the dosage, or add an anticholinergic. For depression, try an antidepressant (preferably a selective serotonin reuptake inhibitor). If a likely contributing factor can be identified, then initiate specific treatment.

Figure
ANTIPSYCHOTICS IMPROVE NEGATIVE SYMPTOMS THROUGH THEIR EFFECT ON PSYCHOSIS

Source: Adapted from Tandon et al. J Psychiatric Res. 1993;27:341-347.

Antipsychotics improve negative symptoms through their effect on positive (psychotic) symptoms, but they do not affect secondary components—such as environmental deprivation and depression—or the primary components of deterioration and premorbid symptoms. Typical and atypical antipsychotics have similar effects on positive symptoms, but atypical antipsychotics carry a lower risk of extrapyramidal side effects.

Empiric therapy—trying one agent and then another in an effort to reduce negative symptoms—is appropriate if done systematically and sequentially. Medications that are found not to be helpful should be discontinued. Electroconvulsive therapy is not effective in treating negative symptoms.

Related resources

• Greden JF, Tandon R (eds). Negative schizophrenic symptoms: pathophysiology and clinical implications. Washington, DC: American Psychiatric Press, 1991.
• Keefe RSE, McEvoy JP (eds). Negative symptom and cognitive deficit treatment response in schizophrenia. Washington, DC: American Psychiatric Press, 2001.

Drug brand names

• Chlorpromazine • Thorazine
• Clozapine • Clozaril
• Haloperidol • Haldol
• Olanzapine • Zyprexa
• Quetiapine • Seroquel
• Risperidone • Risperdal
• Ziprasidone • Geodon

Depression, anxiety, and psychosis are common complications of Parkinson’s disease (PD) and of the medications used in antiparkinsonian treatment. These psychiatric problems impair patients’ functioning throughout the course of the chronic degenerative disease.

Because medication side effects often call for adjustments and trade-offs in PD treatment, a team effort by the psychiatrist, neurologist, patient, and caregiver is the most effective approach to decision-making. From our experience in such collaborations, here’s what you need to know about PD to be a most-valuable player on that treatment team.

Presentation of PD

The classic triad of PD features consists of a pill-rolling tremor, rigidity, and bradykinesia or slowness of movement. Other common features include postural instability, flexed posture, and other motor-freezing phenomena.

Freezing phenomena occur in the later stages of PD, as the response to dopaminergic therapy becomes erratic and unpredictable. Freezing can range from hesitation—such as when the patient tries to turn or is in a doorway—to transient episodes of total inability to move. These episodes are extremely distressing for both patients and caregivers.

Patients rarely present with the full complement of symptoms, but the presence of tremor at rest and/or bradykinesia is essential for the diagnosis. While motor signs dominate the presentation, cognitive symptoms such as shortened attention span, visuospatial impairment, personality changes, and dementia are also frequently present.

Average age of diagnosis is 60, and more men are affected than women (male-to-female ratio is 3:2). Many causative factors—including genetics and environmental toxins—have been implicated, but the disorder’s etiology remains unknown.

Drug treatment side effects

PD results from the loss of neurons in the substantia nigra that produce the neurotransmitter dopamine. Pharmacologic treatment emphasizes dopamine replacement, dopamine receptor stimulation, or prevention of enzymatic breakdown of dopamine in the synaptic cleft. As treatment of PD is symptomatic and not curative, medications are instituted only when the disease begins to cause functional impairment.

Treatment begins with dopamine agonists (Table). As dopamine agonist monotherapy becomes less effective, levodopa therapy is initiated. Blocking the enzymatic breakdown of dopamine with catechol-O-methyltransferase inhibitors is the next therapeutic strategy.

Within 5 years of starting levodopa therapy 75% of patients experience unsatisfactory motor response, from unpredictable fluctuations to wearing-off phenomena (in which a dose of levodopa does not last as long as it once did). Treatment of advanced PD is complicated by the emergence of psychiatric symptoms, such as hallucinations and psychosis, as dopamine levels are increased in an attempt to smooth the motor response.

The significantly distressing level of disability associated with the prominent side effects of pharmacologic treatment has led to interest in surgical interventions. These range from pallidotomy to implantation of basal ganglia stimulators to transplantation of fetal striatal neurons. The possibility of neuroprotection has also been extensively investigated, with mixed results.

Psychiatric complications of PD

Depression. Clearly, the stress of anticipating and coping with a relentless degenerative disease helps to trigger depression and anxiety in patients with PD. Depression is the most common psychiatric syndrome, with prevalence in PD as high as 42%.¹ Patients with a history of depression are at particular risk.² Those with recent deterioration or advancing severity of PD, akinesia, history of falls, or cognitive impairment are also at increased risk for depression.

Table

MEDICATIONS COMMONLY USED IN MANAGING PARKINSON’S DISEASE

Depression correlates well with the patient’s perception of his or her degree of PD-related disability. Depression symptoms seem to peak early in the illness following diagnosis and in advanced disease.³

Patients may present with symptoms meeting diagnostic criteria ranging from dysthymic disorder to minor depression to major depressive disorder.^1,4 Although they will frequently endorse suicidal ideation, patients with PD have a low rate of suicide. Diagnosing depression, however, may be difficult because its symptoms overlap with those of the underlying neurologic disease:

• Diminished affect and psychomotor slowing may be secondary to the motor features of parkinsonism.
• Diminished concentration may be secondary to cognitive decline rather than depression.

Patients also frequently have a chief complaint of diminished energy or fatigue that should trigger further investigation into other depressive symptoms.^4,5

In addition to the obvious additional suffering it causes, depression in PD predicts impaired social, physical, and role functioning.⁶ Depression in the PD patient also results in higher distress for caregivers.⁷ In one study, depression was identified as a risk factor for development of psychosis in PD patients.⁸

Anxiety is a frequent problem for PD patients, with a prevalence of 33 to 40%.^9,10 Anxiety in PD typically presents with symptoms of panic disorder, generalized anxiety disorder, or social phobia.¹¹ It is comorbid with depression in up to 92% of cases and—like depression—frequently predates the onset of motor symptoms.¹²

Anxiety symptoms have been correlated, although not consistently, with the on-off motor phenomenon often found in advanced PD.¹³ They can also be an adverse effect of many of the antiparkinsonian medications, including anticholinergics, dopamine agonists, catechol-O-methyltransferase inhibitors, and selegiline. Both anxiety and depression have been associated with an increased risk for falls.¹⁴

Psychotic symptoms. Up to 25% of PD patients experience delusions or hallucinations.¹⁵ Risk factors include dementia, sleep disturbance, and—most commonly—the use of dopaminergic agents. Up to one-fifth of patients using dopaminergic drugs experience psychotic symptoms.¹⁶

Psychotic symptoms can occur with or without the clouded sensorium characteristic of delirium. Psychotic symptoms with an associated confusional state can be associated with use of anticholinergic agents and drugs such as selegiline and amantadine.¹⁷ Catechol-O-methyltransferase inhibitors cause more sustained dopaminergic activity of levodopa, which can result in psychotic symptoms. Therefore, the use of all known classes of antiparkinsonian medications has been associated with drug-induced psychosis.

In advanced PD, paranoid delusions, delusions of spousal infidelity, and visual hallucinations are common, whereas negative symptoms and thought disturbances are not.¹⁸ Psychosis may be a more important contributor to caregiver distress than the motor symptoms of PD and may be more likely than any other factor to lead to nursing home placement of the PD patient (Box 1).¹⁵

Psychiatric interventions

Goals for psychiatric treatment of depression, anxiety, and psychosis associated with PD seem relatively straightforward:

• improvement or remission of psychiatric symptoms
• restoration of optimal patient functioning.

Ideally, these goals would be achieved without causing sedation, orthostatic hypotension, or exacerbating motor symptoms. The older age of patients and the progressive nature of this neurodegenerative disorder predispose patients to cognitive side effects. Unfortunately, despite the high prevalence of psychiatric disturbances in PD, evidence with which to evaluate treatment efficacy and safety and to guide treatment selection is extremely limited.

For depression associated with PD, extensive clinical experience supports the efficacy of tricyclic antidepressants. Even so, selective serotonin reuptake inhibitors (SSRIs) are the preferred treatment, although only open-label trials and case reports support their efficacy.^5,12 Compared with tricyclics, SSRIs exhibit a relative lack of problems with sedation, orthostatic hypotension, and memory-impairing anticholinergic side effects. While case reports have cited worsening of motor symptoms with SSRIs, a recent prospective study found no significant worsening of PD symptoms during treatment with citalopram, fluoxetine, fluvoxamine, or sertraline.¹⁹ Co-administration of an SSRI with selegiline is not absolutely contraindicated, but the combination does carry a very small risk of development of serotonin syndrome.^1,5

Box 1

Data are even more scant on the safe use of other antidepressants in PD. Electroconvulsive therapy has been proven helpful in refractory cases and sometimes results in transient motor symptom improvement.^1,5,12 While clinical experience suggests that psychotherapy frequently helps, no extensive controlled studies exist. One small study suggests the efficacy of structured cognitive psychotherapy.²⁰

Anxiety. No studies have examined the treatment of anxiety in PD patients. Given the extremely high comorbidity of anxiety with depression, antidepressants should probably be considered as a first-line pharmacotherapy. Benzodiazepines should be used cautiously, as they increase the risk of falls, sedation, and confusion in older patients. One small controlled study found that buspirone was well tolerated in PD patients at low dosages (10 to 40 mg/d), but anxiety did not improve. At high dosages (100 mg/d), anxiety worsened.²¹

Psychosis. Data on use of antipsychotic agents in PD are also limited, but some evidence supports their use in treating PD-related psychotic symptoms. While conventional antipsychotics can help control psychosis, the potential is high for worsening of parkinsonian symptoms due to D2 receptor blockade.

Among the atypical antipsychotics, clozapine has been most extensively studied in PD and has been shown in open and double-blind trials to be effective and well tolerated at low dosages (6.25 to 50 mg/d). A limited number of open studies of some of the newer atypicals have been performed. While extreme caution must be used in comparing data from these studies due to highly variable dosing and other study design issues, clozapine and quetiapine appear to be the agents best tolerated by PD patients.^12,18,22 Initial antipsychotic dosing should be low and escalation cautious—regardless of the agent chosen—because of the dose-related potential for worsening of parkinsonian symptoms, sedation, and orthostatic hypotension.

A team approach to treatment

Because psychiatric and PD symptoms and treatments are closely interrelated, the psychiatrist, neurologist, patient, and caregiver must collaborate for the best therapeutic result. A simplistic approach to treatment can result in a catastrophic downward spiral in patient functioning.

Often, compromises must be made between optimal control of parkinsonian and psychiatric symptoms to achieve the best overall patient function. Patients and caregivers must be counseled about possible psychiatric symptoms associated with PD and antiparkinsonian therapy, as well as the potential for adverse effects from psychiatric medications. With this knowledge, patients and caregivers can help assess the severity of symptoms and set treatment priorities, depending on how symptoms may be affecting the patient’s level of functioning. For example, if an effective antiparkinsonian regimen has triggered infrequent, nondistressing hallucinations with preserved insight, intervention may not be required beyond patient and caregiver education (Box 2).

Patient workup. When intervention is required for psychiatric symptoms, it should begin with careful neurologic evaluation. Triggering factors such as infections (commonly urinary tract infections and pneumonia), metabolic disorders (hyperglycemia, hypothyroidism), subdural hematomas (if the patient is falling), and drug interactions should be ruled out or appropriately addressed.

Next, try to sequentially eliminate antiparkinsonian medications until the psychosis resolves or motor function worsens.²³ Because of considerable overlap between PD symptoms and depression (psychomotor retardation, fatigue, and anergia), optimizing PD therapy sometimes can result in substantial psychiatric improvement. Some evidence also suggests that the dopamine agonist pramipexole may be effective in treating both PD and depression.⁵

When psychiatric medications are necessary for depression, anxiety, or psychosis, carefully review target symptoms, treatment expectations, and possible adverse effects with the patient and caregiver. Keep in mind the progressive nature of PD and, in addition to frequent monitoring, educate and encourage caregivers to immediately report any suspected adverse effects.

Any motor function deterioration should trigger a re-evaluation of psychotropic medications before you presume that the patient’s PD is progressing. Because antiparkinsonian drug regimens change over time, review the patient’s medications at each appointment, and alert patients and caregivers to potential psychiatric complications of any new medication.

Caregiver treatment In addition to treating the patient, it is important to monitor the impact of psychiatric symptoms and PD on the patient’s caregiver. Frequently assess whether the caregiver and patient have adequate social supports, and address any emerging needs. Useful interventions include caregiver counseling, referrals to support groups, and respite care.²⁴

Box 2

Related resources

• Parkinson’s Disease Foundation: http://www.pdf.org
• American Parkinson Disease Association: http://apdaparkinson.com
• National Parkinson Foundation: http://www.parkinson.org
• Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease 2001: treatment guidelines. Neurology 2001;56:5(suppl):S1-S88.

Drug brand names

• Alprazolam • Xanax
• Amantadine • Symmetrel
• Benztropine • Cogentin
• Biperiden • Akineton
• Buspirone • Buspar
• Carbidopa-levodopa • Sinemet
• Citalopram • Celexa
• Clozapine • Clozaril
• Entacapone • Comtan
• Fluvoxamine • Luvox
• Hyoscyamine • Levsin
• Paroxetine • Paxil
• Pergolide • Permax
• Pramipexole • Mirapex
• Ropinirole • Requip
• Selegeline • Eldepryl
• Sertraline • Zoloft
• Tolcapone • Tasmar
• Trihexyphenidyl • Artane
• Trifluoperazine • Stelazine

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Depression, anxiety, and psychosis are common complications of Parkinson’s disease (PD) and of the medications used in antiparkinsonian treatment. These psychiatric problems impair patients’ functioning throughout the course of the chronic degenerative disease.

Because medication side effects often call for adjustments and trade-offs in PD treatment, a team effort by the psychiatrist, neurologist, patient, and caregiver is the most effective approach to decision-making. From our experience in such collaborations, here’s what you need to know about PD to be a most-valuable player on that treatment team.

Presentation of PD

The classic triad of PD features consists of a pill-rolling tremor, rigidity, and bradykinesia or slowness of movement. Other common features include postural instability, flexed posture, and other motor-freezing phenomena.

Freezing phenomena occur in the later stages of PD, as the response to dopaminergic therapy becomes erratic and unpredictable. Freezing can range from hesitation—such as when the patient tries to turn or is in a doorway—to transient episodes of total inability to move. These episodes are extremely distressing for both patients and caregivers.

Patients rarely present with the full complement of symptoms, but the presence of tremor at rest and/or bradykinesia is essential for the diagnosis. While motor signs dominate the presentation, cognitive symptoms such as shortened attention span, visuospatial impairment, personality changes, and dementia are also frequently present.

Average age of diagnosis is 60, and more men are affected than women (male-to-female ratio is 3:2). Many causative factors—including genetics and environmental toxins—have been implicated, but the disorder’s etiology remains unknown.

Drug treatment side effects

PD results from the loss of neurons in the substantia nigra that produce the neurotransmitter dopamine. Pharmacologic treatment emphasizes dopamine replacement, dopamine receptor stimulation, or prevention of enzymatic breakdown of dopamine in the synaptic cleft. As treatment of PD is symptomatic and not curative, medications are instituted only when the disease begins to cause functional impairment.

Treatment begins with dopamine agonists (Table). As dopamine agonist monotherapy becomes less effective, levodopa therapy is initiated. Blocking the enzymatic breakdown of dopamine with catechol-O-methyltransferase inhibitors is the next therapeutic strategy.

Within 5 years of starting levodopa therapy 75% of patients experience unsatisfactory motor response, from unpredictable fluctuations to wearing-off phenomena (in which a dose of levodopa does not last as long as it once did). Treatment of advanced PD is complicated by the emergence of psychiatric symptoms, such as hallucinations and psychosis, as dopamine levels are increased in an attempt to smooth the motor response.

The significantly distressing level of disability associated with the prominent side effects of pharmacologic treatment has led to interest in surgical interventions. These range from pallidotomy to implantation of basal ganglia stimulators to transplantation of fetal striatal neurons. The possibility of neuroprotection has also been extensively investigated, with mixed results.

Psychiatric complications of PD

Depression. Clearly, the stress of anticipating and coping with a relentless degenerative disease helps to trigger depression and anxiety in patients with PD. Depression is the most common psychiatric syndrome, with prevalence in PD as high as 42%.¹ Patients with a history of depression are at particular risk.² Those with recent deterioration or advancing severity of PD, akinesia, history of falls, or cognitive impairment are also at increased risk for depression.

Table

MEDICATIONS COMMONLY USED IN MANAGING PARKINSON’S DISEASE

Depression correlates well with the patient’s perception of his or her degree of PD-related disability. Depression symptoms seem to peak early in the illness following diagnosis and in advanced disease.³

Patients may present with symptoms meeting diagnostic criteria ranging from dysthymic disorder to minor depression to major depressive disorder.^1,4 Although they will frequently endorse suicidal ideation, patients with PD have a low rate of suicide. Diagnosing depression, however, may be difficult because its symptoms overlap with those of the underlying neurologic disease:

• Diminished affect and psychomotor slowing may be secondary to the motor features of parkinsonism.
• Diminished concentration may be secondary to cognitive decline rather than depression.

Patients also frequently have a chief complaint of diminished energy or fatigue that should trigger further investigation into other depressive symptoms.^4,5

In addition to the obvious additional suffering it causes, depression in PD predicts impaired social, physical, and role functioning.⁶ Depression in the PD patient also results in higher distress for caregivers.⁷ In one study, depression was identified as a risk factor for development of psychosis in PD patients.⁸

Anxiety is a frequent problem for PD patients, with a prevalence of 33 to 40%.^9,10 Anxiety in PD typically presents with symptoms of panic disorder, generalized anxiety disorder, or social phobia.¹¹ It is comorbid with depression in up to 92% of cases and—like depression—frequently predates the onset of motor symptoms.¹²

Anxiety symptoms have been correlated, although not consistently, with the on-off motor phenomenon often found in advanced PD.¹³ They can also be an adverse effect of many of the antiparkinsonian medications, including anticholinergics, dopamine agonists, catechol-O-methyltransferase inhibitors, and selegiline. Both anxiety and depression have been associated with an increased risk for falls.¹⁴

Psychotic symptoms. Up to 25% of PD patients experience delusions or hallucinations.¹⁵ Risk factors include dementia, sleep disturbance, and—most commonly—the use of dopaminergic agents. Up to one-fifth of patients using dopaminergic drugs experience psychotic symptoms.¹⁶

Psychotic symptoms can occur with or without the clouded sensorium characteristic of delirium. Psychotic symptoms with an associated confusional state can be associated with use of anticholinergic agents and drugs such as selegiline and amantadine.¹⁷ Catechol-O-methyltransferase inhibitors cause more sustained dopaminergic activity of levodopa, which can result in psychotic symptoms. Therefore, the use of all known classes of antiparkinsonian medications has been associated with drug-induced psychosis.

In advanced PD, paranoid delusions, delusions of spousal infidelity, and visual hallucinations are common, whereas negative symptoms and thought disturbances are not.¹⁸ Psychosis may be a more important contributor to caregiver distress than the motor symptoms of PD and may be more likely than any other factor to lead to nursing home placement of the PD patient (Box 1).¹⁵

Psychiatric interventions

Goals for psychiatric treatment of depression, anxiety, and psychosis associated with PD seem relatively straightforward:

• improvement or remission of psychiatric symptoms
• restoration of optimal patient functioning.

Ideally, these goals would be achieved without causing sedation, orthostatic hypotension, or exacerbating motor symptoms. The older age of patients and the progressive nature of this neurodegenerative disorder predispose patients to cognitive side effects. Unfortunately, despite the high prevalence of psychiatric disturbances in PD, evidence with which to evaluate treatment efficacy and safety and to guide treatment selection is extremely limited.

For depression associated with PD, extensive clinical experience supports the efficacy of tricyclic antidepressants. Even so, selective serotonin reuptake inhibitors (SSRIs) are the preferred treatment, although only open-label trials and case reports support their efficacy.^5,12 Compared with tricyclics, SSRIs exhibit a relative lack of problems with sedation, orthostatic hypotension, and memory-impairing anticholinergic side effects. While case reports have cited worsening of motor symptoms with SSRIs, a recent prospective study found no significant worsening of PD symptoms during treatment with citalopram, fluoxetine, fluvoxamine, or sertraline.¹⁹ Co-administration of an SSRI with selegiline is not absolutely contraindicated, but the combination does carry a very small risk of development of serotonin syndrome.^1,5

Box 1

Data are even more scant on the safe use of other antidepressants in PD. Electroconvulsive therapy has been proven helpful in refractory cases and sometimes results in transient motor symptom improvement.^1,5,12 While clinical experience suggests that psychotherapy frequently helps, no extensive controlled studies exist. One small study suggests the efficacy of structured cognitive psychotherapy.²⁰

Anxiety. No studies have examined the treatment of anxiety in PD patients. Given the extremely high comorbidity of anxiety with depression, antidepressants should probably be considered as a first-line pharmacotherapy. Benzodiazepines should be used cautiously, as they increase the risk of falls, sedation, and confusion in older patients. One small controlled study found that buspirone was well tolerated in PD patients at low dosages (10 to 40 mg/d), but anxiety did not improve. At high dosages (100 mg/d), anxiety worsened.²¹

Psychosis. Data on use of antipsychotic agents in PD are also limited, but some evidence supports their use in treating PD-related psychotic symptoms. While conventional antipsychotics can help control psychosis, the potential is high for worsening of parkinsonian symptoms due to D2 receptor blockade.

Among the atypical antipsychotics, clozapine has been most extensively studied in PD and has been shown in open and double-blind trials to be effective and well tolerated at low dosages (6.25 to 50 mg/d). A limited number of open studies of some of the newer atypicals have been performed. While extreme caution must be used in comparing data from these studies due to highly variable dosing and other study design issues, clozapine and quetiapine appear to be the agents best tolerated by PD patients.^12,18,22 Initial antipsychotic dosing should be low and escalation cautious—regardless of the agent chosen—because of the dose-related potential for worsening of parkinsonian symptoms, sedation, and orthostatic hypotension.

A team approach to treatment

Because psychiatric and PD symptoms and treatments are closely interrelated, the psychiatrist, neurologist, patient, and caregiver must collaborate for the best therapeutic result. A simplistic approach to treatment can result in a catastrophic downward spiral in patient functioning.

Often, compromises must be made between optimal control of parkinsonian and psychiatric symptoms to achieve the best overall patient function. Patients and caregivers must be counseled about possible psychiatric symptoms associated with PD and antiparkinsonian therapy, as well as the potential for adverse effects from psychiatric medications. With this knowledge, patients and caregivers can help assess the severity of symptoms and set treatment priorities, depending on how symptoms may be affecting the patient’s level of functioning. For example, if an effective antiparkinsonian regimen has triggered infrequent, nondistressing hallucinations with preserved insight, intervention may not be required beyond patient and caregiver education (Box 2).

Patient workup. When intervention is required for psychiatric symptoms, it should begin with careful neurologic evaluation. Triggering factors such as infections (commonly urinary tract infections and pneumonia), metabolic disorders (hyperglycemia, hypothyroidism), subdural hematomas (if the patient is falling), and drug interactions should be ruled out or appropriately addressed.

Next, try to sequentially eliminate antiparkinsonian medications until the psychosis resolves or motor function worsens.²³ Because of considerable overlap between PD symptoms and depression (psychomotor retardation, fatigue, and anergia), optimizing PD therapy sometimes can result in substantial psychiatric improvement. Some evidence also suggests that the dopamine agonist pramipexole may be effective in treating both PD and depression.⁵

When psychiatric medications are necessary for depression, anxiety, or psychosis, carefully review target symptoms, treatment expectations, and possible adverse effects with the patient and caregiver. Keep in mind the progressive nature of PD and, in addition to frequent monitoring, educate and encourage caregivers to immediately report any suspected adverse effects.

Any motor function deterioration should trigger a re-evaluation of psychotropic medications before you presume that the patient’s PD is progressing. Because antiparkinsonian drug regimens change over time, review the patient’s medications at each appointment, and alert patients and caregivers to potential psychiatric complications of any new medication.

Caregiver treatment In addition to treating the patient, it is important to monitor the impact of psychiatric symptoms and PD on the patient’s caregiver. Frequently assess whether the caregiver and patient have adequate social supports, and address any emerging needs. Useful interventions include caregiver counseling, referrals to support groups, and respite care.²⁴

Box 2

Related resources

• Parkinson’s Disease Foundation: http://www.pdf.org
• American Parkinson Disease Association: http://apdaparkinson.com
• National Parkinson Foundation: http://www.parkinson.org
• Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease 2001: treatment guidelines. Neurology 2001;56:5(suppl):S1-S88.

Drug brand names

• Alprazolam • Xanax
• Amantadine • Symmetrel
• Benztropine • Cogentin
• Biperiden • Akineton
• Buspirone • Buspar
• Carbidopa-levodopa • Sinemet
• Citalopram • Celexa
• Clozapine • Clozaril
• Entacapone • Comtan
• Fluvoxamine • Luvox
• Hyoscyamine • Levsin
• Paroxetine • Paxil
• Pergolide • Permax
• Pramipexole • Mirapex
• Ropinirole • Requip
• Selegeline • Eldepryl
• Sertraline • Zoloft
• Tolcapone • Tasmar
• Trihexyphenidyl • Artane
• Trifluoperazine • Stelazine

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Depression, anxiety, and psychosis are common complications of Parkinson’s disease (PD) and of the medications used in antiparkinsonian treatment. These psychiatric problems impair patients’ functioning throughout the course of the chronic degenerative disease.

Because medication side effects often call for adjustments and trade-offs in PD treatment, a team effort by the psychiatrist, neurologist, patient, and caregiver is the most effective approach to decision-making. From our experience in such collaborations, here’s what you need to know about PD to be a most-valuable player on that treatment team.

Presentation of PD

The classic triad of PD features consists of a pill-rolling tremor, rigidity, and bradykinesia or slowness of movement. Other common features include postural instability, flexed posture, and other motor-freezing phenomena.

Freezing phenomena occur in the later stages of PD, as the response to dopaminergic therapy becomes erratic and unpredictable. Freezing can range from hesitation—such as when the patient tries to turn or is in a doorway—to transient episodes of total inability to move. These episodes are extremely distressing for both patients and caregivers.

Patients rarely present with the full complement of symptoms, but the presence of tremor at rest and/or bradykinesia is essential for the diagnosis. While motor signs dominate the presentation, cognitive symptoms such as shortened attention span, visuospatial impairment, personality changes, and dementia are also frequently present.

Average age of diagnosis is 60, and more men are affected than women (male-to-female ratio is 3:2). Many causative factors—including genetics and environmental toxins—have been implicated, but the disorder’s etiology remains unknown.

Drug treatment side effects

PD results from the loss of neurons in the substantia nigra that produce the neurotransmitter dopamine. Pharmacologic treatment emphasizes dopamine replacement, dopamine receptor stimulation, or prevention of enzymatic breakdown of dopamine in the synaptic cleft. As treatment of PD is symptomatic and not curative, medications are instituted only when the disease begins to cause functional impairment.

Treatment begins with dopamine agonists (Table). As dopamine agonist monotherapy becomes less effective, levodopa therapy is initiated. Blocking the enzymatic breakdown of dopamine with catechol-O-methyltransferase inhibitors is the next therapeutic strategy.

Within 5 years of starting levodopa therapy 75% of patients experience unsatisfactory motor response, from unpredictable fluctuations to wearing-off phenomena (in which a dose of levodopa does not last as long as it once did). Treatment of advanced PD is complicated by the emergence of psychiatric symptoms, such as hallucinations and psychosis, as dopamine levels are increased in an attempt to smooth the motor response.

The significantly distressing level of disability associated with the prominent side effects of pharmacologic treatment has led to interest in surgical interventions. These range from pallidotomy to implantation of basal ganglia stimulators to transplantation of fetal striatal neurons. The possibility of neuroprotection has also been extensively investigated, with mixed results.

Psychiatric complications of PD

Depression. Clearly, the stress of anticipating and coping with a relentless degenerative disease helps to trigger depression and anxiety in patients with PD. Depression is the most common psychiatric syndrome, with prevalence in PD as high as 42%.¹ Patients with a history of depression are at particular risk.² Those with recent deterioration or advancing severity of PD, akinesia, history of falls, or cognitive impairment are also at increased risk for depression.

Table

MEDICATIONS COMMONLY USED IN MANAGING PARKINSON’S DISEASE

Depression correlates well with the patient’s perception of his or her degree of PD-related disability. Depression symptoms seem to peak early in the illness following diagnosis and in advanced disease.³

Patients may present with symptoms meeting diagnostic criteria ranging from dysthymic disorder to minor depression to major depressive disorder.^1,4 Although they will frequently endorse suicidal ideation, patients with PD have a low rate of suicide. Diagnosing depression, however, may be difficult because its symptoms overlap with those of the underlying neurologic disease:

• Diminished affect and psychomotor slowing may be secondary to the motor features of parkinsonism.
• Diminished concentration may be secondary to cognitive decline rather than depression.

Patients also frequently have a chief complaint of diminished energy or fatigue that should trigger further investigation into other depressive symptoms.^4,5

In addition to the obvious additional suffering it causes, depression in PD predicts impaired social, physical, and role functioning.⁶ Depression in the PD patient also results in higher distress for caregivers.⁷ In one study, depression was identified as a risk factor for development of psychosis in PD patients.⁸

Anxiety is a frequent problem for PD patients, with a prevalence of 33 to 40%.^9,10 Anxiety in PD typically presents with symptoms of panic disorder, generalized anxiety disorder, or social phobia.¹¹ It is comorbid with depression in up to 92% of cases and—like depression—frequently predates the onset of motor symptoms.¹²

Anxiety symptoms have been correlated, although not consistently, with the on-off motor phenomenon often found in advanced PD.¹³ They can also be an adverse effect of many of the antiparkinsonian medications, including anticholinergics, dopamine agonists, catechol-O-methyltransferase inhibitors, and selegiline. Both anxiety and depression have been associated with an increased risk for falls.¹⁴

Psychotic symptoms. Up to 25% of PD patients experience delusions or hallucinations.¹⁵ Risk factors include dementia, sleep disturbance, and—most commonly—the use of dopaminergic agents. Up to one-fifth of patients using dopaminergic drugs experience psychotic symptoms.¹⁶

Psychotic symptoms can occur with or without the clouded sensorium characteristic of delirium. Psychotic symptoms with an associated confusional state can be associated with use of anticholinergic agents and drugs such as selegiline and amantadine.¹⁷ Catechol-O-methyltransferase inhibitors cause more sustained dopaminergic activity of levodopa, which can result in psychotic symptoms. Therefore, the use of all known classes of antiparkinsonian medications has been associated with drug-induced psychosis.

In advanced PD, paranoid delusions, delusions of spousal infidelity, and visual hallucinations are common, whereas negative symptoms and thought disturbances are not.¹⁸ Psychosis may be a more important contributor to caregiver distress than the motor symptoms of PD and may be more likely than any other factor to lead to nursing home placement of the PD patient (Box 1).¹⁵

Psychiatric interventions

Goals for psychiatric treatment of depression, anxiety, and psychosis associated with PD seem relatively straightforward:

• improvement or remission of psychiatric symptoms
• restoration of optimal patient functioning.

Ideally, these goals would be achieved without causing sedation, orthostatic hypotension, or exacerbating motor symptoms. The older age of patients and the progressive nature of this neurodegenerative disorder predispose patients to cognitive side effects. Unfortunately, despite the high prevalence of psychiatric disturbances in PD, evidence with which to evaluate treatment efficacy and safety and to guide treatment selection is extremely limited.

For depression associated with PD, extensive clinical experience supports the efficacy of tricyclic antidepressants. Even so, selective serotonin reuptake inhibitors (SSRIs) are the preferred treatment, although only open-label trials and case reports support their efficacy.^5,12 Compared with tricyclics, SSRIs exhibit a relative lack of problems with sedation, orthostatic hypotension, and memory-impairing anticholinergic side effects. While case reports have cited worsening of motor symptoms with SSRIs, a recent prospective study found no significant worsening of PD symptoms during treatment with citalopram, fluoxetine, fluvoxamine, or sertraline.¹⁹ Co-administration of an SSRI with selegiline is not absolutely contraindicated, but the combination does carry a very small risk of development of serotonin syndrome.^1,5

Box 1

Data are even more scant on the safe use of other antidepressants in PD. Electroconvulsive therapy has been proven helpful in refractory cases and sometimes results in transient motor symptom improvement.^1,5,12 While clinical experience suggests that psychotherapy frequently helps, no extensive controlled studies exist. One small study suggests the efficacy of structured cognitive psychotherapy.²⁰

Anxiety. No studies have examined the treatment of anxiety in PD patients. Given the extremely high comorbidity of anxiety with depression, antidepressants should probably be considered as a first-line pharmacotherapy. Benzodiazepines should be used cautiously, as they increase the risk of falls, sedation, and confusion in older patients. One small controlled study found that buspirone was well tolerated in PD patients at low dosages (10 to 40 mg/d), but anxiety did not improve. At high dosages (100 mg/d), anxiety worsened.²¹

Psychosis. Data on use of antipsychotic agents in PD are also limited, but some evidence supports their use in treating PD-related psychotic symptoms. While conventional antipsychotics can help control psychosis, the potential is high for worsening of parkinsonian symptoms due to D2 receptor blockade.

Among the atypical antipsychotics, clozapine has been most extensively studied in PD and has been shown in open and double-blind trials to be effective and well tolerated at low dosages (6.25 to 50 mg/d). A limited number of open studies of some of the newer atypicals have been performed. While extreme caution must be used in comparing data from these studies due to highly variable dosing and other study design issues, clozapine and quetiapine appear to be the agents best tolerated by PD patients.^12,18,22 Initial antipsychotic dosing should be low and escalation cautious—regardless of the agent chosen—because of the dose-related potential for worsening of parkinsonian symptoms, sedation, and orthostatic hypotension.

A team approach to treatment

Because psychiatric and PD symptoms and treatments are closely interrelated, the psychiatrist, neurologist, patient, and caregiver must collaborate for the best therapeutic result. A simplistic approach to treatment can result in a catastrophic downward spiral in patient functioning.

Often, compromises must be made between optimal control of parkinsonian and psychiatric symptoms to achieve the best overall patient function. Patients and caregivers must be counseled about possible psychiatric symptoms associated with PD and antiparkinsonian therapy, as well as the potential for adverse effects from psychiatric medications. With this knowledge, patients and caregivers can help assess the severity of symptoms and set treatment priorities, depending on how symptoms may be affecting the patient’s level of functioning. For example, if an effective antiparkinsonian regimen has triggered infrequent, nondistressing hallucinations with preserved insight, intervention may not be required beyond patient and caregiver education (Box 2).

Patient workup. When intervention is required for psychiatric symptoms, it should begin with careful neurologic evaluation. Triggering factors such as infections (commonly urinary tract infections and pneumonia), metabolic disorders (hyperglycemia, hypothyroidism), subdural hematomas (if the patient is falling), and drug interactions should be ruled out or appropriately addressed.

Next, try to sequentially eliminate antiparkinsonian medications until the psychosis resolves or motor function worsens.²³ Because of considerable overlap between PD symptoms and depression (psychomotor retardation, fatigue, and anergia), optimizing PD therapy sometimes can result in substantial psychiatric improvement. Some evidence also suggests that the dopamine agonist pramipexole may be effective in treating both PD and depression.⁵

When psychiatric medications are necessary for depression, anxiety, or psychosis, carefully review target symptoms, treatment expectations, and possible adverse effects with the patient and caregiver. Keep in mind the progressive nature of PD and, in addition to frequent monitoring, educate and encourage caregivers to immediately report any suspected adverse effects.

Any motor function deterioration should trigger a re-evaluation of psychotropic medications before you presume that the patient’s PD is progressing. Because antiparkinsonian drug regimens change over time, review the patient’s medications at each appointment, and alert patients and caregivers to potential psychiatric complications of any new medication.

Caregiver treatment In addition to treating the patient, it is important to monitor the impact of psychiatric symptoms and PD on the patient’s caregiver. Frequently assess whether the caregiver and patient have adequate social supports, and address any emerging needs. Useful interventions include caregiver counseling, referrals to support groups, and respite care.²⁴

Box 2

Related resources

• Parkinson’s Disease Foundation: http://www.pdf.org
• American Parkinson Disease Association: http://apdaparkinson.com
• National Parkinson Foundation: http://www.parkinson.org
• Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease 2001: treatment guidelines. Neurology 2001;56:5(suppl):S1-S88.

Drug brand names

• Alprazolam • Xanax
• Amantadine • Symmetrel
• Benztropine • Cogentin
• Biperiden • Akineton
• Buspirone • Buspar
• Carbidopa-levodopa • Sinemet
• Citalopram • Celexa
• Clozapine • Clozaril
• Entacapone • Comtan
• Fluvoxamine • Luvox
• Hyoscyamine • Levsin
• Paroxetine • Paxil
• Pergolide • Permax
• Pramipexole • Mirapex
• Ropinirole • Requip
• Selegeline • Eldepryl
• Sertraline • Zoloft
• Tolcapone • Tasmar
• Trihexyphenidyl • Artane
• Trifluoperazine • Stelazine

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

A growing body of evidence suggests that psychiatrists have much to offer patients with severe irritable bowel syndrome (IBS). Behavioral and psychotherapeutic approaches are showing promise in relieving both GI and mood disturbances.

Treating patients with IBS with medications designed to influence only gut function can be frustrating. Those with refractory symptoms may be extremely sensitive to drug side effects, and they often report that medical management worsens or does not improve their symptoms. They experiment with alternative medicines and wander from physician to physician in a disappointing search for a “cure.”

Let’s look at evidence on the efficacy of individual and group behavioral therapies, hypnotherapy, biofeedback, and combination medical and behavioral treatment.

Psychotherapeutic approaches

IBS is a common gastrointestinal disorder that is characterized by abdominal discomfort and changes in bowel habits (Boxes 1 and 2). Patients with severe IBS symptoms often bring significant psychological impairment and psychosocial trauma to clinical encounters.^1,2 They respond poorly to standard medical management, and evidence supporting the efficacy of medical treatments for IBS remains weak.^3,4

Box 1

In 1983, the first controlled trial of psychodynamic psychotherapy for IBS showed dramatic reductions in symptoms.⁵ A subsequent series of high-quality articles in the early 1990s also showed that interpersonal psychotherapy (with greater interaction between therapist and patient) could significantly decrease IBS symptoms.

Persistent improvement. In one randomized controlled trial,⁶ 102 patients with IBS received either standard medical treatment or 10 hours of dynamically oriented individual psychotherapy in combination with standard medical treatment. After 3 months, patients who received psychotherapy showed significantly greater improvement in somatic symptoms and emotional well-being, compared with those who received medical treatment only.

Interestingly, this difference persisted 1 year after the study ended. GI symptoms and the emotional well-being of patients who received combination therapy continued to improve, whereas the physical and emotional status of those who received only standard medical treatment deteriorated.

In a second study,⁷ 101 patients with severe IBS symptoms continued to receive medical treatment but were randomly divided into two groups:

• Study subjects received 8 hours of dynamically oriented psychotherapy.
• Control patients met with a psychiatrist who engaged in “supportive listening” but delivered no psychotherapy. This strategy was adopted to control for the effect of the psychiatrist’s presence.

Assessments included patients’ self-reports of symptoms, ratings of GI symptoms by the treating gastroenterologists, and measures of depression, anxiety, and health care utilization. Patients who received psychotherapy reported significant improvements in bowel symptoms (e.g., diarrhea, constipation, bloating, and abdominal pain). Likewise, the gastroenterologist who rated patients’ GI symptoms felt that those who received psychotherapy improved significantly across the entire spectrum of GI symptoms. The improvements were maintained at 1-year follow-up.

By comparison, the control patients reported worsening symptoms, as did subjects who dropped out. Patients who received psychotherapy also made significantly fewer outpatient visits to gastroenterologists, compared with controls (p<0.001).

Cognitive-behavioral therapy

Cognitive-behavioral therapy (CBT) is emerging as a major psychotherapeutic tool for treating mood disorders, anxiety disorders, and somatic syndromes associated with psychosocial distress. CBT also is showing promise for patients with moderate to severe IBS and those with IBS and concomitant anxiety or mood disorders. Studies consistently show that CBT is superior to standard medical management or the use of support groups or other behavioral treatments alone.

Reduced symptoms. In an early trial of CBT, 17 patients with IBS experienced significantly less abdominal pain and diarrhea after participating in a program of progressive relaxation, education about bowel functioning, use of thermal biofeedback, and stress coping techniques based on CBT. Overall, 64% of the patients improved.⁸

The same investigators then assigned 90 patients to 12 sessions of CBT, given over 8 weeks with or without meditation and biofeedback. Patients with axis I psychiatric diagnoses tended to respond poorly to CBT. The authors concluded that a careful pretreatment psychological workup is important to identify patients with IBS who would benefit most from CBT.⁹

As a follow-up, these investigators randomly assigned 20 patients to intensive individualized CBT (10 sessions over 8 weeks) or 8 weeks of daily GI symptom monitoring. Patients who received CBT had significantly fewer GI symptoms than did the symptom-monitoring group (p = 0.005). With CBT, 80% improved clinically, compared with only 10% in the control group. Improvements in the CBT group persisted at 3 months’ follow-up. Improved GI symptoms also were correlated with increased positive thoughts and reduced negative automatic thoughts (i.e., negative self-image).¹⁰

Box 2

Group therapy. In a study of group rather than individualized CBT, 45 patients with severe IBS symptoms were randomly assigned to either a group CBT module (n = 25) or a waiting list control group (n = 20). Patients received eight 2-hour group CBT sessions over 3 months, then were followed an average of 2.25 years. Their abdominal pain, number of successful coping behavioral strategies, and avoidance of negative situations improved significantly—compared with the waiting list controls—and persisted during follow-up. The authors concluded that group CBT is effective for alleviating IBS symptoms and improving patients’ coping strategies.¹¹

CBT vs. support groups. In a study comparing the effectiveness of CBT and an IBS self-help support group, 34 patients were randomly assigned to:

• individualized CBT (study group)
• a self-help support group
• or a symptom-monitoring waiting list (control group).

Each group was followed for 8 weeks. GI symptoms were reduced significantly in patients who received individualized CBT, compared with the support group or controls. Anxiety and depression in the CBT group also remained significantly improved 3 months later, compared with both other groups.¹²

Group psychotherapy

Group psychotherapy for IBS treatment can be more cost-effective than individual therapy, but its success depends on whether patients accept a group format. Data on the use of group psychotherapeutic approaches are largely favorable.

As described previously, one study demonstrated that group CBT reduced abdominal pain and diarrhea and improved symptoms overall.¹¹ In another study, 20 patients with refractory IBS underwent 6 weeks of group behavioral and didactic psychotherapy. GI symptoms, dysphoria, and psychological distress improved significantly in all patients, and their interpersonal sensitivity and hostility were reduced. These improvements persisted 6 months later.¹²

A recent review suggests that cognitive-behavioral group psychotherapy may be highly effective in patients with IBS. These authors concluded that CBT can improve patients’ mood and other emotional symptoms, reduce their pain, and improve well-being and coping ability.¹⁴

Hypnotherapy

Researchers in Manchester, UK, have shown excellent results with hypnotherapy for patients with severe refractory IBS. Although their data seem to have established the ability of hypnotherapy to improve the GI and non-GI symptoms of IBS, corroborating evidence is needed from other centers. In this regard, some preliminary evidence is emerging.

Manchester group. In the first trial by the Manchester group, 30 patients received seven half-hour sessions of hypnotherapy (study group) or supportive psychotherapy and placebo (control group). Patients who received hypnotherapy also were given a tape for home autohypnosis after the third session.

Patients who received hypnotherapy improved dramatically in all GI symptoms— including abdominal pain, bloating, and bowel habits—and in their sense of well-being. This effect persisted 3 months later. The control patients’ abdominal pain, bloating, and well-being improved somewhat, but their bowel habits did not improve.¹⁵

The same investigators then studied 30 patients with IBS to assess the effect of hypnotherapy on rectal physiology. Fifteen patients received hypnotherapy, and 15 received relaxation exercises. Rectal sensitivity was measured using anorectal manometry at the start and finish of the intervention.

For patients with diarrhea-predominant IBS, rectal sensitivity was significantly reduced during hypnosis and after the full course of hypnotherapy, compared with controls (p<0.05). In patients with constipation-predominant IBS, a trend towards normalized rectal sensitivity did not reach statistical significance. The investigators concluded that symptomatic improvement of IBS after hypnotherapy may be related to changes in visceral sensitivity of the colon.¹⁶

These investigators later studied changes in distal colonic motility in 18 patients undergoing hypnotherapy for IBS. As the patients’ hypnotically induced anger or excitement increased, colonic motility decreased significantly (p<0.01) The investigators concluded that hypnosis may be a useful tool to investigate the effects of emotion on physiologic function.¹⁷

Using more contemporary outcome measures and diagnostic criteria, these investigators later showed that hypnotherapy significantly improved:

• IBS symptoms (abdominal pain and bloating, bowel habit, nausea, flatulence, urinary symptoms, lethargy, backache, and dyspareunia)
• quality of life (psychological and physical well-being, mood, locus of control, and work attitude).

Patients treated with hypnosis also took less time away from work (p = 0.02) and visited their physicians less often (p = 0.056), compared with controls.¹⁸

Other hypnosis studies. In the United States, another group randomly assigned 12 patients to gut-directed hypnotherapy or symptom monitoring. Subjects were matched by concurrent psychiatric diagnosis, susceptibility to hypnosis, and demographic features.

In findings similar to those of the Manchester group, primary IBS symptoms (abdominal pain, constipation, and flatulence) of patients who received hypnotherapy improved more than those of controls (p = 0.016). Anxiety, as measured by the Spielberger State-Trait Anxiety Inventory (STAXI), also decreased significantly. Treatment-induced gains were well-maintained 2 months later. No significant correlation was found between initial sensitivity to hypnosis and subsequent response to hypnotherapy. A positive relationship was seen between the presence of psychiatric diagnoses and overall levels of improvement.

This study suggests that hypnotherapy can be useful for treating IBS and can be easily adapted to different clinical settings and treatment populations.¹⁹ A similar study using gut-directed hypnotherapy found significant improvement in 27 IBS patients treated with short-term hypnosis, and symptom improvement persisted after treatment.²⁰

Biofeedback

The role of biofeedback in IBS treatment remains ill-defined. To be considered as a treatment option, biofeedback must meet or exceed the benefits being achieved with psychotherapy, hypnotherapy, and other behavioral approaches.

In gastroenterology, biofeedback has been used mainly to treat constipation and specifically for outlet constipation due to pelvic floor dysfunction. Anorectal probes to measure rectal pressure in the resting state and during defecation can reveal a pattern of pelvic floor dysfunction. Studies have demonstrated up to 67% improvement in constipation symptoms using biofeedback. Use of anorectal biofeedback in adults with IBS also appears promising, but more controlled trials are needed.²¹

Anorectal biofeedback has also been used effectively to treat fecal incontinence in children and adults, achieving success rates of 70% or better. In IBS, however, the benefit of biofeedback is less clear. Studies of multicomponent treatment—combining biofeedback with CBT techniques—suggest improvement rates in the 50 to 60% range. However, these findings need to be compared with other treatments for IBS.

Combination treatment

Medical treatment of IBS is progressing. Antidepressant therapy, particularly using tricyclics, has shown moderate benefit.²² Newer medications such as alosetron and tegaserod, which modulate serotonin metabolism in the gut, have been developed. Alosetron and tegaserod have shown significantly greater efficacy compared with placebo for treatment of women with the diarrhea-predominant and constipation-predominant types of IBS, respectively.

Alosetron was voluntarily withdrawn from clinical use in 2000 because of reports of serious GI events associated with its use, including ischemic colitis in a small number of patients (about 3 women in 1,000). Because of the drug’s efficacy in IBS, however, the FDA recently approved its rerelease with a restricted indication—it is to be used only in women with severe diarrhea-predominant IBS who have not responded to conventional IBS treatment. The drug’s manufacturer also is implementing a risk management plan designed to reduce the potential for serious GI side effects.

Table

PSYCHOTHERAPY AS TREATMENT FOR IRRITABLE BOWEL SYNDROME

Tegaserod, a serotonin-4 receptor (5HT4) agonist, was approved by the FDA in July. It is indicated for short-term treatment of women with IBS whose primary bowel symptom is constipation.

Combination therapy—medical management plus psychotherapy—may represent the future of IBS treatment (Table). This approach was examined recently in a randomized study of 24 IBS patients who received standard medical treatment alone or in combination with behavioral therapy. The behavioral component included patient education, helping patients shape a plausible model for their illness, progressive muscle relaxation, cognitive coping strategies, problem-solving education, and assertiveness and social skills training. All patients were treated in 10 individual therapy sessions of approximately 1 hour each by one of two psychotherapists across 10 weeks.

Compared with medical treatment alone, patients treated with combination therapy showed significantly improved GI symptoms (p < 0.001) and psychological symptoms (p = 0.01) in terms of both patient report and objective psychological measures. Outcomes are enhanced for patients with severe IBS, the investigators concluded, when behavioral therapy is added to thoughtful medical management.²³

Related resource

• International Foundation for Functional Gastrointestinal Disorders. www.iffgd.org

Drug brand names

• Alosetron • Lotronex
• Tegaserod • Zelnorm

Disclosure

The author reports that he serves as a consultant to Novartis Pharmaceuticals Corp. He reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

A growing body of evidence suggests that psychiatrists have much to offer patients with severe irritable bowel syndrome (IBS). Behavioral and psychotherapeutic approaches are showing promise in relieving both GI and mood disturbances.

Treating patients with IBS with medications designed to influence only gut function can be frustrating. Those with refractory symptoms may be extremely sensitive to drug side effects, and they often report that medical management worsens or does not improve their symptoms. They experiment with alternative medicines and wander from physician to physician in a disappointing search for a “cure.”

Let’s look at evidence on the efficacy of individual and group behavioral therapies, hypnotherapy, biofeedback, and combination medical and behavioral treatment.

Psychotherapeutic approaches

IBS is a common gastrointestinal disorder that is characterized by abdominal discomfort and changes in bowel habits (Boxes 1 and 2). Patients with severe IBS symptoms often bring significant psychological impairment and psychosocial trauma to clinical encounters.^1,2 They respond poorly to standard medical management, and evidence supporting the efficacy of medical treatments for IBS remains weak.^3,4

Box 1

In 1983, the first controlled trial of psychodynamic psychotherapy for IBS showed dramatic reductions in symptoms.⁵ A subsequent series of high-quality articles in the early 1990s also showed that interpersonal psychotherapy (with greater interaction between therapist and patient) could significantly decrease IBS symptoms.

Persistent improvement. In one randomized controlled trial,⁶ 102 patients with IBS received either standard medical treatment or 10 hours of dynamically oriented individual psychotherapy in combination with standard medical treatment. After 3 months, patients who received psychotherapy showed significantly greater improvement in somatic symptoms and emotional well-being, compared with those who received medical treatment only.

Interestingly, this difference persisted 1 year after the study ended. GI symptoms and the emotional well-being of patients who received combination therapy continued to improve, whereas the physical and emotional status of those who received only standard medical treatment deteriorated.

In a second study,⁷ 101 patients with severe IBS symptoms continued to receive medical treatment but were randomly divided into two groups:

• Study subjects received 8 hours of dynamically oriented psychotherapy.
• Control patients met with a psychiatrist who engaged in “supportive listening” but delivered no psychotherapy. This strategy was adopted to control for the effect of the psychiatrist’s presence.

Assessments included patients’ self-reports of symptoms, ratings of GI symptoms by the treating gastroenterologists, and measures of depression, anxiety, and health care utilization. Patients who received psychotherapy reported significant improvements in bowel symptoms (e.g., diarrhea, constipation, bloating, and abdominal pain). Likewise, the gastroenterologist who rated patients’ GI symptoms felt that those who received psychotherapy improved significantly across the entire spectrum of GI symptoms. The improvements were maintained at 1-year follow-up.

By comparison, the control patients reported worsening symptoms, as did subjects who dropped out. Patients who received psychotherapy also made significantly fewer outpatient visits to gastroenterologists, compared with controls (p<0.001).

Cognitive-behavioral therapy

Cognitive-behavioral therapy (CBT) is emerging as a major psychotherapeutic tool for treating mood disorders, anxiety disorders, and somatic syndromes associated with psychosocial distress. CBT also is showing promise for patients with moderate to severe IBS and those with IBS and concomitant anxiety or mood disorders. Studies consistently show that CBT is superior to standard medical management or the use of support groups or other behavioral treatments alone.

Reduced symptoms. In an early trial of CBT, 17 patients with IBS experienced significantly less abdominal pain and diarrhea after participating in a program of progressive relaxation, education about bowel functioning, use of thermal biofeedback, and stress coping techniques based on CBT. Overall, 64% of the patients improved.⁸

The same investigators then assigned 90 patients to 12 sessions of CBT, given over 8 weeks with or without meditation and biofeedback. Patients with axis I psychiatric diagnoses tended to respond poorly to CBT. The authors concluded that a careful pretreatment psychological workup is important to identify patients with IBS who would benefit most from CBT.⁹

As a follow-up, these investigators randomly assigned 20 patients to intensive individualized CBT (10 sessions over 8 weeks) or 8 weeks of daily GI symptom monitoring. Patients who received CBT had significantly fewer GI symptoms than did the symptom-monitoring group (p = 0.005). With CBT, 80% improved clinically, compared with only 10% in the control group. Improvements in the CBT group persisted at 3 months’ follow-up. Improved GI symptoms also were correlated with increased positive thoughts and reduced negative automatic thoughts (i.e., negative self-image).¹⁰

Box 2

Group therapy. In a study of group rather than individualized CBT, 45 patients with severe IBS symptoms were randomly assigned to either a group CBT module (n = 25) or a waiting list control group (n = 20). Patients received eight 2-hour group CBT sessions over 3 months, then were followed an average of 2.25 years. Their abdominal pain, number of successful coping behavioral strategies, and avoidance of negative situations improved significantly—compared with the waiting list controls—and persisted during follow-up. The authors concluded that group CBT is effective for alleviating IBS symptoms and improving patients’ coping strategies.¹¹

CBT vs. support groups. In a study comparing the effectiveness of CBT and an IBS self-help support group, 34 patients were randomly assigned to:

• individualized CBT (study group)
• a self-help support group
• or a symptom-monitoring waiting list (control group).

Each group was followed for 8 weeks. GI symptoms were reduced significantly in patients who received individualized CBT, compared with the support group or controls. Anxiety and depression in the CBT group also remained significantly improved 3 months later, compared with both other groups.¹²

Group psychotherapy

Group psychotherapy for IBS treatment can be more cost-effective than individual therapy, but its success depends on whether patients accept a group format. Data on the use of group psychotherapeutic approaches are largely favorable.

As described previously, one study demonstrated that group CBT reduced abdominal pain and diarrhea and improved symptoms overall.¹¹ In another study, 20 patients with refractory IBS underwent 6 weeks of group behavioral and didactic psychotherapy. GI symptoms, dysphoria, and psychological distress improved significantly in all patients, and their interpersonal sensitivity and hostility were reduced. These improvements persisted 6 months later.¹²

A recent review suggests that cognitive-behavioral group psychotherapy may be highly effective in patients with IBS. These authors concluded that CBT can improve patients’ mood and other emotional symptoms, reduce their pain, and improve well-being and coping ability.¹⁴

Hypnotherapy

Researchers in Manchester, UK, have shown excellent results with hypnotherapy for patients with severe refractory IBS. Although their data seem to have established the ability of hypnotherapy to improve the GI and non-GI symptoms of IBS, corroborating evidence is needed from other centers. In this regard, some preliminary evidence is emerging.

Manchester group. In the first trial by the Manchester group, 30 patients received seven half-hour sessions of hypnotherapy (study group) or supportive psychotherapy and placebo (control group). Patients who received hypnotherapy also were given a tape for home autohypnosis after the third session.

Patients who received hypnotherapy improved dramatically in all GI symptoms— including abdominal pain, bloating, and bowel habits—and in their sense of well-being. This effect persisted 3 months later. The control patients’ abdominal pain, bloating, and well-being improved somewhat, but their bowel habits did not improve.¹⁵

The same investigators then studied 30 patients with IBS to assess the effect of hypnotherapy on rectal physiology. Fifteen patients received hypnotherapy, and 15 received relaxation exercises. Rectal sensitivity was measured using anorectal manometry at the start and finish of the intervention.

For patients with diarrhea-predominant IBS, rectal sensitivity was significantly reduced during hypnosis and after the full course of hypnotherapy, compared with controls (p<0.05). In patients with constipation-predominant IBS, a trend towards normalized rectal sensitivity did not reach statistical significance. The investigators concluded that symptomatic improvement of IBS after hypnotherapy may be related to changes in visceral sensitivity of the colon.¹⁶

These investigators later studied changes in distal colonic motility in 18 patients undergoing hypnotherapy for IBS. As the patients’ hypnotically induced anger or excitement increased, colonic motility decreased significantly (p<0.01) The investigators concluded that hypnosis may be a useful tool to investigate the effects of emotion on physiologic function.¹⁷

Using more contemporary outcome measures and diagnostic criteria, these investigators later showed that hypnotherapy significantly improved:

• IBS symptoms (abdominal pain and bloating, bowel habit, nausea, flatulence, urinary symptoms, lethargy, backache, and dyspareunia)
• quality of life (psychological and physical well-being, mood, locus of control, and work attitude).

Patients treated with hypnosis also took less time away from work (p = 0.02) and visited their physicians less often (p = 0.056), compared with controls.¹⁸

Other hypnosis studies. In the United States, another group randomly assigned 12 patients to gut-directed hypnotherapy or symptom monitoring. Subjects were matched by concurrent psychiatric diagnosis, susceptibility to hypnosis, and demographic features.

In findings similar to those of the Manchester group, primary IBS symptoms (abdominal pain, constipation, and flatulence) of patients who received hypnotherapy improved more than those of controls (p = 0.016). Anxiety, as measured by the Spielberger State-Trait Anxiety Inventory (STAXI), also decreased significantly. Treatment-induced gains were well-maintained 2 months later. No significant correlation was found between initial sensitivity to hypnosis and subsequent response to hypnotherapy. A positive relationship was seen between the presence of psychiatric diagnoses and overall levels of improvement.

This study suggests that hypnotherapy can be useful for treating IBS and can be easily adapted to different clinical settings and treatment populations.¹⁹ A similar study using gut-directed hypnotherapy found significant improvement in 27 IBS patients treated with short-term hypnosis, and symptom improvement persisted after treatment.²⁰

Biofeedback

The role of biofeedback in IBS treatment remains ill-defined. To be considered as a treatment option, biofeedback must meet or exceed the benefits being achieved with psychotherapy, hypnotherapy, and other behavioral approaches.

In gastroenterology, biofeedback has been used mainly to treat constipation and specifically for outlet constipation due to pelvic floor dysfunction. Anorectal probes to measure rectal pressure in the resting state and during defecation can reveal a pattern of pelvic floor dysfunction. Studies have demonstrated up to 67% improvement in constipation symptoms using biofeedback. Use of anorectal biofeedback in adults with IBS also appears promising, but more controlled trials are needed.²¹

Anorectal biofeedback has also been used effectively to treat fecal incontinence in children and adults, achieving success rates of 70% or better. In IBS, however, the benefit of biofeedback is less clear. Studies of multicomponent treatment—combining biofeedback with CBT techniques—suggest improvement rates in the 50 to 60% range. However, these findings need to be compared with other treatments for IBS.

Combination treatment

Medical treatment of IBS is progressing. Antidepressant therapy, particularly using tricyclics, has shown moderate benefit.²² Newer medications such as alosetron and tegaserod, which modulate serotonin metabolism in the gut, have been developed. Alosetron and tegaserod have shown significantly greater efficacy compared with placebo for treatment of women with the diarrhea-predominant and constipation-predominant types of IBS, respectively.

Alosetron was voluntarily withdrawn from clinical use in 2000 because of reports of serious GI events associated with its use, including ischemic colitis in a small number of patients (about 3 women in 1,000). Because of the drug’s efficacy in IBS, however, the FDA recently approved its rerelease with a restricted indication—it is to be used only in women with severe diarrhea-predominant IBS who have not responded to conventional IBS treatment. The drug’s manufacturer also is implementing a risk management plan designed to reduce the potential for serious GI side effects.

Table

PSYCHOTHERAPY AS TREATMENT FOR IRRITABLE BOWEL SYNDROME

Tegaserod, a serotonin-4 receptor (5HT4) agonist, was approved by the FDA in July. It is indicated for short-term treatment of women with IBS whose primary bowel symptom is constipation.

Combination therapy—medical management plus psychotherapy—may represent the future of IBS treatment (Table). This approach was examined recently in a randomized study of 24 IBS patients who received standard medical treatment alone or in combination with behavioral therapy. The behavioral component included patient education, helping patients shape a plausible model for their illness, progressive muscle relaxation, cognitive coping strategies, problem-solving education, and assertiveness and social skills training. All patients were treated in 10 individual therapy sessions of approximately 1 hour each by one of two psychotherapists across 10 weeks.

Compared with medical treatment alone, patients treated with combination therapy showed significantly improved GI symptoms (p < 0.001) and psychological symptoms (p = 0.01) in terms of both patient report and objective psychological measures. Outcomes are enhanced for patients with severe IBS, the investigators concluded, when behavioral therapy is added to thoughtful medical management.²³

Related resource

• International Foundation for Functional Gastrointestinal Disorders. www.iffgd.org

Drug brand names

• Alosetron • Lotronex
• Tegaserod • Zelnorm

Disclosure

The author reports that he serves as a consultant to Novartis Pharmaceuticals Corp. He reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

A growing body of evidence suggests that psychiatrists have much to offer patients with severe irritable bowel syndrome (IBS). Behavioral and psychotherapeutic approaches are showing promise in relieving both GI and mood disturbances.

Treating patients with IBS with medications designed to influence only gut function can be frustrating. Those with refractory symptoms may be extremely sensitive to drug side effects, and they often report that medical management worsens or does not improve their symptoms. They experiment with alternative medicines and wander from physician to physician in a disappointing search for a “cure.”

Let’s look at evidence on the efficacy of individual and group behavioral therapies, hypnotherapy, biofeedback, and combination medical and behavioral treatment.

Psychotherapeutic approaches

IBS is a common gastrointestinal disorder that is characterized by abdominal discomfort and changes in bowel habits (Boxes 1 and 2). Patients with severe IBS symptoms often bring significant psychological impairment and psychosocial trauma to clinical encounters.^1,2 They respond poorly to standard medical management, and evidence supporting the efficacy of medical treatments for IBS remains weak.^3,4

Box 1

In 1983, the first controlled trial of psychodynamic psychotherapy for IBS showed dramatic reductions in symptoms.⁵ A subsequent series of high-quality articles in the early 1990s also showed that interpersonal psychotherapy (with greater interaction between therapist and patient) could significantly decrease IBS symptoms.

Persistent improvement. In one randomized controlled trial,⁶ 102 patients with IBS received either standard medical treatment or 10 hours of dynamically oriented individual psychotherapy in combination with standard medical treatment. After 3 months, patients who received psychotherapy showed significantly greater improvement in somatic symptoms and emotional well-being, compared with those who received medical treatment only.

Interestingly, this difference persisted 1 year after the study ended. GI symptoms and the emotional well-being of patients who received combination therapy continued to improve, whereas the physical and emotional status of those who received only standard medical treatment deteriorated.

In a second study,⁷ 101 patients with severe IBS symptoms continued to receive medical treatment but were randomly divided into two groups:

• Study subjects received 8 hours of dynamically oriented psychotherapy.
• Control patients met with a psychiatrist who engaged in “supportive listening” but delivered no psychotherapy. This strategy was adopted to control for the effect of the psychiatrist’s presence.

Assessments included patients’ self-reports of symptoms, ratings of GI symptoms by the treating gastroenterologists, and measures of depression, anxiety, and health care utilization. Patients who received psychotherapy reported significant improvements in bowel symptoms (e.g., diarrhea, constipation, bloating, and abdominal pain). Likewise, the gastroenterologist who rated patients’ GI symptoms felt that those who received psychotherapy improved significantly across the entire spectrum of GI symptoms. The improvements were maintained at 1-year follow-up.

By comparison, the control patients reported worsening symptoms, as did subjects who dropped out. Patients who received psychotherapy also made significantly fewer outpatient visits to gastroenterologists, compared with controls (p<0.001).

Cognitive-behavioral therapy

Cognitive-behavioral therapy (CBT) is emerging as a major psychotherapeutic tool for treating mood disorders, anxiety disorders, and somatic syndromes associated with psychosocial distress. CBT also is showing promise for patients with moderate to severe IBS and those with IBS and concomitant anxiety or mood disorders. Studies consistently show that CBT is superior to standard medical management or the use of support groups or other behavioral treatments alone.

Reduced symptoms. In an early trial of CBT, 17 patients with IBS experienced significantly less abdominal pain and diarrhea after participating in a program of progressive relaxation, education about bowel functioning, use of thermal biofeedback, and stress coping techniques based on CBT. Overall, 64% of the patients improved.⁸

The same investigators then assigned 90 patients to 12 sessions of CBT, given over 8 weeks with or without meditation and biofeedback. Patients with axis I psychiatric diagnoses tended to respond poorly to CBT. The authors concluded that a careful pretreatment psychological workup is important to identify patients with IBS who would benefit most from CBT.⁹

As a follow-up, these investigators randomly assigned 20 patients to intensive individualized CBT (10 sessions over 8 weeks) or 8 weeks of daily GI symptom monitoring. Patients who received CBT had significantly fewer GI symptoms than did the symptom-monitoring group (p = 0.005). With CBT, 80% improved clinically, compared with only 10% in the control group. Improvements in the CBT group persisted at 3 months’ follow-up. Improved GI symptoms also were correlated with increased positive thoughts and reduced negative automatic thoughts (i.e., negative self-image).¹⁰

Box 2

Group therapy. In a study of group rather than individualized CBT, 45 patients with severe IBS symptoms were randomly assigned to either a group CBT module (n = 25) or a waiting list control group (n = 20). Patients received eight 2-hour group CBT sessions over 3 months, then were followed an average of 2.25 years. Their abdominal pain, number of successful coping behavioral strategies, and avoidance of negative situations improved significantly—compared with the waiting list controls—and persisted during follow-up. The authors concluded that group CBT is effective for alleviating IBS symptoms and improving patients’ coping strategies.¹¹

CBT vs. support groups. In a study comparing the effectiveness of CBT and an IBS self-help support group, 34 patients were randomly assigned to:

• individualized CBT (study group)
• a self-help support group
• or a symptom-monitoring waiting list (control group).

Each group was followed for 8 weeks. GI symptoms were reduced significantly in patients who received individualized CBT, compared with the support group or controls. Anxiety and depression in the CBT group also remained significantly improved 3 months later, compared with both other groups.¹²

Group psychotherapy

Group psychotherapy for IBS treatment can be more cost-effective than individual therapy, but its success depends on whether patients accept a group format. Data on the use of group psychotherapeutic approaches are largely favorable.

As described previously, one study demonstrated that group CBT reduced abdominal pain and diarrhea and improved symptoms overall.¹¹ In another study, 20 patients with refractory IBS underwent 6 weeks of group behavioral and didactic psychotherapy. GI symptoms, dysphoria, and psychological distress improved significantly in all patients, and their interpersonal sensitivity and hostility were reduced. These improvements persisted 6 months later.¹²

A recent review suggests that cognitive-behavioral group psychotherapy may be highly effective in patients with IBS. These authors concluded that CBT can improve patients’ mood and other emotional symptoms, reduce their pain, and improve well-being and coping ability.¹⁴

Hypnotherapy

Researchers in Manchester, UK, have shown excellent results with hypnotherapy for patients with severe refractory IBS. Although their data seem to have established the ability of hypnotherapy to improve the GI and non-GI symptoms of IBS, corroborating evidence is needed from other centers. In this regard, some preliminary evidence is emerging.

Manchester group. In the first trial by the Manchester group, 30 patients received seven half-hour sessions of hypnotherapy (study group) or supportive psychotherapy and placebo (control group). Patients who received hypnotherapy also were given a tape for home autohypnosis after the third session.

Patients who received hypnotherapy improved dramatically in all GI symptoms— including abdominal pain, bloating, and bowel habits—and in their sense of well-being. This effect persisted 3 months later. The control patients’ abdominal pain, bloating, and well-being improved somewhat, but their bowel habits did not improve.¹⁵

The same investigators then studied 30 patients with IBS to assess the effect of hypnotherapy on rectal physiology. Fifteen patients received hypnotherapy, and 15 received relaxation exercises. Rectal sensitivity was measured using anorectal manometry at the start and finish of the intervention.

For patients with diarrhea-predominant IBS, rectal sensitivity was significantly reduced during hypnosis and after the full course of hypnotherapy, compared with controls (p<0.05). In patients with constipation-predominant IBS, a trend towards normalized rectal sensitivity did not reach statistical significance. The investigators concluded that symptomatic improvement of IBS after hypnotherapy may be related to changes in visceral sensitivity of the colon.¹⁶

These investigators later studied changes in distal colonic motility in 18 patients undergoing hypnotherapy for IBS. As the patients’ hypnotically induced anger or excitement increased, colonic motility decreased significantly (p<0.01) The investigators concluded that hypnosis may be a useful tool to investigate the effects of emotion on physiologic function.¹⁷

Using more contemporary outcome measures and diagnostic criteria, these investigators later showed that hypnotherapy significantly improved:

• IBS symptoms (abdominal pain and bloating, bowel habit, nausea, flatulence, urinary symptoms, lethargy, backache, and dyspareunia)
• quality of life (psychological and physical well-being, mood, locus of control, and work attitude).

Patients treated with hypnosis also took less time away from work (p = 0.02) and visited their physicians less often (p = 0.056), compared with controls.¹⁸

Other hypnosis studies. In the United States, another group randomly assigned 12 patients to gut-directed hypnotherapy or symptom monitoring. Subjects were matched by concurrent psychiatric diagnosis, susceptibility to hypnosis, and demographic features.

In findings similar to those of the Manchester group, primary IBS symptoms (abdominal pain, constipation, and flatulence) of patients who received hypnotherapy improved more than those of controls (p = 0.016). Anxiety, as measured by the Spielberger State-Trait Anxiety Inventory (STAXI), also decreased significantly. Treatment-induced gains were well-maintained 2 months later. No significant correlation was found between initial sensitivity to hypnosis and subsequent response to hypnotherapy. A positive relationship was seen between the presence of psychiatric diagnoses and overall levels of improvement.

This study suggests that hypnotherapy can be useful for treating IBS and can be easily adapted to different clinical settings and treatment populations.¹⁹ A similar study using gut-directed hypnotherapy found significant improvement in 27 IBS patients treated with short-term hypnosis, and symptom improvement persisted after treatment.²⁰

Biofeedback

The role of biofeedback in IBS treatment remains ill-defined. To be considered as a treatment option, biofeedback must meet or exceed the benefits being achieved with psychotherapy, hypnotherapy, and other behavioral approaches.

In gastroenterology, biofeedback has been used mainly to treat constipation and specifically for outlet constipation due to pelvic floor dysfunction. Anorectal probes to measure rectal pressure in the resting state and during defecation can reveal a pattern of pelvic floor dysfunction. Studies have demonstrated up to 67% improvement in constipation symptoms using biofeedback. Use of anorectal biofeedback in adults with IBS also appears promising, but more controlled trials are needed.²¹

Anorectal biofeedback has also been used effectively to treat fecal incontinence in children and adults, achieving success rates of 70% or better. In IBS, however, the benefit of biofeedback is less clear. Studies of multicomponent treatment—combining biofeedback with CBT techniques—suggest improvement rates in the 50 to 60% range. However, these findings need to be compared with other treatments for IBS.

Combination treatment

Medical treatment of IBS is progressing. Antidepressant therapy, particularly using tricyclics, has shown moderate benefit.²² Newer medications such as alosetron and tegaserod, which modulate serotonin metabolism in the gut, have been developed. Alosetron and tegaserod have shown significantly greater efficacy compared with placebo for treatment of women with the diarrhea-predominant and constipation-predominant types of IBS, respectively.

Alosetron was voluntarily withdrawn from clinical use in 2000 because of reports of serious GI events associated with its use, including ischemic colitis in a small number of patients (about 3 women in 1,000). Because of the drug’s efficacy in IBS, however, the FDA recently approved its rerelease with a restricted indication—it is to be used only in women with severe diarrhea-predominant IBS who have not responded to conventional IBS treatment. The drug’s manufacturer also is implementing a risk management plan designed to reduce the potential for serious GI side effects.

Table

PSYCHOTHERAPY AS TREATMENT FOR IRRITABLE BOWEL SYNDROME

Tegaserod, a serotonin-4 receptor (5HT4) agonist, was approved by the FDA in July. It is indicated for short-term treatment of women with IBS whose primary bowel symptom is constipation.

Combination therapy—medical management plus psychotherapy—may represent the future of IBS treatment (Table). This approach was examined recently in a randomized study of 24 IBS patients who received standard medical treatment alone or in combination with behavioral therapy. The behavioral component included patient education, helping patients shape a plausible model for their illness, progressive muscle relaxation, cognitive coping strategies, problem-solving education, and assertiveness and social skills training. All patients were treated in 10 individual therapy sessions of approximately 1 hour each by one of two psychotherapists across 10 weeks.

Compared with medical treatment alone, patients treated with combination therapy showed significantly improved GI symptoms (p < 0.001) and psychological symptoms (p = 0.01) in terms of both patient report and objective psychological measures. Outcomes are enhanced for patients with severe IBS, the investigators concluded, when behavioral therapy is added to thoughtful medical management.²³

Related resource

• International Foundation for Functional Gastrointestinal Disorders. www.iffgd.org

Drug brand names

• Alosetron • Lotronex
• Tegaserod • Zelnorm

Disclosure

The author reports that he serves as a consultant to Novartis Pharmaceuticals Corp. He reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Roughly 50 million adult Americans have hypertension.¹ Chances are some of them are—or soon will be—under your care.

Hypertension is common among patients with psychiatric disorders, particularly in those with chronic mental conditions.² Medication-associated weight gain and other reactions to psychotropics, drug-drug interactions, lack of exercise, adverse dietary habits, and pre-existing medical conditions all predispose psychiatric patients to hypertension.

Yet hypertension often goes undetected in psychiatric patients. Hypertension many times is asymptomatic—about 50% of all people with the disorder don’t even know they have it.³ Some symptoms of uncontrolled hypertension—fatigue, headache, palpitations, and dizziness—are also associated with many psychiatric disorders. As a result, psychiatrists may attempt to manage the symptoms but miss the hypertension.

Psychiatrists need to be alert for hypertension, either as a possible contributing factor to a mental disorder or as a potential side effect of a psychiatric disorder or treatment. The following diagnostic and treatment strategies will help you detect and manage this common condition.

Causes of hypertension in mental illness

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines elevated blood pressure as 140 mm Hg systolic and/or 90 mm Hg diastolic. The diagnosis of hypertension should be based on the average of two or more blood pressure readings at each of two or more visits after initial screening.

All patients with elevated blood pressure have an underlying physiologic abnormality that is causing their hypertension. The disorder falls within the following two categories:

• essential hypertension, emanating from an unknown cause
• secondary hypertension, resulting from an underlying, discoverable, often treatable cause.

Researchers have speculated that certain psychiatric disorders might cause, or be risk factors for, hypertension. Anxiety or panic disorders have been associated with acute (and perhaps chronic) blood pressure elevations.² Some research suggests that patients with alexithymia are at risk for developing hypertension.⁴

Other studies suggest that hypertensive patients with certain psychological disorders (e.g., depression) or social factors (e.g., substance abuse) are less likely than nonaffected patients to self-report the presence of hypertension and less likely to receive medical attention for it.⁵

Psychiatric drugs also may affect blood pressure by one of two mechanisms:

• Pharmacodynamic—direct effects at the site of action (e.g., receptors) via physiologic mechanisms (Table 1). For example, amphetamines act directly on the sympathetic nervous system to elevate blood pressure.
• Pharmacokinetic—indirect effects on blood pressure via drug/drug interactions that alter the absorption, distribution, metabolism, or clearance of antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, and salt intake restrictions can raise lithium levels. The calcium-channel blockers verapamil and diltiazem can unpredictably increase or decrease lithium levels, but the combination generally is safe. Verapamil also raises tricyclic antidepressant levels. Monoamine oxidase inhibitors (MAOIs) used in tandem with the antihypertensive reserpine can cause hypomania. Beta-blocker levels are increased when used in concert with selective serotonin reuptake inhibitors. Use of carbamazepine with calcium-channel blockers can elevate carbamazapine levels and diminish the effectiveness of the calcium-channel blocker.

Table 1

POSSIBLE PHARMACODYNAMIC EFFECTS OFPSYCHIATRIC MEDICATIONS ON BLOOD PRESSURE

Symptoms, complications of high blood pressure

Symptoms that may be associated with high blood pressure include headaches, dizziness, lightheadedness, fatigue, palpitations, and chest discomfort. Patients may also experience symptoms secondary to end-organ damage (e.g., shortness of breath from congestive heart failure).

Most people, however, experience no symptoms when their blood pressure is elevated. This is one reason most people with hypertension do not adequately control their blood pressure.

Aside from the long-term end-organ damage caused by persistently elevated blood pressure, hypertension also has been found to cause psychiatric disorders, though not directly. For example, post-MI depression is well-recognized. Hypertension may also cause multi-infarct dementia with resultant depression, paranoia, or other psychotic features.

The psychological burden of having chronic and usually incurable (though controllable) hypertension may worsen depression or anxiety disorders. Patients with a chronic psychiatric illness generally have a higher incidence of chronic medical problems.

Likewise, patients with chronic medical disorders have a higher incidence of psychiatric complaints.⁶

Patient evaluation

When evaluating the patient with elevated blood pressure, it is important to:

• detect and confirm hypertension
• detect target-organ disease (e.g., renal damage or congestive heart failure)
• identify other cardiovascular risk factors (e.g., diabetes mellitus, hyperlipidemia, obesity)
• identify secondary causes of hypertension, such as endocrine abnormalities (e.g., hyperaldosteronism, thyroid disorders), kidney disease, obstructive sleep apnea, and response to medications.

Table 2

ANTIHYPERTENSIVE MEDICATIONS AND SIDE EFFECTS

A thorough history and physical examination should be performed to assess these four areas. Routine laboratory testing for the hypertensive patient should include a urinalysis, a complete blood count, an assessment of blood chemistries (potassium, sodium, creatinine, fasting glucose, fasting lipid profile), and a 12-lead electrocardiogram.

Treating hypertension

Many medications are used to treat hypertension. Most classes of antihypertensive agents have been shown to be about equally effective in lowering blood pressure.

All other factors being equal, the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) recommends initial treatment with a diuretic or beta-blocker. These classes of drugs have been shown to significantly reduce overall hypertension-related mortality.

Most patients with hypertension—particularly the elderly, patients with diabetes mellitus, and those with renal disease—will need two or more agents to control their blood pressure. Avoid prescribing agents that may worsen an existing condition (e.g., beta-blockers may worsen bronchospasm in patients with asthma). Use agents that may help improve comorbid conditions (e.g., beta-blockers have been shown to reduce mortality in patients with previous MI).

Box

Potential side effects, some of which mimic or are commonly found in psychiatric disorders, must be considered when choosing an antihypertensive agent. Table 2 lists nine classes of antihypertensives and some associated side effects. Also consider the agent’s cost, convenience of administration, direct-to-consumer advertising, and the patient’s age or race. For example, beta-blockers tend to be less effective in black or elderly patients than in other demographic groups.

Nonpharmacologic hypertension management emphasizes weight reduction, moderation of alcohol intake, regular aerobic exercise, dietary restriction of sodium, and smoking cessation. Most studies of these behavioral interventions have demonstrated a short-term benefit in decreasing blood pressure, but long-term adherence to them is disappointing. Relaxation therapies and biofeedback have been advocated for hypertension, but proof of their efficacy is lacking.⁷

As more is learned about genetic and other causes of hypertension, more-effective treatments for hypertension could become available (Box).

Treating high-risk groups

Special considerations apply to two patient groups with a high prevalence of hypertension—those age 65 and older and those with diabetes.

Older patients. Treatment benefits are more pronounced in patients age 65 or older because of their greater absolute risk for cardiovascular events. Also, systolic blood pressures increase with aging as the arterial tree becomes progressively less distensible.

Older patients often will require more than one drug to control their blood pressure. The initial dosages should be low and gradually titrated upward as needed. To minimize side effects, use smaller doses of multiple agents that are well tolerated instead of high-dose monotherapy.

A diuretic is often recommended as initial treatment for older patients, though a long-acting dihydropyridine calcium-channel blocker is a reasonable alternative. An ACE inhibitor is recommended for older patients with diabetes, systolic congestive heart failure, or previous MI. An alpha blocker should not be used as initial therapy for hypertension in the elderly because of relative lack of efficacy in preventing cardiovascular events.

Patients with diabetes. Aggressive blood pressure control is especially important in the patient with diabetes, which is the leading cause of end-stage renal disease. Most patients with diabetes also have hypertension—which accelerates their renal disease as well as cardiovascular disease. Blood pressure control goals significantly below 140/90 mm Hg are recommended (120 to 135 mm Hg systolic, 80 to 85 mm Hg diastolic) if diabetes is present.

ACE inhibitors or angiotensin receptor blockers are preferred for initial treatment of hypertension in diabetes, especially if proteinuria is present. Some authorities feel the level of blood pressure control in diabetes is more important than the agent(s) chosen to achieve that control. Most patients with hypertension and diabetes are not controlled on a single antihypertensive drug, and a diuretic is often added.

Psychological aspects of hypertension management

The diagnosis of hypertension and a resulting perception of loss of health or longevity may trigger a grief reaction in some patients.

Several psychological aspects to hypertension treatment make it difficult to achieve long-term control. Patients may become discouraged as dosages are increased and more medications are added. Asymptomatic patients may have no incentive to control their blood pressure. Many report, “I don’t feel any better” when their blood pressure comes down.

Because the goal of hypertension therapy is control rather than cure, the patient must commit to long-term treatment. Lifestyle changes such as dietary sodium restriction, smoking cessation, and weight loss may be difficult to achieve, especially for patients already dealing with a psychiatric disorder.

Also, the cost of treatment—the price of medications and initial and follow-up laboratory studies, plus the expense of follow-up office visits (possibly requiring time off work)—may be high.

Psychiatrists can help by offering moral support and encouraging patients to manage their medical problems, risk factors, and overall health. Psychiatrists can also educate patients on the importance of blood pressure control in preventing cardiovascular morbidity and mortality.

Brief cognitive-behaviorial therapy can identify the individual’s state of change (precontemplation, contemplation, preparation, action, or maintenance). Process techniques (such as consciousness-raising, commitment, or self-reevaluation) appropriate to the stage of change may then be employed.

For example, a patient in the precontemplation stage may resist returning to his or her primary care doctor to begin treatment for high blood pressure, employing such reasoning as, “I can’t afford those expensive office visits, and the medications would cost too much anyway.”

The psychiatrist might then apply consciousness-raising to motivate the patient: “How serious do you think it is to have high blood pressure that isn’t controlled? Are you aware that many people with high blood pressure are treated by means other than medications, or that many blood pressure medications are inexpensive?”

Providing relaxation techniques or a 12-week course of buproprion also can enhance the efficacy of smoking cessation efforts.

Related resources

• Drugs for hypertension. The Medical Letter 2001;43(1099):17-22.
• Some drugs that cause psychiatric symptoms. The Medical Letter 1998;40(1020):21-4.
• Hypertension—Journal of the American Heart Association. http://hyper.ahajournals.org/
• National Heart, Lung, and Blood institute’s Cardiovascular information site. http://www.nhlbi.nih.gov/health/public/heart/index.htm#hbp

Drug brand names

• Bupropion • Wellbutrin
• Guanadrel • Hylorel
• Lisinopril • Prinivil, Zestril
• Losartan • Hyzaar
• Ramipril • Altace
• Reserpine • Diutensen-R
• Valsartan • Diovan
• Venlafaxine • Effexor
• (Numerous other drugs mentioned in this article are available generically)

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Roughly 50 million adult Americans have hypertension.¹ Chances are some of them are—or soon will be—under your care.

Hypertension is common among patients with psychiatric disorders, particularly in those with chronic mental conditions.² Medication-associated weight gain and other reactions to psychotropics, drug-drug interactions, lack of exercise, adverse dietary habits, and pre-existing medical conditions all predispose psychiatric patients to hypertension.

Yet hypertension often goes undetected in psychiatric patients. Hypertension many times is asymptomatic—about 50% of all people with the disorder don’t even know they have it.³ Some symptoms of uncontrolled hypertension—fatigue, headache, palpitations, and dizziness—are also associated with many psychiatric disorders. As a result, psychiatrists may attempt to manage the symptoms but miss the hypertension.

Psychiatrists need to be alert for hypertension, either as a possible contributing factor to a mental disorder or as a potential side effect of a psychiatric disorder or treatment. The following diagnostic and treatment strategies will help you detect and manage this common condition.

Causes of hypertension in mental illness

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines elevated blood pressure as 140 mm Hg systolic and/or 90 mm Hg diastolic. The diagnosis of hypertension should be based on the average of two or more blood pressure readings at each of two or more visits after initial screening.

All patients with elevated blood pressure have an underlying physiologic abnormality that is causing their hypertension. The disorder falls within the following two categories:

• essential hypertension, emanating from an unknown cause
• secondary hypertension, resulting from an underlying, discoverable, often treatable cause.

Researchers have speculated that certain psychiatric disorders might cause, or be risk factors for, hypertension. Anxiety or panic disorders have been associated with acute (and perhaps chronic) blood pressure elevations.² Some research suggests that patients with alexithymia are at risk for developing hypertension.⁴

Other studies suggest that hypertensive patients with certain psychological disorders (e.g., depression) or social factors (e.g., substance abuse) are less likely than nonaffected patients to self-report the presence of hypertension and less likely to receive medical attention for it.⁵

Psychiatric drugs also may affect blood pressure by one of two mechanisms:

• Pharmacodynamic—direct effects at the site of action (e.g., receptors) via physiologic mechanisms (Table 1). For example, amphetamines act directly on the sympathetic nervous system to elevate blood pressure.
• Pharmacokinetic—indirect effects on blood pressure via drug/drug interactions that alter the absorption, distribution, metabolism, or clearance of antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, and salt intake restrictions can raise lithium levels. The calcium-channel blockers verapamil and diltiazem can unpredictably increase or decrease lithium levels, but the combination generally is safe. Verapamil also raises tricyclic antidepressant levels. Monoamine oxidase inhibitors (MAOIs) used in tandem with the antihypertensive reserpine can cause hypomania. Beta-blocker levels are increased when used in concert with selective serotonin reuptake inhibitors. Use of carbamazepine with calcium-channel blockers can elevate carbamazapine levels and diminish the effectiveness of the calcium-channel blocker.

Table 1

POSSIBLE PHARMACODYNAMIC EFFECTS OFPSYCHIATRIC MEDICATIONS ON BLOOD PRESSURE

Symptoms, complications of high blood pressure

Symptoms that may be associated with high blood pressure include headaches, dizziness, lightheadedness, fatigue, palpitations, and chest discomfort. Patients may also experience symptoms secondary to end-organ damage (e.g., shortness of breath from congestive heart failure).

Most people, however, experience no symptoms when their blood pressure is elevated. This is one reason most people with hypertension do not adequately control their blood pressure.

Aside from the long-term end-organ damage caused by persistently elevated blood pressure, hypertension also has been found to cause psychiatric disorders, though not directly. For example, post-MI depression is well-recognized. Hypertension may also cause multi-infarct dementia with resultant depression, paranoia, or other psychotic features.

The psychological burden of having chronic and usually incurable (though controllable) hypertension may worsen depression or anxiety disorders. Patients with a chronic psychiatric illness generally have a higher incidence of chronic medical problems.

Likewise, patients with chronic medical disorders have a higher incidence of psychiatric complaints.⁶

Patient evaluation

When evaluating the patient with elevated blood pressure, it is important to:

• detect and confirm hypertension
• detect target-organ disease (e.g., renal damage or congestive heart failure)
• identify other cardiovascular risk factors (e.g., diabetes mellitus, hyperlipidemia, obesity)
• identify secondary causes of hypertension, such as endocrine abnormalities (e.g., hyperaldosteronism, thyroid disorders), kidney disease, obstructive sleep apnea, and response to medications.

Table 2

ANTIHYPERTENSIVE MEDICATIONS AND SIDE EFFECTS

A thorough history and physical examination should be performed to assess these four areas. Routine laboratory testing for the hypertensive patient should include a urinalysis, a complete blood count, an assessment of blood chemistries (potassium, sodium, creatinine, fasting glucose, fasting lipid profile), and a 12-lead electrocardiogram.

Treating hypertension

Many medications are used to treat hypertension. Most classes of antihypertensive agents have been shown to be about equally effective in lowering blood pressure.

All other factors being equal, the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) recommends initial treatment with a diuretic or beta-blocker. These classes of drugs have been shown to significantly reduce overall hypertension-related mortality.

Most patients with hypertension—particularly the elderly, patients with diabetes mellitus, and those with renal disease—will need two or more agents to control their blood pressure. Avoid prescribing agents that may worsen an existing condition (e.g., beta-blockers may worsen bronchospasm in patients with asthma). Use agents that may help improve comorbid conditions (e.g., beta-blockers have been shown to reduce mortality in patients with previous MI).

Box

Potential side effects, some of which mimic or are commonly found in psychiatric disorders, must be considered when choosing an antihypertensive agent. Table 2 lists nine classes of antihypertensives and some associated side effects. Also consider the agent’s cost, convenience of administration, direct-to-consumer advertising, and the patient’s age or race. For example, beta-blockers tend to be less effective in black or elderly patients than in other demographic groups.

Nonpharmacologic hypertension management emphasizes weight reduction, moderation of alcohol intake, regular aerobic exercise, dietary restriction of sodium, and smoking cessation. Most studies of these behavioral interventions have demonstrated a short-term benefit in decreasing blood pressure, but long-term adherence to them is disappointing. Relaxation therapies and biofeedback have been advocated for hypertension, but proof of their efficacy is lacking.⁷

As more is learned about genetic and other causes of hypertension, more-effective treatments for hypertension could become available (Box).

Treating high-risk groups

Special considerations apply to two patient groups with a high prevalence of hypertension—those age 65 and older and those with diabetes.

Older patients. Treatment benefits are more pronounced in patients age 65 or older because of their greater absolute risk for cardiovascular events. Also, systolic blood pressures increase with aging as the arterial tree becomes progressively less distensible.

Older patients often will require more than one drug to control their blood pressure. The initial dosages should be low and gradually titrated upward as needed. To minimize side effects, use smaller doses of multiple agents that are well tolerated instead of high-dose monotherapy.

A diuretic is often recommended as initial treatment for older patients, though a long-acting dihydropyridine calcium-channel blocker is a reasonable alternative. An ACE inhibitor is recommended for older patients with diabetes, systolic congestive heart failure, or previous MI. An alpha blocker should not be used as initial therapy for hypertension in the elderly because of relative lack of efficacy in preventing cardiovascular events.

Patients with diabetes. Aggressive blood pressure control is especially important in the patient with diabetes, which is the leading cause of end-stage renal disease. Most patients with diabetes also have hypertension—which accelerates their renal disease as well as cardiovascular disease. Blood pressure control goals significantly below 140/90 mm Hg are recommended (120 to 135 mm Hg systolic, 80 to 85 mm Hg diastolic) if diabetes is present.

ACE inhibitors or angiotensin receptor blockers are preferred for initial treatment of hypertension in diabetes, especially if proteinuria is present. Some authorities feel the level of blood pressure control in diabetes is more important than the agent(s) chosen to achieve that control. Most patients with hypertension and diabetes are not controlled on a single antihypertensive drug, and a diuretic is often added.

Psychological aspects of hypertension management

The diagnosis of hypertension and a resulting perception of loss of health or longevity may trigger a grief reaction in some patients.

Several psychological aspects to hypertension treatment make it difficult to achieve long-term control. Patients may become discouraged as dosages are increased and more medications are added. Asymptomatic patients may have no incentive to control their blood pressure. Many report, “I don’t feel any better” when their blood pressure comes down.

Because the goal of hypertension therapy is control rather than cure, the patient must commit to long-term treatment. Lifestyle changes such as dietary sodium restriction, smoking cessation, and weight loss may be difficult to achieve, especially for patients already dealing with a psychiatric disorder.

Also, the cost of treatment—the price of medications and initial and follow-up laboratory studies, plus the expense of follow-up office visits (possibly requiring time off work)—may be high.

Psychiatrists can help by offering moral support and encouraging patients to manage their medical problems, risk factors, and overall health. Psychiatrists can also educate patients on the importance of blood pressure control in preventing cardiovascular morbidity and mortality.

Brief cognitive-behaviorial therapy can identify the individual’s state of change (precontemplation, contemplation, preparation, action, or maintenance). Process techniques (such as consciousness-raising, commitment, or self-reevaluation) appropriate to the stage of change may then be employed.

For example, a patient in the precontemplation stage may resist returning to his or her primary care doctor to begin treatment for high blood pressure, employing such reasoning as, “I can’t afford those expensive office visits, and the medications would cost too much anyway.”

The psychiatrist might then apply consciousness-raising to motivate the patient: “How serious do you think it is to have high blood pressure that isn’t controlled? Are you aware that many people with high blood pressure are treated by means other than medications, or that many blood pressure medications are inexpensive?”

Providing relaxation techniques or a 12-week course of buproprion also can enhance the efficacy of smoking cessation efforts.

Related resources

• Drugs for hypertension. The Medical Letter 2001;43(1099):17-22.
• Some drugs that cause psychiatric symptoms. The Medical Letter 1998;40(1020):21-4.
• Hypertension—Journal of the American Heart Association. http://hyper.ahajournals.org/
• National Heart, Lung, and Blood institute’s Cardiovascular information site. http://www.nhlbi.nih.gov/health/public/heart/index.htm#hbp

Drug brand names

• Bupropion • Wellbutrin
• Guanadrel • Hylorel
• Lisinopril • Prinivil, Zestril
• Losartan • Hyzaar
• Ramipril • Altace
• Reserpine • Diutensen-R
• Valsartan • Diovan
• Venlafaxine • Effexor
• (Numerous other drugs mentioned in this article are available generically)

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Roughly 50 million adult Americans have hypertension.¹ Chances are some of them are—or soon will be—under your care.

Hypertension is common among patients with psychiatric disorders, particularly in those with chronic mental conditions.² Medication-associated weight gain and other reactions to psychotropics, drug-drug interactions, lack of exercise, adverse dietary habits, and pre-existing medical conditions all predispose psychiatric patients to hypertension.

Yet hypertension often goes undetected in psychiatric patients. Hypertension many times is asymptomatic—about 50% of all people with the disorder don’t even know they have it.³ Some symptoms of uncontrolled hypertension—fatigue, headache, palpitations, and dizziness—are also associated with many psychiatric disorders. As a result, psychiatrists may attempt to manage the symptoms but miss the hypertension.

Psychiatrists need to be alert for hypertension, either as a possible contributing factor to a mental disorder or as a potential side effect of a psychiatric disorder or treatment. The following diagnostic and treatment strategies will help you detect and manage this common condition.

Causes of hypertension in mental illness

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines elevated blood pressure as 140 mm Hg systolic and/or 90 mm Hg diastolic. The diagnosis of hypertension should be based on the average of two or more blood pressure readings at each of two or more visits after initial screening.

All patients with elevated blood pressure have an underlying physiologic abnormality that is causing their hypertension. The disorder falls within the following two categories:

• essential hypertension, emanating from an unknown cause
• secondary hypertension, resulting from an underlying, discoverable, often treatable cause.

Researchers have speculated that certain psychiatric disorders might cause, or be risk factors for, hypertension. Anxiety or panic disorders have been associated with acute (and perhaps chronic) blood pressure elevations.² Some research suggests that patients with alexithymia are at risk for developing hypertension.⁴

Other studies suggest that hypertensive patients with certain psychological disorders (e.g., depression) or social factors (e.g., substance abuse) are less likely than nonaffected patients to self-report the presence of hypertension and less likely to receive medical attention for it.⁵

Psychiatric drugs also may affect blood pressure by one of two mechanisms:

• Pharmacodynamic—direct effects at the site of action (e.g., receptors) via physiologic mechanisms (Table 1). For example, amphetamines act directly on the sympathetic nervous system to elevate blood pressure.
• Pharmacokinetic—indirect effects on blood pressure via drug/drug interactions that alter the absorption, distribution, metabolism, or clearance of antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, and salt intake restrictions can raise lithium levels. The calcium-channel blockers verapamil and diltiazem can unpredictably increase or decrease lithium levels, but the combination generally is safe. Verapamil also raises tricyclic antidepressant levels. Monoamine oxidase inhibitors (MAOIs) used in tandem with the antihypertensive reserpine can cause hypomania. Beta-blocker levels are increased when used in concert with selective serotonin reuptake inhibitors. Use of carbamazepine with calcium-channel blockers can elevate carbamazapine levels and diminish the effectiveness of the calcium-channel blocker.

Table 1

POSSIBLE PHARMACODYNAMIC EFFECTS OFPSYCHIATRIC MEDICATIONS ON BLOOD PRESSURE

Symptoms, complications of high blood pressure

Symptoms that may be associated with high blood pressure include headaches, dizziness, lightheadedness, fatigue, palpitations, and chest discomfort. Patients may also experience symptoms secondary to end-organ damage (e.g., shortness of breath from congestive heart failure).

Most people, however, experience no symptoms when their blood pressure is elevated. This is one reason most people with hypertension do not adequately control their blood pressure.

Aside from the long-term end-organ damage caused by persistently elevated blood pressure, hypertension also has been found to cause psychiatric disorders, though not directly. For example, post-MI depression is well-recognized. Hypertension may also cause multi-infarct dementia with resultant depression, paranoia, or other psychotic features.

The psychological burden of having chronic and usually incurable (though controllable) hypertension may worsen depression or anxiety disorders. Patients with a chronic psychiatric illness generally have a higher incidence of chronic medical problems.

Likewise, patients with chronic medical disorders have a higher incidence of psychiatric complaints.⁶

Patient evaluation

When evaluating the patient with elevated blood pressure, it is important to:

• detect and confirm hypertension
• detect target-organ disease (e.g., renal damage or congestive heart failure)
• identify other cardiovascular risk factors (e.g., diabetes mellitus, hyperlipidemia, obesity)
• identify secondary causes of hypertension, such as endocrine abnormalities (e.g., hyperaldosteronism, thyroid disorders), kidney disease, obstructive sleep apnea, and response to medications.

Table 2

ANTIHYPERTENSIVE MEDICATIONS AND SIDE EFFECTS

A thorough history and physical examination should be performed to assess these four areas. Routine laboratory testing for the hypertensive patient should include a urinalysis, a complete blood count, an assessment of blood chemistries (potassium, sodium, creatinine, fasting glucose, fasting lipid profile), and a 12-lead electrocardiogram.

Treating hypertension

Many medications are used to treat hypertension. Most classes of antihypertensive agents have been shown to be about equally effective in lowering blood pressure.

All other factors being equal, the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) recommends initial treatment with a diuretic or beta-blocker. These classes of drugs have been shown to significantly reduce overall hypertension-related mortality.

Most patients with hypertension—particularly the elderly, patients with diabetes mellitus, and those with renal disease—will need two or more agents to control their blood pressure. Avoid prescribing agents that may worsen an existing condition (e.g., beta-blockers may worsen bronchospasm in patients with asthma). Use agents that may help improve comorbid conditions (e.g., beta-blockers have been shown to reduce mortality in patients with previous MI).

Box

Potential side effects, some of which mimic or are commonly found in psychiatric disorders, must be considered when choosing an antihypertensive agent. Table 2 lists nine classes of antihypertensives and some associated side effects. Also consider the agent’s cost, convenience of administration, direct-to-consumer advertising, and the patient’s age or race. For example, beta-blockers tend to be less effective in black or elderly patients than in other demographic groups.

Nonpharmacologic hypertension management emphasizes weight reduction, moderation of alcohol intake, regular aerobic exercise, dietary restriction of sodium, and smoking cessation. Most studies of these behavioral interventions have demonstrated a short-term benefit in decreasing blood pressure, but long-term adherence to them is disappointing. Relaxation therapies and biofeedback have been advocated for hypertension, but proof of their efficacy is lacking.⁷

As more is learned about genetic and other causes of hypertension, more-effective treatments for hypertension could become available (Box).

Treating high-risk groups

Special considerations apply to two patient groups with a high prevalence of hypertension—those age 65 and older and those with diabetes.

Older patients. Treatment benefits are more pronounced in patients age 65 or older because of their greater absolute risk for cardiovascular events. Also, systolic blood pressures increase with aging as the arterial tree becomes progressively less distensible.

Older patients often will require more than one drug to control their blood pressure. The initial dosages should be low and gradually titrated upward as needed. To minimize side effects, use smaller doses of multiple agents that are well tolerated instead of high-dose monotherapy.

A diuretic is often recommended as initial treatment for older patients, though a long-acting dihydropyridine calcium-channel blocker is a reasonable alternative. An ACE inhibitor is recommended for older patients with diabetes, systolic congestive heart failure, or previous MI. An alpha blocker should not be used as initial therapy for hypertension in the elderly because of relative lack of efficacy in preventing cardiovascular events.

Patients with diabetes. Aggressive blood pressure control is especially important in the patient with diabetes, which is the leading cause of end-stage renal disease. Most patients with diabetes also have hypertension—which accelerates their renal disease as well as cardiovascular disease. Blood pressure control goals significantly below 140/90 mm Hg are recommended (120 to 135 mm Hg systolic, 80 to 85 mm Hg diastolic) if diabetes is present.

ACE inhibitors or angiotensin receptor blockers are preferred for initial treatment of hypertension in diabetes, especially if proteinuria is present. Some authorities feel the level of blood pressure control in diabetes is more important than the agent(s) chosen to achieve that control. Most patients with hypertension and diabetes are not controlled on a single antihypertensive drug, and a diuretic is often added.

Psychological aspects of hypertension management

The diagnosis of hypertension and a resulting perception of loss of health or longevity may trigger a grief reaction in some patients.

Several psychological aspects to hypertension treatment make it difficult to achieve long-term control. Patients may become discouraged as dosages are increased and more medications are added. Asymptomatic patients may have no incentive to control their blood pressure. Many report, “I don’t feel any better” when their blood pressure comes down.

Because the goal of hypertension therapy is control rather than cure, the patient must commit to long-term treatment. Lifestyle changes such as dietary sodium restriction, smoking cessation, and weight loss may be difficult to achieve, especially for patients already dealing with a psychiatric disorder.

Also, the cost of treatment—the price of medications and initial and follow-up laboratory studies, plus the expense of follow-up office visits (possibly requiring time off work)—may be high.

Psychiatrists can help by offering moral support and encouraging patients to manage their medical problems, risk factors, and overall health. Psychiatrists can also educate patients on the importance of blood pressure control in preventing cardiovascular morbidity and mortality.

Brief cognitive-behaviorial therapy can identify the individual’s state of change (precontemplation, contemplation, preparation, action, or maintenance). Process techniques (such as consciousness-raising, commitment, or self-reevaluation) appropriate to the stage of change may then be employed.

For example, a patient in the precontemplation stage may resist returning to his or her primary care doctor to begin treatment for high blood pressure, employing such reasoning as, “I can’t afford those expensive office visits, and the medications would cost too much anyway.”

The psychiatrist might then apply consciousness-raising to motivate the patient: “How serious do you think it is to have high blood pressure that isn’t controlled? Are you aware that many people with high blood pressure are treated by means other than medications, or that many blood pressure medications are inexpensive?”

Providing relaxation techniques or a 12-week course of buproprion also can enhance the efficacy of smoking cessation efforts.

Related resources

• Drugs for hypertension. The Medical Letter 2001;43(1099):17-22.
• Some drugs that cause psychiatric symptoms. The Medical Letter 1998;40(1020):21-4.
• Hypertension—Journal of the American Heart Association. http://hyper.ahajournals.org/
• National Heart, Lung, and Blood institute’s Cardiovascular information site. http://www.nhlbi.nih.gov/health/public/heart/index.htm#hbp

Drug brand names

• Bupropion • Wellbutrin
• Guanadrel • Hylorel
• Lisinopril • Prinivil, Zestril
• Losartan • Hyzaar
• Ramipril • Altace
• Reserpine • Diutensen-R
• Valsartan • Diovan
• Venlafaxine • Effexor
• (Numerous other drugs mentioned in this article are available generically)

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Behaviors during seizures can mimic psychiatric disorders, and patients with epilepsy have higher-than-normal rates of many types of psychiatric illness. That’s why it is important for psychiatrists to be familiar with epilepsy and electroencephalography (EEG)—the key diagnostic tool for epileptic disorders.

As a neurologist who specializes in epilepsy treatment, I offer five case studies that highlight basic concepts about epilepsy and EEGs. My goal is to help psychiatrists answer common clinical questions such as:

• If a patient with bipolar illness has an abnormal EEG, should this guide the treatment choice?
• In a patient with episodes of fear, tachycardia, and other autonomic symptoms, how does one differentiate between panic attacks, complex partial seizures, and psychogenic nonepileptic seizures?
• When is EEG indicated in a patient with attention-deficit/hyperactivity disorder (ADHD)?
• Can complex partial status epilepticus present as a psychiatric disorder?
• In patients with epilepsy, why is it important to categorize psychiatric symptoms as ictal (occurring at the time of seizure), interictal (between seizures), or postictal (following seizures)?

How EEG is used today

EEG is used mainly to evaluate epilepsy and diffuse brain dysfunction (e.g., coma and confusional states). Modern brain imaging, including magnetic resonance imaging (MRI) and computerized tomography (CT), has replaced EEG for evaluating structural brain abnormalities.

Two basic EEG findings with which psychiatrists should be familiar are slowing and epileptiform activity:

Slowing is a nonspecific finding that indicates dysfunction of the underlying white matter, with or without gray matter involvement. Focal slowing indicates a focal area of cortical dysfunction usually caused by a focal structural lesion (tumor, stroke, trauma, etc.), although a lesion is not always found. Brain imaging, usually MRI, is indicated.

Epileptiform activity, which is seen as spikes or sharp waves, indicates potential for epileptic seizures (Box). EEG technologists may use activation procedures such as hyperventilation and photic stimulation to enhance the ability of EEG to detect epileptiform activity. Special electrodes (e.g., anterior temporal electrodes) may be used to improve recordings taken from the temporal lobe. In selected inpatients, epilepsy centers may use sphenoidal electrodes—wires inserted under the skin of the cheek to record temporal lobe activity.

Video/EEG monitoring has been used since the 1960s and is the gold standard in evaluating patients with seizures or episodes that resemble seizures. The technique involves simultaneously recording brain activity on an EEG and behavior on tape or digital video. Usually patients are admitted to a specialized hospital unit, medications are reduced or discontinued, and the seizures or other behaviors are recorded. Neurologists with special training in EEG and epilepsy evaluate the EEG for changes before, during, and after the behavioral event. Clinical characteristics of seizures and nonepileptic events detected on the video also help with the evaluation.

Video/EEG is most helpful in:

• determining whether the events are epileptic or nonepileptic
• determining—if epileptic—the precise seizure type for treatment decisions
• localizing the site of seizure onset in patients with medication-resistant epilepsy who may be candidates for epilepsy surgery

Normal variants occur frequently on EEG and may be misinterpreted because they resemble epileptiform activity. They include:

• benign epileptiform transients of sleep
• mu rhythm
• rhythmic midtemporal variant
• subclinical rhythmic epileptiform discharge in adults.

Experienced electroencephalographers can readily identify these normal variants, but some neurologists may misidentify or misinterpret these EEG findings, potentially leading to unnecessary treatment with antiepileptic drugs.

Hundreds of medications can alter an EEG, usually by increasing either slowing or beta activity. The most common change is excessive beta activity, which is seen in most patients taking benzodiazepines or barbiturates. Enhanced beta activity is an appropriate response of a normal brain to certain medications and does not indicate underlying brain pathology.

If a patient with psychiatric illness has seizure-like episodes, an abnormal EEG may help in diagnosis. A neurologist can help direct the patient evaluation. Whether or not interictal EEG abnormalities are present, video/EEG monitoring can often make the diagnosis by capturing the events.

Case 1: Does this patient have epilepsy?

For Mr. A, age 27, lithium has stabilized his bipolar I disorder for 2 years without significant adverse effects. An EEG ordered for unknown reasons by his primary care physician shows large amounts of beta activity and a single sharp wave from the right temporal region. Should you add an antiepileptic drug to his regimen?

In this patient, lithium probably caused the large amounts of beta activity. A rule of thumb says that if an EEG shows increased beta activity, a medication is almost certainly the cause. If an EEG finds increased generalized slowing, medication effect is one of many possible causes.

The single sharp wave from the right temporal lobe raises the possibility of increased susceptibility to seizures but is not diagnostic of epilepsy. There is no indication to change the patient’s treatment regimen if he is well controlled without adverse effects from his current medications and there is no clear history of clinical seizures. In short, treat the patient, not the EEG.

Box

EEGs: EPILEPTIFORM ACTIVITY INDICATES POTENTIAL FOR SEIZURES

On an EEG, epileptiform activity is seen as spikes or sharp waves and indicates potential for epileptic seizures.

• Focal epileptiform activity is consistent with seizures of focal origin (e.g., simple partial, complex partial, or partial onset seizure with secondary generalization into tonic-clonic seizure).
• Generalized epileptiform activity is consistent with seizures of generalized onset (e.g., absence, myoclonic, or primary generalized tonic-clonic seizure).

Interictal spikes (between seizures) are consistent with, but not diagnostic of, seizures and epilepsy. An ictal discharge (rhythmic, persistent epileptiform activity) on an EEG accompanied by a clinical change in behavior is diagnostic of a seizure.

Focal epileptiform activity

Generalized epileptiform activity

Based on early studies, EEG results can show epileptiform activity in some normal brains.¹ On the other hand, only about 50% of patients with epilepsy will show epileptiform activity on a single EEG. Thus, some EEG abnormalities in psychiatric patients may not be related to either epilepsy or the psychiatric disorder, and a normal EEG does not exclude the possibility of epileptic seizures.

Question the patient for a history of other factors that may predispose him or her to seizures, such as:

• family history of seizures
• previous traumatic brain injury
• structural brain abnormality.

In light of this EEG, brain MRI is indicated. In this case the patient could be counseled to avoid seizure triggers (e.g., sleep deprivation). Because a long list of medications can lower the seizure threshold, the clinician must weigh the risks and benefits of using any medication in patients with increased susceptibility for seizures.

Case 2: Seizures or panic attacks?

Mr. B, age 31, is referred by his primary care physician for “spells” that began several years ago and recently increased in frequency to three to four times per week. The episodes start with a feeling of fear, “butterflies” in his stomach, and hyperventilation. These feelings intensify within minutes; each episode lasts 10 to 30 minutes.

The patient is usually aware of his surroundings during the episodes but twice has lost consciousness for less than 1 minute. There is no evidence of incontinence or tongue biting. Four years ago, the patient was involved in a motor vehicle accident and lost consciousness for about 30 minutes.

An EEG shows intermittent slowing from the left temporal region, and brain MRI is normal. Treatment with a benzodiazepine shortens the attacks. Where do you proceed from here?

Mr. B presents a diagnostic dilemma. Characteristics of his episodes may be seen in panic attacks, temporal lobe complex partial seizures, and psychogenic nonepileptic seizures, which is the preferred term for pseudoseizures (Table).²

One option would be to see how he responds to an agent that would treat seizures but not panic attacks (e.g., carbamazepine) or one that would treat panic attacks but not seizures (e.g., a selective serotonin reuptake inhibitor). Because his episodes are frequent, however, a more appropriate option would be to admit him for video/EEG monitoring, which can distinguish among these possible diagnoses with almost 100% accuracy.

Case 3: Attention disorder or epilepsy?

Miss C, age 9, is referred for possible ADHD. Her teachers notice she has difficulty following lessons in class but is intelligent and usually motivated. Her grades have been dropping. Her family reports she has episodes during which she stares and is unable to answer questions for 3 to 5 seconds, but she exhibits no other seizure-like manifestations. A trial of methylphenidate has not improved the symptoms. What should you try next?

This patient presents with symptoms that could be consistent with absence seizures. EEG would be diagnostic if it showed generalized spike and wave. Absence seizures (sometimes called petit mal) usually present in childhood and are characterized by recurrent brief staring spells with no postictal confusion or other clinical manifestations.

Patients with childhood absence epilepsy are usually of normal intelligence and only rarely have other associated seizure types (e.g., myoclonus or tonic-clonic). Seizures of approximately 3 to 5 seconds may occur up to 100 times a day and thus may be mistaken for attention problems.

EEG shows characteristic generalized three-per-second spike and wave, which is often precipitated by hyperventilation or photic stimulation. Ethosuximide or valproate can completely control seizures in most cases.

Case 4: Emergency use of EEG

Ms. D, age 21, is brought to the emergency department by her mother with symptoms of confusion. Ms. D has a long history of temporal lobe complex partial seizures, and her mother thinks she may have missed some doses of her antiepileptic drugs (carbamazepine and valproate). Yesterday Ms. D had two complex partial seizures but returned to baseline. Today she had three complex partial seizures within 2 hours and has not returned to baseline.

When you interview Ms. D she is alert but only intermittently oriented to date and location. She makes a variety of paraphasic speech errors. She is talking about heaven and angels and several times asks if you are the devil. Evaluation by the emergency physician discloses no toxic, metabolic, or infectious cause for her symptoms. Other than mental status, her neurologic examination is normal and shows no evidence of motor seizure activity. What would you suggest next?

This patient presents with complex partial seizures occurring in sequence without return to normal between seizures, followed by a continuous state of altered consciousness. This cluster of symptoms and signs is consistent with complex partial status epilepticus.

Emergency EEG is diagnostic. If the EEG is positive for status epilepticus, recommended treatment is IV benzodiazepines along with other IV antiepileptic drugs.

Complex partial status epilepticus can have a variety of triggers, including drug overdose, hyperthyroidism, brain tumor, or carcinomatous meningitis.³ In this case, the most likely trigger is medication noncompliance.

Complex partial or other forms of nonconvulsive status epilepticus occur in up to 37% of hospitalized patients with altered consciousness of uncertain etiology.³ EEG is required to confirm the diagnosis, but many hospitals do not have EEG technologists on call nights and weekends.

Table

THE FEARFUL PATIENT: PANIC ATTACK, SEIZURE DISORDER, OR PSYCHOGENIC?

In my experience, a patient who later was referred to me for seizure control was once admitted to a psychiatry ward for 4 days because of unidentified complex partial status epilepticus. When someone finally restarted her carbamazepine, she returned to normal in a few days. Six months after she became my patient, she presented with identical symptoms. An EEG within hours of symptom onset showed continuous EEG ictal activity from the left temporal lobe. When we administered IV lorazepam, her EEG normalized within minutes and her confusion and delusional symptoms resolved in 20 minutes.

Case 5: Seizure clusters followed by agitation

Mr. E, 32, has had complex partial and tonic-clonic seizures since age 14. He presents with chronic depressive symptoms and independent episodes of agitated behavior with psychotic features lasting hours after seizure clusters. His seizures have continued despite trials of different antiepileptic drugs, and he currently is receiving phenytoin and valproate. He is referred to you to diagnose and treat the psychiatric symptoms.

He scores a 28 on the Beck Depression Inventory, which indicates moderate depression,⁴ but he is not suicidal. He reports that although his depression symptoms are constant, his psychotic features occur only after a series of closely-spaced seizures. How do you approach this problem?

Based on the history, this patient has both mild interictal depression and postictal psychosis. In patients with epilepsy, psychiatric symptoms are categorized as:

• ictal (occur only during a seizure)
• interictal (may wax and wane but are present chronically, usually with no relation to seizure occurrence)
• or postictal (appear within 7 days after a lucid interval following a seizure or—more often—a series of seizures).⁵

Interictal psychiatric disorders include depression, bipolar disorder, and psychotic disorders. If the psychiatric disorder is truly interictal and has no clear relation to seizure occurrence, it should be treated like any other psychiatric illness with appropriate medications. One should not automatically add another antiepileptic drug (AED), because AEDs as a class have more adverse effects and more drug interactions than commonly used antidepressants.

Begin by examining the AEDs the patient is receiving. For example, phenobarbital and, to a lesser extent, phenytoin are associated with depression and should be used in patients with depression only when other AEDs have failed.

Ictal and postictal psychiatric symptoms should be treated acutely. Postictal symptoms may include psychosis, depression, mania, or anxiety. A short course of benzodiazepines is often helpful; the use of neuroleptics is dictated by the intensity and quality of the postictal symptoms.

Ictal depression-like symptoms can be seen with temporal lobe complex partial seizures. Many patients with these seizures have simple partial seizures (auras) that manifest as brief (usually less than 1 minute) intense feelings of fear or impending doom, or of “the life drained out” of them. These symptoms may arise from seizures involving mesial temporal regions. They do not usually require treatment besides AEDs.

The idea that patients with temporal lobe epilepsy may have a particular personality type is controversial. Retrospective data first suggested that certain traits (e.g., altered sexual behavior, anger, emotionality and obsessionalism, hypergraphia, and hyper-religiosity) could be found consistently in patients with temporal lobe epilepsy.⁶ This personality inventory was sometimes used to diagnose epilepsy. Subsequent studies have not validated the original data, although the cluster of personality traits can certainly occur in some patients.^7-9

Related resources

• Epilepsy Foundation. www.epilepsyfoundation.org
• Engel J, Pedley TA (eds). Epilepsy: A comprehensive textbook. Philadelphia: Lippincott-Raven, 1998.

Drug brand names

• Carbamazepine • Tegretol
• Ethosuximide • Zarontin
• Lorazepam • Ativan
• Phenytoin • Dilantin
• Valproate • Depakote

Disclosure

The author reports that he receives research/grant support from, is a consultant to, and is on the speakers’ bureau of GlaxoSmithKline, UCBPharma, and Ortho-McNeil Pharmaceuticals; receives research/grant support from and is a consultant to Schwarz Pharma; is a consultant to Pfizer Inc., Elan Pharmaceuticals, and Shire Pharmaceuticals; and is on the speakers’ bureau of Abbott Laboratories, Cyberonics, and Shire Pharmaceuticals.

Behaviors during seizures can mimic psychiatric disorders, and patients with epilepsy have higher-than-normal rates of many types of psychiatric illness. That’s why it is important for psychiatrists to be familiar with epilepsy and electroencephalography (EEG)—the key diagnostic tool for epileptic disorders.

As a neurologist who specializes in epilepsy treatment, I offer five case studies that highlight basic concepts about epilepsy and EEGs. My goal is to help psychiatrists answer common clinical questions such as:

• If a patient with bipolar illness has an abnormal EEG, should this guide the treatment choice?
• In a patient with episodes of fear, tachycardia, and other autonomic symptoms, how does one differentiate between panic attacks, complex partial seizures, and psychogenic nonepileptic seizures?
• When is EEG indicated in a patient with attention-deficit/hyperactivity disorder (ADHD)?
• Can complex partial status epilepticus present as a psychiatric disorder?
• In patients with epilepsy, why is it important to categorize psychiatric symptoms as ictal (occurring at the time of seizure), interictal (between seizures), or postictal (following seizures)?

How EEG is used today

EEG is used mainly to evaluate epilepsy and diffuse brain dysfunction (e.g., coma and confusional states). Modern brain imaging, including magnetic resonance imaging (MRI) and computerized tomography (CT), has replaced EEG for evaluating structural brain abnormalities.

Two basic EEG findings with which psychiatrists should be familiar are slowing and epileptiform activity:

Slowing is a nonspecific finding that indicates dysfunction of the underlying white matter, with or without gray matter involvement. Focal slowing indicates a focal area of cortical dysfunction usually caused by a focal structural lesion (tumor, stroke, trauma, etc.), although a lesion is not always found. Brain imaging, usually MRI, is indicated.

Epileptiform activity, which is seen as spikes or sharp waves, indicates potential for epileptic seizures (Box). EEG technologists may use activation procedures such as hyperventilation and photic stimulation to enhance the ability of EEG to detect epileptiform activity. Special electrodes (e.g., anterior temporal electrodes) may be used to improve recordings taken from the temporal lobe. In selected inpatients, epilepsy centers may use sphenoidal electrodes—wires inserted under the skin of the cheek to record temporal lobe activity.

Video/EEG monitoring has been used since the 1960s and is the gold standard in evaluating patients with seizures or episodes that resemble seizures. The technique involves simultaneously recording brain activity on an EEG and behavior on tape or digital video. Usually patients are admitted to a specialized hospital unit, medications are reduced or discontinued, and the seizures or other behaviors are recorded. Neurologists with special training in EEG and epilepsy evaluate the EEG for changes before, during, and after the behavioral event. Clinical characteristics of seizures and nonepileptic events detected on the video also help with the evaluation.

Video/EEG is most helpful in:

• determining whether the events are epileptic or nonepileptic
• determining—if epileptic—the precise seizure type for treatment decisions
• localizing the site of seizure onset in patients with medication-resistant epilepsy who may be candidates for epilepsy surgery

Normal variants occur frequently on EEG and may be misinterpreted because they resemble epileptiform activity. They include:

• benign epileptiform transients of sleep
• mu rhythm
• rhythmic midtemporal variant
• subclinical rhythmic epileptiform discharge in adults.

Experienced electroencephalographers can readily identify these normal variants, but some neurologists may misidentify or misinterpret these EEG findings, potentially leading to unnecessary treatment with antiepileptic drugs.

Hundreds of medications can alter an EEG, usually by increasing either slowing or beta activity. The most common change is excessive beta activity, which is seen in most patients taking benzodiazepines or barbiturates. Enhanced beta activity is an appropriate response of a normal brain to certain medications and does not indicate underlying brain pathology.

If a patient with psychiatric illness has seizure-like episodes, an abnormal EEG may help in diagnosis. A neurologist can help direct the patient evaluation. Whether or not interictal EEG abnormalities are present, video/EEG monitoring can often make the diagnosis by capturing the events.

Case 1: Does this patient have epilepsy?

For Mr. A, age 27, lithium has stabilized his bipolar I disorder for 2 years without significant adverse effects. An EEG ordered for unknown reasons by his primary care physician shows large amounts of beta activity and a single sharp wave from the right temporal region. Should you add an antiepileptic drug to his regimen?

In this patient, lithium probably caused the large amounts of beta activity. A rule of thumb says that if an EEG shows increased beta activity, a medication is almost certainly the cause. If an EEG finds increased generalized slowing, medication effect is one of many possible causes.

The single sharp wave from the right temporal lobe raises the possibility of increased susceptibility to seizures but is not diagnostic of epilepsy. There is no indication to change the patient’s treatment regimen if he is well controlled without adverse effects from his current medications and there is no clear history of clinical seizures. In short, treat the patient, not the EEG.

Box

EEGs: EPILEPTIFORM ACTIVITY INDICATES POTENTIAL FOR SEIZURES

On an EEG, epileptiform activity is seen as spikes or sharp waves and indicates potential for epileptic seizures.

• Focal epileptiform activity is consistent with seizures of focal origin (e.g., simple partial, complex partial, or partial onset seizure with secondary generalization into tonic-clonic seizure).
• Generalized epileptiform activity is consistent with seizures of generalized onset (e.g., absence, myoclonic, or primary generalized tonic-clonic seizure).

Interictal spikes (between seizures) are consistent with, but not diagnostic of, seizures and epilepsy. An ictal discharge (rhythmic, persistent epileptiform activity) on an EEG accompanied by a clinical change in behavior is diagnostic of a seizure.

Focal epileptiform activity

Generalized epileptiform activity

Based on early studies, EEG results can show epileptiform activity in some normal brains.¹ On the other hand, only about 50% of patients with epilepsy will show epileptiform activity on a single EEG. Thus, some EEG abnormalities in psychiatric patients may not be related to either epilepsy or the psychiatric disorder, and a normal EEG does not exclude the possibility of epileptic seizures.

Question the patient for a history of other factors that may predispose him or her to seizures, such as:

• family history of seizures
• previous traumatic brain injury
• structural brain abnormality.

In light of this EEG, brain MRI is indicated. In this case the patient could be counseled to avoid seizure triggers (e.g., sleep deprivation). Because a long list of medications can lower the seizure threshold, the clinician must weigh the risks and benefits of using any medication in patients with increased susceptibility for seizures.

Case 2: Seizures or panic attacks?

Mr. B, age 31, is referred by his primary care physician for “spells” that began several years ago and recently increased in frequency to three to four times per week. The episodes start with a feeling of fear, “butterflies” in his stomach, and hyperventilation. These feelings intensify within minutes; each episode lasts 10 to 30 minutes.

The patient is usually aware of his surroundings during the episodes but twice has lost consciousness for less than 1 minute. There is no evidence of incontinence or tongue biting. Four years ago, the patient was involved in a motor vehicle accident and lost consciousness for about 30 minutes.

An EEG shows intermittent slowing from the left temporal region, and brain MRI is normal. Treatment with a benzodiazepine shortens the attacks. Where do you proceed from here?

Mr. B presents a diagnostic dilemma. Characteristics of his episodes may be seen in panic attacks, temporal lobe complex partial seizures, and psychogenic nonepileptic seizures, which is the preferred term for pseudoseizures (Table).²

One option would be to see how he responds to an agent that would treat seizures but not panic attacks (e.g., carbamazepine) or one that would treat panic attacks but not seizures (e.g., a selective serotonin reuptake inhibitor). Because his episodes are frequent, however, a more appropriate option would be to admit him for video/EEG monitoring, which can distinguish among these possible diagnoses with almost 100% accuracy.

Case 3: Attention disorder or epilepsy?

Miss C, age 9, is referred for possible ADHD. Her teachers notice she has difficulty following lessons in class but is intelligent and usually motivated. Her grades have been dropping. Her family reports she has episodes during which she stares and is unable to answer questions for 3 to 5 seconds, but she exhibits no other seizure-like manifestations. A trial of methylphenidate has not improved the symptoms. What should you try next?

This patient presents with symptoms that could be consistent with absence seizures. EEG would be diagnostic if it showed generalized spike and wave. Absence seizures (sometimes called petit mal) usually present in childhood and are characterized by recurrent brief staring spells with no postictal confusion or other clinical manifestations.

Patients with childhood absence epilepsy are usually of normal intelligence and only rarely have other associated seizure types (e.g., myoclonus or tonic-clonic). Seizures of approximately 3 to 5 seconds may occur up to 100 times a day and thus may be mistaken for attention problems.

EEG shows characteristic generalized three-per-second spike and wave, which is often precipitated by hyperventilation or photic stimulation. Ethosuximide or valproate can completely control seizures in most cases.

Case 4: Emergency use of EEG

Ms. D, age 21, is brought to the emergency department by her mother with symptoms of confusion. Ms. D has a long history of temporal lobe complex partial seizures, and her mother thinks she may have missed some doses of her antiepileptic drugs (carbamazepine and valproate). Yesterday Ms. D had two complex partial seizures but returned to baseline. Today she had three complex partial seizures within 2 hours and has not returned to baseline.

When you interview Ms. D she is alert but only intermittently oriented to date and location. She makes a variety of paraphasic speech errors. She is talking about heaven and angels and several times asks if you are the devil. Evaluation by the emergency physician discloses no toxic, metabolic, or infectious cause for her symptoms. Other than mental status, her neurologic examination is normal and shows no evidence of motor seizure activity. What would you suggest next?

This patient presents with complex partial seizures occurring in sequence without return to normal between seizures, followed by a continuous state of altered consciousness. This cluster of symptoms and signs is consistent with complex partial status epilepticus.

Emergency EEG is diagnostic. If the EEG is positive for status epilepticus, recommended treatment is IV benzodiazepines along with other IV antiepileptic drugs.

Complex partial status epilepticus can have a variety of triggers, including drug overdose, hyperthyroidism, brain tumor, or carcinomatous meningitis.³ In this case, the most likely trigger is medication noncompliance.

Complex partial or other forms of nonconvulsive status epilepticus occur in up to 37% of hospitalized patients with altered consciousness of uncertain etiology.³ EEG is required to confirm the diagnosis, but many hospitals do not have EEG technologists on call nights and weekends.

Table

THE FEARFUL PATIENT: PANIC ATTACK, SEIZURE DISORDER, OR PSYCHOGENIC?

In my experience, a patient who later was referred to me for seizure control was once admitted to a psychiatry ward for 4 days because of unidentified complex partial status epilepticus. When someone finally restarted her carbamazepine, she returned to normal in a few days. Six months after she became my patient, she presented with identical symptoms. An EEG within hours of symptom onset showed continuous EEG ictal activity from the left temporal lobe. When we administered IV lorazepam, her EEG normalized within minutes and her confusion and delusional symptoms resolved in 20 minutes.

Case 5: Seizure clusters followed by agitation

Mr. E, 32, has had complex partial and tonic-clonic seizures since age 14. He presents with chronic depressive symptoms and independent episodes of agitated behavior with psychotic features lasting hours after seizure clusters. His seizures have continued despite trials of different antiepileptic drugs, and he currently is receiving phenytoin and valproate. He is referred to you to diagnose and treat the psychiatric symptoms.

He scores a 28 on the Beck Depression Inventory, which indicates moderate depression,⁴ but he is not suicidal. He reports that although his depression symptoms are constant, his psychotic features occur only after a series of closely-spaced seizures. How do you approach this problem?

Based on the history, this patient has both mild interictal depression and postictal psychosis. In patients with epilepsy, psychiatric symptoms are categorized as:

• ictal (occur only during a seizure)
• interictal (may wax and wane but are present chronically, usually with no relation to seizure occurrence)
• or postictal (appear within 7 days after a lucid interval following a seizure or—more often—a series of seizures).⁵

Interictal psychiatric disorders include depression, bipolar disorder, and psychotic disorders. If the psychiatric disorder is truly interictal and has no clear relation to seizure occurrence, it should be treated like any other psychiatric illness with appropriate medications. One should not automatically add another antiepileptic drug (AED), because AEDs as a class have more adverse effects and more drug interactions than commonly used antidepressants.

Begin by examining the AEDs the patient is receiving. For example, phenobarbital and, to a lesser extent, phenytoin are associated with depression and should be used in patients with depression only when other AEDs have failed.

Ictal and postictal psychiatric symptoms should be treated acutely. Postictal symptoms may include psychosis, depression, mania, or anxiety. A short course of benzodiazepines is often helpful; the use of neuroleptics is dictated by the intensity and quality of the postictal symptoms.

Ictal depression-like symptoms can be seen with temporal lobe complex partial seizures. Many patients with these seizures have simple partial seizures (auras) that manifest as brief (usually less than 1 minute) intense feelings of fear or impending doom, or of “the life drained out” of them. These symptoms may arise from seizures involving mesial temporal regions. They do not usually require treatment besides AEDs.

The idea that patients with temporal lobe epilepsy may have a particular personality type is controversial. Retrospective data first suggested that certain traits (e.g., altered sexual behavior, anger, emotionality and obsessionalism, hypergraphia, and hyper-religiosity) could be found consistently in patients with temporal lobe epilepsy.⁶ This personality inventory was sometimes used to diagnose epilepsy. Subsequent studies have not validated the original data, although the cluster of personality traits can certainly occur in some patients.^7-9

Related resources

• Epilepsy Foundation. www.epilepsyfoundation.org
• Engel J, Pedley TA (eds). Epilepsy: A comprehensive textbook. Philadelphia: Lippincott-Raven, 1998.

Drug brand names

• Carbamazepine • Tegretol
• Ethosuximide • Zarontin
• Lorazepam • Ativan
• Phenytoin • Dilantin
• Valproate • Depakote

Disclosure

The author reports that he receives research/grant support from, is a consultant to, and is on the speakers’ bureau of GlaxoSmithKline, UCBPharma, and Ortho-McNeil Pharmaceuticals; receives research/grant support from and is a consultant to Schwarz Pharma; is a consultant to Pfizer Inc., Elan Pharmaceuticals, and Shire Pharmaceuticals; and is on the speakers’ bureau of Abbott Laboratories, Cyberonics, and Shire Pharmaceuticals.

Behaviors during seizures can mimic psychiatric disorders, and patients with epilepsy have higher-than-normal rates of many types of psychiatric illness. That’s why it is important for psychiatrists to be familiar with epilepsy and electroencephalography (EEG)—the key diagnostic tool for epileptic disorders.

As a neurologist who specializes in epilepsy treatment, I offer five case studies that highlight basic concepts about epilepsy and EEGs. My goal is to help psychiatrists answer common clinical questions such as:

• If a patient with bipolar illness has an abnormal EEG, should this guide the treatment choice?
• In a patient with episodes of fear, tachycardia, and other autonomic symptoms, how does one differentiate between panic attacks, complex partial seizures, and psychogenic nonepileptic seizures?
• When is EEG indicated in a patient with attention-deficit/hyperactivity disorder (ADHD)?
• Can complex partial status epilepticus present as a psychiatric disorder?
• In patients with epilepsy, why is it important to categorize psychiatric symptoms as ictal (occurring at the time of seizure), interictal (between seizures), or postictal (following seizures)?

How EEG is used today

EEG is used mainly to evaluate epilepsy and diffuse brain dysfunction (e.g., coma and confusional states). Modern brain imaging, including magnetic resonance imaging (MRI) and computerized tomography (CT), has replaced EEG for evaluating structural brain abnormalities.

Two basic EEG findings with which psychiatrists should be familiar are slowing and epileptiform activity:

Slowing is a nonspecific finding that indicates dysfunction of the underlying white matter, with or without gray matter involvement. Focal slowing indicates a focal area of cortical dysfunction usually caused by a focal structural lesion (tumor, stroke, trauma, etc.), although a lesion is not always found. Brain imaging, usually MRI, is indicated.

Epileptiform activity, which is seen as spikes or sharp waves, indicates potential for epileptic seizures (Box). EEG technologists may use activation procedures such as hyperventilation and photic stimulation to enhance the ability of EEG to detect epileptiform activity. Special electrodes (e.g., anterior temporal electrodes) may be used to improve recordings taken from the temporal lobe. In selected inpatients, epilepsy centers may use sphenoidal electrodes—wires inserted under the skin of the cheek to record temporal lobe activity.

Video/EEG monitoring has been used since the 1960s and is the gold standard in evaluating patients with seizures or episodes that resemble seizures. The technique involves simultaneously recording brain activity on an EEG and behavior on tape or digital video. Usually patients are admitted to a specialized hospital unit, medications are reduced or discontinued, and the seizures or other behaviors are recorded. Neurologists with special training in EEG and epilepsy evaluate the EEG for changes before, during, and after the behavioral event. Clinical characteristics of seizures and nonepileptic events detected on the video also help with the evaluation.

Video/EEG is most helpful in:

• determining whether the events are epileptic or nonepileptic
• determining—if epileptic—the precise seizure type for treatment decisions
• localizing the site of seizure onset in patients with medication-resistant epilepsy who may be candidates for epilepsy surgery

Normal variants occur frequently on EEG and may be misinterpreted because they resemble epileptiform activity. They include:

• benign epileptiform transients of sleep
• mu rhythm
• rhythmic midtemporal variant
• subclinical rhythmic epileptiform discharge in adults.

Experienced electroencephalographers can readily identify these normal variants, but some neurologists may misidentify or misinterpret these EEG findings, potentially leading to unnecessary treatment with antiepileptic drugs.

Hundreds of medications can alter an EEG, usually by increasing either slowing or beta activity. The most common change is excessive beta activity, which is seen in most patients taking benzodiazepines or barbiturates. Enhanced beta activity is an appropriate response of a normal brain to certain medications and does not indicate underlying brain pathology.

If a patient with psychiatric illness has seizure-like episodes, an abnormal EEG may help in diagnosis. A neurologist can help direct the patient evaluation. Whether or not interictal EEG abnormalities are present, video/EEG monitoring can often make the diagnosis by capturing the events.

Case 1: Does this patient have epilepsy?

For Mr. A, age 27, lithium has stabilized his bipolar I disorder for 2 years without significant adverse effects. An EEG ordered for unknown reasons by his primary care physician shows large amounts of beta activity and a single sharp wave from the right temporal region. Should you add an antiepileptic drug to his regimen?

In this patient, lithium probably caused the large amounts of beta activity. A rule of thumb says that if an EEG shows increased beta activity, a medication is almost certainly the cause. If an EEG finds increased generalized slowing, medication effect is one of many possible causes.

The single sharp wave from the right temporal lobe raises the possibility of increased susceptibility to seizures but is not diagnostic of epilepsy. There is no indication to change the patient’s treatment regimen if he is well controlled without adverse effects from his current medications and there is no clear history of clinical seizures. In short, treat the patient, not the EEG.

Box

EEGs: EPILEPTIFORM ACTIVITY INDICATES POTENTIAL FOR SEIZURES

On an EEG, epileptiform activity is seen as spikes or sharp waves and indicates potential for epileptic seizures.

• Focal epileptiform activity is consistent with seizures of focal origin (e.g., simple partial, complex partial, or partial onset seizure with secondary generalization into tonic-clonic seizure).
• Generalized epileptiform activity is consistent with seizures of generalized onset (e.g., absence, myoclonic, or primary generalized tonic-clonic seizure).

Interictal spikes (between seizures) are consistent with, but not diagnostic of, seizures and epilepsy. An ictal discharge (rhythmic, persistent epileptiform activity) on an EEG accompanied by a clinical change in behavior is diagnostic of a seizure.

Focal epileptiform activity

Generalized epileptiform activity

Based on early studies, EEG results can show epileptiform activity in some normal brains.¹ On the other hand, only about 50% of patients with epilepsy will show epileptiform activity on a single EEG. Thus, some EEG abnormalities in psychiatric patients may not be related to either epilepsy or the psychiatric disorder, and a normal EEG does not exclude the possibility of epileptic seizures.

Question the patient for a history of other factors that may predispose him or her to seizures, such as:

• family history of seizures
• previous traumatic brain injury
• structural brain abnormality.

In light of this EEG, brain MRI is indicated. In this case the patient could be counseled to avoid seizure triggers (e.g., sleep deprivation). Because a long list of medications can lower the seizure threshold, the clinician must weigh the risks and benefits of using any medication in patients with increased susceptibility for seizures.

Case 2: Seizures or panic attacks?

Mr. B, age 31, is referred by his primary care physician for “spells” that began several years ago and recently increased in frequency to three to four times per week. The episodes start with a feeling of fear, “butterflies” in his stomach, and hyperventilation. These feelings intensify within minutes; each episode lasts 10 to 30 minutes.

The patient is usually aware of his surroundings during the episodes but twice has lost consciousness for less than 1 minute. There is no evidence of incontinence or tongue biting. Four years ago, the patient was involved in a motor vehicle accident and lost consciousness for about 30 minutes.

An EEG shows intermittent slowing from the left temporal region, and brain MRI is normal. Treatment with a benzodiazepine shortens the attacks. Where do you proceed from here?

Mr. B presents a diagnostic dilemma. Characteristics of his episodes may be seen in panic attacks, temporal lobe complex partial seizures, and psychogenic nonepileptic seizures, which is the preferred term for pseudoseizures (Table).²

One option would be to see how he responds to an agent that would treat seizures but not panic attacks (e.g., carbamazepine) or one that would treat panic attacks but not seizures (e.g., a selective serotonin reuptake inhibitor). Because his episodes are frequent, however, a more appropriate option would be to admit him for video/EEG monitoring, which can distinguish among these possible diagnoses with almost 100% accuracy.

Case 3: Attention disorder or epilepsy?

Miss C, age 9, is referred for possible ADHD. Her teachers notice she has difficulty following lessons in class but is intelligent and usually motivated. Her grades have been dropping. Her family reports she has episodes during which she stares and is unable to answer questions for 3 to 5 seconds, but she exhibits no other seizure-like manifestations. A trial of methylphenidate has not improved the symptoms. What should you try next?

This patient presents with symptoms that could be consistent with absence seizures. EEG would be diagnostic if it showed generalized spike and wave. Absence seizures (sometimes called petit mal) usually present in childhood and are characterized by recurrent brief staring spells with no postictal confusion or other clinical manifestations.

Patients with childhood absence epilepsy are usually of normal intelligence and only rarely have other associated seizure types (e.g., myoclonus or tonic-clonic). Seizures of approximately 3 to 5 seconds may occur up to 100 times a day and thus may be mistaken for attention problems.

EEG shows characteristic generalized three-per-second spike and wave, which is often precipitated by hyperventilation or photic stimulation. Ethosuximide or valproate can completely control seizures in most cases.

Case 4: Emergency use of EEG

Ms. D, age 21, is brought to the emergency department by her mother with symptoms of confusion. Ms. D has a long history of temporal lobe complex partial seizures, and her mother thinks she may have missed some doses of her antiepileptic drugs (carbamazepine and valproate). Yesterday Ms. D had two complex partial seizures but returned to baseline. Today she had three complex partial seizures within 2 hours and has not returned to baseline.

When you interview Ms. D she is alert but only intermittently oriented to date and location. She makes a variety of paraphasic speech errors. She is talking about heaven and angels and several times asks if you are the devil. Evaluation by the emergency physician discloses no toxic, metabolic, or infectious cause for her symptoms. Other than mental status, her neurologic examination is normal and shows no evidence of motor seizure activity. What would you suggest next?

This patient presents with complex partial seizures occurring in sequence without return to normal between seizures, followed by a continuous state of altered consciousness. This cluster of symptoms and signs is consistent with complex partial status epilepticus.

Emergency EEG is diagnostic. If the EEG is positive for status epilepticus, recommended treatment is IV benzodiazepines along with other IV antiepileptic drugs.

Complex partial status epilepticus can have a variety of triggers, including drug overdose, hyperthyroidism, brain tumor, or carcinomatous meningitis.³ In this case, the most likely trigger is medication noncompliance.

Complex partial or other forms of nonconvulsive status epilepticus occur in up to 37% of hospitalized patients with altered consciousness of uncertain etiology.³ EEG is required to confirm the diagnosis, but many hospitals do not have EEG technologists on call nights and weekends.

Table

THE FEARFUL PATIENT: PANIC ATTACK, SEIZURE DISORDER, OR PSYCHOGENIC?

In my experience, a patient who later was referred to me for seizure control was once admitted to a psychiatry ward for 4 days because of unidentified complex partial status epilepticus. When someone finally restarted her carbamazepine, she returned to normal in a few days. Six months after she became my patient, she presented with identical symptoms. An EEG within hours of symptom onset showed continuous EEG ictal activity from the left temporal lobe. When we administered IV lorazepam, her EEG normalized within minutes and her confusion and delusional symptoms resolved in 20 minutes.

Case 5: Seizure clusters followed by agitation

Mr. E, 32, has had complex partial and tonic-clonic seizures since age 14. He presents with chronic depressive symptoms and independent episodes of agitated behavior with psychotic features lasting hours after seizure clusters. His seizures have continued despite trials of different antiepileptic drugs, and he currently is receiving phenytoin and valproate. He is referred to you to diagnose and treat the psychiatric symptoms.

He scores a 28 on the Beck Depression Inventory, which indicates moderate depression,⁴ but he is not suicidal. He reports that although his depression symptoms are constant, his psychotic features occur only after a series of closely-spaced seizures. How do you approach this problem?

Based on the history, this patient has both mild interictal depression and postictal psychosis. In patients with epilepsy, psychiatric symptoms are categorized as:

• ictal (occur only during a seizure)
• interictal (may wax and wane but are present chronically, usually with no relation to seizure occurrence)
• or postictal (appear within 7 days after a lucid interval following a seizure or—more often—a series of seizures).⁵

Interictal psychiatric disorders include depression, bipolar disorder, and psychotic disorders. If the psychiatric disorder is truly interictal and has no clear relation to seizure occurrence, it should be treated like any other psychiatric illness with appropriate medications. One should not automatically add another antiepileptic drug (AED), because AEDs as a class have more adverse effects and more drug interactions than commonly used antidepressants.

Begin by examining the AEDs the patient is receiving. For example, phenobarbital and, to a lesser extent, phenytoin are associated with depression and should be used in patients with depression only when other AEDs have failed.

Ictal and postictal psychiatric symptoms should be treated acutely. Postictal symptoms may include psychosis, depression, mania, or anxiety. A short course of benzodiazepines is often helpful; the use of neuroleptics is dictated by the intensity and quality of the postictal symptoms.

Ictal depression-like symptoms can be seen with temporal lobe complex partial seizures. Many patients with these seizures have simple partial seizures (auras) that manifest as brief (usually less than 1 minute) intense feelings of fear or impending doom, or of “the life drained out” of them. These symptoms may arise from seizures involving mesial temporal regions. They do not usually require treatment besides AEDs.

The idea that patients with temporal lobe epilepsy may have a particular personality type is controversial. Retrospective data first suggested that certain traits (e.g., altered sexual behavior, anger, emotionality and obsessionalism, hypergraphia, and hyper-religiosity) could be found consistently in patients with temporal lobe epilepsy.⁶ This personality inventory was sometimes used to diagnose epilepsy. Subsequent studies have not validated the original data, although the cluster of personality traits can certainly occur in some patients.^7-9

Related resources

• Epilepsy Foundation. www.epilepsyfoundation.org
• Engel J, Pedley TA (eds). Epilepsy: A comprehensive textbook. Philadelphia: Lippincott-Raven, 1998.

Drug brand names

• Carbamazepine • Tegretol
• Ethosuximide • Zarontin
• Lorazepam • Ativan
• Phenytoin • Dilantin
• Valproate • Depakote

Disclosure

The author reports that he receives research/grant support from, is a consultant to, and is on the speakers’ bureau of GlaxoSmithKline, UCBPharma, and Ortho-McNeil Pharmaceuticals; receives research/grant support from and is a consultant to Schwarz Pharma; is a consultant to Pfizer Inc., Elan Pharmaceuticals, and Shire Pharmaceuticals; and is on the speakers’ bureau of Abbott Laboratories, Cyberonics, and Shire Pharmaceuticals.

Many of us—and our patients—enjoy computer games, and at first glance computer gaming and psychiatry appear to have little in common. Yet computer gaming has spurred the growth of cyber technology by demanding high-level capabilities in computer hardware and software. Games initially were developed and played in two dimensions, but—with improved graphic cards and software rendering engines—they can now be three-dimensional. Some games are realistic enough to stimulate nausea and vertigo.

Overexposure to especially graphic computer games has been blamed for causing violent behavior in some individuals.¹ Jeanne B. Funk, PhD, of the University of Toledo department of psychology, testified before the U.S. Senate Commerce Committee regarding the impact of interactive violence on children.²

Avatar psychotherapy. Some computer games also have therapeutic properties, however. John Suler, PhD, of the psychology department at Rider University (Lawrenceville, NJ), writes about “Avatar psychotherapy,” in which an avatar—a personal manifestation in a virtual world—can be used to facilitate psychotherapy.³ Such an environment can permit role-playing, enable fantasies, and allow psychiatrists to explore transference and countertransference issues.

“The Sims,” a popular people simulator game (http://thesims.ea.com/), has also been considered useful for therapy as a “technology of self.”⁴ One resident physician at the UC Davis psychiatry department uses this game in therapy with adolescents to facilitate expression of family dynamics. Although this technology does not replace traditional psychotherapy, it clearly augments and provides unique benefits.

Virtual fears. In 1995, members of the Georgia Tech computer science department and Emory University department of psychiatry in Atlanta created the Graphics Visualization & Usability Center,⁵ a project using virtual reality and exposure therapy. Patients wear a head-mounted display and other devices to track their movements in the virtual world. With virtual reality technology, patients can be exposed to a feared stimulus in a safe, computer-generated environment.

This technology has been used to treat acrophobia, fear of flying, and posttraumatic stress disorder. Its benefits include cost effectiveness, high patient acceptance, and effective therapy for patients with imagination deficits.

The developers of virtrual reality therapy have now formed a company called Virtually Better to provide this technology to other therapists.⁶ Although the technology currently is not applicable to the individual psychiatrist, this tool is expected to be widely available in the coming years with ever-improving and more affordable computing power.

Telemedicine. Virtual reality is also being used to link providers and patients through telemedicine or video conferencing. In clinical practice, telemedicine offers many advantages, such as the ability to reach patients in wide geographic areas, cost effectiveness, and linking of specialists to primary providers.⁷

Patients appreciate traveling less and are quite satisfied with their virtual visits. In fact, patients with schizophrenia prefer telemedicine to real office visits.⁸

One of telemedicine’s downsides has been its expense, requiring dedicated ISDN lines and specialized equipment. Other issues include licensing, confidentiality, reimbursement, and adherence to practice guidelines.⁹ For readers interested in this technology, the American Telemedicine Association Web site (www.americantelemed.org) is a good starting point. As high-speed Internet access becomes more widely available, telemedicine is poised to overtake e-mail as the next communication tool.

Summary. These virtual methods are still considered quite novel and are not yet part of mainstream psychiatry. The technology is not quite mature but is rapidly improving with new hardware and software developments. Its cost, although a barrier today, is diminishing fast. Patient acceptance is likely to grow over time among our increasingly technology-savvy public. With Internet connectivity and improved visual and audio capabilities of computers at affordable prices, virtual reality could soon play a significant new role in psychiatric care.

Many of us—and our patients—enjoy computer games, and at first glance computer gaming and psychiatry appear to have little in common. Yet computer gaming has spurred the growth of cyber technology by demanding high-level capabilities in computer hardware and software. Games initially were developed and played in two dimensions, but—with improved graphic cards and software rendering engines—they can now be three-dimensional. Some games are realistic enough to stimulate nausea and vertigo.

Overexposure to especially graphic computer games has been blamed for causing violent behavior in some individuals.¹ Jeanne B. Funk, PhD, of the University of Toledo department of psychology, testified before the U.S. Senate Commerce Committee regarding the impact of interactive violence on children.²

Avatar psychotherapy. Some computer games also have therapeutic properties, however. John Suler, PhD, of the psychology department at Rider University (Lawrenceville, NJ), writes about “Avatar psychotherapy,” in which an avatar—a personal manifestation in a virtual world—can be used to facilitate psychotherapy.³ Such an environment can permit role-playing, enable fantasies, and allow psychiatrists to explore transference and countertransference issues.

“The Sims,” a popular people simulator game (http://thesims.ea.com/), has also been considered useful for therapy as a “technology of self.”⁴ One resident physician at the UC Davis psychiatry department uses this game in therapy with adolescents to facilitate expression of family dynamics. Although this technology does not replace traditional psychotherapy, it clearly augments and provides unique benefits.

Virtual fears. In 1995, members of the Georgia Tech computer science department and Emory University department of psychiatry in Atlanta created the Graphics Visualization & Usability Center,⁵ a project using virtual reality and exposure therapy. Patients wear a head-mounted display and other devices to track their movements in the virtual world. With virtual reality technology, patients can be exposed to a feared stimulus in a safe, computer-generated environment.

This technology has been used to treat acrophobia, fear of flying, and posttraumatic stress disorder. Its benefits include cost effectiveness, high patient acceptance, and effective therapy for patients with imagination deficits.

The developers of virtrual reality therapy have now formed a company called Virtually Better to provide this technology to other therapists.⁶ Although the technology currently is not applicable to the individual psychiatrist, this tool is expected to be widely available in the coming years with ever-improving and more affordable computing power.

Telemedicine. Virtual reality is also being used to link providers and patients through telemedicine or video conferencing. In clinical practice, telemedicine offers many advantages, such as the ability to reach patients in wide geographic areas, cost effectiveness, and linking of specialists to primary providers.⁷

Patients appreciate traveling less and are quite satisfied with their virtual visits. In fact, patients with schizophrenia prefer telemedicine to real office visits.⁸

One of telemedicine’s downsides has been its expense, requiring dedicated ISDN lines and specialized equipment. Other issues include licensing, confidentiality, reimbursement, and adherence to practice guidelines.⁹ For readers interested in this technology, the American Telemedicine Association Web site (www.americantelemed.org) is a good starting point. As high-speed Internet access becomes more widely available, telemedicine is poised to overtake e-mail as the next communication tool.

Summary. These virtual methods are still considered quite novel and are not yet part of mainstream psychiatry. The technology is not quite mature but is rapidly improving with new hardware and software developments. Its cost, although a barrier today, is diminishing fast. Patient acceptance is likely to grow over time among our increasingly technology-savvy public. With Internet connectivity and improved visual and audio capabilities of computers at affordable prices, virtual reality could soon play a significant new role in psychiatric care.

Many of us—and our patients—enjoy computer games, and at first glance computer gaming and psychiatry appear to have little in common. Yet computer gaming has spurred the growth of cyber technology by demanding high-level capabilities in computer hardware and software. Games initially were developed and played in two dimensions, but—with improved graphic cards and software rendering engines—they can now be three-dimensional. Some games are realistic enough to stimulate nausea and vertigo.

Overexposure to especially graphic computer games has been blamed for causing violent behavior in some individuals.¹ Jeanne B. Funk, PhD, of the University of Toledo department of psychology, testified before the U.S. Senate Commerce Committee regarding the impact of interactive violence on children.²

Avatar psychotherapy. Some computer games also have therapeutic properties, however. John Suler, PhD, of the psychology department at Rider University (Lawrenceville, NJ), writes about “Avatar psychotherapy,” in which an avatar—a personal manifestation in a virtual world—can be used to facilitate psychotherapy.³ Such an environment can permit role-playing, enable fantasies, and allow psychiatrists to explore transference and countertransference issues.

“The Sims,” a popular people simulator game (http://thesims.ea.com/), has also been considered useful for therapy as a “technology of self.”⁴ One resident physician at the UC Davis psychiatry department uses this game in therapy with adolescents to facilitate expression of family dynamics. Although this technology does not replace traditional psychotherapy, it clearly augments and provides unique benefits.

Virtual fears. In 1995, members of the Georgia Tech computer science department and Emory University department of psychiatry in Atlanta created the Graphics Visualization & Usability Center,⁵ a project using virtual reality and exposure therapy. Patients wear a head-mounted display and other devices to track their movements in the virtual world. With virtual reality technology, patients can be exposed to a feared stimulus in a safe, computer-generated environment.

This technology has been used to treat acrophobia, fear of flying, and posttraumatic stress disorder. Its benefits include cost effectiveness, high patient acceptance, and effective therapy for patients with imagination deficits.

The developers of virtrual reality therapy have now formed a company called Virtually Better to provide this technology to other therapists.⁶ Although the technology currently is not applicable to the individual psychiatrist, this tool is expected to be widely available in the coming years with ever-improving and more affordable computing power.

Telemedicine. Virtual reality is also being used to link providers and patients through telemedicine or video conferencing. In clinical practice, telemedicine offers many advantages, such as the ability to reach patients in wide geographic areas, cost effectiveness, and linking of specialists to primary providers.⁷

Patients appreciate traveling less and are quite satisfied with their virtual visits. In fact, patients with schizophrenia prefer telemedicine to real office visits.⁸

One of telemedicine’s downsides has been its expense, requiring dedicated ISDN lines and specialized equipment. Other issues include licensing, confidentiality, reimbursement, and adherence to practice guidelines.⁹ For readers interested in this technology, the American Telemedicine Association Web site (www.americantelemed.org) is a good starting point. As high-speed Internet access becomes more widely available, telemedicine is poised to overtake e-mail as the next communication tool.

Summary. These virtual methods are still considered quite novel and are not yet part of mainstream psychiatry. The technology is not quite mature but is rapidly improving with new hardware and software developments. Its cost, although a barrier today, is diminishing fast. Patient acceptance is likely to grow over time among our increasingly technology-savvy public. With Internet connectivity and improved visual and audio capabilities of computers at affordable prices, virtual reality could soon play a significant new role in psychiatric care.