Evidence-Based Reviews

WEB AUDIO
Listen to Dr. Muskin discuss the patient-physician dynamic

Two strangers meet in the hospital cafeteria. Mrs. R, an elderly woman, asks Dr. W, a first-year medical resident, for help in getting a bottle of soda from the cooler. Afterward, Dr. W comments to a colleague with whom she is having lunch, “That woman reminds me of my grandmother.”

What does that comment reflect about Dr. W? It is a statement about the doctor’s transference. That is, she is aware of elements about Mrs. R that evoke internal responses appropriate to a prior important relationship.

What if Mrs. R was to subsequently faint, require admission to the hospital, and become Dr. W’s patient? If Dr. W’s comment indicates transference, would the same reaction to Mrs. R now be countertransference? Does that change if the doctor is unaware of emotions Mrs. R evokes? Is it still countertransference whether Dr. W is caring and compassionate, overly involved with Mrs. R, or—unaware of negative feelings associated with “grandmothers”—avoids the patient?

This article explores how complex internal experiences play out in the general medical setting and discusses how psychiatric consultants can help medical/surgical colleagues understand and manage difficult patient-physician relationships.

The therapeutic dyad

Countertransference and transference are concepts embedded in psychodynamic thinking. They are part of how many people think about interpersonal relations, whether or not they use these terms. Countertransference and transference may be conscious, but they always have an unconscious component. Factors that influence what will be transference and countertransference in adult life have both:

• a biological component because part of personality is genetic
  
• a psychological component based upon experiences throughout life ( Box 1 ).¹
  

Box 1

Transference is experiencing and/or relating to someone in the present as if that person was a significant individual from the past. The concept implies that all personal relationships contain elements of transference(s). That is, we all have the potential to displace or transfer to current situations infantile and internal conflicts that are out of place and thus not appropriate to the present person and/or situation.

Countertransference is a dimensional concept, not an all-or-nothing experience. Some reactions to patients are based entirely upon their transference to us and have nothing to do with us (therapists) as people. Others derive mostly from psychodynamics within the therapist ( Box 2 ). Countertransference has evolved to incorporate responses evoked by a combination of:

• the patient’s transference
  
• the therapist’s unique psychodynamics
  
• the real relationship in the therapeutic dyad.²
  

Box 2

 

Patients with medical illness

Psychiatrists think of countertransference as a psychological situation occurring in the office or on an inpatient psychiatric unit. We focus our attention on how we feel and what we think while working with patients. We talk about our reactions to patients in supervision, rounds, case conferences, and other situations where mental health professionals discuss patients.

Our medical/surgical colleagues’ reactions to patients often correlate with certain patient presentations and may have little to do with the actual person who is the patient.⁴ The medical setting provides an opportunity for countertransference to occur in the absence of apparent transference.

Somatic illness imposes on patients some degree of regression. This regression and attempts to cope with it are inherent to somatic illness and hospitalization. Several schemas⁵ describe basic coping mechanisms common to most patients ( Table ).^6,7 Recognizing a patient’s character style or personality type may help clinicians predict their countertransference when interacting with that patient. Uncooperative patients and those perceived as “difficult” are particularly likely to evoke negative countertransference.⁸

Table

Patients’ response to illness,
with common countertransference by medical staff

Patient’s coping mechanisms	Staff’s countertransference
Dependent personality
• Unconsciously wishes for unlimited care • Depends on others to feel secure • May make excessive requests of staff	• Gratification at being able to take care of patient’s needs • Resentment if patient’s needs seem insatiable
Obsessional personality
• Meticulous self-discipline • Illness represents loss of control • Will try to gain mastery over illness by focusing on details, information	• Relief at patient’s willingness to actively participate • Power struggle is possible
Histrionic personality
• Outgoing, colorful, lively • Attractiveness and sexuality important • Needs to feel the center of attention • Illness represents defect, loss of physical beauty	• Warm initial engagement • Fear of crossing boundaries • Wonder about veracity of complaints
Masochistic personality
• Satisfies unconscious needs by suffering • Needs to play victim role	• Frustration when reassurance does not help • May unconsciously play into patient’s need for punishment
Paranoid personality
• Pervasive doubt of others’ motivations • Often questions motives for interventions • Illness represents threat to safety	• Wary of lack of alliance • Anger that patient questions treatment motives • Frustrated at inability to form a trusting relationship with patient • Unsettled by lack of connection
Narcissistic personality
• Grandiose sense of self, which protects against shame, humiliation • May demand superior care, insult junior team members	• May feel flattered by ability to treat patient as VIP • May alternately feel devalued, wonder about competence
Source: References 6,7

CASE CONTINUED: No longer ‘grandmotherly’

Mrs. R and Dr. W are now in a patient-physician relationship. Dr. W is no longer handing Mrs. R a bottle of soda but is inquiring about her life, use of alcohol and other drugs, intimate activities, etc. Mrs. R reacts with anger at the “personal questions.” In addition, Dr. W orders tests that are uncomfortable for Mrs. R, who refuses to cooperate with some procedures.

Dr. W’s memories of her grandmother (who was encouraging, supportive, and loving) color her experience of Mrs. R. She ignores nursing staff’s complaints about Mrs. R being demanding and difficult as the patient becomes aggressive and increasingly confused.

Unable to see the patient as she really is, Dr. W becomes angry and defends Mrs. R’s behavior. The nurses feel Dr. W is unrealistic and ignore her at the nursing station. Late on a Friday night, Mrs. R becomes paranoid, hallucinating that “demons” are in her room. She tries to elope from the hospital. Dr. W is off for the weekend, and the staff requests an emergency psychiatric consultation.

Mrs. R evokes a reaction from the nurses because of how she interacts with them. Dr. W’s response—based on her experience of her grandmother—has nothing to do with the way Mrs. R relates interpersonally but reflects a reaction to the patient’s gender and age. Both reactions would be countertransference, using the modern definition.

If reactions to a patient such as Mrs. R are positive, no one seems to notice and the reactions might or might not influence her care. If the reactions are negative, they might influence her care and generate a request for a psychiatric consultation.

Countertransference might have a negative effect on patient care. For example, if a physician were to avoid Mrs. R because she is uncooperative, and if the nursing staff is intolerant of the patient’s confusion and agitation, she might be labeled as “demented” and be given medication without anyone exploring the etiology of her behavior.

 

Some patients cannot communicate because of neurologic disorders, intubation, language barriers, or because they are unconscious when admitted. Without information from the patient, medical staff may form ideas about the patient based on their unconscious fantasies. These fantasies may influence the patient’s care.⁹ Psychiatric consultants are not immune to countertransference, but we come into situations with the opportunity to experience all participants from the outside.

CASE CONTINUED: The psychiatric consultation

During the interview, the psychiatrist asks Mrs. R if she takes any medications. She retorts that she always takes “Centrum” at bed-time and demands to know why she is not getting her “vitamins.” She is given oxazepam and falls asleep.

The psychiatrist recommends benzodiazepine detoxification, suspecting Mrs. R is taking prazepam at home from an old prescription (when the medication was a brand called “Centrax”). This suspicion is confirmed when Mrs. R’s family brings in a large shopping bag of medications she has collected over decades, and Mrs. R identifies her nighttime “vitamin.”

A full evaluation for delirium is completed over the next 2 days. Mrs. R’s confusion and aggressive behavior respond to oxazepam.

Patients with particular character styles evoke predictable reactions from others, including psychotherapists. Discussing these reactions has been a part of psychiatric training for decades. A subset of patients has been described as “hateful,” as they routinely evoke extremely negative responses.¹⁰ Whether their primary disorder is psychiatric, medical, or some of both, these patients evoke strong countertransference reactions.

Psychiatrists may be comfortable discussing a “narcissistic patient, a dependent clinger with borderline features,” but our medical colleagues might not share our comfort with psychiatric jargon.¹¹ It may be more useful to say to medical staff that the patient “thinks of himself as very important, cannot accept his need to be taken care of, and tends to see things in black and white.”

Managing difficult patients

The characterizations that follow describe unconscious reactions to types of individuals who are routinely experienced as “difficult” patients. Some patients may exhibit a mixture of character styles ( Table ) and do not easily fall into 1 category. The concepts can be useful in clarifying the reactions that patients evoke in medical staff.

‘Dependent’ patients. Some patients demand continuous attention but are unaware of their insatiable neediness. Early in treatment, they may evoke positive countertransference because they are intensely grateful for attention. They can be enticing, unconsciously seductive, and gratifying to their doctors. Over time, they drain and exhaust their physicians, who resort to avoidance and wish to get rid of these patients.

Recommendation. Set limits to prevent the patient from feeling rejected or an actual rejection when he or she is transferred to another doctor’s care. Coach physicians to:

• ask patients to “Tell me what is most important for us to discuss today”
  
• be clear how long the visit will last.
  

Reassuring the patient that other issues will be addressed in the next visit prevents the physician from feeling overwhelmed by the patient consuming too much time.

‘Entitled’ patients. Another type of “difficult” patient projects an air of entitlement, which typically reflects an underlying insatiable neediness. They may use intimidation, guilt, and threats of punishment to get their doctors to provide the care they demand. These patients appear powerful (even though they may possess no special status), and they may be overtly devaluing of the physician while simultaneously demanding special attention.

The doctor resents the patient’s entitlement but develops an expectable countertransference fear that he or she will get in trouble if the demands are not met. Wishes to retaliate and “put the patient in his or her place” are common.

Recommendation. Saying, “It is understandable that you want the best care, and I plan to give you the best care,” makes it clear to the patient that the physician hears the patient’s concerns. Advise the physician to request the patient’s “understanding and compassion” for other patients who also need the physician’s time and attention.

‘Help-rejecting’ patients. “Help-rejecting” patients demand care but show little faith in treatment and do not follow treatment plans. The harder the physician tries to help, the less likely the plan will succeed. For these patients, treatment success evokes a fear of abandonment; thus, treatment must fail to maintain the relationship.

Common countertransference reactions are initial anxiety that the treatment plan was not adequate, followed by anger and depression as the physician feels stuck with a patient for whom nothing works.

 

Recommendation. Setting realistic goals for treatment helps the physician guide the patient, who expects to be told not to return the moment he or she gets better. Telling the patient that medical care does not stop when a particular malady is treated speaks to the patient’s fear of being abandoned.

When the patient adheres only partially to the plan and a psychiatric consultant is called for an “uncooperative” patient, help the doctor understand how the patient sees the world. It is the patient’s psychological needs—not the physician’s failure—that control the outcome of the care.

‘Self-destructive’ patients may appear unaware of their dangerous actions. They evoke malice from their doctors, who feel the patients are purposely engaging in life-threatening behaviors. The patients’ unconscious dependence remains unknown as their denial of the consequences of their behavior frightens and angers those involved in their care. Some of these patients cannot be stopped before their actions cause them permanent harm or death.

Recommendation. You might remind the physician that we all are entitled to live our lives as we choose. To decompress intense feelings, advise the physician to share, without blaming the patient, what medical staff can realistically do. Saying “We’ll do the best we can” (rather than “Treatment is useless for someone like you”) permits the patient to receive the degree of care he or she can accept without the physician feeling helpless. Understanding our limitations and obligations is part of using our countertransference to aid in patient care.

CASE CONTINUED: Feeling better

When Dr. W returns on Monday, she angrily calls the psychiatrist to complain that her patient has been placed on a benzodiazepine and at the “implication” that Mrs. R was abusing medication. When they talk in person, the psychiatrist explains the situation to Dr. W and suggests they meet with Mrs. R together.

Mrs. R is embarrassed when told about her behavior, identifies the pill, and admits taking prazepam for several weeks prior to hospitalization. She says she never understood how a vitamin could help her sleep so well. No longer delirious, Mrs. R is pleasant and asks many questions. She is surprised that “so young” a doctor was assigned to her case and asks if the chief of medicine could be brought in, as she is on the board of directors of another hospital. “No offense, dear,” she says to Dr. W; “I’m sure you did an excellent job, but usually only senior doctors take care of me.”

Later, Dr. W talks with the psychiatric consultant about her chance meeting with Mrs. R in the cafeteria and the discord with the nursing staff. She notes that she was doing an elective in another country when her grandmother died. She realizes that her feelings about her grandmother are superimposed on the patient, resulting in an inability to see the patient as she really is.

Dr. W accepts the psychiatrist’s suggestion to repair her relationship with the nurses with an apology. She now notes that Mrs. R is nothing like her grandmother and seems “pretty stuck up.” She is glad to be off the case and accepts the psychiatrist’s idea that Mrs. R’s need to feel important should not make Dr. W feel bad about herself.

Related resources

• Gabbard GO, ed. Countertransference issues in psychiatric treatment. In: Oldham JM, Riba MB, eds. Review of psychiatry series. Washington, DC: American Psychiatric Publishing, Inc.; 1999.
  
• Blumenfield M, Strain JJ, Grossman S. Psychodynamic approach. In: Blumenfield M, Strain JJ, eds. Psychosomatic medicine. Philadelphia, PA: Lippincott, Williams and Wilkins; 2006:817-828.
  

Drug brand names

• Oxazepam • Serax
  
• Prazepam • Centrax
  

Disclosure

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

WEB AUDIO
Listen to Dr. Muskin discuss the patient-physician dynamic

Two strangers meet in the hospital cafeteria. Mrs. R, an elderly woman, asks Dr. W, a first-year medical resident, for help in getting a bottle of soda from the cooler. Afterward, Dr. W comments to a colleague with whom she is having lunch, “That woman reminds me of my grandmother.”

What does that comment reflect about Dr. W? It is a statement about the doctor’s transference. That is, she is aware of elements about Mrs. R that evoke internal responses appropriate to a prior important relationship.

What if Mrs. R was to subsequently faint, require admission to the hospital, and become Dr. W’s patient? If Dr. W’s comment indicates transference, would the same reaction to Mrs. R now be countertransference? Does that change if the doctor is unaware of emotions Mrs. R evokes? Is it still countertransference whether Dr. W is caring and compassionate, overly involved with Mrs. R, or—unaware of negative feelings associated with “grandmothers”—avoids the patient?

This article explores how complex internal experiences play out in the general medical setting and discusses how psychiatric consultants can help medical/surgical colleagues understand and manage difficult patient-physician relationships.

The therapeutic dyad

Countertransference and transference are concepts embedded in psychodynamic thinking. They are part of how many people think about interpersonal relations, whether or not they use these terms. Countertransference and transference may be conscious, but they always have an unconscious component. Factors that influence what will be transference and countertransference in adult life have both:

• a biological component because part of personality is genetic
  
• a psychological component based upon experiences throughout life ( Box 1 ).¹
  

Box 1

Transference is experiencing and/or relating to someone in the present as if that person was a significant individual from the past. The concept implies that all personal relationships contain elements of transference(s). That is, we all have the potential to displace or transfer to current situations infantile and internal conflicts that are out of place and thus not appropriate to the present person and/or situation.

Countertransference is a dimensional concept, not an all-or-nothing experience. Some reactions to patients are based entirely upon their transference to us and have nothing to do with us (therapists) as people. Others derive mostly from psychodynamics within the therapist ( Box 2 ). Countertransference has evolved to incorporate responses evoked by a combination of:

• the patient’s transference
  
• the therapist’s unique psychodynamics
  
• the real relationship in the therapeutic dyad.²
  

Box 2

 

Patients with medical illness

Psychiatrists think of countertransference as a psychological situation occurring in the office or on an inpatient psychiatric unit. We focus our attention on how we feel and what we think while working with patients. We talk about our reactions to patients in supervision, rounds, case conferences, and other situations where mental health professionals discuss patients.

Our medical/surgical colleagues’ reactions to patients often correlate with certain patient presentations and may have little to do with the actual person who is the patient.⁴ The medical setting provides an opportunity for countertransference to occur in the absence of apparent transference.

Somatic illness imposes on patients some degree of regression. This regression and attempts to cope with it are inherent to somatic illness and hospitalization. Several schemas⁵ describe basic coping mechanisms common to most patients ( Table ).^6,7 Recognizing a patient’s character style or personality type may help clinicians predict their countertransference when interacting with that patient. Uncooperative patients and those perceived as “difficult” are particularly likely to evoke negative countertransference.⁸

Table

Patients’ response to illness,
with common countertransference by medical staff

Patient’s coping mechanisms	Staff’s countertransference
Dependent personality
• Unconsciously wishes for unlimited care • Depends on others to feel secure • May make excessive requests of staff	• Gratification at being able to take care of patient’s needs • Resentment if patient’s needs seem insatiable
Obsessional personality
• Meticulous self-discipline • Illness represents loss of control • Will try to gain mastery over illness by focusing on details, information	• Relief at patient’s willingness to actively participate • Power struggle is possible
Histrionic personality
• Outgoing, colorful, lively • Attractiveness and sexuality important • Needs to feel the center of attention • Illness represents defect, loss of physical beauty	• Warm initial engagement • Fear of crossing boundaries • Wonder about veracity of complaints
Masochistic personality
• Satisfies unconscious needs by suffering • Needs to play victim role	• Frustration when reassurance does not help • May unconsciously play into patient’s need for punishment
Paranoid personality
• Pervasive doubt of others’ motivations • Often questions motives for interventions • Illness represents threat to safety	• Wary of lack of alliance • Anger that patient questions treatment motives • Frustrated at inability to form a trusting relationship with patient • Unsettled by lack of connection
Narcissistic personality
• Grandiose sense of self, which protects against shame, humiliation • May demand superior care, insult junior team members	• May feel flattered by ability to treat patient as VIP • May alternately feel devalued, wonder about competence
Source: References 6,7

CASE CONTINUED: No longer ‘grandmotherly’

Mrs. R and Dr. W are now in a patient-physician relationship. Dr. W is no longer handing Mrs. R a bottle of soda but is inquiring about her life, use of alcohol and other drugs, intimate activities, etc. Mrs. R reacts with anger at the “personal questions.” In addition, Dr. W orders tests that are uncomfortable for Mrs. R, who refuses to cooperate with some procedures.

Dr. W’s memories of her grandmother (who was encouraging, supportive, and loving) color her experience of Mrs. R. She ignores nursing staff’s complaints about Mrs. R being demanding and difficult as the patient becomes aggressive and increasingly confused.

Unable to see the patient as she really is, Dr. W becomes angry and defends Mrs. R’s behavior. The nurses feel Dr. W is unrealistic and ignore her at the nursing station. Late on a Friday night, Mrs. R becomes paranoid, hallucinating that “demons” are in her room. She tries to elope from the hospital. Dr. W is off for the weekend, and the staff requests an emergency psychiatric consultation.

Mrs. R evokes a reaction from the nurses because of how she interacts with them. Dr. W’s response—based on her experience of her grandmother—has nothing to do with the way Mrs. R relates interpersonally but reflects a reaction to the patient’s gender and age. Both reactions would be countertransference, using the modern definition.

If reactions to a patient such as Mrs. R are positive, no one seems to notice and the reactions might or might not influence her care. If the reactions are negative, they might influence her care and generate a request for a psychiatric consultation.

Countertransference might have a negative effect on patient care. For example, if a physician were to avoid Mrs. R because she is uncooperative, and if the nursing staff is intolerant of the patient’s confusion and agitation, she might be labeled as “demented” and be given medication without anyone exploring the etiology of her behavior.

 

Some patients cannot communicate because of neurologic disorders, intubation, language barriers, or because they are unconscious when admitted. Without information from the patient, medical staff may form ideas about the patient based on their unconscious fantasies. These fantasies may influence the patient’s care.⁹ Psychiatric consultants are not immune to countertransference, but we come into situations with the opportunity to experience all participants from the outside.

CASE CONTINUED: The psychiatric consultation

During the interview, the psychiatrist asks Mrs. R if she takes any medications. She retorts that she always takes “Centrum” at bed-time and demands to know why she is not getting her “vitamins.” She is given oxazepam and falls asleep.

The psychiatrist recommends benzodiazepine detoxification, suspecting Mrs. R is taking prazepam at home from an old prescription (when the medication was a brand called “Centrax”). This suspicion is confirmed when Mrs. R’s family brings in a large shopping bag of medications she has collected over decades, and Mrs. R identifies her nighttime “vitamin.”

A full evaluation for delirium is completed over the next 2 days. Mrs. R’s confusion and aggressive behavior respond to oxazepam.

Patients with particular character styles evoke predictable reactions from others, including psychotherapists. Discussing these reactions has been a part of psychiatric training for decades. A subset of patients has been described as “hateful,” as they routinely evoke extremely negative responses.¹⁰ Whether their primary disorder is psychiatric, medical, or some of both, these patients evoke strong countertransference reactions.

Psychiatrists may be comfortable discussing a “narcissistic patient, a dependent clinger with borderline features,” but our medical colleagues might not share our comfort with psychiatric jargon.¹¹ It may be more useful to say to medical staff that the patient “thinks of himself as very important, cannot accept his need to be taken care of, and tends to see things in black and white.”

Managing difficult patients

The characterizations that follow describe unconscious reactions to types of individuals who are routinely experienced as “difficult” patients. Some patients may exhibit a mixture of character styles ( Table ) and do not easily fall into 1 category. The concepts can be useful in clarifying the reactions that patients evoke in medical staff.

‘Dependent’ patients. Some patients demand continuous attention but are unaware of their insatiable neediness. Early in treatment, they may evoke positive countertransference because they are intensely grateful for attention. They can be enticing, unconsciously seductive, and gratifying to their doctors. Over time, they drain and exhaust their physicians, who resort to avoidance and wish to get rid of these patients.

Recommendation. Set limits to prevent the patient from feeling rejected or an actual rejection when he or she is transferred to another doctor’s care. Coach physicians to:

• ask patients to “Tell me what is most important for us to discuss today”
  
• be clear how long the visit will last.
  

Reassuring the patient that other issues will be addressed in the next visit prevents the physician from feeling overwhelmed by the patient consuming too much time.

‘Entitled’ patients. Another type of “difficult” patient projects an air of entitlement, which typically reflects an underlying insatiable neediness. They may use intimidation, guilt, and threats of punishment to get their doctors to provide the care they demand. These patients appear powerful (even though they may possess no special status), and they may be overtly devaluing of the physician while simultaneously demanding special attention.

The doctor resents the patient’s entitlement but develops an expectable countertransference fear that he or she will get in trouble if the demands are not met. Wishes to retaliate and “put the patient in his or her place” are common.

Recommendation. Saying, “It is understandable that you want the best care, and I plan to give you the best care,” makes it clear to the patient that the physician hears the patient’s concerns. Advise the physician to request the patient’s “understanding and compassion” for other patients who also need the physician’s time and attention.

‘Help-rejecting’ patients. “Help-rejecting” patients demand care but show little faith in treatment and do not follow treatment plans. The harder the physician tries to help, the less likely the plan will succeed. For these patients, treatment success evokes a fear of abandonment; thus, treatment must fail to maintain the relationship.

Common countertransference reactions are initial anxiety that the treatment plan was not adequate, followed by anger and depression as the physician feels stuck with a patient for whom nothing works.

 

Recommendation. Setting realistic goals for treatment helps the physician guide the patient, who expects to be told not to return the moment he or she gets better. Telling the patient that medical care does not stop when a particular malady is treated speaks to the patient’s fear of being abandoned.

When the patient adheres only partially to the plan and a psychiatric consultant is called for an “uncooperative” patient, help the doctor understand how the patient sees the world. It is the patient’s psychological needs—not the physician’s failure—that control the outcome of the care.

‘Self-destructive’ patients may appear unaware of their dangerous actions. They evoke malice from their doctors, who feel the patients are purposely engaging in life-threatening behaviors. The patients’ unconscious dependence remains unknown as their denial of the consequences of their behavior frightens and angers those involved in their care. Some of these patients cannot be stopped before their actions cause them permanent harm or death.

Recommendation. You might remind the physician that we all are entitled to live our lives as we choose. To decompress intense feelings, advise the physician to share, without blaming the patient, what medical staff can realistically do. Saying “We’ll do the best we can” (rather than “Treatment is useless for someone like you”) permits the patient to receive the degree of care he or she can accept without the physician feeling helpless. Understanding our limitations and obligations is part of using our countertransference to aid in patient care.

CASE CONTINUED: Feeling better

When Dr. W returns on Monday, she angrily calls the psychiatrist to complain that her patient has been placed on a benzodiazepine and at the “implication” that Mrs. R was abusing medication. When they talk in person, the psychiatrist explains the situation to Dr. W and suggests they meet with Mrs. R together.

Mrs. R is embarrassed when told about her behavior, identifies the pill, and admits taking prazepam for several weeks prior to hospitalization. She says she never understood how a vitamin could help her sleep so well. No longer delirious, Mrs. R is pleasant and asks many questions. She is surprised that “so young” a doctor was assigned to her case and asks if the chief of medicine could be brought in, as she is on the board of directors of another hospital. “No offense, dear,” she says to Dr. W; “I’m sure you did an excellent job, but usually only senior doctors take care of me.”

Later, Dr. W talks with the psychiatric consultant about her chance meeting with Mrs. R in the cafeteria and the discord with the nursing staff. She notes that she was doing an elective in another country when her grandmother died. She realizes that her feelings about her grandmother are superimposed on the patient, resulting in an inability to see the patient as she really is.

Dr. W accepts the psychiatrist’s suggestion to repair her relationship with the nurses with an apology. She now notes that Mrs. R is nothing like her grandmother and seems “pretty stuck up.” She is glad to be off the case and accepts the psychiatrist’s idea that Mrs. R’s need to feel important should not make Dr. W feel bad about herself.

Related resources

• Gabbard GO, ed. Countertransference issues in psychiatric treatment. In: Oldham JM, Riba MB, eds. Review of psychiatry series. Washington, DC: American Psychiatric Publishing, Inc.; 1999.
  
• Blumenfield M, Strain JJ, Grossman S. Psychodynamic approach. In: Blumenfield M, Strain JJ, eds. Psychosomatic medicine. Philadelphia, PA: Lippincott, Williams and Wilkins; 2006:817-828.
  

Drug brand names

• Oxazepam • Serax
  
• Prazepam • Centrax
  

Disclosure

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

WEB AUDIO
Listen to Dr. Muskin discuss the patient-physician dynamic

Two strangers meet in the hospital cafeteria. Mrs. R, an elderly woman, asks Dr. W, a first-year medical resident, for help in getting a bottle of soda from the cooler. Afterward, Dr. W comments to a colleague with whom she is having lunch, “That woman reminds me of my grandmother.”

What does that comment reflect about Dr. W? It is a statement about the doctor’s transference. That is, she is aware of elements about Mrs. R that evoke internal responses appropriate to a prior important relationship.

What if Mrs. R was to subsequently faint, require admission to the hospital, and become Dr. W’s patient? If Dr. W’s comment indicates transference, would the same reaction to Mrs. R now be countertransference? Does that change if the doctor is unaware of emotions Mrs. R evokes? Is it still countertransference whether Dr. W is caring and compassionate, overly involved with Mrs. R, or—unaware of negative feelings associated with “grandmothers”—avoids the patient?

This article explores how complex internal experiences play out in the general medical setting and discusses how psychiatric consultants can help medical/surgical colleagues understand and manage difficult patient-physician relationships.

The therapeutic dyad

Countertransference and transference are concepts embedded in psychodynamic thinking. They are part of how many people think about interpersonal relations, whether or not they use these terms. Countertransference and transference may be conscious, but they always have an unconscious component. Factors that influence what will be transference and countertransference in adult life have both:

• a biological component because part of personality is genetic
  
• a psychological component based upon experiences throughout life ( Box 1 ).¹
  

Box 1

Transference is experiencing and/or relating to someone in the present as if that person was a significant individual from the past. The concept implies that all personal relationships contain elements of transference(s). That is, we all have the potential to displace or transfer to current situations infantile and internal conflicts that are out of place and thus not appropriate to the present person and/or situation.

Countertransference is a dimensional concept, not an all-or-nothing experience. Some reactions to patients are based entirely upon their transference to us and have nothing to do with us (therapists) as people. Others derive mostly from psychodynamics within the therapist ( Box 2 ). Countertransference has evolved to incorporate responses evoked by a combination of:

• the patient’s transference
  
• the therapist’s unique psychodynamics
  
• the real relationship in the therapeutic dyad.²
  

Box 2

 

Patients with medical illness

Psychiatrists think of countertransference as a psychological situation occurring in the office or on an inpatient psychiatric unit. We focus our attention on how we feel and what we think while working with patients. We talk about our reactions to patients in supervision, rounds, case conferences, and other situations where mental health professionals discuss patients.

Our medical/surgical colleagues’ reactions to patients often correlate with certain patient presentations and may have little to do with the actual person who is the patient.⁴ The medical setting provides an opportunity for countertransference to occur in the absence of apparent transference.

Somatic illness imposes on patients some degree of regression. This regression and attempts to cope with it are inherent to somatic illness and hospitalization. Several schemas⁵ describe basic coping mechanisms common to most patients ( Table ).^6,7 Recognizing a patient’s character style or personality type may help clinicians predict their countertransference when interacting with that patient. Uncooperative patients and those perceived as “difficult” are particularly likely to evoke negative countertransference.⁸

Table

Patients’ response to illness,
with common countertransference by medical staff

Patient’s coping mechanisms	Staff’s countertransference
Dependent personality
• Unconsciously wishes for unlimited care • Depends on others to feel secure • May make excessive requests of staff	• Gratification at being able to take care of patient’s needs • Resentment if patient’s needs seem insatiable
Obsessional personality
• Meticulous self-discipline • Illness represents loss of control • Will try to gain mastery over illness by focusing on details, information	• Relief at patient’s willingness to actively participate • Power struggle is possible
Histrionic personality
• Outgoing, colorful, lively • Attractiveness and sexuality important • Needs to feel the center of attention • Illness represents defect, loss of physical beauty	• Warm initial engagement • Fear of crossing boundaries • Wonder about veracity of complaints
Masochistic personality
• Satisfies unconscious needs by suffering • Needs to play victim role	• Frustration when reassurance does not help • May unconsciously play into patient’s need for punishment
Paranoid personality
• Pervasive doubt of others’ motivations • Often questions motives for interventions • Illness represents threat to safety	• Wary of lack of alliance • Anger that patient questions treatment motives • Frustrated at inability to form a trusting relationship with patient • Unsettled by lack of connection
Narcissistic personality
• Grandiose sense of self, which protects against shame, humiliation • May demand superior care, insult junior team members	• May feel flattered by ability to treat patient as VIP • May alternately feel devalued, wonder about competence
Source: References 6,7

CASE CONTINUED: No longer ‘grandmotherly’

Mrs. R and Dr. W are now in a patient-physician relationship. Dr. W is no longer handing Mrs. R a bottle of soda but is inquiring about her life, use of alcohol and other drugs, intimate activities, etc. Mrs. R reacts with anger at the “personal questions.” In addition, Dr. W orders tests that are uncomfortable for Mrs. R, who refuses to cooperate with some procedures.

Dr. W’s memories of her grandmother (who was encouraging, supportive, and loving) color her experience of Mrs. R. She ignores nursing staff’s complaints about Mrs. R being demanding and difficult as the patient becomes aggressive and increasingly confused.

Unable to see the patient as she really is, Dr. W becomes angry and defends Mrs. R’s behavior. The nurses feel Dr. W is unrealistic and ignore her at the nursing station. Late on a Friday night, Mrs. R becomes paranoid, hallucinating that “demons” are in her room. She tries to elope from the hospital. Dr. W is off for the weekend, and the staff requests an emergency psychiatric consultation.

Mrs. R evokes a reaction from the nurses because of how she interacts with them. Dr. W’s response—based on her experience of her grandmother—has nothing to do with the way Mrs. R relates interpersonally but reflects a reaction to the patient’s gender and age. Both reactions would be countertransference, using the modern definition.

If reactions to a patient such as Mrs. R are positive, no one seems to notice and the reactions might or might not influence her care. If the reactions are negative, they might influence her care and generate a request for a psychiatric consultation.

Countertransference might have a negative effect on patient care. For example, if a physician were to avoid Mrs. R because she is uncooperative, and if the nursing staff is intolerant of the patient’s confusion and agitation, she might be labeled as “demented” and be given medication without anyone exploring the etiology of her behavior.

 

Some patients cannot communicate because of neurologic disorders, intubation, language barriers, or because they are unconscious when admitted. Without information from the patient, medical staff may form ideas about the patient based on their unconscious fantasies. These fantasies may influence the patient’s care.⁹ Psychiatric consultants are not immune to countertransference, but we come into situations with the opportunity to experience all participants from the outside.

CASE CONTINUED: The psychiatric consultation

During the interview, the psychiatrist asks Mrs. R if she takes any medications. She retorts that she always takes “Centrum” at bed-time and demands to know why she is not getting her “vitamins.” She is given oxazepam and falls asleep.

The psychiatrist recommends benzodiazepine detoxification, suspecting Mrs. R is taking prazepam at home from an old prescription (when the medication was a brand called “Centrax”). This suspicion is confirmed when Mrs. R’s family brings in a large shopping bag of medications she has collected over decades, and Mrs. R identifies her nighttime “vitamin.”

A full evaluation for delirium is completed over the next 2 days. Mrs. R’s confusion and aggressive behavior respond to oxazepam.

Patients with particular character styles evoke predictable reactions from others, including psychotherapists. Discussing these reactions has been a part of psychiatric training for decades. A subset of patients has been described as “hateful,” as they routinely evoke extremely negative responses.¹⁰ Whether their primary disorder is psychiatric, medical, or some of both, these patients evoke strong countertransference reactions.

Psychiatrists may be comfortable discussing a “narcissistic patient, a dependent clinger with borderline features,” but our medical colleagues might not share our comfort with psychiatric jargon.¹¹ It may be more useful to say to medical staff that the patient “thinks of himself as very important, cannot accept his need to be taken care of, and tends to see things in black and white.”

Managing difficult patients

The characterizations that follow describe unconscious reactions to types of individuals who are routinely experienced as “difficult” patients. Some patients may exhibit a mixture of character styles ( Table ) and do not easily fall into 1 category. The concepts can be useful in clarifying the reactions that patients evoke in medical staff.

‘Dependent’ patients. Some patients demand continuous attention but are unaware of their insatiable neediness. Early in treatment, they may evoke positive countertransference because they are intensely grateful for attention. They can be enticing, unconsciously seductive, and gratifying to their doctors. Over time, they drain and exhaust their physicians, who resort to avoidance and wish to get rid of these patients.

Recommendation. Set limits to prevent the patient from feeling rejected or an actual rejection when he or she is transferred to another doctor’s care. Coach physicians to:

• ask patients to “Tell me what is most important for us to discuss today”
  
• be clear how long the visit will last.
  

Reassuring the patient that other issues will be addressed in the next visit prevents the physician from feeling overwhelmed by the patient consuming too much time.

‘Entitled’ patients. Another type of “difficult” patient projects an air of entitlement, which typically reflects an underlying insatiable neediness. They may use intimidation, guilt, and threats of punishment to get their doctors to provide the care they demand. These patients appear powerful (even though they may possess no special status), and they may be overtly devaluing of the physician while simultaneously demanding special attention.

The doctor resents the patient’s entitlement but develops an expectable countertransference fear that he or she will get in trouble if the demands are not met. Wishes to retaliate and “put the patient in his or her place” are common.

Recommendation. Saying, “It is understandable that you want the best care, and I plan to give you the best care,” makes it clear to the patient that the physician hears the patient’s concerns. Advise the physician to request the patient’s “understanding and compassion” for other patients who also need the physician’s time and attention.

‘Help-rejecting’ patients. “Help-rejecting” patients demand care but show little faith in treatment and do not follow treatment plans. The harder the physician tries to help, the less likely the plan will succeed. For these patients, treatment success evokes a fear of abandonment; thus, treatment must fail to maintain the relationship.

Common countertransference reactions are initial anxiety that the treatment plan was not adequate, followed by anger and depression as the physician feels stuck with a patient for whom nothing works.

 

Recommendation. Setting realistic goals for treatment helps the physician guide the patient, who expects to be told not to return the moment he or she gets better. Telling the patient that medical care does not stop when a particular malady is treated speaks to the patient’s fear of being abandoned.

When the patient adheres only partially to the plan and a psychiatric consultant is called for an “uncooperative” patient, help the doctor understand how the patient sees the world. It is the patient’s psychological needs—not the physician’s failure—that control the outcome of the care.

‘Self-destructive’ patients may appear unaware of their dangerous actions. They evoke malice from their doctors, who feel the patients are purposely engaging in life-threatening behaviors. The patients’ unconscious dependence remains unknown as their denial of the consequences of their behavior frightens and angers those involved in their care. Some of these patients cannot be stopped before their actions cause them permanent harm or death.

Recommendation. You might remind the physician that we all are entitled to live our lives as we choose. To decompress intense feelings, advise the physician to share, without blaming the patient, what medical staff can realistically do. Saying “We’ll do the best we can” (rather than “Treatment is useless for someone like you”) permits the patient to receive the degree of care he or she can accept without the physician feeling helpless. Understanding our limitations and obligations is part of using our countertransference to aid in patient care.

CASE CONTINUED: Feeling better

When Dr. W returns on Monday, she angrily calls the psychiatrist to complain that her patient has been placed on a benzodiazepine and at the “implication” that Mrs. R was abusing medication. When they talk in person, the psychiatrist explains the situation to Dr. W and suggests they meet with Mrs. R together.

Mrs. R is embarrassed when told about her behavior, identifies the pill, and admits taking prazepam for several weeks prior to hospitalization. She says she never understood how a vitamin could help her sleep so well. No longer delirious, Mrs. R is pleasant and asks many questions. She is surprised that “so young” a doctor was assigned to her case and asks if the chief of medicine could be brought in, as she is on the board of directors of another hospital. “No offense, dear,” she says to Dr. W; “I’m sure you did an excellent job, but usually only senior doctors take care of me.”

Later, Dr. W talks with the psychiatric consultant about her chance meeting with Mrs. R in the cafeteria and the discord with the nursing staff. She notes that she was doing an elective in another country when her grandmother died. She realizes that her feelings about her grandmother are superimposed on the patient, resulting in an inability to see the patient as she really is.

Dr. W accepts the psychiatrist’s suggestion to repair her relationship with the nurses with an apology. She now notes that Mrs. R is nothing like her grandmother and seems “pretty stuck up.” She is glad to be off the case and accepts the psychiatrist’s idea that Mrs. R’s need to feel important should not make Dr. W feel bad about herself.

Related resources

• Gabbard GO, ed. Countertransference issues in psychiatric treatment. In: Oldham JM, Riba MB, eds. Review of psychiatry series. Washington, DC: American Psychiatric Publishing, Inc.; 1999.
  
• Blumenfield M, Strain JJ, Grossman S. Psychodynamic approach. In: Blumenfield M, Strain JJ, eds. Psychosomatic medicine. Philadelphia, PA: Lippincott, Williams and Wilkins; 2006:817-828.
  

Drug brand names

• Oxazepam • Serax
  
• Prazepam • Centrax
  

Disclosure

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

Comment on this article

Mr. B, age 35, is admitted for the fourth time to the inpatient service with hallucinations and delusions related to chronic schizophrenia. After appropriate attempts to control his symptoms, he has begun to respond to usual treatment with an atypical antipsychotic. He remains a “partial responder,” however, at the maximum FDA-approved dosage listed in the package insert (PI). What do you do next?

Because of this author’s (NSK) dual training in medicine and forensic psychiatry, other clinicians often ask me about patients such as Mr. B. Prescribing for patients who do not respond to standard dosages can create anxiety about going “off-label.” This article describes how to manage potential risk to yourself and your patient by communicating effectively and documenting informed consent.

What are the options?

To effectively treat Mr. B’s symptoms, you could:

• change medications and start over
  
• augment with a second atypical antipsychotic
  
• stay with the antipsychotic to which he has shown partial response, but go above the PI dosing.
  

Each strategy could pose problems, but most psychopharmacologists would choose the third option—the most logical one.

Changing medications is attractive, but the choice of an atypical antipsychotic with relative metabolic neutrality is limited, and “switching” is time-consuming. When a drug begins to show efficacy, most clinicians won’t opt to “change horses midstream”—especially if managed care is pressuring for rapid discharge.

Augmentation introduces polypharmacy and potential drug-drug interactions. Very little evidence guides us in combining antipsychotics, as most manufacturers will never study the coadministration of 2 branded medications with the same indication.

Only a few case reports have described combining atypical antipsychotics.^1-4 Moreover, many managed care providers and governmental payers/regulators will not pay for polypharmacy with 2 atypical antipsychotics or will allow it only during cross-tapering from one agent to another.

‘High-dose’ monotherapy is the choice most often taken by clinicians and experts. Pharmaceutical manufacturers study a wide range of doses during medication development. Two pivotal trials form the basis of the New Drug Application for FDA approval and largely dictate the PI language.

Don’t misconstrue the PI dosing as optimal for a specific medication or patient. Historically, FDA-approved dosing for atypical antipsychotics has been too high (risperidone, aripiprazole) or too low (ziprasidone, quetiapine) for many patients we treat, even when the medications are used as indicated. This problem is magnified when clinicians try to make individual patients (N=1) resemble the average pooled analysis of the clinical trial group (N>200) and find that the individual patient may be a low-dose, average-dose, or high-dose responder (Table 1).

Informed prescribing. Polypharmacy is a complex issue because essentially no pharmacokinetic or pharmacodynamic studies have examined the simultaneous use of ≥3 psychotropics. When a pharmacist or drug interaction computer alerts you to a potential drug-drug interaction, the warning is almost always theoretical. No real data exist about coadministering most medications.

Physicians may query a manufacturer about off-label, above-PI dosing data by contacting the company’s medical information department or asking a pharmaceutical representative. What you receive will vary by manufacturer, but in almost every case you will get the safety data you want. Occasionally you also will get efficacy data, which is nice but not crucial. An online literature search of MEDLINE is another way to obtain this information.

Table 1

Patient factors that influence response to medication

Patient body mass, age, race, ethnicity, and gender
Variability in medication absorption
Hepatic metabolizing factors
How ‘sick’ the patient is, compared with those in pivotal clinical trials
Patient’s behavior, lifestyle, habits, and diet
Comorbid medical conditions
Other psychiatric and nonpsychiatric pharmacotherapy

Liability risk?

Every clinician I’ve met prescribes drugs off-label, whether in terms of dose, indication, or age limits in the PI as published in the Physicians’ Desk Reference (PDR).⁵ Still, nearly all describe to me the following nightmare, in which they “violated” the PI and “something bad” happens.

They are sitting in court on the witness stand, white-knuckled and sweaty, as a plaintiff’s attorney strolls up to them, PDR in hand, and says: “Doctor, isn’t this the Bible, and you violated the Bible?” And thus is born the fear of a malpractice claim, predicated on off-label dosing.

Off-label prescribing is rarely the only issue in a lawsuit, according to Denny Rodriguez, assistant vice president, claims, Professional Risk Management Services (PRMS), Inc.—manager of The Psychiatrists’ Program endorsed by the American Psychiatric Association. When raised, allegations related to off-label prescribing are among many presented by the plaintiff under the rubric of treatment that violated the standard of care.

 

Contrary to the plaintiff’s allegations, off-label prescribing rarely violates the standard of care because it has valid clinical and scientific bases. And don’t acknowledge the PDR as “the Bible,” which it is not; it’s a compilation of PIs. The FDA affirms that once a product is approved for marketing, a physician may choose to prescribe it for off-label use (Box).⁵

Box

Standard of care

The real issue for practitioners is the “standard of care.” Violating the standard of care—what a similarly trained clinician would do under similar circumstances—is the first step on the slippery slope to malpractice. Here we can be quite sure that the standard of care and evidence-based medicine are in sync and support the use of off-label, high-dose monotherapy.

Properly documenting your reasoning helps to demonstrate that your prescribing meets the standard of care. Always document and obtain informed consent. Also stay up-to-date about:

• medications you prescribe
  
• emerging evidence and safety information
  
• appropriate patient monitoring for clinical response and adverse effects.⁸
  

Black boxes and bold lettering

The FDA may mandate that a manufacturer highlight certain information on a PI in 3 ways—bold lettering, black-box warning, and red lettering, in order of presumed increasing seriousness. This system is meant to draw prescribers’ attention to potential safety problems with pharmaceutical agents. No psychiatric medications carry red-letter warnings, a classification usually reserved for antineoplastic agents.

At one time the FDA relied on evidenced-based data to determine the need for warnings. Recently, however, when a problem has been identified with one agent, the FDA has tended to require all drugs in that agent’s class to carry similar—if not identical—PI warnings. In psychiatry, the FDA has ordered suicide precautions on all antidepressants and metabolic syndrome/hyperglycemia warnings on all atypical antipsychotics, despite evidence of differences in potential risks associated with medications within classes. For example, clinical trials have shown a higher risk of obesity and diabetes among patients receiving olanzapine compared with those receiving ziprasidone.⁷

The FDA’s action appears to “level the playing field,” giving patients the misperception that any treatment would carry an equal risk. Therefore, when you prescribe a drug that carries a class-wide warning in its PI, present the evidence in a balanced, objective manner so that the patient can make an informed decision.

Managing risk

Your best protection against liability is to communicate effectively with the patient and document that communication—including informed consent—in the medical record.⁸ Obtain and document informed consent whenever:

• you initiate a drug or other treatment
  
• treatment extends beyond the PI-recommended maximum dose.
  

Similarly, when a new side-effect warning or safety information about a medication emerges, update the informed consent discussion and re-obtain and re-document the patient’s consent. When warnings are discussed on the nightly news or the Internet, patients prescribed that medication will expect you to address this. Informed consent discussions are an excellent way to discover and address patients’ concerns and ensure that they have realistic expectations about treatment.

Potential benefits for patients from updating informed consent include:

• changes in medications or dosages based on the new information
  
• closer monitoring of potential side effects and other actions
  
• empowerment to make decisions about stopping a medication or trying alternate medications or treatments.
  

Documentation also reflects individualization of care, the patient’s involvement, and your clinical judgment and decision-making—all critical elements of a record that supports good patient care and protects both patient and clinician.

Documenting informed consent

What to include. View informed consent as an ongoing discussion, not a document that needs to be put into a chart to comply with a legal mandate. Documenting informed consent may be as simple as going through the process and then including pertinent points in the medical record (Table 2). The following is an example of a medical record entry used by one author (NSK) to document an initial informed consent discussion:

 

“I have explained to the patient the reasons for prescribing the above medication, the expected benefits and potential side effects, the treatment alternatives and possible risks and benefits of the alternatives, and the expected course w/o treatment. The patient asked appropriate questions and appeared to understand the answers. (I discussed off-label use.) I provided information from the manufacturer (or some other source). The patient has decided to try this medication and to be followed.”

Caveats. Avoid “cutting and pasting” language for each informed consent discussion into each medical record. Make your discussion and its documentation reflect each individual’s treatment plan. If you use a preprinted consent/medications side-effect form (as required by many institutions and clinics), consider entering a personalized notation into the progress notes as needed, such as when:

• you prescribe medications with high risk for serious side effects
  
• you use off-label prescribing that is not customary
  
• a patient needs extra assistance to follow the treatment plan.⁸
  

The procedure’s formality helps a patient focus on the consent process, making it less likely that he/she will later believe he/she was not adequately informed. The signed form supports the assertion that the consent process took place and establishes at least some of what was disclosed. The signed form and the clinician’s entry in the record documenting the informed consent discussion will be beneficial should malpractice litigation allege consent issues.

Table 2

Informed consent: Pertinent points to document

Proposed treatment
Potential side effects (most common)
Potential side effects (most dangerous)
Potential side effects that might make a patient anxious, such as those included in recent FDA statements, changes in labeling, or advertisers’ consumer marketing messages
Alternatives, including their potential side effects
Course without treatment
Demonstration of patient’s comprehension of warnings and opportunity to ask questions

Preprinted forms. A disadvantage of preprinted forms is the difficulty in knowing what information to include. If the form’s content is very broad, then important information may not be disclosed. If the form is very specific and attempts to list all possible complications, one could presume that any complication not listed was not disclosed. If you incorporate an informed consent form into your practice:

• include all significant and material risks on the form
  
• state on the form that the risks “include, but are not limited to” those listed on the form
  
• have thorough informed consent discussions with patients
  
• enter into the medical record your discussion and a copy of the form signed by the patient.
  

What to disclose. Clinicians often struggle with how much information to disclose to patients. In general, include what a reasonable person would need to know to make an informed decision. A practical way to think about this is to ask yourself the following questions:

• What information would I want a physician to disclose to my loved one (parent, child, spouse, etc.) if I was not present and my loved one needed to give consent to a treatment recommendation?
  
• Is this information of the type that a reasonable person could say: “I wouldn’t have consented if the doctor had told me that”? If you think so, then provide this information to your patient.
  

Patient resources. Medication information sheets can enhance informed consent and patients’ understanding and retention of information about medications you prescribe. The FDA’s Web site (www.fda.gov) offers printable patient education sheets on hundreds of medications, medication guides, and other resources (see Related Resources).⁶ Many manufacturers also offer patient education information at their Web sites, via pharmaceutical representatives, and as part of the PI.

Related resources

• Food and Drug Administration (FDA). Information sheets on hundreds of FDA-approved drugs, listed alphabetically. www.fda.gov/cder/drug/DrugSafety/DrugIndex.htm.
  
• FDA. Drug safety information for consumers and healthcare professionals. www.fda.gov/cder/index.html.
  

Drug brand names

• Aripiprazole • Abilify
  
• Olanzapine • Zyprexa
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Ziprasidone • Geodon
  

Disclosures

Dr. Kaye receives research support from Pfizer Inc. and Takeda Pharmaceutical and is a consultant to and speaker for Pfizer Inc., AstraZeneca, and GlaxoSmithKline.

Jacqueline Melonas is a full-time employee of PRMS, Inc. PRMS, Inc. contracts with Eli Lilly and Company to provide risk management content related to the management of medical malpractice liability.

Comment on this article

Mr. B, age 35, is admitted for the fourth time to the inpatient service with hallucinations and delusions related to chronic schizophrenia. After appropriate attempts to control his symptoms, he has begun to respond to usual treatment with an atypical antipsychotic. He remains a “partial responder,” however, at the maximum FDA-approved dosage listed in the package insert (PI). What do you do next?

Because of this author’s (NSK) dual training in medicine and forensic psychiatry, other clinicians often ask me about patients such as Mr. B. Prescribing for patients who do not respond to standard dosages can create anxiety about going “off-label.” This article describes how to manage potential risk to yourself and your patient by communicating effectively and documenting informed consent.

What are the options?

To effectively treat Mr. B’s symptoms, you could:

• change medications and start over
  
• augment with a second atypical antipsychotic
  
• stay with the antipsychotic to which he has shown partial response, but go above the PI dosing.
  

Each strategy could pose problems, but most psychopharmacologists would choose the third option—the most logical one.

Changing medications is attractive, but the choice of an atypical antipsychotic with relative metabolic neutrality is limited, and “switching” is time-consuming. When a drug begins to show efficacy, most clinicians won’t opt to “change horses midstream”—especially if managed care is pressuring for rapid discharge.

Augmentation introduces polypharmacy and potential drug-drug interactions. Very little evidence guides us in combining antipsychotics, as most manufacturers will never study the coadministration of 2 branded medications with the same indication.

Only a few case reports have described combining atypical antipsychotics.^1-4 Moreover, many managed care providers and governmental payers/regulators will not pay for polypharmacy with 2 atypical antipsychotics or will allow it only during cross-tapering from one agent to another.

‘High-dose’ monotherapy is the choice most often taken by clinicians and experts. Pharmaceutical manufacturers study a wide range of doses during medication development. Two pivotal trials form the basis of the New Drug Application for FDA approval and largely dictate the PI language.

Don’t misconstrue the PI dosing as optimal for a specific medication or patient. Historically, FDA-approved dosing for atypical antipsychotics has been too high (risperidone, aripiprazole) or too low (ziprasidone, quetiapine) for many patients we treat, even when the medications are used as indicated. This problem is magnified when clinicians try to make individual patients (N=1) resemble the average pooled analysis of the clinical trial group (N>200) and find that the individual patient may be a low-dose, average-dose, or high-dose responder (Table 1).

Informed prescribing. Polypharmacy is a complex issue because essentially no pharmacokinetic or pharmacodynamic studies have examined the simultaneous use of ≥3 psychotropics. When a pharmacist or drug interaction computer alerts you to a potential drug-drug interaction, the warning is almost always theoretical. No real data exist about coadministering most medications.

Physicians may query a manufacturer about off-label, above-PI dosing data by contacting the company’s medical information department or asking a pharmaceutical representative. What you receive will vary by manufacturer, but in almost every case you will get the safety data you want. Occasionally you also will get efficacy data, which is nice but not crucial. An online literature search of MEDLINE is another way to obtain this information.

Table 1

Patient factors that influence response to medication

Patient body mass, age, race, ethnicity, and gender
Variability in medication absorption
Hepatic metabolizing factors
How ‘sick’ the patient is, compared with those in pivotal clinical trials
Patient’s behavior, lifestyle, habits, and diet
Comorbid medical conditions
Other psychiatric and nonpsychiatric pharmacotherapy

Liability risk?

Every clinician I’ve met prescribes drugs off-label, whether in terms of dose, indication, or age limits in the PI as published in the Physicians’ Desk Reference (PDR).⁵ Still, nearly all describe to me the following nightmare, in which they “violated” the PI and “something bad” happens.

They are sitting in court on the witness stand, white-knuckled and sweaty, as a plaintiff’s attorney strolls up to them, PDR in hand, and says: “Doctor, isn’t this the Bible, and you violated the Bible?” And thus is born the fear of a malpractice claim, predicated on off-label dosing.

Off-label prescribing is rarely the only issue in a lawsuit, according to Denny Rodriguez, assistant vice president, claims, Professional Risk Management Services (PRMS), Inc.—manager of The Psychiatrists’ Program endorsed by the American Psychiatric Association. When raised, allegations related to off-label prescribing are among many presented by the plaintiff under the rubric of treatment that violated the standard of care.

 

Contrary to the plaintiff’s allegations, off-label prescribing rarely violates the standard of care because it has valid clinical and scientific bases. And don’t acknowledge the PDR as “the Bible,” which it is not; it’s a compilation of PIs. The FDA affirms that once a product is approved for marketing, a physician may choose to prescribe it for off-label use (Box).⁵

Box

Standard of care

The real issue for practitioners is the “standard of care.” Violating the standard of care—what a similarly trained clinician would do under similar circumstances—is the first step on the slippery slope to malpractice. Here we can be quite sure that the standard of care and evidence-based medicine are in sync and support the use of off-label, high-dose monotherapy.

Properly documenting your reasoning helps to demonstrate that your prescribing meets the standard of care. Always document and obtain informed consent. Also stay up-to-date about:

• medications you prescribe
  
• emerging evidence and safety information
  
• appropriate patient monitoring for clinical response and adverse effects.⁸
  

Black boxes and bold lettering

The FDA may mandate that a manufacturer highlight certain information on a PI in 3 ways—bold lettering, black-box warning, and red lettering, in order of presumed increasing seriousness. This system is meant to draw prescribers’ attention to potential safety problems with pharmaceutical agents. No psychiatric medications carry red-letter warnings, a classification usually reserved for antineoplastic agents.

At one time the FDA relied on evidenced-based data to determine the need for warnings. Recently, however, when a problem has been identified with one agent, the FDA has tended to require all drugs in that agent’s class to carry similar—if not identical—PI warnings. In psychiatry, the FDA has ordered suicide precautions on all antidepressants and metabolic syndrome/hyperglycemia warnings on all atypical antipsychotics, despite evidence of differences in potential risks associated with medications within classes. For example, clinical trials have shown a higher risk of obesity and diabetes among patients receiving olanzapine compared with those receiving ziprasidone.⁷

The FDA’s action appears to “level the playing field,” giving patients the misperception that any treatment would carry an equal risk. Therefore, when you prescribe a drug that carries a class-wide warning in its PI, present the evidence in a balanced, objective manner so that the patient can make an informed decision.

Managing risk

Your best protection against liability is to communicate effectively with the patient and document that communication—including informed consent—in the medical record.⁸ Obtain and document informed consent whenever:

• you initiate a drug or other treatment
  
• treatment extends beyond the PI-recommended maximum dose.
  

Similarly, when a new side-effect warning or safety information about a medication emerges, update the informed consent discussion and re-obtain and re-document the patient’s consent. When warnings are discussed on the nightly news or the Internet, patients prescribed that medication will expect you to address this. Informed consent discussions are an excellent way to discover and address patients’ concerns and ensure that they have realistic expectations about treatment.

Potential benefits for patients from updating informed consent include:

• changes in medications or dosages based on the new information
  
• closer monitoring of potential side effects and other actions
  
• empowerment to make decisions about stopping a medication or trying alternate medications or treatments.
  

Documentation also reflects individualization of care, the patient’s involvement, and your clinical judgment and decision-making—all critical elements of a record that supports good patient care and protects both patient and clinician.

Documenting informed consent

What to include. View informed consent as an ongoing discussion, not a document that needs to be put into a chart to comply with a legal mandate. Documenting informed consent may be as simple as going through the process and then including pertinent points in the medical record (Table 2). The following is an example of a medical record entry used by one author (NSK) to document an initial informed consent discussion:

 

“I have explained to the patient the reasons for prescribing the above medication, the expected benefits and potential side effects, the treatment alternatives and possible risks and benefits of the alternatives, and the expected course w/o treatment. The patient asked appropriate questions and appeared to understand the answers. (I discussed off-label use.) I provided information from the manufacturer (or some other source). The patient has decided to try this medication and to be followed.”

Caveats. Avoid “cutting and pasting” language for each informed consent discussion into each medical record. Make your discussion and its documentation reflect each individual’s treatment plan. If you use a preprinted consent/medications side-effect form (as required by many institutions and clinics), consider entering a personalized notation into the progress notes as needed, such as when:

• you prescribe medications with high risk for serious side effects
  
• you use off-label prescribing that is not customary
  
• a patient needs extra assistance to follow the treatment plan.⁸
  

The procedure’s formality helps a patient focus on the consent process, making it less likely that he/she will later believe he/she was not adequately informed. The signed form supports the assertion that the consent process took place and establishes at least some of what was disclosed. The signed form and the clinician’s entry in the record documenting the informed consent discussion will be beneficial should malpractice litigation allege consent issues.

Table 2

Informed consent: Pertinent points to document

Proposed treatment
Potential side effects (most common)
Potential side effects (most dangerous)
Potential side effects that might make a patient anxious, such as those included in recent FDA statements, changes in labeling, or advertisers’ consumer marketing messages
Alternatives, including their potential side effects
Course without treatment
Demonstration of patient’s comprehension of warnings and opportunity to ask questions

Preprinted forms. A disadvantage of preprinted forms is the difficulty in knowing what information to include. If the form’s content is very broad, then important information may not be disclosed. If the form is very specific and attempts to list all possible complications, one could presume that any complication not listed was not disclosed. If you incorporate an informed consent form into your practice:

• include all significant and material risks on the form
  
• state on the form that the risks “include, but are not limited to” those listed on the form
  
• have thorough informed consent discussions with patients
  
• enter into the medical record your discussion and a copy of the form signed by the patient.
  

What to disclose. Clinicians often struggle with how much information to disclose to patients. In general, include what a reasonable person would need to know to make an informed decision. A practical way to think about this is to ask yourself the following questions:

• What information would I want a physician to disclose to my loved one (parent, child, spouse, etc.) if I was not present and my loved one needed to give consent to a treatment recommendation?
  
• Is this information of the type that a reasonable person could say: “I wouldn’t have consented if the doctor had told me that”? If you think so, then provide this information to your patient.
  

Patient resources. Medication information sheets can enhance informed consent and patients’ understanding and retention of information about medications you prescribe. The FDA’s Web site (www.fda.gov) offers printable patient education sheets on hundreds of medications, medication guides, and other resources (see Related Resources).⁶ Many manufacturers also offer patient education information at their Web sites, via pharmaceutical representatives, and as part of the PI.

Related resources

• Food and Drug Administration (FDA). Information sheets on hundreds of FDA-approved drugs, listed alphabetically. www.fda.gov/cder/drug/DrugSafety/DrugIndex.htm.
  
• FDA. Drug safety information for consumers and healthcare professionals. www.fda.gov/cder/index.html.
  

Drug brand names

• Aripiprazole • Abilify
  
• Olanzapine • Zyprexa
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Ziprasidone • Geodon
  

Disclosures

Dr. Kaye receives research support from Pfizer Inc. and Takeda Pharmaceutical and is a consultant to and speaker for Pfizer Inc., AstraZeneca, and GlaxoSmithKline.

Jacqueline Melonas is a full-time employee of PRMS, Inc. PRMS, Inc. contracts with Eli Lilly and Company to provide risk management content related to the management of medical malpractice liability.

Comment on this article

Mr. B, age 35, is admitted for the fourth time to the inpatient service with hallucinations and delusions related to chronic schizophrenia. After appropriate attempts to control his symptoms, he has begun to respond to usual treatment with an atypical antipsychotic. He remains a “partial responder,” however, at the maximum FDA-approved dosage listed in the package insert (PI). What do you do next?

Because of this author’s (NSK) dual training in medicine and forensic psychiatry, other clinicians often ask me about patients such as Mr. B. Prescribing for patients who do not respond to standard dosages can create anxiety about going “off-label.” This article describes how to manage potential risk to yourself and your patient by communicating effectively and documenting informed consent.

What are the options?

To effectively treat Mr. B’s symptoms, you could:

• change medications and start over
  
• augment with a second atypical antipsychotic
  
• stay with the antipsychotic to which he has shown partial response, but go above the PI dosing.
  

Each strategy could pose problems, but most psychopharmacologists would choose the third option—the most logical one.

Changing medications is attractive, but the choice of an atypical antipsychotic with relative metabolic neutrality is limited, and “switching” is time-consuming. When a drug begins to show efficacy, most clinicians won’t opt to “change horses midstream”—especially if managed care is pressuring for rapid discharge.

Augmentation introduces polypharmacy and potential drug-drug interactions. Very little evidence guides us in combining antipsychotics, as most manufacturers will never study the coadministration of 2 branded medications with the same indication.

Only a few case reports have described combining atypical antipsychotics.^1-4 Moreover, many managed care providers and governmental payers/regulators will not pay for polypharmacy with 2 atypical antipsychotics or will allow it only during cross-tapering from one agent to another.

‘High-dose’ monotherapy is the choice most often taken by clinicians and experts. Pharmaceutical manufacturers study a wide range of doses during medication development. Two pivotal trials form the basis of the New Drug Application for FDA approval and largely dictate the PI language.

Don’t misconstrue the PI dosing as optimal for a specific medication or patient. Historically, FDA-approved dosing for atypical antipsychotics has been too high (risperidone, aripiprazole) or too low (ziprasidone, quetiapine) for many patients we treat, even when the medications are used as indicated. This problem is magnified when clinicians try to make individual patients (N=1) resemble the average pooled analysis of the clinical trial group (N>200) and find that the individual patient may be a low-dose, average-dose, or high-dose responder (Table 1).

Informed prescribing. Polypharmacy is a complex issue because essentially no pharmacokinetic or pharmacodynamic studies have examined the simultaneous use of ≥3 psychotropics. When a pharmacist or drug interaction computer alerts you to a potential drug-drug interaction, the warning is almost always theoretical. No real data exist about coadministering most medications.

Physicians may query a manufacturer about off-label, above-PI dosing data by contacting the company’s medical information department or asking a pharmaceutical representative. What you receive will vary by manufacturer, but in almost every case you will get the safety data you want. Occasionally you also will get efficacy data, which is nice but not crucial. An online literature search of MEDLINE is another way to obtain this information.

Table 1

Patient factors that influence response to medication

Patient body mass, age, race, ethnicity, and gender
Variability in medication absorption
Hepatic metabolizing factors
How ‘sick’ the patient is, compared with those in pivotal clinical trials
Patient’s behavior, lifestyle, habits, and diet
Comorbid medical conditions
Other psychiatric and nonpsychiatric pharmacotherapy

Liability risk?

Every clinician I’ve met prescribes drugs off-label, whether in terms of dose, indication, or age limits in the PI as published in the Physicians’ Desk Reference (PDR).⁵ Still, nearly all describe to me the following nightmare, in which they “violated” the PI and “something bad” happens.

They are sitting in court on the witness stand, white-knuckled and sweaty, as a plaintiff’s attorney strolls up to them, PDR in hand, and says: “Doctor, isn’t this the Bible, and you violated the Bible?” And thus is born the fear of a malpractice claim, predicated on off-label dosing.

Off-label prescribing is rarely the only issue in a lawsuit, according to Denny Rodriguez, assistant vice president, claims, Professional Risk Management Services (PRMS), Inc.—manager of The Psychiatrists’ Program endorsed by the American Psychiatric Association. When raised, allegations related to off-label prescribing are among many presented by the plaintiff under the rubric of treatment that violated the standard of care.

 

Contrary to the plaintiff’s allegations, off-label prescribing rarely violates the standard of care because it has valid clinical and scientific bases. And don’t acknowledge the PDR as “the Bible,” which it is not; it’s a compilation of PIs. The FDA affirms that once a product is approved for marketing, a physician may choose to prescribe it for off-label use (Box).⁵

Box

Standard of care

The real issue for practitioners is the “standard of care.” Violating the standard of care—what a similarly trained clinician would do under similar circumstances—is the first step on the slippery slope to malpractice. Here we can be quite sure that the standard of care and evidence-based medicine are in sync and support the use of off-label, high-dose monotherapy.

Properly documenting your reasoning helps to demonstrate that your prescribing meets the standard of care. Always document and obtain informed consent. Also stay up-to-date about:

• medications you prescribe
  
• emerging evidence and safety information
  
• appropriate patient monitoring for clinical response and adverse effects.⁸
  

Black boxes and bold lettering

The FDA may mandate that a manufacturer highlight certain information on a PI in 3 ways—bold lettering, black-box warning, and red lettering, in order of presumed increasing seriousness. This system is meant to draw prescribers’ attention to potential safety problems with pharmaceutical agents. No psychiatric medications carry red-letter warnings, a classification usually reserved for antineoplastic agents.

At one time the FDA relied on evidenced-based data to determine the need for warnings. Recently, however, when a problem has been identified with one agent, the FDA has tended to require all drugs in that agent’s class to carry similar—if not identical—PI warnings. In psychiatry, the FDA has ordered suicide precautions on all antidepressants and metabolic syndrome/hyperglycemia warnings on all atypical antipsychotics, despite evidence of differences in potential risks associated with medications within classes. For example, clinical trials have shown a higher risk of obesity and diabetes among patients receiving olanzapine compared with those receiving ziprasidone.⁷

The FDA’s action appears to “level the playing field,” giving patients the misperception that any treatment would carry an equal risk. Therefore, when you prescribe a drug that carries a class-wide warning in its PI, present the evidence in a balanced, objective manner so that the patient can make an informed decision.

Managing risk

Your best protection against liability is to communicate effectively with the patient and document that communication—including informed consent—in the medical record.⁸ Obtain and document informed consent whenever:

• you initiate a drug or other treatment
  
• treatment extends beyond the PI-recommended maximum dose.
  

Similarly, when a new side-effect warning or safety information about a medication emerges, update the informed consent discussion and re-obtain and re-document the patient’s consent. When warnings are discussed on the nightly news or the Internet, patients prescribed that medication will expect you to address this. Informed consent discussions are an excellent way to discover and address patients’ concerns and ensure that they have realistic expectations about treatment.

Potential benefits for patients from updating informed consent include:

• changes in medications or dosages based on the new information
  
• closer monitoring of potential side effects and other actions
  
• empowerment to make decisions about stopping a medication or trying alternate medications or treatments.
  

Documentation also reflects individualization of care, the patient’s involvement, and your clinical judgment and decision-making—all critical elements of a record that supports good patient care and protects both patient and clinician.

Documenting informed consent

What to include. View informed consent as an ongoing discussion, not a document that needs to be put into a chart to comply with a legal mandate. Documenting informed consent may be as simple as going through the process and then including pertinent points in the medical record (Table 2). The following is an example of a medical record entry used by one author (NSK) to document an initial informed consent discussion:

 

“I have explained to the patient the reasons for prescribing the above medication, the expected benefits and potential side effects, the treatment alternatives and possible risks and benefits of the alternatives, and the expected course w/o treatment. The patient asked appropriate questions and appeared to understand the answers. (I discussed off-label use.) I provided information from the manufacturer (or some other source). The patient has decided to try this medication and to be followed.”

Caveats. Avoid “cutting and pasting” language for each informed consent discussion into each medical record. Make your discussion and its documentation reflect each individual’s treatment plan. If you use a preprinted consent/medications side-effect form (as required by many institutions and clinics), consider entering a personalized notation into the progress notes as needed, such as when:

• you prescribe medications with high risk for serious side effects
  
• you use off-label prescribing that is not customary
  
• a patient needs extra assistance to follow the treatment plan.⁸
  

The procedure’s formality helps a patient focus on the consent process, making it less likely that he/she will later believe he/she was not adequately informed. The signed form supports the assertion that the consent process took place and establishes at least some of what was disclosed. The signed form and the clinician’s entry in the record documenting the informed consent discussion will be beneficial should malpractice litigation allege consent issues.

Table 2

Informed consent: Pertinent points to document

Proposed treatment
Potential side effects (most common)
Potential side effects (most dangerous)
Potential side effects that might make a patient anxious, such as those included in recent FDA statements, changes in labeling, or advertisers’ consumer marketing messages
Alternatives, including their potential side effects
Course without treatment
Demonstration of patient’s comprehension of warnings and opportunity to ask questions

Preprinted forms. A disadvantage of preprinted forms is the difficulty in knowing what information to include. If the form’s content is very broad, then important information may not be disclosed. If the form is very specific and attempts to list all possible complications, one could presume that any complication not listed was not disclosed. If you incorporate an informed consent form into your practice:

• include all significant and material risks on the form
  
• state on the form that the risks “include, but are not limited to” those listed on the form
  
• have thorough informed consent discussions with patients
  
• enter into the medical record your discussion and a copy of the form signed by the patient.
  

What to disclose. Clinicians often struggle with how much information to disclose to patients. In general, include what a reasonable person would need to know to make an informed decision. A practical way to think about this is to ask yourself the following questions:

• What information would I want a physician to disclose to my loved one (parent, child, spouse, etc.) if I was not present and my loved one needed to give consent to a treatment recommendation?
  
• Is this information of the type that a reasonable person could say: “I wouldn’t have consented if the doctor had told me that”? If you think so, then provide this information to your patient.
  

Patient resources. Medication information sheets can enhance informed consent and patients’ understanding and retention of information about medications you prescribe. The FDA’s Web site (www.fda.gov) offers printable patient education sheets on hundreds of medications, medication guides, and other resources (see Related Resources).⁶ Many manufacturers also offer patient education information at their Web sites, via pharmaceutical representatives, and as part of the PI.

Related resources

• Food and Drug Administration (FDA). Information sheets on hundreds of FDA-approved drugs, listed alphabetically. www.fda.gov/cder/drug/DrugSafety/DrugIndex.htm.
  
• FDA. Drug safety information for consumers and healthcare professionals. www.fda.gov/cder/index.html.
  

Drug brand names

• Aripiprazole • Abilify
  
• Olanzapine • Zyprexa
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Ziprasidone • Geodon
  

Disclosures

Dr. Kaye receives research support from Pfizer Inc. and Takeda Pharmaceutical and is a consultant to and speaker for Pfizer Inc., AstraZeneca, and GlaxoSmithKline.

Jacqueline Melonas is a full-time employee of PRMS, Inc. PRMS, Inc. contracts with Eli Lilly and Company to provide risk management content related to the management of medical malpractice liability.

Dr. Keenan is associate professor, department of medicine, University of California, Davis.

Principal Source: U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.—Discussant: Craig R. Keenan, MD

Psychiatric patients—especially those with schizophrenia or taking atypical antipsychotics—are at risk for developing type 2 diabetes mellitus (T2DM) and prediabetes conditions. T2DM can be present for years without significant symptoms and even asymptomatic conditions increase the risk of cardiovascular, renal, retinal, and neurologic complications.

Despite a need for T2DM screening and treatment, expert guidelines disagree on who and how to screen (Table 1). Although testing patients who have diabetes symptoms—including polyuria, polydipsia, and weight loss—is indicated, some medical groups advocate screening asymptomatic persons for T2DM.

Screening recommendations

Consensus guidelines. In 2004, the American Diabetes Association (ADA), American Psychiatric Association (APA), American Association of Clinical Endocrinologists (AACE), and North American Association for the Study of Obesity (NAASO) created consensus guidelines for screening psychiatric patients receiving atypical antipsychotics. In addition to diabetes risk, psychiatric patients are at higher risk for metabolic syndrome, dyslipidemia, obesity, and hypertension.¹ The ADA, APA, AACE, and NAASO recommend regularly screening for weight gain and dyslipidemia, obtaining baseline values of fasting plasma glucose (FPG), rechecking FPG after 3 months, and then screening annually for diabetes or prediabetes. For patients with risk factors for diabetes and those who develop diabetes or prediabetes while taking an atypical antipsychotic, consider an atypical with a lower risk of diabetes—specifically aripiprazole or ziprasidone.¹ For psychiatric patients who do not take atypicals, there is no consensus on who and how to screen for T2DM.

The U.S. Preventive Services Task Force (USPSTF) recommends screening only adults with hypertension.² Its review found insufficient evidence that early detection and treatment leads to improved clinical outcomes in asymptomatic adults.

The ADA recommends more liberal screening, including individuals age ≥45 or anyone age <45 who is overweight and has any other diabetes risk factors.³ The ADA admits that no trials show a benefit of screening asymptomatic patients but notes that the duration of glycemic burden predicts adverse outcomes and effective interventions for diabetes and prediabetes are available.

AACE guidelines recommend screening starting at age 30 if the patient has risk factors for T2DM. This is the only group that includes psychiatric illness as a risk factor.⁴

European Association for the Study of Diabetes (EASD) guidelines calculate a risk score based on common risk factors to determine who should be screened and recommend using the oral glucose tolerance test (OGTT) rather the FPG.⁵ The OGTT identifies more cases of diabetes and pre-diabetes but takes >2 hours to administer.

Table 1

General population screening recommendations for type 2 diabetes mellitus or prediabetes

Organization	Year	Whom to screen	How to screen
U.S. Preventive Services Task Force (USPSTF)	2008	Asymptomatic adults with sustained blood pressure >135/80 mmHg (treated or untreated)	FPG or OGTT every 3 years
American Diabetes Association (ADA)	2009	All adults age ≥45 Adults of any age with BMI >25 kg/m2 and ≥1 risk factors for diabetes (Table 2)	FPG or 2-hour OGTT every 3 years or more frequently, depending on initial results and risks
American Association of Clinical Endocrinologists (AACE)	2007	All adults age ≥30 with risk factors for diabetes (Table 2)	FPG or 2-hour OGTT (frequency not specified)
European Association for the Study of Diabetes (EASD) and European Society of Cardiology (ESC)	2007	All adults with elevated risk score*	OGTT (frequency not indicated)
FPG: fasting plasma glucose; OGTT: oral glucose tolerance test (75 gm glucose load); BMI: body mass index
*Risk scoring tool available at www.diabetes.fi/english/risktest

Discussion

Despite a lack evidence showing benefit to the screened population, treating diabetes and its comorbidities improves outcomes, and the potential risks of therapy are low. Therefore, it seems reasonable to screen more patients than the USPSTF recommends.

Using the EASD risk score is intriguing, but difficult to implement in a busy practice. Therefore, I recommend following the AACE guidelines, which recognize psychiatric illness as a risk factor, for screening psychiatric patients who are not receiving atypicals.

Annually screen psychiatric patients age ≥30, especially those with schizophrenia or affective disorders. I also follow the ADA guidelines and screen overweight adults age ≤30 if they have any of the other risk factors listed in Table 2. The most common risk factors seen in practice are being a member of a high-risk ethnic group, hypertension, lipid abnormalities, and cardiovascular disease. For overweight adults without other risk factors, I start screening at age 30.

 

Other practitioners can be more or less conservative and still be within accepted guidelines. The FPG—glucose level drawn from a vein after at least 8 hours of fasting—is probably the easiest screening test in practice. Any patient with a value >100mg/dL should be referred to the patient’s primary care physician. Any patient who develops diabetes symptoms—including polyuria, polydipsia, and weight loss—should be tested immediately. The hemoglobin A1C test is not recommended for screening.

Table 2

Risk factors identified for diabetes or prediabetes

American Diabetes Association (ADA)

BMI >25 kg/m2 physical inactivity first-degree relative with diabetes members of high-risk ethnic populations (African-American, Latino, Native American, Asian, Pacific Islander) women who delivered a baby >9 lb or had gestational diabetes hypertension high-density lipoproteins cholesterol <35 mg/dL and/or triglyceride level >250 mg/dL women with polycystic ovarian syndrome impaired glucose tolerance or impaired fasting glucose on previous testing conditions associated with insulin resistance, such as severe obesity or acanthosis nigricans history of cardiovascular disease

American Association of Clinical Endocrinologists

All of the risk factors identified by the ADA, except for conditions associated with insulin resistance, such as severe obesity or acanthosis nigricans psychiatric illness

Clinical presentation

Screening detects overt diabetes and can identify prediabetes. Prediabetes includes conditions of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). IFG is defined as a fasting glucose of 100 to 125 mg/dL, and IGT is defined as having a 2-hour glucose of 140 to 199 mg/dL on an OGTT.

Approximately one-quarter of the adult population has prediabetes, and interventions can prevent the progression of prediabetes to overt diabetes and reverse prediabetes. The Diabetes Prevention Trial found that lifestyle measures—including exercise and diet—were most effective, with a 53% reduction in the rate of progression to diabetes.⁶ Metformin also was effective, but less so than lifestyle measures alone.

Treatment slows the development or progression of microvascular complications, such as retinopathy, nephropathy, and neuropathy. Aggressive treatment of comorbid conditions, including hyperlipidemia and hypertension, also reduces the risk of cardiovascular events.

Drug brand names

• Aripiprazole • Abilify
• Metformin • Glucophage
• Ziprasidone • Geodon

Related resources

• American Diabetes Association. Diabetes risk calculator. www.diabetes.org/risk-test.jsp.
• Dagogo-Jack S. The role of antipsychotic agents in the development of diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009;5(1):22-23. Quick, up-to-date review of the association between atypical antipsychotics and diabetes mellitus.

Disclosure

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

Dr. Keenan is associate professor, department of medicine, University of California, Davis.

Principal Source: U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.—Discussant: Craig R. Keenan, MD

Psychiatric patients—especially those with schizophrenia or taking atypical antipsychotics—are at risk for developing type 2 diabetes mellitus (T2DM) and prediabetes conditions. T2DM can be present for years without significant symptoms and even asymptomatic conditions increase the risk of cardiovascular, renal, retinal, and neurologic complications.

Despite a need for T2DM screening and treatment, expert guidelines disagree on who and how to screen (Table 1). Although testing patients who have diabetes symptoms—including polyuria, polydipsia, and weight loss—is indicated, some medical groups advocate screening asymptomatic persons for T2DM.

Screening recommendations

Consensus guidelines. In 2004, the American Diabetes Association (ADA), American Psychiatric Association (APA), American Association of Clinical Endocrinologists (AACE), and North American Association for the Study of Obesity (NAASO) created consensus guidelines for screening psychiatric patients receiving atypical antipsychotics. In addition to diabetes risk, psychiatric patients are at higher risk for metabolic syndrome, dyslipidemia, obesity, and hypertension.¹ The ADA, APA, AACE, and NAASO recommend regularly screening for weight gain and dyslipidemia, obtaining baseline values of fasting plasma glucose (FPG), rechecking FPG after 3 months, and then screening annually for diabetes or prediabetes. For patients with risk factors for diabetes and those who develop diabetes or prediabetes while taking an atypical antipsychotic, consider an atypical with a lower risk of diabetes—specifically aripiprazole or ziprasidone.¹ For psychiatric patients who do not take atypicals, there is no consensus on who and how to screen for T2DM.

The U.S. Preventive Services Task Force (USPSTF) recommends screening only adults with hypertension.² Its review found insufficient evidence that early detection and treatment leads to improved clinical outcomes in asymptomatic adults.

The ADA recommends more liberal screening, including individuals age ≥45 or anyone age <45 who is overweight and has any other diabetes risk factors.³ The ADA admits that no trials show a benefit of screening asymptomatic patients but notes that the duration of glycemic burden predicts adverse outcomes and effective interventions for diabetes and prediabetes are available.

AACE guidelines recommend screening starting at age 30 if the patient has risk factors for T2DM. This is the only group that includes psychiatric illness as a risk factor.⁴

European Association for the Study of Diabetes (EASD) guidelines calculate a risk score based on common risk factors to determine who should be screened and recommend using the oral glucose tolerance test (OGTT) rather the FPG.⁵ The OGTT identifies more cases of diabetes and pre-diabetes but takes >2 hours to administer.

Table 1

General population screening recommendations for type 2 diabetes mellitus or prediabetes

Organization	Year	Whom to screen	How to screen
U.S. Preventive Services Task Force (USPSTF)	2008	Asymptomatic adults with sustained blood pressure >135/80 mmHg (treated or untreated)	FPG or OGTT every 3 years
American Diabetes Association (ADA)	2009	All adults age ≥45 Adults of any age with BMI >25 kg/m2 and ≥1 risk factors for diabetes (Table 2)	FPG or 2-hour OGTT every 3 years or more frequently, depending on initial results and risks
American Association of Clinical Endocrinologists (AACE)	2007	All adults age ≥30 with risk factors for diabetes (Table 2)	FPG or 2-hour OGTT (frequency not specified)
European Association for the Study of Diabetes (EASD) and European Society of Cardiology (ESC)	2007	All adults with elevated risk score*	OGTT (frequency not indicated)
FPG: fasting plasma glucose; OGTT: oral glucose tolerance test (75 gm glucose load); BMI: body mass index
*Risk scoring tool available at www.diabetes.fi/english/risktest

Discussion

Despite a lack evidence showing benefit to the screened population, treating diabetes and its comorbidities improves outcomes, and the potential risks of therapy are low. Therefore, it seems reasonable to screen more patients than the USPSTF recommends.

Using the EASD risk score is intriguing, but difficult to implement in a busy practice. Therefore, I recommend following the AACE guidelines, which recognize psychiatric illness as a risk factor, for screening psychiatric patients who are not receiving atypicals.

Annually screen psychiatric patients age ≥30, especially those with schizophrenia or affective disorders. I also follow the ADA guidelines and screen overweight adults age ≤30 if they have any of the other risk factors listed in Table 2. The most common risk factors seen in practice are being a member of a high-risk ethnic group, hypertension, lipid abnormalities, and cardiovascular disease. For overweight adults without other risk factors, I start screening at age 30.

 

Other practitioners can be more or less conservative and still be within accepted guidelines. The FPG—glucose level drawn from a vein after at least 8 hours of fasting—is probably the easiest screening test in practice. Any patient with a value >100mg/dL should be referred to the patient’s primary care physician. Any patient who develops diabetes symptoms—including polyuria, polydipsia, and weight loss—should be tested immediately. The hemoglobin A1C test is not recommended for screening.

Table 2

Risk factors identified for diabetes or prediabetes

American Diabetes Association (ADA)

BMI >25 kg/m2 physical inactivity first-degree relative with diabetes members of high-risk ethnic populations (African-American, Latino, Native American, Asian, Pacific Islander) women who delivered a baby >9 lb or had gestational diabetes hypertension high-density lipoproteins cholesterol <35 mg/dL and/or triglyceride level >250 mg/dL women with polycystic ovarian syndrome impaired glucose tolerance or impaired fasting glucose on previous testing conditions associated with insulin resistance, such as severe obesity or acanthosis nigricans history of cardiovascular disease

American Association of Clinical Endocrinologists

All of the risk factors identified by the ADA, except for conditions associated with insulin resistance, such as severe obesity or acanthosis nigricans psychiatric illness

Clinical presentation

Screening detects overt diabetes and can identify prediabetes. Prediabetes includes conditions of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). IFG is defined as a fasting glucose of 100 to 125 mg/dL, and IGT is defined as having a 2-hour glucose of 140 to 199 mg/dL on an OGTT.

Approximately one-quarter of the adult population has prediabetes, and interventions can prevent the progression of prediabetes to overt diabetes and reverse prediabetes. The Diabetes Prevention Trial found that lifestyle measures—including exercise and diet—were most effective, with a 53% reduction in the rate of progression to diabetes.⁶ Metformin also was effective, but less so than lifestyle measures alone.

Treatment slows the development or progression of microvascular complications, such as retinopathy, nephropathy, and neuropathy. Aggressive treatment of comorbid conditions, including hyperlipidemia and hypertension, also reduces the risk of cardiovascular events.

Drug brand names

• Aripiprazole • Abilify
• Metformin • Glucophage
• Ziprasidone • Geodon

Related resources

• American Diabetes Association. Diabetes risk calculator. www.diabetes.org/risk-test.jsp.
• Dagogo-Jack S. The role of antipsychotic agents in the development of diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009;5(1):22-23. Quick, up-to-date review of the association between atypical antipsychotics and diabetes mellitus.

Disclosure

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

Dr. Keenan is associate professor, department of medicine, University of California, Davis.

Principal Source: U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.—Discussant: Craig R. Keenan, MD

Psychiatric patients—especially those with schizophrenia or taking atypical antipsychotics—are at risk for developing type 2 diabetes mellitus (T2DM) and prediabetes conditions. T2DM can be present for years without significant symptoms and even asymptomatic conditions increase the risk of cardiovascular, renal, retinal, and neurologic complications.

Despite a need for T2DM screening and treatment, expert guidelines disagree on who and how to screen (Table 1). Although testing patients who have diabetes symptoms—including polyuria, polydipsia, and weight loss—is indicated, some medical groups advocate screening asymptomatic persons for T2DM.

Screening recommendations

Consensus guidelines. In 2004, the American Diabetes Association (ADA), American Psychiatric Association (APA), American Association of Clinical Endocrinologists (AACE), and North American Association for the Study of Obesity (NAASO) created consensus guidelines for screening psychiatric patients receiving atypical antipsychotics. In addition to diabetes risk, psychiatric patients are at higher risk for metabolic syndrome, dyslipidemia, obesity, and hypertension.¹ The ADA, APA, AACE, and NAASO recommend regularly screening for weight gain and dyslipidemia, obtaining baseline values of fasting plasma glucose (FPG), rechecking FPG after 3 months, and then screening annually for diabetes or prediabetes. For patients with risk factors for diabetes and those who develop diabetes or prediabetes while taking an atypical antipsychotic, consider an atypical with a lower risk of diabetes—specifically aripiprazole or ziprasidone.¹ For psychiatric patients who do not take atypicals, there is no consensus on who and how to screen for T2DM.

The U.S. Preventive Services Task Force (USPSTF) recommends screening only adults with hypertension.² Its review found insufficient evidence that early detection and treatment leads to improved clinical outcomes in asymptomatic adults.

The ADA recommends more liberal screening, including individuals age ≥45 or anyone age <45 who is overweight and has any other diabetes risk factors.³ The ADA admits that no trials show a benefit of screening asymptomatic patients but notes that the duration of glycemic burden predicts adverse outcomes and effective interventions for diabetes and prediabetes are available.

AACE guidelines recommend screening starting at age 30 if the patient has risk factors for T2DM. This is the only group that includes psychiatric illness as a risk factor.⁴

European Association for the Study of Diabetes (EASD) guidelines calculate a risk score based on common risk factors to determine who should be screened and recommend using the oral glucose tolerance test (OGTT) rather the FPG.⁵ The OGTT identifies more cases of diabetes and pre-diabetes but takes >2 hours to administer.

Table 1

General population screening recommendations for type 2 diabetes mellitus or prediabetes

Organization	Year	Whom to screen	How to screen
U.S. Preventive Services Task Force (USPSTF)	2008	Asymptomatic adults with sustained blood pressure >135/80 mmHg (treated or untreated)	FPG or OGTT every 3 years
American Diabetes Association (ADA)	2009	All adults age ≥45 Adults of any age with BMI >25 kg/m2 and ≥1 risk factors for diabetes (Table 2)	FPG or 2-hour OGTT every 3 years or more frequently, depending on initial results and risks
American Association of Clinical Endocrinologists (AACE)	2007	All adults age ≥30 with risk factors for diabetes (Table 2)	FPG or 2-hour OGTT (frequency not specified)
European Association for the Study of Diabetes (EASD) and European Society of Cardiology (ESC)	2007	All adults with elevated risk score*	OGTT (frequency not indicated)
FPG: fasting plasma glucose; OGTT: oral glucose tolerance test (75 gm glucose load); BMI: body mass index
*Risk scoring tool available at www.diabetes.fi/english/risktest

Discussion

Despite a lack evidence showing benefit to the screened population, treating diabetes and its comorbidities improves outcomes, and the potential risks of therapy are low. Therefore, it seems reasonable to screen more patients than the USPSTF recommends.

Using the EASD risk score is intriguing, but difficult to implement in a busy practice. Therefore, I recommend following the AACE guidelines, which recognize psychiatric illness as a risk factor, for screening psychiatric patients who are not receiving atypicals.

Annually screen psychiatric patients age ≥30, especially those with schizophrenia or affective disorders. I also follow the ADA guidelines and screen overweight adults age ≤30 if they have any of the other risk factors listed in Table 2. The most common risk factors seen in practice are being a member of a high-risk ethnic group, hypertension, lipid abnormalities, and cardiovascular disease. For overweight adults without other risk factors, I start screening at age 30.

 

Other practitioners can be more or less conservative and still be within accepted guidelines. The FPG—glucose level drawn from a vein after at least 8 hours of fasting—is probably the easiest screening test in practice. Any patient with a value >100mg/dL should be referred to the patient’s primary care physician. Any patient who develops diabetes symptoms—including polyuria, polydipsia, and weight loss—should be tested immediately. The hemoglobin A1C test is not recommended for screening.

Table 2

Risk factors identified for diabetes or prediabetes

American Diabetes Association (ADA)

BMI >25 kg/m2 physical inactivity first-degree relative with diabetes members of high-risk ethnic populations (African-American, Latino, Native American, Asian, Pacific Islander) women who delivered a baby >9 lb or had gestational diabetes hypertension high-density lipoproteins cholesterol <35 mg/dL and/or triglyceride level >250 mg/dL women with polycystic ovarian syndrome impaired glucose tolerance or impaired fasting glucose on previous testing conditions associated with insulin resistance, such as severe obesity or acanthosis nigricans history of cardiovascular disease

American Association of Clinical Endocrinologists

All of the risk factors identified by the ADA, except for conditions associated with insulin resistance, such as severe obesity or acanthosis nigricans psychiatric illness

Clinical presentation

Screening detects overt diabetes and can identify prediabetes. Prediabetes includes conditions of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). IFG is defined as a fasting glucose of 100 to 125 mg/dL, and IGT is defined as having a 2-hour glucose of 140 to 199 mg/dL on an OGTT.

Approximately one-quarter of the adult population has prediabetes, and interventions can prevent the progression of prediabetes to overt diabetes and reverse prediabetes. The Diabetes Prevention Trial found that lifestyle measures—including exercise and diet—were most effective, with a 53% reduction in the rate of progression to diabetes.⁶ Metformin also was effective, but less so than lifestyle measures alone.

Treatment slows the development or progression of microvascular complications, such as retinopathy, nephropathy, and neuropathy. Aggressive treatment of comorbid conditions, including hyperlipidemia and hypertension, also reduces the risk of cardiovascular events.

Drug brand names

• Aripiprazole • Abilify
• Metformin • Glucophage
• Ziprasidone • Geodon

Related resources

• American Diabetes Association. Diabetes risk calculator. www.diabetes.org/risk-test.jsp.
• Dagogo-Jack S. The role of antipsychotic agents in the development of diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009;5(1):22-23. Quick, up-to-date review of the association between atypical antipsychotics and diabetes mellitus.

Disclosure

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

WEB AUDIO
Listen to Dr. Stanford discuss,
"Is fibromyalgia a somatoform disorder?

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Patients with fibromyalgia are a heterogeneous group, yet many describe a common experience: seeing multiple physicians who seem unable or unwilling to provide a diagnosis or treat their symptoms. This situation may be changing with the recent FDA approval of an anticonvulsant and 2 antidepressants for managing fibromyalgia symptoms.

These medications—pregabalin, duloxetine, and milnacipran—reflect a revised understanding of fibromyalgia as a CNS condition, rather than an inflammatory process in the muscles or connective tissue. As a result, psychiatrists—because of our experience with CNS phenomena and managing antidepressant and anticonvulsant medications—are likely to play a larger role in treating fibromyalgia.

CASE REPORT: ‘Just too tired’

Ms. D, age 50, has a history of migraine headaches and is referred by her primary physician for evaluation of depression and anxiety. She reports deteriorating mood over 6 months, beginning when a minor car accident left her “very sore the next day.”

“Nothing helps” the persistent pain in her back, shoulders, and thighs, which she rates as 7 to 8 on a 0-to-10 pain scale. She describes an intense ache, “like having the flu,” that worsens with activity and in stressful situations. She also experiences nausea and intermittent diarrhea, debilitating fatigue, and sleep disturbance.

Ms. D reports she is depressed because she feels “just too tired” after work to keep up with social activities or housework. Her physician’s referral notes a normal physical exam except for tenderness over her upper back and hips. Laboratory testing is negative.

Making the diagnosis

American College of Rheumatology (ACR) criteria for fibromyalgia require widespread pain for at least 3 months. “Widespread” is defined as pain in the axial skeleton, left and right sides of the body, and above and below the waist. Pain must be found in at least 11 of 18 tender point sites on digital palpation using a force of approximately 4 kg/cm².¹ For many fibromyalgia patients, however, musculoskeletal pain is not their most problematic symptom (Table 1). They may suffer:

• migraine and tension headaches (10% to 80% of patients)
  
• irritable bowel syndrome (32% to 80%)²
  
• mood disorders (major depressive disorder [62%], bipolar disorder [11%])
  
• anxiety disorders (panic disorder [29%], posttraumatic stress disorder [21%], social phobia [19%]).³
  

ACR criteria are useful in research but lack many common symptoms and comorbidities. A structured interview that follows the DSM-IV-TR format incorporates other symptoms into the diagnosis (Table 2).⁴

Because patients with fibromyalgia often meet criteria for somatization or somatoform disorders, how to classify them—as medically or psychiatrically ill—is controversial. Some patients believe their mood or anxiety problem stems from the difficulty they experience dealing with their physical symptoms, and if they could feel better physically they would not be depressed or anxious. Others believe their psychiatric symptoms impede their ability to help themselves feel better.

Consider fibromyalgia in any patient with widespread pain of unknown cause. Before making the diagnosis, rule out other illnesses that present with similar symptoms (Table 3). Because many patients newly diagnosed with fibromyalgia worry that something “more serious” may be going on, confirm the diagnosis with appropriate testing and physical examination, usually by a rheumatologist or primary care physician.

Table 1

Medical and cognitive symptoms related to fibromyalgia

Neurologic Tension/migraine headache
Psychiatric Memory and cognitive difficulties Mood disturbance Anxiety disorders
Ear, nose, throat Sicca symptoms Vasomotor rhinitis Vestibular complaints
Cardiovascular Neurally mediated hypotension Mitral valve prolapse Noncardiac chest pain
Gastrointestinal Esophageal dysmotility Irritable bowel syndrome
Urological Interstitial cystitis
Gynecological Vulvodynia Chronic pelvic pain
Oral/dental Temporomandibular joint syndrome
Other (general) Chronic fatigue syndrome Sleep disturbances Idiopathic low back pain Multiple chemical sensitivity

Table 2

Fibromyalgia: Structured interview for diagnosis

A. Generalized pain affecting the axial, plus upper and lower segments, plus left and rights sides of the body
Either B or C:
B. At least 11 of 18 reproducible tender points
C. At least 4 of the following symptoms: Generalized fatigue Headaches Sleep disturbance Neuropsychiatric complaints Numbness, tingling sensations Irritable bowel symptoms
D. It cannot be established that disturbance was due to another systematic condition
Source: Reference 4

Table 3

Differentiating fibromyalgia from illnesses with similar symptoms

Illness	Tests to differentiate from primary fibromyalgia
Rheumatic diseases Osteoarthritis Spondyloarthropathies, rheumatoid arthritis Systemic lupus erythematosus, polymyalgia rheumatica Osteomalacia Myopathy	Radiographs Rheumatic markers (antinuclear antibody, rheumatoid factor, antibodies) Inflammatory markers (ESR, C-reactive protein) Vitamin D level CPK
Neurologic Multiple sclerosis, Chiari’s malformation, spinal stenosis, radiculopathy Neuropathy	MRI EMG
Endocrine Hypothyroidism Diabetes	TSH Basic chemistry panel with fasting glucose
Other Infectious   Lyme disease   Hepatitis Anemia Cancers	CBC Lyme titer Hepatitis antibody panel, liver function tests Hemoglobin/hematocrit Routine cancer screening tests, bone scan, blood chemistries specific for suspected primary cancer
ESR: erythrocyte sedimentation rate; CPK: creatine phosphokinase; EMG: electromyography; TSH: thyroid-stimulating hormone; CBC: complete blood count

 

CASE CONTINUED: Central pain sensitization

As you elicit more details about Ms. D’s mood, she continues to focus on her physical symptoms. She states that some days she wishes to die because her pain gets so bad, but she denies any plan or intent to harm herself. She worries that her symptoms will worsen and that she will become completely disabled.

Her primary physician attempted to relieve Ms. D’s pain with multiple trials of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclobenzaprine. She says she gained no benefit from the NSAIDs and discontinued the muscle relaxant because it made her too sleepy. Fibromyalgia affects 3.5% of women and 0.5% of men.⁵ It runs in families with histories of fibromyalgia and major mood and anxiety disorders, suggesting genetic links.⁶ Defects in genes controlling serotonin and norepinephrine have been implicated.^7-9

Fibromyalgia patients show lower levels of serotonin, norepinephrine, and dopamine metabolites in cerebrospinal fluid (CSF), compared with controls.¹⁰ These neurotransmitters may inhibit descending pain pathways in the CNS, and low levels in the brain and spinal cord may inhibit CNS regulation of pain impulses from the periphery.¹¹

Although many patients describe muscle pain, evidence suggests central pain augmentation rather than an abnormality of muscle or connective tissue.¹² Some studies have found evidence of “windup,” in which second-order neurons in the spinal cord become sensitized by repeated signals from first-order neurons in the periphery, resulting in amplified and prolonged pain signals traveling to the brain.¹³

Levels of substance P—a primary transmitter of pain impulses—are significantly higher in CSF of fibromyalgia patients compared with controls.¹⁴ This finding, in addition to low levels of serotonin and norepinephrine, indicates that pain signals are ascending unchecked to be processed by the brain.

Neuroimaging studies confirm this observation. In a study using functional magnetic resonance imaging (fMRI), researchers applied pressure to the thumbnails of fibromyalgia patients and controls until each subject reported pain:

• Twice as much pressure was required before controls rated their pain at a level similar to that of fibromyalgia patients.
  
• When controls and fibromyalgia patients reported similar pain, a very high degree of overlap was seen in brain areas responsible for pain processing. This indicates that fibromyalgia patients and controls were experiencing the pain they reported in the same way.¹⁵
  

Treating the whole patient

As a clinician who specializes in fibromyalgia, I counteract my patients’ and my own frustration with this condition by structuring office visits, determining realistic treatment goals, and treating all symptoms as part of a common syndrome rather than individual illnesses.

Structure office visits. Before every visit, have patients rate each symptom domain and write their top 2 or 3 concerns for that day (Click here for a sample form). Focusing on the patient’s most troublesome symptoms can help both of you feel greater satisfaction with treatment.

Educate patients. Ask them to discuss their beliefs about fibromyalgia; many know others with this condition or have researched diagnosis and treatment. Before developing a treatment plan, explain that their symptoms are chronic and all part of the same syndrome. Describe their pain as a complex phenomenon with possible peripheral and CNS components. Guide them to reputable Web sites and resources (see Related Resources).

Set realistic expectations. Many patients expect to resume an energetic and pain-free life, which usually is not the case with fibromyalgia (Box). Most medications are considered successful if they reduce pain by 30% to 50%, and side effects can be problematic. Discuss side effects before treatment begins to reduce patients’ anxiety and improve compliance in the first weeks.

Cognitive-behavioral therapy (CBT) for fibromyalgia incorporates relaxation techniques, helping patients view symptoms as manageable, reinforcing adaptive coping skills, and teaching them how to monitor thoughts, feelings, and behavior to change the view that they are helpless victims. A modest course of 6 weekly group CBT sessions significantly improved physical functioning in 25% of fibromyalgia patients (n=76) compared with 12% in a standard-care group (n=69), even though patients’ pain severity did not improve.¹⁶

Recommend exercise, lifestyle changes. Aerobic exercise can significantly improve well-being and physical functioning in fibromyalgia patients.¹⁷ Low-impact aerobics, such as done in warm water, usually are well tolerated, although any low-impact exercise can help. Because fibromyalgia symptoms often increase with physical activity, counsel patients to begin with a few minutes daily and increase very slowly each week.

 

Lifestyle changes are as important as medications in controlling fibromyalgia symptoms. In addition to exercise, recommend that patients:

• follow a daily routine
  
• pace activity to avoid exacerbating symptoms
  
• reduce stress.
  

Sometimes, I use the analogy of diabetes: treating fibromyalgia with medication but without changing lifestyle is like prescribing medication for a diabetic patient without changing diet. Follow up on this “homework” at each visit to reinforce that patients helping themselves is an important part of treatment.

Box

New direction with medications

Pregabalin is an anticonvulsant that binds to the alpha-2-delta subunits of neurons’ voltage-gated calcium channels. This activity reduces calcium influx at nerve terminals and inhibits release of excitatory neurotransmitters, such as substance P and glutamate.¹⁸ In June 2007, pregabalin was the first medication FDA-approved for fibromyalgia.

Two placebo-controlled trials^19,20 showed that pregabalin at 150 mg bid, 225 mg bid, or 300 mg bid significantly reduced weekly mean pain scores in fibromyalgia patients. Click here for details of these trials. The most common side effects—dizziness, somnolence, peripheral edema, blurred vision, and weight gain—were regarded as mild to moderate in 87% of patients.²¹

Although a dosage of 300 mg bid also was studied, the FDA approved pregabalin at dosages of 150 mg bid and 225 mg bid for fibromyalgia.²²

Duloxetine is a serotonin/norepinephrine reuptake inhibitor (SNRI) thought to inhibit dorsal horn neurons’ response to peripheral pain signals by increasing serotonin and norepinephrine in the brain and spinal cord. This SNRI was first FDA-approved for diabetic peripheral neuropathic pain and major depressive disorder. Approval for fibromyalgia at 60 mg/d in June 2008 was based on 2 placebo-controlled, double-blind, 12-week trials comprising 874 patients.^23,24Click here for detailed findings of these studies and a 6-month fixed-dose trial.²⁵

In clinical trials, duloxetine dosages of 60 mg/d and 120 mg/d were significantly more effective than placebo. The most common side effects were nausea, constipation, excessive sweating, and somnolence.^23-25

Milnacipran is an SNRI that was approved for treating fibromyalgia in January 2009 at dosages of 50 mg bid and 100 mg bid. Like other SNRIs, milnacipran is thought to work by inhibiting pain signals through increasing serotonin and norepinephrine in the brain and spinal cord. Milnacipran has a higher selectivity for norepinephrine reuptake compared with duloxetine, which may mean these medications will have different effects in different patients. Although milnacipran is approved as an antidepressant in other countries, the FDA has not approved it for treating depression in the United States.

Click here for details of a 15-week, double-blind, placebo-controlled trial of milnacipran in patients with fibromyalgia. Side effects in clinical trials were similar to those of duloxetine, with nausea, constipation, and increased sweating being most prominent.²⁶

 

Other medications, such as the first-line agent amitriptyline, have shown beneficial effects in fibromyalgia but are not FDA-approved for this indication (Table 4).^27-32

Choosing medications. When prescribing one of the FDA-approved medications to treat fibromyalgia, consider their benefits and side effects.

Pregabalin may be a beneficial first choice for patients who report pain and sleep as major issues. Although the medication’s label recommends starting with twice-daily dosing, patients might better tolerate an initial dose of 50 to 75 mg in the evening, with the morning dose added later. Pregabalin can be useful in patients taking multiple medications because of its renal clearance, resulting in low risk of interactions with drugs metabolized by liver enzymes. It also can be useful in patients who have not tolerated antidepressants in the past or in whom antidepressants are contraindicated.

If a patient has a history of depression or discontinuing medications because of sedating side effects, an antidepressant such as duloxetine or milnacipran may be more successful than starting with pregabalin. In general, if a patient does not respond to one of these SNRIs, moving on to the other might help. Milnacipran’s more selective effect on norepinephrine could be beneficial for some patients, especially those with excessive fatigue. Others, especially those with a high level of anxiety, might respond better to a more balanced SNRI such as duloxetine.

Table 4

Off-label medications shown to benefit patients with fibromyalgia

Drug	Comment
Amitriptyline27,28	Considered first-line because of studies supporting its use, low cost, and wide availability; may be associated with more side effects than newer medications
Gabapentin29	Possible alternative to pregabalin but may not be as well tolerated
Tramadol30	May help with breakthrough pain; use with extreme caution in patients taking antidepressants because of serotonin syndrome risk
Fluoxetine31	Dosages of 40 to 60 mg/d may help patients who do not tolerate SNRIs
Venlafaxine32	Dosages of 150 to 225 mg/d may be an alternative to other SNRIs
SNRIs: serotonin/norepinephrine reuptake inhibitors

CASE CONTINUED: Not as hopeless

Ms. D’s primary care physician confirms your presumptive diagnosis of fibromyalgia. He prescribes a trial of amitriptyline, which she does not tolerate well because of sedation and weight gain. At her next psychiatric visit, she tells you she remains very frustrated about her physical symptoms and reports that her doctor “has given up on me.”

You discuss what a fibromyalgia diagnosis means to her and educate her about the syndrome. You refer her to a colleague who does CBT with chronic pain patients and start her on a low dose of duloxetine (30 mg once daily) to minimize side effects. You discuss possible side effects and that she may need a higher dose to notice improvement in her pain. She seems receptive to starting a graded exercise program, and you encourage her to reduce physical and emotional stress in her life.

When she returns, she reports her pain is somewhat improved and medication side effects have subsided. She is not as hopeless and tells you she is up to 10 minutes of walking daily. You increase duloxetine to 60 mg/d and reinforce her ability to exercise and manage her stress.

Related Resources

• Arthritis Foundation. Fibromyalgia. www.arthritis.org/disease-center.php?disease_id=10.
  
• National Fibromyalgia Association. www.fmaware.org.
  
• Self-management program for patients with fibromyalgia, cosponsored by the National Fibromyalgia Association and Eli Lilly and Company. www.knowfibro.com.
  

Drug Brand Names

• Amitriptyline • Elavil, Endep
  
• Cyclobenzaprine • Flexeril
  
• Duloxetine • Cymbalta
  
• Fluoxetine • Prozac
  
• Gabapentin • Neurontin
  
• Milnacipran • Savella
  
• Pregabalin • Lyrica
  
• Tramadol • Ultram, Ultracet
  
• Venlafaxine • Effexor, Effexor XR
  

Disclosure

Dr. Stanford receives grant/research support from Eli Lilly and Company, Pfizer, Cypress Bioscience, and Allergan.

WEB AUDIO
Listen to Dr. Stanford discuss,
"Is fibromyalgia a somatoform disorder?

Comment on this article

Patients with fibromyalgia are a heterogeneous group, yet many describe a common experience: seeing multiple physicians who seem unable or unwilling to provide a diagnosis or treat their symptoms. This situation may be changing with the recent FDA approval of an anticonvulsant and 2 antidepressants for managing fibromyalgia symptoms.

These medications—pregabalin, duloxetine, and milnacipran—reflect a revised understanding of fibromyalgia as a CNS condition, rather than an inflammatory process in the muscles or connective tissue. As a result, psychiatrists—because of our experience with CNS phenomena and managing antidepressant and anticonvulsant medications—are likely to play a larger role in treating fibromyalgia.

CASE REPORT: ‘Just too tired’

Ms. D, age 50, has a history of migraine headaches and is referred by her primary physician for evaluation of depression and anxiety. She reports deteriorating mood over 6 months, beginning when a minor car accident left her “very sore the next day.”

“Nothing helps” the persistent pain in her back, shoulders, and thighs, which she rates as 7 to 8 on a 0-to-10 pain scale. She describes an intense ache, “like having the flu,” that worsens with activity and in stressful situations. She also experiences nausea and intermittent diarrhea, debilitating fatigue, and sleep disturbance.

Ms. D reports she is depressed because she feels “just too tired” after work to keep up with social activities or housework. Her physician’s referral notes a normal physical exam except for tenderness over her upper back and hips. Laboratory testing is negative.

Making the diagnosis

American College of Rheumatology (ACR) criteria for fibromyalgia require widespread pain for at least 3 months. “Widespread” is defined as pain in the axial skeleton, left and right sides of the body, and above and below the waist. Pain must be found in at least 11 of 18 tender point sites on digital palpation using a force of approximately 4 kg/cm².¹ For many fibromyalgia patients, however, musculoskeletal pain is not their most problematic symptom (Table 1). They may suffer:

• migraine and tension headaches (10% to 80% of patients)
  
• irritable bowel syndrome (32% to 80%)²
  
• mood disorders (major depressive disorder [62%], bipolar disorder [11%])
  
• anxiety disorders (panic disorder [29%], posttraumatic stress disorder [21%], social phobia [19%]).³
  

ACR criteria are useful in research but lack many common symptoms and comorbidities. A structured interview that follows the DSM-IV-TR format incorporates other symptoms into the diagnosis (Table 2).⁴

Because patients with fibromyalgia often meet criteria for somatization or somatoform disorders, how to classify them—as medically or psychiatrically ill—is controversial. Some patients believe their mood or anxiety problem stems from the difficulty they experience dealing with their physical symptoms, and if they could feel better physically they would not be depressed or anxious. Others believe their psychiatric symptoms impede their ability to help themselves feel better.

Consider fibromyalgia in any patient with widespread pain of unknown cause. Before making the diagnosis, rule out other illnesses that present with similar symptoms (Table 3). Because many patients newly diagnosed with fibromyalgia worry that something “more serious” may be going on, confirm the diagnosis with appropriate testing and physical examination, usually by a rheumatologist or primary care physician.

Table 1

Medical and cognitive symptoms related to fibromyalgia

Neurologic Tension/migraine headache
Psychiatric Memory and cognitive difficulties Mood disturbance Anxiety disorders
Ear, nose, throat Sicca symptoms Vasomotor rhinitis Vestibular complaints
Cardiovascular Neurally mediated hypotension Mitral valve prolapse Noncardiac chest pain
Gastrointestinal Esophageal dysmotility Irritable bowel syndrome
Urological Interstitial cystitis
Gynecological Vulvodynia Chronic pelvic pain
Oral/dental Temporomandibular joint syndrome
Other (general) Chronic fatigue syndrome Sleep disturbances Idiopathic low back pain Multiple chemical sensitivity

Table 2

Fibromyalgia: Structured interview for diagnosis

A. Generalized pain affecting the axial, plus upper and lower segments, plus left and rights sides of the body
Either B or C:
B. At least 11 of 18 reproducible tender points
C. At least 4 of the following symptoms: Generalized fatigue Headaches Sleep disturbance Neuropsychiatric complaints Numbness, tingling sensations Irritable bowel symptoms
D. It cannot be established that disturbance was due to another systematic condition
Source: Reference 4

Table 3

Differentiating fibromyalgia from illnesses with similar symptoms

Illness	Tests to differentiate from primary fibromyalgia
Rheumatic diseases Osteoarthritis Spondyloarthropathies, rheumatoid arthritis Systemic lupus erythematosus, polymyalgia rheumatica Osteomalacia Myopathy	Radiographs Rheumatic markers (antinuclear antibody, rheumatoid factor, antibodies) Inflammatory markers (ESR, C-reactive protein) Vitamin D level CPK
Neurologic Multiple sclerosis, Chiari’s malformation, spinal stenosis, radiculopathy Neuropathy	MRI EMG
Endocrine Hypothyroidism Diabetes	TSH Basic chemistry panel with fasting glucose
Other Infectious   Lyme disease   Hepatitis Anemia Cancers	CBC Lyme titer Hepatitis antibody panel, liver function tests Hemoglobin/hematocrit Routine cancer screening tests, bone scan, blood chemistries specific for suspected primary cancer
ESR: erythrocyte sedimentation rate; CPK: creatine phosphokinase; EMG: electromyography; TSH: thyroid-stimulating hormone; CBC: complete blood count

 

CASE CONTINUED: Central pain sensitization

As you elicit more details about Ms. D’s mood, she continues to focus on her physical symptoms. She states that some days she wishes to die because her pain gets so bad, but she denies any plan or intent to harm herself. She worries that her symptoms will worsen and that she will become completely disabled.

Her primary physician attempted to relieve Ms. D’s pain with multiple trials of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclobenzaprine. She says she gained no benefit from the NSAIDs and discontinued the muscle relaxant because it made her too sleepy. Fibromyalgia affects 3.5% of women and 0.5% of men.⁵ It runs in families with histories of fibromyalgia and major mood and anxiety disorders, suggesting genetic links.⁶ Defects in genes controlling serotonin and norepinephrine have been implicated.^7-9

Fibromyalgia patients show lower levels of serotonin, norepinephrine, and dopamine metabolites in cerebrospinal fluid (CSF), compared with controls.¹⁰ These neurotransmitters may inhibit descending pain pathways in the CNS, and low levels in the brain and spinal cord may inhibit CNS regulation of pain impulses from the periphery.¹¹

Although many patients describe muscle pain, evidence suggests central pain augmentation rather than an abnormality of muscle or connective tissue.¹² Some studies have found evidence of “windup,” in which second-order neurons in the spinal cord become sensitized by repeated signals from first-order neurons in the periphery, resulting in amplified and prolonged pain signals traveling to the brain.¹³

Levels of substance P—a primary transmitter of pain impulses—are significantly higher in CSF of fibromyalgia patients compared with controls.¹⁴ This finding, in addition to low levels of serotonin and norepinephrine, indicates that pain signals are ascending unchecked to be processed by the brain.

Neuroimaging studies confirm this observation. In a study using functional magnetic resonance imaging (fMRI), researchers applied pressure to the thumbnails of fibromyalgia patients and controls until each subject reported pain:

• Twice as much pressure was required before controls rated their pain at a level similar to that of fibromyalgia patients.
  
• When controls and fibromyalgia patients reported similar pain, a very high degree of overlap was seen in brain areas responsible for pain processing. This indicates that fibromyalgia patients and controls were experiencing the pain they reported in the same way.¹⁵
  

Treating the whole patient

As a clinician who specializes in fibromyalgia, I counteract my patients’ and my own frustration with this condition by structuring office visits, determining realistic treatment goals, and treating all symptoms as part of a common syndrome rather than individual illnesses.

Structure office visits. Before every visit, have patients rate each symptom domain and write their top 2 or 3 concerns for that day (Click here for a sample form). Focusing on the patient’s most troublesome symptoms can help both of you feel greater satisfaction with treatment.

Educate patients. Ask them to discuss their beliefs about fibromyalgia; many know others with this condition or have researched diagnosis and treatment. Before developing a treatment plan, explain that their symptoms are chronic and all part of the same syndrome. Describe their pain as a complex phenomenon with possible peripheral and CNS components. Guide them to reputable Web sites and resources (see Related Resources).

Set realistic expectations. Many patients expect to resume an energetic and pain-free life, which usually is not the case with fibromyalgia (Box). Most medications are considered successful if they reduce pain by 30% to 50%, and side effects can be problematic. Discuss side effects before treatment begins to reduce patients’ anxiety and improve compliance in the first weeks.

Cognitive-behavioral therapy (CBT) for fibromyalgia incorporates relaxation techniques, helping patients view symptoms as manageable, reinforcing adaptive coping skills, and teaching them how to monitor thoughts, feelings, and behavior to change the view that they are helpless victims. A modest course of 6 weekly group CBT sessions significantly improved physical functioning in 25% of fibromyalgia patients (n=76) compared with 12% in a standard-care group (n=69), even though patients’ pain severity did not improve.¹⁶

Recommend exercise, lifestyle changes. Aerobic exercise can significantly improve well-being and physical functioning in fibromyalgia patients.¹⁷ Low-impact aerobics, such as done in warm water, usually are well tolerated, although any low-impact exercise can help. Because fibromyalgia symptoms often increase with physical activity, counsel patients to begin with a few minutes daily and increase very slowly each week.

 

Lifestyle changes are as important as medications in controlling fibromyalgia symptoms. In addition to exercise, recommend that patients:

• follow a daily routine
  
• pace activity to avoid exacerbating symptoms
  
• reduce stress.
  

Sometimes, I use the analogy of diabetes: treating fibromyalgia with medication but without changing lifestyle is like prescribing medication for a diabetic patient without changing diet. Follow up on this “homework” at each visit to reinforce that patients helping themselves is an important part of treatment.

Box

New direction with medications

Pregabalin is an anticonvulsant that binds to the alpha-2-delta subunits of neurons’ voltage-gated calcium channels. This activity reduces calcium influx at nerve terminals and inhibits release of excitatory neurotransmitters, such as substance P and glutamate.¹⁸ In June 2007, pregabalin was the first medication FDA-approved for fibromyalgia.

Two placebo-controlled trials^19,20 showed that pregabalin at 150 mg bid, 225 mg bid, or 300 mg bid significantly reduced weekly mean pain scores in fibromyalgia patients. Click here for details of these trials. The most common side effects—dizziness, somnolence, peripheral edema, blurred vision, and weight gain—were regarded as mild to moderate in 87% of patients.²¹

Although a dosage of 300 mg bid also was studied, the FDA approved pregabalin at dosages of 150 mg bid and 225 mg bid for fibromyalgia.²²

Duloxetine is a serotonin/norepinephrine reuptake inhibitor (SNRI) thought to inhibit dorsal horn neurons’ response to peripheral pain signals by increasing serotonin and norepinephrine in the brain and spinal cord. This SNRI was first FDA-approved for diabetic peripheral neuropathic pain and major depressive disorder. Approval for fibromyalgia at 60 mg/d in June 2008 was based on 2 placebo-controlled, double-blind, 12-week trials comprising 874 patients.^23,24Click here for detailed findings of these studies and a 6-month fixed-dose trial.²⁵

In clinical trials, duloxetine dosages of 60 mg/d and 120 mg/d were significantly more effective than placebo. The most common side effects were nausea, constipation, excessive sweating, and somnolence.^23-25

Milnacipran is an SNRI that was approved for treating fibromyalgia in January 2009 at dosages of 50 mg bid and 100 mg bid. Like other SNRIs, milnacipran is thought to work by inhibiting pain signals through increasing serotonin and norepinephrine in the brain and spinal cord. Milnacipran has a higher selectivity for norepinephrine reuptake compared with duloxetine, which may mean these medications will have different effects in different patients. Although milnacipran is approved as an antidepressant in other countries, the FDA has not approved it for treating depression in the United States.

Click here for details of a 15-week, double-blind, placebo-controlled trial of milnacipran in patients with fibromyalgia. Side effects in clinical trials were similar to those of duloxetine, with nausea, constipation, and increased sweating being most prominent.²⁶

 

Other medications, such as the first-line agent amitriptyline, have shown beneficial effects in fibromyalgia but are not FDA-approved for this indication (Table 4).^27-32

Choosing medications. When prescribing one of the FDA-approved medications to treat fibromyalgia, consider their benefits and side effects.

Pregabalin may be a beneficial first choice for patients who report pain and sleep as major issues. Although the medication’s label recommends starting with twice-daily dosing, patients might better tolerate an initial dose of 50 to 75 mg in the evening, with the morning dose added later. Pregabalin can be useful in patients taking multiple medications because of its renal clearance, resulting in low risk of interactions with drugs metabolized by liver enzymes. It also can be useful in patients who have not tolerated antidepressants in the past or in whom antidepressants are contraindicated.

If a patient has a history of depression or discontinuing medications because of sedating side effects, an antidepressant such as duloxetine or milnacipran may be more successful than starting with pregabalin. In general, if a patient does not respond to one of these SNRIs, moving on to the other might help. Milnacipran’s more selective effect on norepinephrine could be beneficial for some patients, especially those with excessive fatigue. Others, especially those with a high level of anxiety, might respond better to a more balanced SNRI such as duloxetine.

Table 4

Off-label medications shown to benefit patients with fibromyalgia

Drug	Comment
Amitriptyline27,28	Considered first-line because of studies supporting its use, low cost, and wide availability; may be associated with more side effects than newer medications
Gabapentin29	Possible alternative to pregabalin but may not be as well tolerated
Tramadol30	May help with breakthrough pain; use with extreme caution in patients taking antidepressants because of serotonin syndrome risk
Fluoxetine31	Dosages of 40 to 60 mg/d may help patients who do not tolerate SNRIs
Venlafaxine32	Dosages of 150 to 225 mg/d may be an alternative to other SNRIs
SNRIs: serotonin/norepinephrine reuptake inhibitors

CASE CONTINUED: Not as hopeless

Ms. D’s primary care physician confirms your presumptive diagnosis of fibromyalgia. He prescribes a trial of amitriptyline, which she does not tolerate well because of sedation and weight gain. At her next psychiatric visit, she tells you she remains very frustrated about her physical symptoms and reports that her doctor “has given up on me.”

You discuss what a fibromyalgia diagnosis means to her and educate her about the syndrome. You refer her to a colleague who does CBT with chronic pain patients and start her on a low dose of duloxetine (30 mg once daily) to minimize side effects. You discuss possible side effects and that she may need a higher dose to notice improvement in her pain. She seems receptive to starting a graded exercise program, and you encourage her to reduce physical and emotional stress in her life.

When she returns, she reports her pain is somewhat improved and medication side effects have subsided. She is not as hopeless and tells you she is up to 10 minutes of walking daily. You increase duloxetine to 60 mg/d and reinforce her ability to exercise and manage her stress.

Related Resources

• Arthritis Foundation. Fibromyalgia. www.arthritis.org/disease-center.php?disease_id=10.
  
• National Fibromyalgia Association. www.fmaware.org.
  
• Self-management program for patients with fibromyalgia, cosponsored by the National Fibromyalgia Association and Eli Lilly and Company. www.knowfibro.com.
  

Drug Brand Names

• Amitriptyline • Elavil, Endep
  
• Cyclobenzaprine • Flexeril
  
• Duloxetine • Cymbalta
  
• Fluoxetine • Prozac
  
• Gabapentin • Neurontin
  
• Milnacipran • Savella
  
• Pregabalin • Lyrica
  
• Tramadol • Ultram, Ultracet
  
• Venlafaxine • Effexor, Effexor XR
  

Disclosure

Dr. Stanford receives grant/research support from Eli Lilly and Company, Pfizer, Cypress Bioscience, and Allergan.

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"Is fibromyalgia a somatoform disorder?

Comment on this article

Patients with fibromyalgia are a heterogeneous group, yet many describe a common experience: seeing multiple physicians who seem unable or unwilling to provide a diagnosis or treat their symptoms. This situation may be changing with the recent FDA approval of an anticonvulsant and 2 antidepressants for managing fibromyalgia symptoms.

These medications—pregabalin, duloxetine, and milnacipran—reflect a revised understanding of fibromyalgia as a CNS condition, rather than an inflammatory process in the muscles or connective tissue. As a result, psychiatrists—because of our experience with CNS phenomena and managing antidepressant and anticonvulsant medications—are likely to play a larger role in treating fibromyalgia.

CASE REPORT: ‘Just too tired’

Ms. D, age 50, has a history of migraine headaches and is referred by her primary physician for evaluation of depression and anxiety. She reports deteriorating mood over 6 months, beginning when a minor car accident left her “very sore the next day.”

“Nothing helps” the persistent pain in her back, shoulders, and thighs, which she rates as 7 to 8 on a 0-to-10 pain scale. She describes an intense ache, “like having the flu,” that worsens with activity and in stressful situations. She also experiences nausea and intermittent diarrhea, debilitating fatigue, and sleep disturbance.

Ms. D reports she is depressed because she feels “just too tired” after work to keep up with social activities or housework. Her physician’s referral notes a normal physical exam except for tenderness over her upper back and hips. Laboratory testing is negative.

Making the diagnosis

American College of Rheumatology (ACR) criteria for fibromyalgia require widespread pain for at least 3 months. “Widespread” is defined as pain in the axial skeleton, left and right sides of the body, and above and below the waist. Pain must be found in at least 11 of 18 tender point sites on digital palpation using a force of approximately 4 kg/cm².¹ For many fibromyalgia patients, however, musculoskeletal pain is not their most problematic symptom (Table 1). They may suffer:

• migraine and tension headaches (10% to 80% of patients)
  
• irritable bowel syndrome (32% to 80%)²
  
• mood disorders (major depressive disorder [62%], bipolar disorder [11%])
  
• anxiety disorders (panic disorder [29%], posttraumatic stress disorder [21%], social phobia [19%]).³
  

ACR criteria are useful in research but lack many common symptoms and comorbidities. A structured interview that follows the DSM-IV-TR format incorporates other symptoms into the diagnosis (Table 2).⁴

Because patients with fibromyalgia often meet criteria for somatization or somatoform disorders, how to classify them—as medically or psychiatrically ill—is controversial. Some patients believe their mood or anxiety problem stems from the difficulty they experience dealing with their physical symptoms, and if they could feel better physically they would not be depressed or anxious. Others believe their psychiatric symptoms impede their ability to help themselves feel better.

Consider fibromyalgia in any patient with widespread pain of unknown cause. Before making the diagnosis, rule out other illnesses that present with similar symptoms (Table 3). Because many patients newly diagnosed with fibromyalgia worry that something “more serious” may be going on, confirm the diagnosis with appropriate testing and physical examination, usually by a rheumatologist or primary care physician.

Table 1

Medical and cognitive symptoms related to fibromyalgia

Neurologic Tension/migraine headache
Psychiatric Memory and cognitive difficulties Mood disturbance Anxiety disorders
Ear, nose, throat Sicca symptoms Vasomotor rhinitis Vestibular complaints
Cardiovascular Neurally mediated hypotension Mitral valve prolapse Noncardiac chest pain
Gastrointestinal Esophageal dysmotility Irritable bowel syndrome
Urological Interstitial cystitis
Gynecological Vulvodynia Chronic pelvic pain
Oral/dental Temporomandibular joint syndrome
Other (general) Chronic fatigue syndrome Sleep disturbances Idiopathic low back pain Multiple chemical sensitivity

Table 2

Fibromyalgia: Structured interview for diagnosis

A. Generalized pain affecting the axial, plus upper and lower segments, plus left and rights sides of the body
Either B or C:
B. At least 11 of 18 reproducible tender points
C. At least 4 of the following symptoms: Generalized fatigue Headaches Sleep disturbance Neuropsychiatric complaints Numbness, tingling sensations Irritable bowel symptoms
D. It cannot be established that disturbance was due to another systematic condition
Source: Reference 4

Table 3

Differentiating fibromyalgia from illnesses with similar symptoms

Illness	Tests to differentiate from primary fibromyalgia
Rheumatic diseases Osteoarthritis Spondyloarthropathies, rheumatoid arthritis Systemic lupus erythematosus, polymyalgia rheumatica Osteomalacia Myopathy	Radiographs Rheumatic markers (antinuclear antibody, rheumatoid factor, antibodies) Inflammatory markers (ESR, C-reactive protein) Vitamin D level CPK
Neurologic Multiple sclerosis, Chiari’s malformation, spinal stenosis, radiculopathy Neuropathy	MRI EMG
Endocrine Hypothyroidism Diabetes	TSH Basic chemistry panel with fasting glucose
Other Infectious   Lyme disease   Hepatitis Anemia Cancers	CBC Lyme titer Hepatitis antibody panel, liver function tests Hemoglobin/hematocrit Routine cancer screening tests, bone scan, blood chemistries specific for suspected primary cancer
ESR: erythrocyte sedimentation rate; CPK: creatine phosphokinase; EMG: electromyography; TSH: thyroid-stimulating hormone; CBC: complete blood count

 

CASE CONTINUED: Central pain sensitization

As you elicit more details about Ms. D’s mood, she continues to focus on her physical symptoms. She states that some days she wishes to die because her pain gets so bad, but she denies any plan or intent to harm herself. She worries that her symptoms will worsen and that she will become completely disabled.

Her primary physician attempted to relieve Ms. D’s pain with multiple trials of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclobenzaprine. She says she gained no benefit from the NSAIDs and discontinued the muscle relaxant because it made her too sleepy. Fibromyalgia affects 3.5% of women and 0.5% of men.⁵ It runs in families with histories of fibromyalgia and major mood and anxiety disorders, suggesting genetic links.⁶ Defects in genes controlling serotonin and norepinephrine have been implicated.^7-9

Fibromyalgia patients show lower levels of serotonin, norepinephrine, and dopamine metabolites in cerebrospinal fluid (CSF), compared with controls.¹⁰ These neurotransmitters may inhibit descending pain pathways in the CNS, and low levels in the brain and spinal cord may inhibit CNS regulation of pain impulses from the periphery.¹¹

Although many patients describe muscle pain, evidence suggests central pain augmentation rather than an abnormality of muscle or connective tissue.¹² Some studies have found evidence of “windup,” in which second-order neurons in the spinal cord become sensitized by repeated signals from first-order neurons in the periphery, resulting in amplified and prolonged pain signals traveling to the brain.¹³

Levels of substance P—a primary transmitter of pain impulses—are significantly higher in CSF of fibromyalgia patients compared with controls.¹⁴ This finding, in addition to low levels of serotonin and norepinephrine, indicates that pain signals are ascending unchecked to be processed by the brain.

Neuroimaging studies confirm this observation. In a study using functional magnetic resonance imaging (fMRI), researchers applied pressure to the thumbnails of fibromyalgia patients and controls until each subject reported pain:

• Twice as much pressure was required before controls rated their pain at a level similar to that of fibromyalgia patients.
  
• When controls and fibromyalgia patients reported similar pain, a very high degree of overlap was seen in brain areas responsible for pain processing. This indicates that fibromyalgia patients and controls were experiencing the pain they reported in the same way.¹⁵
  

Treating the whole patient

As a clinician who specializes in fibromyalgia, I counteract my patients’ and my own frustration with this condition by structuring office visits, determining realistic treatment goals, and treating all symptoms as part of a common syndrome rather than individual illnesses.

Structure office visits. Before every visit, have patients rate each symptom domain and write their top 2 or 3 concerns for that day (Click here for a sample form). Focusing on the patient’s most troublesome symptoms can help both of you feel greater satisfaction with treatment.

Educate patients. Ask them to discuss their beliefs about fibromyalgia; many know others with this condition or have researched diagnosis and treatment. Before developing a treatment plan, explain that their symptoms are chronic and all part of the same syndrome. Describe their pain as a complex phenomenon with possible peripheral and CNS components. Guide them to reputable Web sites and resources (see Related Resources).

Set realistic expectations. Many patients expect to resume an energetic and pain-free life, which usually is not the case with fibromyalgia (Box). Most medications are considered successful if they reduce pain by 30% to 50%, and side effects can be problematic. Discuss side effects before treatment begins to reduce patients’ anxiety and improve compliance in the first weeks.

Cognitive-behavioral therapy (CBT) for fibromyalgia incorporates relaxation techniques, helping patients view symptoms as manageable, reinforcing adaptive coping skills, and teaching them how to monitor thoughts, feelings, and behavior to change the view that they are helpless victims. A modest course of 6 weekly group CBT sessions significantly improved physical functioning in 25% of fibromyalgia patients (n=76) compared with 12% in a standard-care group (n=69), even though patients’ pain severity did not improve.¹⁶

Recommend exercise, lifestyle changes. Aerobic exercise can significantly improve well-being and physical functioning in fibromyalgia patients.¹⁷ Low-impact aerobics, such as done in warm water, usually are well tolerated, although any low-impact exercise can help. Because fibromyalgia symptoms often increase with physical activity, counsel patients to begin with a few minutes daily and increase very slowly each week.

 

Lifestyle changes are as important as medications in controlling fibromyalgia symptoms. In addition to exercise, recommend that patients:

• follow a daily routine
  
• pace activity to avoid exacerbating symptoms
  
• reduce stress.
  

Sometimes, I use the analogy of diabetes: treating fibromyalgia with medication but without changing lifestyle is like prescribing medication for a diabetic patient without changing diet. Follow up on this “homework” at each visit to reinforce that patients helping themselves is an important part of treatment.

Box

New direction with medications

Pregabalin is an anticonvulsant that binds to the alpha-2-delta subunits of neurons’ voltage-gated calcium channels. This activity reduces calcium influx at nerve terminals and inhibits release of excitatory neurotransmitters, such as substance P and glutamate.¹⁸ In June 2007, pregabalin was the first medication FDA-approved for fibromyalgia.

Two placebo-controlled trials^19,20 showed that pregabalin at 150 mg bid, 225 mg bid, or 300 mg bid significantly reduced weekly mean pain scores in fibromyalgia patients. Click here for details of these trials. The most common side effects—dizziness, somnolence, peripheral edema, blurred vision, and weight gain—were regarded as mild to moderate in 87% of patients.²¹

Although a dosage of 300 mg bid also was studied, the FDA approved pregabalin at dosages of 150 mg bid and 225 mg bid for fibromyalgia.²²

Duloxetine is a serotonin/norepinephrine reuptake inhibitor (SNRI) thought to inhibit dorsal horn neurons’ response to peripheral pain signals by increasing serotonin and norepinephrine in the brain and spinal cord. This SNRI was first FDA-approved for diabetic peripheral neuropathic pain and major depressive disorder. Approval for fibromyalgia at 60 mg/d in June 2008 was based on 2 placebo-controlled, double-blind, 12-week trials comprising 874 patients.^23,24Click here for detailed findings of these studies and a 6-month fixed-dose trial.²⁵

In clinical trials, duloxetine dosages of 60 mg/d and 120 mg/d were significantly more effective than placebo. The most common side effects were nausea, constipation, excessive sweating, and somnolence.^23-25

Milnacipran is an SNRI that was approved for treating fibromyalgia in January 2009 at dosages of 50 mg bid and 100 mg bid. Like other SNRIs, milnacipran is thought to work by inhibiting pain signals through increasing serotonin and norepinephrine in the brain and spinal cord. Milnacipran has a higher selectivity for norepinephrine reuptake compared with duloxetine, which may mean these medications will have different effects in different patients. Although milnacipran is approved as an antidepressant in other countries, the FDA has not approved it for treating depression in the United States.

Click here for details of a 15-week, double-blind, placebo-controlled trial of milnacipran in patients with fibromyalgia. Side effects in clinical trials were similar to those of duloxetine, with nausea, constipation, and increased sweating being most prominent.²⁶

 

Other medications, such as the first-line agent amitriptyline, have shown beneficial effects in fibromyalgia but are not FDA-approved for this indication (Table 4).^27-32

Choosing medications. When prescribing one of the FDA-approved medications to treat fibromyalgia, consider their benefits and side effects.

Pregabalin may be a beneficial first choice for patients who report pain and sleep as major issues. Although the medication’s label recommends starting with twice-daily dosing, patients might better tolerate an initial dose of 50 to 75 mg in the evening, with the morning dose added later. Pregabalin can be useful in patients taking multiple medications because of its renal clearance, resulting in low risk of interactions with drugs metabolized by liver enzymes. It also can be useful in patients who have not tolerated antidepressants in the past or in whom antidepressants are contraindicated.

If a patient has a history of depression or discontinuing medications because of sedating side effects, an antidepressant such as duloxetine or milnacipran may be more successful than starting with pregabalin. In general, if a patient does not respond to one of these SNRIs, moving on to the other might help. Milnacipran’s more selective effect on norepinephrine could be beneficial for some patients, especially those with excessive fatigue. Others, especially those with a high level of anxiety, might respond better to a more balanced SNRI such as duloxetine.

Table 4

Off-label medications shown to benefit patients with fibromyalgia

Drug	Comment
Amitriptyline27,28	Considered first-line because of studies supporting its use, low cost, and wide availability; may be associated with more side effects than newer medications
Gabapentin29	Possible alternative to pregabalin but may not be as well tolerated
Tramadol30	May help with breakthrough pain; use with extreme caution in patients taking antidepressants because of serotonin syndrome risk
Fluoxetine31	Dosages of 40 to 60 mg/d may help patients who do not tolerate SNRIs
Venlafaxine32	Dosages of 150 to 225 mg/d may be an alternative to other SNRIs
SNRIs: serotonin/norepinephrine reuptake inhibitors

CASE CONTINUED: Not as hopeless

Ms. D’s primary care physician confirms your presumptive diagnosis of fibromyalgia. He prescribes a trial of amitriptyline, which she does not tolerate well because of sedation and weight gain. At her next psychiatric visit, she tells you she remains very frustrated about her physical symptoms and reports that her doctor “has given up on me.”

You discuss what a fibromyalgia diagnosis means to her and educate her about the syndrome. You refer her to a colleague who does CBT with chronic pain patients and start her on a low dose of duloxetine (30 mg once daily) to minimize side effects. You discuss possible side effects and that she may need a higher dose to notice improvement in her pain. She seems receptive to starting a graded exercise program, and you encourage her to reduce physical and emotional stress in her life.

When she returns, she reports her pain is somewhat improved and medication side effects have subsided. She is not as hopeless and tells you she is up to 10 minutes of walking daily. You increase duloxetine to 60 mg/d and reinforce her ability to exercise and manage her stress.

Related Resources

• Arthritis Foundation. Fibromyalgia. www.arthritis.org/disease-center.php?disease_id=10.
  
• National Fibromyalgia Association. www.fmaware.org.
  
• Self-management program for patients with fibromyalgia, cosponsored by the National Fibromyalgia Association and Eli Lilly and Company. www.knowfibro.com.
  

Drug Brand Names

• Amitriptyline • Elavil, Endep
  
• Cyclobenzaprine • Flexeril
  
• Duloxetine • Cymbalta
  
• Fluoxetine • Prozac
  
• Gabapentin • Neurontin
  
• Milnacipran • Savella
  
• Pregabalin • Lyrica
  
• Tramadol • Ultram, Ultracet
  
• Venlafaxine • Effexor, Effexor XR
  

Disclosure

Dr. Stanford receives grant/research support from Eli Lilly and Company, Pfizer, Cypress Bioscience, and Allergan.

Comment on this article

Oral habits such as bruxism—compulsive grinding or clenching of the teeth—can be a manifestation of obsessive-compulsive disorder (OCD) and other anxiety disorders.¹ Bruxism also may be a side effect of selective serotonin reuptake inhibitors (SSRIs)^2,3 used to treat OCD⁴ and depression. Other oral conditions can complicate treatment of these disorders (Table 1).

Potentially serious sequelae of bruxism and similar behaviors include:

• wearing down of teeth (more common)
• necrosis of the pulpal tissues that results in non-vital teeth (less common).

The following case underlines the need for early referral to a dentist and close follow-up for patients who have tooth-related behaviors or are taking medications associated with a risk for such behaviors.

Table 1

Oral conditions associated with anxiety disorders and depression

Bruxism
Canker sores
Dry mouth
Temporomandibular joint disorders
Lichen planus (redness or mouth ulcers)
Non-vital teeth
Tooth wear, fracture

CASE REPORT: A compulsive oral habit

Mr. G, age 26, presents to our school of dental medicine with the chief complaint that he needs a crown. On clinical intraoral examination, we find he has multiple restorations, some areas of recurrent tooth decay, and a fractured cusp on a maxillary molar. His mandibular incisors show greater wear on their incisal surfaces than would be expected for a patient his age. This is especially true of his mandibular right lateral incisor (tooth #26) and canine (tooth #27) (Photo 1).

Clinical examination also reveals a restoration on tooth #26 that was consistent with an access cavity drilled for endodontic (root canal) therapy (Photo 2). This finding is consistent with his dental history. Soft tissue examination is within normal limits. He reports that he saw a dentist 7 months earlier but could not afford the fees.

During his medical history, Mr. G states he has mild Tourette’s syndrome that was diagnosed when he was 10. In the early 1990s he tried several medications, including haloperidol and pimozide, as a subject in research studies of Tourette’s. He could not recall the dosages of the medications or for how long he took them. Because these medications did not improve his symptoms, he stopped taking them after the studies ended.

Photo 1 Unexpected tooth wear: A clue to an anxiety-related oral habit

Teeth of a 26-year-old man show greater than expected wear, particularly on the mandibular right lateral incisor (tooth #26) and canine (tooth #27).

Photo 2 Radiographic evidence of tooth non-vitality

Radiolucencies (dark areas) in the bone at the apices of the tooth roots are a radiographic sign of non-vitality. Tooth #26 has undergone root canal.Mr. G reports that when he was in second grade, a psychiatrist diagnosed him with OCD, and has received treatment since then. We observe that while Mr. G is seated, he continually raises his right arm above his head and rubs his fingers together. He reports and demonstrates numerous other compulsive rituals, including head movements and rubbing his elbows against his side. His right elbow has a large scab.

He has been taking sertraline, 150 mg/d, for the past month. He says his psychiatrist prescribed this medication to help him break out of what he describes as episodes where he “gets into a mental loop.” Sertraline has improved Mr. G’s symptoms but they have not resolved.

He further reports that he has begun to “grind” his anterior teeth. Technically, he does not engage in grinding or bruxing; he has a habit of pushing his mandible forward so that his mandibular (lower) teeth are anterior to the maxillary (top) teeth, then forcefully pulling his mandible back so that the lingual (back) surfaces of the mandibular incisors push up against the buccal (outside) surfaces of the maxillary incisors (Photo 3). He states that he engaged in this habit frequently from approximately age 19 to 22. When Mr. G was 22, his dentist reduced the height of tooth #23, which Mr. G says he used “to set things in motion.” The dentist’s maneuver cut down but did not eliminate Mr. G’s habit.

Mr. G had not complained of nor had any clinician asked him about his bruxism-like behavior. He noted that the oral habit began prior to sertraline treatment, thus suggesting no relationship between the medication and the behavior. Interestingly, although some studies have reported bruxism as a side effect of SSRIs,^2,3 at least 1 case report found that SSRIs reduced nocturnal bruxism.¹²

Photo 3 Obsessive-compulsive disorder manifested in Mr. G’s oral habit

 

Starting with his mandible pushed forward so that his mandibular (lower) teeth were anterior to the maxillary (upper) teeth, the patient would forcefully pull his mandible back so that the lingual (back) surfaces of the mandibular incisors pushed against the buccal (outside) surfaces of the maxillary incisors.As part of Mr. G’s dental examination, we take a full series of intraoral radiographs. These reveal radiolucencies at the apices of teeth #23 through #26 (Photo 2). The films also show root canal therapy on tooth #26.

Differential diagnosis for lesions in the periapical region of the mandibular incisors includes periapical cemental dysplasia (PCD), which typically is found in middle-aged African-American females,⁵ and lesions resulting from non-vitality of the teeth. Histopathologically, lesions resulting from the latter include an apical abscess, cyst, or granuloma.

As is customary when periapical lesions are noted, we test the vitality of the affected teeth. None of the affected teeth responded to cold or electric pulp testing, which indicated they were non-vital. Tooth vitality is not affected in PCD, which allowed us to exclude this condition.

Non-vital teeth indicate that the pulpal tissue is necrotic. Most commonly, non-vitality occurs when decay has penetrated the pulp chamber or as a complication of physical trauma. No decay was present on Mr. G’s mandibular anterior teeth and he denied a history of trauma such as a blow to the teeth. This left his oral habit as the likely cause of non-vitality.

Treatment for a non-vital tooth is a root canal, which had been done on tooth #26. We successfully performed root canal on Mr. G’s other non-vital teeth. We informed the patient of reason for his non-vital teeth, and made a protective occlusal guard to try to prevent additional trauma to the affected teeth.

Recognizing oral habits

Restoration of worn teeth, particularly those of the mandibular anterior, is technically difficult and—depending on the nature of the restoration—quite expensive. Endodontic therapy is more successful in teeth without periapical disease.⁶ Thus, preventing tooth-related problems in patients who grind their teeth or engage in other destructive dental behaviors is important.

As this case illustrates, teeth can become non-vital without clinical evidence of tooth wear; clinical evidence may be subtle or nonexistent (note teeth #23, #24, and #25 in Photo 2). Absence of tooth wear is not a reliable sign of tooth vitality. Mild to moderate tooth wear usually goes unnoticed by patients and clinicians.⁷

Patients with bruxism may complain of masticatory muscle soreness or increased wear of the teeth.⁷ In extreme cases, they may self-extract teeth as a result of bruxism.⁸

Screen patients who have anxiety disorders or depression for signs of bruxism or related behaviors (Table 2). If you detect signs of bruxism or related behavior, refer the patient to a dentist. Ask the dentist to look for signs of wear and perform vitality testing of teeth on a regular basis (twice a year is reasonable). Any signs of changes in pulp vitality should be followed up with intraoral periapical radiographs, which these patients might need more frequently than FDA guidelines recommend.⁹

Table 2

Screening for bruxism: 3 questions for patients

1. Do you have pain or discomfort in the jaw or facial muscles, headaches or earaches, or increased tooth sensitivity?
2. Have you noticed changes in the way your teeth fit together or wearing down of your teeth?
3. Has your sleeping partner noticed any noise at night that might be the result of teeth grinding?

An occlusal guard may provide the most definitive tooth protection for patients who engage in bruxism or similar behaviors. Occlusal guards are made of material that is softer than enamel, so the patient will wear away the guard rather than tooth structure. When the guard is worn away, the patient needs a new one.

Pharmacologic strategies for bruxism or related oral habits involving the teeth are not well developed. One short-term, placebo-controlled trial for acute treatment in 10 drug-free patients with sleep bruxism consisted of a predrug night, a placebo night, and a clonazepam night. Clonazepam, 1 mg 30 minutes before bedtime, significantly improved bruxism and sleep quality as determined by objective and subjective measures.¹⁰

Kast¹¹ reported 4 cases in which tiagabine suppressed nocturnal bruxism, trismus, and consequent morning pain in the teeth, masticatory musculature, jaw, and temporomandibular joint areas. This gammaaminobutyric acid reuptake inhibitor anticonvulsant approved for treating partial seizures was dosed at 4 to 8 mg at bedtime. These dosages are lower than those used to treat seizures.

 

Related resources

• American Dental Association. www.ada.org.

Drug brand names

• Clonazepam • Klonopin
• Haloperidol • Haldol
• Pimozide • Orap
• Sertraline • Zoloft
• Tiagabine • Gabitril

Disclosure

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

Comment on this article

Oral habits such as bruxism—compulsive grinding or clenching of the teeth—can be a manifestation of obsessive-compulsive disorder (OCD) and other anxiety disorders.¹ Bruxism also may be a side effect of selective serotonin reuptake inhibitors (SSRIs)^2,3 used to treat OCD⁴ and depression. Other oral conditions can complicate treatment of these disorders (Table 1).

Potentially serious sequelae of bruxism and similar behaviors include:

• wearing down of teeth (more common)
• necrosis of the pulpal tissues that results in non-vital teeth (less common).

The following case underlines the need for early referral to a dentist and close follow-up for patients who have tooth-related behaviors or are taking medications associated with a risk for such behaviors.

Table 1

Oral conditions associated with anxiety disorders and depression

Bruxism
Canker sores
Dry mouth
Temporomandibular joint disorders
Lichen planus (redness or mouth ulcers)
Non-vital teeth
Tooth wear, fracture

CASE REPORT: A compulsive oral habit

Mr. G, age 26, presents to our school of dental medicine with the chief complaint that he needs a crown. On clinical intraoral examination, we find he has multiple restorations, some areas of recurrent tooth decay, and a fractured cusp on a maxillary molar. His mandibular incisors show greater wear on their incisal surfaces than would be expected for a patient his age. This is especially true of his mandibular right lateral incisor (tooth #26) and canine (tooth #27) (Photo 1).

Clinical examination also reveals a restoration on tooth #26 that was consistent with an access cavity drilled for endodontic (root canal) therapy (Photo 2). This finding is consistent with his dental history. Soft tissue examination is within normal limits. He reports that he saw a dentist 7 months earlier but could not afford the fees.

During his medical history, Mr. G states he has mild Tourette’s syndrome that was diagnosed when he was 10. In the early 1990s he tried several medications, including haloperidol and pimozide, as a subject in research studies of Tourette’s. He could not recall the dosages of the medications or for how long he took them. Because these medications did not improve his symptoms, he stopped taking them after the studies ended.

Photo 1 Unexpected tooth wear: A clue to an anxiety-related oral habit

Teeth of a 26-year-old man show greater than expected wear, particularly on the mandibular right lateral incisor (tooth #26) and canine (tooth #27).

Photo 2 Radiographic evidence of tooth non-vitality

Radiolucencies (dark areas) in the bone at the apices of the tooth roots are a radiographic sign of non-vitality. Tooth #26 has undergone root canal.Mr. G reports that when he was in second grade, a psychiatrist diagnosed him with OCD, and has received treatment since then. We observe that while Mr. G is seated, he continually raises his right arm above his head and rubs his fingers together. He reports and demonstrates numerous other compulsive rituals, including head movements and rubbing his elbows against his side. His right elbow has a large scab.

He has been taking sertraline, 150 mg/d, for the past month. He says his psychiatrist prescribed this medication to help him break out of what he describes as episodes where he “gets into a mental loop.” Sertraline has improved Mr. G’s symptoms but they have not resolved.

He further reports that he has begun to “grind” his anterior teeth. Technically, he does not engage in grinding or bruxing; he has a habit of pushing his mandible forward so that his mandibular (lower) teeth are anterior to the maxillary (top) teeth, then forcefully pulling his mandible back so that the lingual (back) surfaces of the mandibular incisors push up against the buccal (outside) surfaces of the maxillary incisors (Photo 3). He states that he engaged in this habit frequently from approximately age 19 to 22. When Mr. G was 22, his dentist reduced the height of tooth #23, which Mr. G says he used “to set things in motion.” The dentist’s maneuver cut down but did not eliminate Mr. G’s habit.

Mr. G had not complained of nor had any clinician asked him about his bruxism-like behavior. He noted that the oral habit began prior to sertraline treatment, thus suggesting no relationship between the medication and the behavior. Interestingly, although some studies have reported bruxism as a side effect of SSRIs,^2,3 at least 1 case report found that SSRIs reduced nocturnal bruxism.¹²

Photo 3 Obsessive-compulsive disorder manifested in Mr. G’s oral habit

 

Starting with his mandible pushed forward so that his mandibular (lower) teeth were anterior to the maxillary (upper) teeth, the patient would forcefully pull his mandible back so that the lingual (back) surfaces of the mandibular incisors pushed against the buccal (outside) surfaces of the maxillary incisors.As part of Mr. G’s dental examination, we take a full series of intraoral radiographs. These reveal radiolucencies at the apices of teeth #23 through #26 (Photo 2). The films also show root canal therapy on tooth #26.

Differential diagnosis for lesions in the periapical region of the mandibular incisors includes periapical cemental dysplasia (PCD), which typically is found in middle-aged African-American females,⁵ and lesions resulting from non-vitality of the teeth. Histopathologically, lesions resulting from the latter include an apical abscess, cyst, or granuloma.

As is customary when periapical lesions are noted, we test the vitality of the affected teeth. None of the affected teeth responded to cold or electric pulp testing, which indicated they were non-vital. Tooth vitality is not affected in PCD, which allowed us to exclude this condition.

Non-vital teeth indicate that the pulpal tissue is necrotic. Most commonly, non-vitality occurs when decay has penetrated the pulp chamber or as a complication of physical trauma. No decay was present on Mr. G’s mandibular anterior teeth and he denied a history of trauma such as a blow to the teeth. This left his oral habit as the likely cause of non-vitality.

Treatment for a non-vital tooth is a root canal, which had been done on tooth #26. We successfully performed root canal on Mr. G’s other non-vital teeth. We informed the patient of reason for his non-vital teeth, and made a protective occlusal guard to try to prevent additional trauma to the affected teeth.

Recognizing oral habits

Restoration of worn teeth, particularly those of the mandibular anterior, is technically difficult and—depending on the nature of the restoration—quite expensive. Endodontic therapy is more successful in teeth without periapical disease.⁶ Thus, preventing tooth-related problems in patients who grind their teeth or engage in other destructive dental behaviors is important.

As this case illustrates, teeth can become non-vital without clinical evidence of tooth wear; clinical evidence may be subtle or nonexistent (note teeth #23, #24, and #25 in Photo 2). Absence of tooth wear is not a reliable sign of tooth vitality. Mild to moderate tooth wear usually goes unnoticed by patients and clinicians.⁷

Patients with bruxism may complain of masticatory muscle soreness or increased wear of the teeth.⁷ In extreme cases, they may self-extract teeth as a result of bruxism.⁸

Screen patients who have anxiety disorders or depression for signs of bruxism or related behaviors (Table 2). If you detect signs of bruxism or related behavior, refer the patient to a dentist. Ask the dentist to look for signs of wear and perform vitality testing of teeth on a regular basis (twice a year is reasonable). Any signs of changes in pulp vitality should be followed up with intraoral periapical radiographs, which these patients might need more frequently than FDA guidelines recommend.⁹

Table 2

Screening for bruxism: 3 questions for patients

1. Do you have pain or discomfort in the jaw or facial muscles, headaches or earaches, or increased tooth sensitivity?
2. Have you noticed changes in the way your teeth fit together or wearing down of your teeth?
3. Has your sleeping partner noticed any noise at night that might be the result of teeth grinding?

An occlusal guard may provide the most definitive tooth protection for patients who engage in bruxism or similar behaviors. Occlusal guards are made of material that is softer than enamel, so the patient will wear away the guard rather than tooth structure. When the guard is worn away, the patient needs a new one.

Pharmacologic strategies for bruxism or related oral habits involving the teeth are not well developed. One short-term, placebo-controlled trial for acute treatment in 10 drug-free patients with sleep bruxism consisted of a predrug night, a placebo night, and a clonazepam night. Clonazepam, 1 mg 30 minutes before bedtime, significantly improved bruxism and sleep quality as determined by objective and subjective measures.¹⁰

Kast¹¹ reported 4 cases in which tiagabine suppressed nocturnal bruxism, trismus, and consequent morning pain in the teeth, masticatory musculature, jaw, and temporomandibular joint areas. This gammaaminobutyric acid reuptake inhibitor anticonvulsant approved for treating partial seizures was dosed at 4 to 8 mg at bedtime. These dosages are lower than those used to treat seizures.

 

Related resources

• American Dental Association. www.ada.org.

Drug brand names

• Clonazepam • Klonopin
• Haloperidol • Haldol
• Pimozide • Orap
• Sertraline • Zoloft
• Tiagabine • Gabitril

Disclosure

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

Comment on this article

Oral habits such as bruxism—compulsive grinding or clenching of the teeth—can be a manifestation of obsessive-compulsive disorder (OCD) and other anxiety disorders.¹ Bruxism also may be a side effect of selective serotonin reuptake inhibitors (SSRIs)^2,3 used to treat OCD⁴ and depression. Other oral conditions can complicate treatment of these disorders (Table 1).

Potentially serious sequelae of bruxism and similar behaviors include:

• wearing down of teeth (more common)
• necrosis of the pulpal tissues that results in non-vital teeth (less common).

The following case underlines the need for early referral to a dentist and close follow-up for patients who have tooth-related behaviors or are taking medications associated with a risk for such behaviors.

Table 1

Oral conditions associated with anxiety disorders and depression

Bruxism
Canker sores
Dry mouth
Temporomandibular joint disorders
Lichen planus (redness or mouth ulcers)
Non-vital teeth
Tooth wear, fracture

CASE REPORT: A compulsive oral habit

Mr. G, age 26, presents to our school of dental medicine with the chief complaint that he needs a crown. On clinical intraoral examination, we find he has multiple restorations, some areas of recurrent tooth decay, and a fractured cusp on a maxillary molar. His mandibular incisors show greater wear on their incisal surfaces than would be expected for a patient his age. This is especially true of his mandibular right lateral incisor (tooth #26) and canine (tooth #27) (Photo 1).

Clinical examination also reveals a restoration on tooth #26 that was consistent with an access cavity drilled for endodontic (root canal) therapy (Photo 2). This finding is consistent with his dental history. Soft tissue examination is within normal limits. He reports that he saw a dentist 7 months earlier but could not afford the fees.

During his medical history, Mr. G states he has mild Tourette’s syndrome that was diagnosed when he was 10. In the early 1990s he tried several medications, including haloperidol and pimozide, as a subject in research studies of Tourette’s. He could not recall the dosages of the medications or for how long he took them. Because these medications did not improve his symptoms, he stopped taking them after the studies ended.

Photo 1 Unexpected tooth wear: A clue to an anxiety-related oral habit

Teeth of a 26-year-old man show greater than expected wear, particularly on the mandibular right lateral incisor (tooth #26) and canine (tooth #27).

Photo 2 Radiographic evidence of tooth non-vitality

Radiolucencies (dark areas) in the bone at the apices of the tooth roots are a radiographic sign of non-vitality. Tooth #26 has undergone root canal.Mr. G reports that when he was in second grade, a psychiatrist diagnosed him with OCD, and has received treatment since then. We observe that while Mr. G is seated, he continually raises his right arm above his head and rubs his fingers together. He reports and demonstrates numerous other compulsive rituals, including head movements and rubbing his elbows against his side. His right elbow has a large scab.

He has been taking sertraline, 150 mg/d, for the past month. He says his psychiatrist prescribed this medication to help him break out of what he describes as episodes where he “gets into a mental loop.” Sertraline has improved Mr. G’s symptoms but they have not resolved.

He further reports that he has begun to “grind” his anterior teeth. Technically, he does not engage in grinding or bruxing; he has a habit of pushing his mandible forward so that his mandibular (lower) teeth are anterior to the maxillary (top) teeth, then forcefully pulling his mandible back so that the lingual (back) surfaces of the mandibular incisors push up against the buccal (outside) surfaces of the maxillary incisors (Photo 3). He states that he engaged in this habit frequently from approximately age 19 to 22. When Mr. G was 22, his dentist reduced the height of tooth #23, which Mr. G says he used “to set things in motion.” The dentist’s maneuver cut down but did not eliminate Mr. G’s habit.

Mr. G had not complained of nor had any clinician asked him about his bruxism-like behavior. He noted that the oral habit began prior to sertraline treatment, thus suggesting no relationship between the medication and the behavior. Interestingly, although some studies have reported bruxism as a side effect of SSRIs,^2,3 at least 1 case report found that SSRIs reduced nocturnal bruxism.¹²

Photo 3 Obsessive-compulsive disorder manifested in Mr. G’s oral habit

 

Starting with his mandible pushed forward so that his mandibular (lower) teeth were anterior to the maxillary (upper) teeth, the patient would forcefully pull his mandible back so that the lingual (back) surfaces of the mandibular incisors pushed against the buccal (outside) surfaces of the maxillary incisors.As part of Mr. G’s dental examination, we take a full series of intraoral radiographs. These reveal radiolucencies at the apices of teeth #23 through #26 (Photo 2). The films also show root canal therapy on tooth #26.

Differential diagnosis for lesions in the periapical region of the mandibular incisors includes periapical cemental dysplasia (PCD), which typically is found in middle-aged African-American females,⁵ and lesions resulting from non-vitality of the teeth. Histopathologically, lesions resulting from the latter include an apical abscess, cyst, or granuloma.

As is customary when periapical lesions are noted, we test the vitality of the affected teeth. None of the affected teeth responded to cold or electric pulp testing, which indicated they were non-vital. Tooth vitality is not affected in PCD, which allowed us to exclude this condition.

Non-vital teeth indicate that the pulpal tissue is necrotic. Most commonly, non-vitality occurs when decay has penetrated the pulp chamber or as a complication of physical trauma. No decay was present on Mr. G’s mandibular anterior teeth and he denied a history of trauma such as a blow to the teeth. This left his oral habit as the likely cause of non-vitality.

Treatment for a non-vital tooth is a root canal, which had been done on tooth #26. We successfully performed root canal on Mr. G’s other non-vital teeth. We informed the patient of reason for his non-vital teeth, and made a protective occlusal guard to try to prevent additional trauma to the affected teeth.

Recognizing oral habits

Restoration of worn teeth, particularly those of the mandibular anterior, is technically difficult and—depending on the nature of the restoration—quite expensive. Endodontic therapy is more successful in teeth without periapical disease.⁶ Thus, preventing tooth-related problems in patients who grind their teeth or engage in other destructive dental behaviors is important.

As this case illustrates, teeth can become non-vital without clinical evidence of tooth wear; clinical evidence may be subtle or nonexistent (note teeth #23, #24, and #25 in Photo 2). Absence of tooth wear is not a reliable sign of tooth vitality. Mild to moderate tooth wear usually goes unnoticed by patients and clinicians.⁷

Patients with bruxism may complain of masticatory muscle soreness or increased wear of the teeth.⁷ In extreme cases, they may self-extract teeth as a result of bruxism.⁸

Screen patients who have anxiety disorders or depression for signs of bruxism or related behaviors (Table 2). If you detect signs of bruxism or related behavior, refer the patient to a dentist. Ask the dentist to look for signs of wear and perform vitality testing of teeth on a regular basis (twice a year is reasonable). Any signs of changes in pulp vitality should be followed up with intraoral periapical radiographs, which these patients might need more frequently than FDA guidelines recommend.⁹

Table 2

Screening for bruxism: 3 questions for patients

1. Do you have pain or discomfort in the jaw or facial muscles, headaches or earaches, or increased tooth sensitivity?
2. Have you noticed changes in the way your teeth fit together or wearing down of your teeth?
3. Has your sleeping partner noticed any noise at night that might be the result of teeth grinding?

An occlusal guard may provide the most definitive tooth protection for patients who engage in bruxism or similar behaviors. Occlusal guards are made of material that is softer than enamel, so the patient will wear away the guard rather than tooth structure. When the guard is worn away, the patient needs a new one.

Pharmacologic strategies for bruxism or related oral habits involving the teeth are not well developed. One short-term, placebo-controlled trial for acute treatment in 10 drug-free patients with sleep bruxism consisted of a predrug night, a placebo night, and a clonazepam night. Clonazepam, 1 mg 30 minutes before bedtime, significantly improved bruxism and sleep quality as determined by objective and subjective measures.¹⁰

Kast¹¹ reported 4 cases in which tiagabine suppressed nocturnal bruxism, trismus, and consequent morning pain in the teeth, masticatory musculature, jaw, and temporomandibular joint areas. This gammaaminobutyric acid reuptake inhibitor anticonvulsant approved for treating partial seizures was dosed at 4 to 8 mg at bedtime. These dosages are lower than those used to treat seizures.

 

Related resources

• American Dental Association. www.ada.org.

Drug brand names

• Clonazepam • Klonopin
• Haloperidol • Haldol
• Pimozide • Orap
• Sertraline • Zoloft
• Tiagabine • Gabitril

Disclosure

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

Comment on this article

In June 2001, Andrea Yates drowned her 5 children ages 6 months to 7 years in the bathtub of their home. She had delusions that her house was bugged and television cameras were monitoring her mothering skills. She came to believe that “the one and only Satan” was within her, and that her children would burn in hell if she did not save their souls while they were still innocent.

Her conviction of capital murder in her first trial was overturned on appeal. She was found not guilty by reason of insanity at her retrial in 2006 and committed to a Texas state mental hospital.¹

Postpartum psychosis (PPP) presents dramatically days to weeks after delivery, with wide-ranging symptoms that can include dysphoric mania and delirium. Because untreated PPP has an estimated 4% risk of infanticide (murder of the infant in the first year of life),² and a 5% risk of suicide,³ psychiatric hospitalization usually is required to protect the mother and her baby.

The diagnosis may be missed, however, because postpartum psychotic symptoms wax and wane and suspiciousness or poor insight cause some women—such as Andrea Yates—to hide their delusional thinking from their families. This article discusses the risk factors, prevention, and treatment of PPP, including a review of:

• infanticide and suicide risks in the postpartum period
  
• increased susceptibility to PPP in women with bipolar disorder and other psychiatric disorders
  
• hospitalization for support and safety of the mother and her infant.
  

Risks of infanticide and suicide

A number of motives exist for infanticide (Table 1).⁴ Psychiatric literature shows that mothers who kill their children often have experienced psychosis, suicidality, depression, and considerable life stress.⁵ Common factors include alcohol use, limited social support, and a personal history of abuse. Studies on infanticide found a significant increase in common psychiatric disorders and financial stress among the mothers. Neonaticide (murder of the infant in the first day of life) generally is not related to PPP because PPP usually does not begin until after the day of delivery.⁶

Among women who develop psychiatric illness, homicidal ideation is more frequent in those with a perinatal onset of psychopathology.⁷ Infanticidal ideas and behavior are associated with psychotic ideas about the infant.⁸ Suicide is the cause of up to 20% of postpartum deaths.⁹

Table 1

Motives for infanticide: Mental illness or something else?

Motives	Examples
Likely related to postpartum psychosis or depression
Altruistic	A depressed or psychotic mother may believe she is sending her baby to heaven to prevent suffering on earth
	A suicidal mother may kill her infant along with herself rather than leave the child alone
Acutely psychotic	A mother kills her baby for no comprehensible reason, such as in response to command hallucinations or the confusion of delirium
Rarely related to postpartum psychosis
Fatal maltreatment	‘Battered child’ syndrome is the most common cause of infanticide; death often occurs after chronic abuse or neglect
	A minority of perpetrators are psychotic; a mother out of touch with reality may have difficulty providing for her infant’s needs
Not likely related to postpartum psychosis
Unwanted child	Parent does not want child because of inconvenience or out-of-wedlock birth
Spouse revenge	Murder of a child to cause emotional suffering for the other parent is the least frequent motive for infanticide
Source: Reference 4

The bipolar connection

Many factors can elevate the risk of PPP, including sleep deprivation in susceptible women, the hormonal shifts after birth, and psychiatric comorbidity (Table 2). Nearly three-fourths (>72%) of mothers with PPP have bipolar disorder or schizoaffective disorder, whereas 12% have schizophrenia.¹⁰ Some authors consider PPP to be bipolar disorder until proven otherwise. Mothers with a history of bipolar disorder or PPP have a 100-fold increase in rates of psychiatric hospitalization in the postpartum period.¹¹

PPP is not categorized as a distinct disorder in DSM-IV-TR, and lack of a consistent terminology has led to differing definitions. Brief psychotic disorder, psychotic disorder not otherwise specified, and affective disorders are sometimes proffered.¹² Some DSM disorders permit the specifier “with postpartum onset” if the symptoms occur in mothers within 4 weeks of birth.

Presentation. PPP is relatively rare, occurring at a rate of 1 to 3 cases per 1,000 births. Symptoms often have an abrupt onset, within days to weeks of delivery.¹⁰ In at least one-half of cases, symptoms begin by the third postpartum day,¹³ when many mothers have been discharged home and may be solely responsible for their infants.

Symptoms include confusion, bizarre behaviors, hallucinations (including rarer types such as tactile and olfactory), mood lability (ranging from euphoria to depression), decreased need for sleep or insomnia, restlessness, agitation, disorganized thinking, and bizarre delusions of relatively rapid onset.¹³ One mother might believe God wants her baby to be sacrificed as the second coming of the Messiah, a second may believe she has special powers, and a third that her baby is defective.

 

Table 2

Postpartum psychosis: Risk factors supported by evidence

Sleep deprivation in susceptible women
Hormonal shifts after birth (primarily the rapid drop in estrogen)
Psychosocial stressors such as marital problems, older age, single motherhood, lower socioeconomic status
Bipolar disorder or schizoaffective disorder
Past history of postpartum psychosis
Family history of postpartum psychosis
Previous psychiatric hospitalization, especially during the prenatal period for a bipolar or psychotic condition
Menstruation or cessation of lactation
Obstetric factors that can cause a small increase in relative risk: first pregnancy delivery complications preterm birth acute Caesarean section long duration of labor
Source: For bibliographic citations

Differential diagnosis

When evaluating a postpartum woman with psychotic symptoms, stay in contact with her obstetrician and the child’s pediatrician. Rule out delirium and organic causes of the mother’s symptoms (Box).¹¹

The psychiatric differential diagnosis includes “baby blues”—mild, transient mood swings, sadness, irritability, anxiety, and insomnia that most new mothers experience in the first postpartum week. Schizophrenia’s delusional thinking and hallucinations have a more gradual onset, compared with those of postpartum psychosis.

Postpartum depression (PPD) occurs in approximately 10% to 15% of new mothers.¹⁴ Depressive symptoms occur within weeks to months after delivery and often coexist with anxious symptoms. Some women with severe depression may present with psychotic symptoms. A mother may experience insomnia, sometimes not being able to sleep when the baby is sleeping. She may lack interest in caring for her baby and experience difficulty bonding.

At times it can be difficult to distinguish PPD from PPP. When evaluating a mother who is referred for “postpartum depression,” consider PPP in the differential diagnosis. A woman with PPD or PPP may report depressed mood, but in PPP this symptom usually is related to rapid mood changes. Other clinical features that point toward PPP are abnormal hallucinations (such as olfactory or tactile), hypomanic or mixed mood symptoms, and confusion.

Box

Suicidal thoughts or thoughts of harming the infant may be present in either PPD or PPP. Both elevate the risk of infanticide; one study found that 41 out of 100 depressed mothers acknowledged having thoughts of harming their infants.¹⁵

Psychosis vs OCD. Psychotic thinking and behaviors also must be differentiated from obsessive thoughts and compulsions.^10,16 Obsessive compulsive disorder (OCD) may be exacerbated or emerge for the first time during the perinatal period.¹⁷

In postpartum OCD, women may experience intrusive thoughts of accidental or purposeful harm to their baby. As opposed to women with PPP, mothers with OCD are not out of touch with reality and their thoughts are ego-dystonic.¹⁷ When these mothers have thoughts of their infants being harmed, they realize that these thoughts are not plans but fears and they try to avoid the thoughts.

Preventing PPP

Bipolar disorder is one of the most difficult disorders to treat during pregnancy because the serious risks of untreated illness must be balanced against the potential teratogenic risk of medications. Nevertheless, proactively managing bipolar disorder during pregnancy may reduce the risk of PPP.¹⁰

Closely monitor women with a history of bipolar disorder or PPP. During pregnancy, counsel them—and their partners—to:

• anticipate that depressive or psychotic symptoms could develop within days after delivery¹⁸
  
• seek treatment immediately if this occurs.
  

Some women will prefer to remain off medication during the first trimester—which is critical in organogenesis—and then restart medication later in pregnancy. This approach is not without risks, however (see Related Resources).

Postpartum medication. Whether or not a woman with bipolar disorder takes medication during pregnancy, consider treatment with mood stabilizers or atypical antipsychotics in the postpartum to prevent PPP (Table 3). Evidence is limited, but a search of PubMed found 1 study in which prophylactic lithium was given late in the third trimester or immediately after delivery to 21 women with a history of bipolar disorder or PPP. Only 2 patients had a psychotic recurrence while on prophylactic lithium; 1 unexplained stillbirth occurred.¹⁹

A retrospective study examined the course of women with bipolar disorder, some of whom were given prophylactic mood stabilizers immediately in the postpartum. One of 14 who received antimanic agents relapsed within the first 3 months postpartum, compared with 8 of 13 who were not so treated.¹⁸

 

Compared with antiepileptics, less information is available about the use of atypical antipsychotics in pregnancy and lactation. Antipsychotics’ potential advantage in women at risk for PPP is that these agents may help prevent or treat both manic and psychotic symptoms.

In a small, naturalistic, prospective study, 11 women at risk for PPP received olanzapine alone or with an antidepressant or mood stabilizer for at least 4 weeks after delivery. Two (18%) experienced a postpartum mood episode, compared with 8 (57%) of 14 other at-risk women who received antidepressants, mood stabilizers, or no medication.²⁰

Breast-feeding. Consider treatment effects on lactation and discuss this with the mother and the baby’s pediatrician, when possible. For useful reviews of risks and benefits of mood stabilizers and antipsychotics during breast-feeding, see Related Resources.

When you discuss breast-feeding, consider possible risks to the neonate as well as potential sleep interruption for the mother. If a mother has a supportive partner, the partner might be put in charge of night-time feedings in a routine combining breast-feeding and bottle-feeding. In some cases you may need to recommend cessation of lactation.²¹

Table 3

Treating postpartum psychosis: Consider 3 components

Component	Recommendations
Hospitalization vs home care	Hospitalize in most cases because of emergent severe symptoms and fluctuating course; base decision on risk evaluation/safety issues for patient and infant After discharge, visiting nurses are useful to help monitor the mother’s condition at home
Psychoeducation	Educate patient, family, and social support network; address risks to mother and infant and risks in future pregnancies
Medication	When prescribing mood stabilizers and/or antipsychotics, consider: whether mother is breast-feeding (discuss with patient, family, and pediatrician) maternal side effects, including sedation

Managing PPP

Early symptoms. Because of its severity and rapid evolution, PPP often presents as a psychiatric emergency. Monitor atrisk patients’ sleep patterns and mood for early signs of psychosis.²² Watch especially for hypomanic symptoms such as elevated or mixed mood and decreased judgment, which are common early in PPP.¹³

A mother with few signs of abnormal mood, good social support, and close follow-up may potentially be safely managed as an outpatient. Initial evaluation and management of PPP usually requires hospitalization, however, because of the risks of suicide, infanticide, and child maltreatment.²³

Hospitalization. Mother-infant bonding is important, but safety is paramount if a mother is psychotic—especially if she is experiencing psychotic thoughts about her infant. If possible, the infant should remain with family members during the mother’s hospitalization. Supervised mother-infant visits are often arranged, as appropriate.

Mood-stabilizing medications, including antipsychotics, are mainstays of treatment.²⁴ In some cases, conventional antipsychotics such as haloperidol may be useful because of a lower risk of weight gain or of sedation that could impair a mother’s ability to respond to her infant. Electroconvulsive therapy often yields rapid symptomatic improvement for mothers with postpartum mood or psychotic symptoms.²⁵

During the mother’s hospitalization, encourage the staff to be supportive and convey hopefulness.²⁶ In an interview study, women who had been treated for PPP said they experienced anger and frustration while hospitalized because they believed that they and their families received inadequate information and support.²⁷

Discharge planning. Assuming that the mother adheres to prescribed treatment, discharge may occur within 1 week. Plan discharge arrangements carefully (Table 4).²⁸ A team approach can be very useful within the outpatient clinic. In the model of the Perinatal Psychiatry Clinic of Connections in suburban Cleveland, OH, the mother’s treatment team includes perinatal psychiatrists, nurses, counsellors, case managers (who do home visits), and peer counselors.

Outpatient civil commitment, in which patients are mandated to accept treatment, is an option in some jurisdictions and could help ensure that patients receive treatment consistently.

Table 4

Discharge planning for safety of mother and infant

Notify child protective services (CPS) depending on the risk to the child. Case-by-case review is needed to assess whether the infant should be removed. CPS may put in place a plan for safety, short of removal. The plan may require that the woman continue psychiatric care
Meet with the patient and family to discuss her diagnosis, the risks, the importance of continued medication adherence, and the need for family or social supports to assist with child care
Consider engaging visiting nurses or doulas to provide help and support at home
Schedule frequent outpatient appointments for the mother after discharge
Consider family therapy after the mother has improved because of her risk for affective episodes outside the postpartum28

 

Related resources

• Altshuler L, Richards M, Yonkers K. Treating bipolar disorder during pregnancy. Current Psychiatry. 2003;2(7):14-26. www.CurrentPsychiatry.com.
  
• Gentile S. Infant safety with antipsychotic therapy in breastfeeding: a systematic review. J Clin Psychiatry. 2008;69(4):666-673.
  
• Miller LJ. Postpartum mood disorders. Washington, DC: American Psychiatric Publishing, Inc; 1999.
  
• Stowe ZN. The use of mood stabilizers during breastfeeding. J Clin Psychiatry. 2007;68(suppl 9):22-28.
  
• Toxicology Data Network (Toxnet). Literature on reproductive risks associated with psychotropics. National Library of Medicine. http://toxnet.nlm.nih.gov.
  

Drug brand names

• Haloperidol • Haldol
  
• Lithium • various
  
• Olanzapine • Zyprexa
  

Disclosures

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

Acknowledgement

Dr. Resnick, a forensic psychiatrist and coauthor of this article, testified for the defense in both trials of Andrea Yates.