Current Psychiatry

I appreciate Dr. McInnis’s article and his recommendation to monitor the comprehensive metabolic profile, including the calcium level, before and during lithium treatment. There is an association among lithium treatment, hypercalcemia, and hyperparathyroid­ism.^1,2 This can occur by lithium reduc­ing parathyroid hormone suppression or stimulating parathyroid glands.³

Surprisingly, many guidelines do not include a recommendation to monitor the calcium level; however, the International Society for Bipolar Disorders and other experts do rec­ommend obtaining a calcium level before initiating lithium therapy and at least annually thereafter.^1,4 If hyper­calcemia is present, assessing lithium and the parathyroid hormone level is recommended.³

Clinicians can continue lithium and monitor calcium if treatment is beneficial, hypercalcemia is mild, and the patient is asymptomatic.² For a symptomatic patient or one who has significant hypercalcemia, clinicians should consider discon­tinuing lithium and monitoring for a normalizing calcium level.² For patients with significant hypercalce­mia who need lithium therapy, con­sultation with an endocrinologist is advised.³

Jonathan R. Scarff, MD
VA Outpatient Clinic
Spartanburg, South Carolina

Dr. McInnis responds
Generally, calcium is included in the com­prehensive biochemistry panel (Table 1). Typically, magnesium or phosphorus is overlooked, and therefore was specifi­cally included in the table of recommen­dations. There is a complex relationship between lithium and calcium; Dr. Scarff’s points highlight this. It is noteworthy that lithium normalizes the calcium ampli­tude during action potentials in neurons derived from induced pluripotent stem cells from persons with BD¹; this sug­gests that there might be a direct mode of action in BD involving lithium and calcium. This finding further emphasizes the importance of monitoring calcium, and the wise clinician will verify that it is included in the comprehensive bio­chemistry panel.

I appreciate Dr. McInnis’s article and his recommendation to monitor the comprehensive metabolic profile, including the calcium level, before and during lithium treatment. There is an association among lithium treatment, hypercalcemia, and hyperparathyroid­ism.^1,2 This can occur by lithium reduc­ing parathyroid hormone suppression or stimulating parathyroid glands.³

Surprisingly, many guidelines do not include a recommendation to monitor the calcium level; however, the International Society for Bipolar Disorders and other experts do rec­ommend obtaining a calcium level before initiating lithium therapy and at least annually thereafter.^1,4 If hyper­calcemia is present, assessing lithium and the parathyroid hormone level is recommended.³

Clinicians can continue lithium and monitor calcium if treatment is beneficial, hypercalcemia is mild, and the patient is asymptomatic.² For a symptomatic patient or one who has significant hypercalcemia, clinicians should consider discon­tinuing lithium and monitoring for a normalizing calcium level.² For patients with significant hypercalce­mia who need lithium therapy, con­sultation with an endocrinologist is advised.³

Jonathan R. Scarff, MD
VA Outpatient Clinic
Spartanburg, South Carolina

Dr. McInnis responds
Generally, calcium is included in the com­prehensive biochemistry panel (Table 1). Typically, magnesium or phosphorus is overlooked, and therefore was specifi­cally included in the table of recommen­dations. There is a complex relationship between lithium and calcium; Dr. Scarff’s points highlight this. It is noteworthy that lithium normalizes the calcium ampli­tude during action potentials in neurons derived from induced pluripotent stem cells from persons with BD¹; this sug­gests that there might be a direct mode of action in BD involving lithium and calcium. This finding further emphasizes the importance of monitoring calcium, and the wise clinician will verify that it is included in the comprehensive bio­chemistry panel.

I appreciate Dr. McInnis’s article and his recommendation to monitor the comprehensive metabolic profile, including the calcium level, before and during lithium treatment. There is an association among lithium treatment, hypercalcemia, and hyperparathyroid­ism.^1,2 This can occur by lithium reduc­ing parathyroid hormone suppression or stimulating parathyroid glands.³

Surprisingly, many guidelines do not include a recommendation to monitor the calcium level; however, the International Society for Bipolar Disorders and other experts do rec­ommend obtaining a calcium level before initiating lithium therapy and at least annually thereafter.^1,4 If hyper­calcemia is present, assessing lithium and the parathyroid hormone level is recommended.³

Clinicians can continue lithium and monitor calcium if treatment is beneficial, hypercalcemia is mild, and the patient is asymptomatic.² For a symptomatic patient or one who has significant hypercalcemia, clinicians should consider discon­tinuing lithium and monitoring for a normalizing calcium level.² For patients with significant hypercalce­mia who need lithium therapy, con­sultation with an endocrinologist is advised.³

Jonathan R. Scarff, MD
VA Outpatient Clinic
Spartanburg, South Carolina

Dr. McInnis responds
Generally, calcium is included in the com­prehensive biochemistry panel (Table 1). Typically, magnesium or phosphorus is overlooked, and therefore was specifi­cally included in the table of recommen­dations. There is a complex relationship between lithium and calcium; Dr. Scarff’s points highlight this. It is noteworthy that lithium normalizes the calcium ampli­tude during action potentials in neurons derived from induced pluripotent stem cells from persons with BD¹; this sug­gests that there might be a direct mode of action in BD involving lithium and calcium. This finding further emphasizes the importance of monitoring calcium, and the wise clinician will verify that it is included in the comprehensive bio­chemistry panel.

I was astonished that Dr. Melvin G. McInnis’ article on using lithium to treat bipolar disorder (BD) (Current Psychiatry, June 2014, p. 38-44; [http://bit.ly/1sszAUr]) did not address all the potential hazards of the medication. He discussed side effects, but only how to manage them so that patients will adhere to treatment.

I have used lithium for patients with BD, and often it is efficacious, although hazardous in overdose. Lithium toxicity can cause cardiac arrhythmias, and must be monitored closely. In addition, the effects of hydration and exercise on the lithium level, especially during summer, often are ignored.

Two of my patients, an adolescent and an adult, were well-maintained on lithium, adhered to treatment, and had no concurrent medical problems, but developed significant toxicity for no reason that I could determine. The adult had a lithium level of 2.0 mEq/L in the emergency room; the adoles­cent had a lithium level of 1.8 mEq/L. Levels this high are considered poten­tially lethal, and because it happened without warning and without a cause that I could determine, I consider lithium to be one of the riskier mood stabilizers. I still prescribe it, but with great caution.

Dr. McInnis also did not mention the possibility of lithium-induced diabetes insipidus, a condition in which the kid­neys are no longer able to concentrate urine and that is marked by excessive urination, concomitant water intake, and low urine specific gravity. It is uncommon, but I have seen it 3 times in 30 years, in a practice that special­izes in psychotherapy and does not see a high percentage of patients with BD. I consider it a condition that must be kept in mind as we follow our patients in long-term treatment.

Mary Davis, MD
Lancaster, Pennsylvania

Dr. McInnis responds
Dr. Davis raises the issue of lithium toxic­ity and provides examples of 2 patients who developed levels of 2.0 mEq/L and 1.8 mEq/L. These levels clearly are well beyond the toxicity threshold of 1.3 mEq/L, and the patients wisely sought urgent care. These scenarios exemplify the need for regular monitoring of the lithium level—in particular, when there is any change in physical or mental health status. Development of significant tox­icity generally has some lead-time with emerging short-term side effects (out­lined in Table 2 of my article), which underscores the importance of discussing the nature of emerging side effects with your patient.

Dr. Davis is correct in noting that the practitioner must be aware of long-term side effects of lithium. I find it helpful to discuss these effects with the patient in the context of short-term (days or weeks), intermediate (weeks or months), and long-term (months or years) time frames (Table 2). Diabetes insipidus is listed as an intermediate side effect.

I am grateful to Dr. Davis for raising the issue of hydration and summer heat, a con­cern among parents and coaches when student athletes practice strenuously for extended hours.¹ Miller et al² found that the concentration of lithium was between 1.2- and 4.6-fold in forearm sweat compared with serum levels, with the implication that heat-induced sweating may lower lithium levels. Jefferson et al³ studied 4 athletes after a 20-km race and found that all had become dehydrated but had a decrease in the serum lithium level. This is contrary to the widely held belief that excessive sweating predis­poses to lithium toxicity. 

BD is among the more lethal psychi­atric disorders, and lithium is among the few medications shown to mitigate sui­cidal behavior.⁴ As with any medication, lithium is not without risk, and there is a clear need for informed medical manage­ment. Any notable change in health sta­tus or physical activity in a patient taking lithium is worthy of review, with recom­mendations based on knowledge of the patient and medical science.

I was astonished that Dr. Melvin G. McInnis’ article on using lithium to treat bipolar disorder (BD) (Current Psychiatry, June 2014, p. 38-44; [http://bit.ly/1sszAUr]) did not address all the potential hazards of the medication. He discussed side effects, but only how to manage them so that patients will adhere to treatment.

I have used lithium for patients with BD, and often it is efficacious, although hazardous in overdose. Lithium toxicity can cause cardiac arrhythmias, and must be monitored closely. In addition, the effects of hydration and exercise on the lithium level, especially during summer, often are ignored.

Two of my patients, an adolescent and an adult, were well-maintained on lithium, adhered to treatment, and had no concurrent medical problems, but developed significant toxicity for no reason that I could determine. The adult had a lithium level of 2.0 mEq/L in the emergency room; the adoles­cent had a lithium level of 1.8 mEq/L. Levels this high are considered poten­tially lethal, and because it happened without warning and without a cause that I could determine, I consider lithium to be one of the riskier mood stabilizers. I still prescribe it, but with great caution.

Dr. McInnis also did not mention the possibility of lithium-induced diabetes insipidus, a condition in which the kid­neys are no longer able to concentrate urine and that is marked by excessive urination, concomitant water intake, and low urine specific gravity. It is uncommon, but I have seen it 3 times in 30 years, in a practice that special­izes in psychotherapy and does not see a high percentage of patients with BD. I consider it a condition that must be kept in mind as we follow our patients in long-term treatment.

Mary Davis, MD
Lancaster, Pennsylvania

Dr. McInnis responds
Dr. Davis raises the issue of lithium toxic­ity and provides examples of 2 patients who developed levels of 2.0 mEq/L and 1.8 mEq/L. These levels clearly are well beyond the toxicity threshold of 1.3 mEq/L, and the patients wisely sought urgent care. These scenarios exemplify the need for regular monitoring of the lithium level—in particular, when there is any change in physical or mental health status. Development of significant tox­icity generally has some lead-time with emerging short-term side effects (out­lined in Table 2 of my article), which underscores the importance of discussing the nature of emerging side effects with your patient.

Dr. Davis is correct in noting that the practitioner must be aware of long-term side effects of lithium. I find it helpful to discuss these effects with the patient in the context of short-term (days or weeks), intermediate (weeks or months), and long-term (months or years) time frames (Table 2). Diabetes insipidus is listed as an intermediate side effect.

I am grateful to Dr. Davis for raising the issue of hydration and summer heat, a con­cern among parents and coaches when student athletes practice strenuously for extended hours.¹ Miller et al² found that the concentration of lithium was between 1.2- and 4.6-fold in forearm sweat compared with serum levels, with the implication that heat-induced sweating may lower lithium levels. Jefferson et al³ studied 4 athletes after a 20-km race and found that all had become dehydrated but had a decrease in the serum lithium level. This is contrary to the widely held belief that excessive sweating predis­poses to lithium toxicity. 

BD is among the more lethal psychi­atric disorders, and lithium is among the few medications shown to mitigate sui­cidal behavior.⁴ As with any medication, lithium is not without risk, and there is a clear need for informed medical manage­ment. Any notable change in health sta­tus or physical activity in a patient taking lithium is worthy of review, with recom­mendations based on knowledge of the patient and medical science.

I was astonished that Dr. Melvin G. McInnis’ article on using lithium to treat bipolar disorder (BD) (Current Psychiatry, June 2014, p. 38-44; [http://bit.ly/1sszAUr]) did not address all the potential hazards of the medication. He discussed side effects, but only how to manage them so that patients will adhere to treatment.

I have used lithium for patients with BD, and often it is efficacious, although hazardous in overdose. Lithium toxicity can cause cardiac arrhythmias, and must be monitored closely. In addition, the effects of hydration and exercise on the lithium level, especially during summer, often are ignored.

Two of my patients, an adolescent and an adult, were well-maintained on lithium, adhered to treatment, and had no concurrent medical problems, but developed significant toxicity for no reason that I could determine. The adult had a lithium level of 2.0 mEq/L in the emergency room; the adoles­cent had a lithium level of 1.8 mEq/L. Levels this high are considered poten­tially lethal, and because it happened without warning and without a cause that I could determine, I consider lithium to be one of the riskier mood stabilizers. I still prescribe it, but with great caution.

Dr. McInnis also did not mention the possibility of lithium-induced diabetes insipidus, a condition in which the kid­neys are no longer able to concentrate urine and that is marked by excessive urination, concomitant water intake, and low urine specific gravity. It is uncommon, but I have seen it 3 times in 30 years, in a practice that special­izes in psychotherapy and does not see a high percentage of patients with BD. I consider it a condition that must be kept in mind as we follow our patients in long-term treatment.

Mary Davis, MD
Lancaster, Pennsylvania

Dr. McInnis responds
Dr. Davis raises the issue of lithium toxic­ity and provides examples of 2 patients who developed levels of 2.0 mEq/L and 1.8 mEq/L. These levels clearly are well beyond the toxicity threshold of 1.3 mEq/L, and the patients wisely sought urgent care. These scenarios exemplify the need for regular monitoring of the lithium level—in particular, when there is any change in physical or mental health status. Development of significant tox­icity generally has some lead-time with emerging short-term side effects (out­lined in Table 2 of my article), which underscores the importance of discussing the nature of emerging side effects with your patient.

Dr. Davis is correct in noting that the practitioner must be aware of long-term side effects of lithium. I find it helpful to discuss these effects with the patient in the context of short-term (days or weeks), intermediate (weeks or months), and long-term (months or years) time frames (Table 2). Diabetes insipidus is listed as an intermediate side effect.

I am grateful to Dr. Davis for raising the issue of hydration and summer heat, a con­cern among parents and coaches when student athletes practice strenuously for extended hours.¹ Miller et al² found that the concentration of lithium was between 1.2- and 4.6-fold in forearm sweat compared with serum levels, with the implication that heat-induced sweating may lower lithium levels. Jefferson et al³ studied 4 athletes after a 20-km race and found that all had become dehydrated but had a decrease in the serum lithium level. This is contrary to the widely held belief that excessive sweating predis­poses to lithium toxicity. 

BD is among the more lethal psychi­atric disorders, and lithium is among the few medications shown to mitigate sui­cidal behavior.⁴ As with any medication, lithium is not without risk, and there is a clear need for informed medical manage­ment. Any notable change in health sta­tus or physical activity in a patient taking lithium is worthy of review, with recom­mendations based on knowledge of the patient and medical science.

DSM-5 criteria for conversion dis­order (or functional neurological symptom disorder) requires find­ings that are incompatible with recog­nized neurologic or medical conditions.¹ Knowledge of signs specific to conversion disorder may help you diagnose the illness with confidence.

We review signs suggestive of conver­sion disorder. These can be remembered using the mnemonic How About Finding Some Conversion Weakness [in an other­wise] Strong Guy/Gal? (Table²).

Inconsistencies in motor function can be observed on examination. Signs may be consciously or unconsciously produced. Although most of the tests mentioned have high positive and negative predictive values (noted in the Table²) they have limited sensitivity and specificity,³ and the presence of a positive sign does not exclude the possibility of comorbid disease.

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

DSM-5 criteria for conversion dis­order (or functional neurological symptom disorder) requires find­ings that are incompatible with recog­nized neurologic or medical conditions.¹ Knowledge of signs specific to conversion disorder may help you diagnose the illness with confidence.

We review signs suggestive of conver­sion disorder. These can be remembered using the mnemonic How About Finding Some Conversion Weakness [in an other­wise] Strong Guy/Gal? (Table²).

Inconsistencies in motor function can be observed on examination. Signs may be consciously or unconsciously produced. Although most of the tests mentioned have high positive and negative predictive values (noted in the Table²) they have limited sensitivity and specificity,³ and the presence of a positive sign does not exclude the possibility of comorbid disease.

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

DSM-5 criteria for conversion dis­order (or functional neurological symptom disorder) requires find­ings that are incompatible with recog­nized neurologic or medical conditions.¹ Knowledge of signs specific to conversion disorder may help you diagnose the illness with confidence.

We review signs suggestive of conver­sion disorder. These can be remembered using the mnemonic How About Finding Some Conversion Weakness [in an other­wise] Strong Guy/Gal? (Table²).

Inconsistencies in motor function can be observed on examination. Signs may be consciously or unconsciously produced. Although most of the tests mentioned have high positive and negative predictive values (noted in the Table²) they have limited sensitivity and specificity,³ and the presence of a positive sign does not exclude the possibility of comorbid disease.

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

Becoming a psychiatrist entails a shift in how we see ourselves and those around us. We learn—sometimes the hard way—about cultural self-assessment and the relative nature of our perspective on social, cultural, and clinical matters. What do I mean?

As psychiatrists in the making, we are unaware that we’ve been given this persona-suit, so to speak, with its social expectations and misperceptions. We start noticing how telling people what we do shapes our interac­tions at cocktail parties, informal gatherings, and in day-to-day life. A new acquaintance might disclose more about herself than she otherwise would or, on the contrary, might become reserved, even guarded. Awkward jokes sometimes are thrown into the mix to lighten the mood. All this is part of the pack­age we’ve been handed, because we chose to specialize in the diagnosis and treatment of mental illness and brain disorders.

So, as I enter my final year of training, I find myself reflecting on just how intense a journey residency has been.

We were physicians first…
We’re psychiatrists now, but first we learned the germ theory of disease, the pathophysiol­ogy of every well-known illness, and the sci­entific basis of the practice of medicine. Many of us weren’t fully aware of the challenges that come with psychiatric training when we signed up. But we powered through— trading set measures and laboratory values for subjective experiences and nonverbal cues. Along the way, we realized that we had to master not only an array of neuropsy­chiatric facts but other implicit skills: “active listening,” the capacity to make on-the-go complex ethical decisions, and the difficult task of being empathetically detached.

It might be only in retrospect that we can appreciate how residency has shaped us in a personal way—almost as much as it has professionally.

We think of physicians broadly as healers who save lives. Psychiatrists are no different; preventing the most hopeless from dying is something that we do the same way a car­diologist prevents a patient from dying of a massive heart attack. Winning the battle over mortality, by whatever imprecise measures of risk we use, ranks at the top of our thera­peutic priorities. We find ourselves scram­bling so that catastrophe never happens on our watch. Sometimes, we don’t stop to realize how much of a lifesaver we are— especially because, as junior residents, we’re too pressed for time to reflect and are focused on mastering clinical skills.

New tool to measure success in residency
The Accreditation Council for Graduate Medical Education (ACGME) recently released the “Milestones Project,”¹ a thor­ough evaluation system for residency pro­grams to apply to their trainees. This is a great effort to push for more field-specific evaluation measures among the specialties.

In psychiatry, subjects now considered when evaluating a resident’s progress and preparedness for promotion include com­petence in applied neuroscience; the prac­titioner’s emotional response to patients’ problems; and regulatory compliance. Ways doctors learn are changing: Emphasis is now on problem-based learning.² Patient safety is a priority; to respect that, we are betting strongly on the physician’s aptitude to provide good care by decreasing burn­out.³ I am pleased to learn that there are ongoing efforts to improve the way we pre­pare psychiatrists.

In line with ACGME practices, residency programs also need to continue revisiting their didactic curricula to include innova­tive, emerging topics. Social media, the antipsychiatry movement, Internet forums, opinionated bloggers, and public figures gone viral—these are some current issues that shouldn’t be ignored during training just because they aren’t discussed in texts or academic journals. Programs that teach and stimulate the inclusion of social sci­ences and critical thinking should yield bet­ter, more holistic psychiatrists.⁴

For me, these avenues of study have made a huge difference. I feel incredibly grateful for the opportunities that my resi­dency program has provided to me as a psychiatrist-in-training, including a year-long course that touches on novel topics, a weekly process group for all residents, and a broad support network to depend on when personal matters arise.

Mentoring: Invaluable part of the process
As part of the journey through residency, we have the opportunity to work alongside renowned academic psychiatrists, most of who also happen to be amazing people. Mentoring has incredible value at this stage of professional development; don’t shy from taking advantage of that opportunity!

Mentors help us make more informed decisions about our career path. I love hear­ing the personal stories that my attending physicians tell. On hectic days, when we are beleaguered by managed care and elec­tronic health records, those stories touch us in ways that abstract learning cannot. Internalizing our role models is a conscious and an unconscious element of the process of becoming a psychiatrist.

About that process: It’s far from perfect, always changing, and only the start of our mastery over the tough but rewarding daily tasks of listening… reflecting… prescribing, and, well, saving lives.


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

Becoming a psychiatrist entails a shift in how we see ourselves and those around us. We learn—sometimes the hard way—about cultural self-assessment and the relative nature of our perspective on social, cultural, and clinical matters. What do I mean?

As psychiatrists in the making, we are unaware that we’ve been given this persona-suit, so to speak, with its social expectations and misperceptions. We start noticing how telling people what we do shapes our interac­tions at cocktail parties, informal gatherings, and in day-to-day life. A new acquaintance might disclose more about herself than she otherwise would or, on the contrary, might become reserved, even guarded. Awkward jokes sometimes are thrown into the mix to lighten the mood. All this is part of the pack­age we’ve been handed, because we chose to specialize in the diagnosis and treatment of mental illness and brain disorders.

So, as I enter my final year of training, I find myself reflecting on just how intense a journey residency has been.

We were physicians first…
We’re psychiatrists now, but first we learned the germ theory of disease, the pathophysiol­ogy of every well-known illness, and the sci­entific basis of the practice of medicine. Many of us weren’t fully aware of the challenges that come with psychiatric training when we signed up. But we powered through— trading set measures and laboratory values for subjective experiences and nonverbal cues. Along the way, we realized that we had to master not only an array of neuropsy­chiatric facts but other implicit skills: “active listening,” the capacity to make on-the-go complex ethical decisions, and the difficult task of being empathetically detached.

It might be only in retrospect that we can appreciate how residency has shaped us in a personal way—almost as much as it has professionally.

We think of physicians broadly as healers who save lives. Psychiatrists are no different; preventing the most hopeless from dying is something that we do the same way a car­diologist prevents a patient from dying of a massive heart attack. Winning the battle over mortality, by whatever imprecise measures of risk we use, ranks at the top of our thera­peutic priorities. We find ourselves scram­bling so that catastrophe never happens on our watch. Sometimes, we don’t stop to realize how much of a lifesaver we are— especially because, as junior residents, we’re too pressed for time to reflect and are focused on mastering clinical skills.

New tool to measure success in residency
The Accreditation Council for Graduate Medical Education (ACGME) recently released the “Milestones Project,”¹ a thor­ough evaluation system for residency pro­grams to apply to their trainees. This is a great effort to push for more field-specific evaluation measures among the specialties.

In psychiatry, subjects now considered when evaluating a resident’s progress and preparedness for promotion include com­petence in applied neuroscience; the prac­titioner’s emotional response to patients’ problems; and regulatory compliance. Ways doctors learn are changing: Emphasis is now on problem-based learning.² Patient safety is a priority; to respect that, we are betting strongly on the physician’s aptitude to provide good care by decreasing burn­out.³ I am pleased to learn that there are ongoing efforts to improve the way we pre­pare psychiatrists.

In line with ACGME practices, residency programs also need to continue revisiting their didactic curricula to include innova­tive, emerging topics. Social media, the antipsychiatry movement, Internet forums, opinionated bloggers, and public figures gone viral—these are some current issues that shouldn’t be ignored during training just because they aren’t discussed in texts or academic journals. Programs that teach and stimulate the inclusion of social sci­ences and critical thinking should yield bet­ter, more holistic psychiatrists.⁴

For me, these avenues of study have made a huge difference. I feel incredibly grateful for the opportunities that my resi­dency program has provided to me as a psychiatrist-in-training, including a year-long course that touches on novel topics, a weekly process group for all residents, and a broad support network to depend on when personal matters arise.

Mentoring: Invaluable part of the process
As part of the journey through residency, we have the opportunity to work alongside renowned academic psychiatrists, most of who also happen to be amazing people. Mentoring has incredible value at this stage of professional development; don’t shy from taking advantage of that opportunity!

Mentors help us make more informed decisions about our career path. I love hear­ing the personal stories that my attending physicians tell. On hectic days, when we are beleaguered by managed care and elec­tronic health records, those stories touch us in ways that abstract learning cannot. Internalizing our role models is a conscious and an unconscious element of the process of becoming a psychiatrist.

About that process: It’s far from perfect, always changing, and only the start of our mastery over the tough but rewarding daily tasks of listening… reflecting… prescribing, and, well, saving lives.


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

Becoming a psychiatrist entails a shift in how we see ourselves and those around us. We learn—sometimes the hard way—about cultural self-assessment and the relative nature of our perspective on social, cultural, and clinical matters. What do I mean?

As psychiatrists in the making, we are unaware that we’ve been given this persona-suit, so to speak, with its social expectations and misperceptions. We start noticing how telling people what we do shapes our interac­tions at cocktail parties, informal gatherings, and in day-to-day life. A new acquaintance might disclose more about herself than she otherwise would or, on the contrary, might become reserved, even guarded. Awkward jokes sometimes are thrown into the mix to lighten the mood. All this is part of the pack­age we’ve been handed, because we chose to specialize in the diagnosis and treatment of mental illness and brain disorders.

So, as I enter my final year of training, I find myself reflecting on just how intense a journey residency has been.

We were physicians first…
We’re psychiatrists now, but first we learned the germ theory of disease, the pathophysiol­ogy of every well-known illness, and the sci­entific basis of the practice of medicine. Many of us weren’t fully aware of the challenges that come with psychiatric training when we signed up. But we powered through— trading set measures and laboratory values for subjective experiences and nonverbal cues. Along the way, we realized that we had to master not only an array of neuropsy­chiatric facts but other implicit skills: “active listening,” the capacity to make on-the-go complex ethical decisions, and the difficult task of being empathetically detached.

It might be only in retrospect that we can appreciate how residency has shaped us in a personal way—almost as much as it has professionally.

We think of physicians broadly as healers who save lives. Psychiatrists are no different; preventing the most hopeless from dying is something that we do the same way a car­diologist prevents a patient from dying of a massive heart attack. Winning the battle over mortality, by whatever imprecise measures of risk we use, ranks at the top of our thera­peutic priorities. We find ourselves scram­bling so that catastrophe never happens on our watch. Sometimes, we don’t stop to realize how much of a lifesaver we are— especially because, as junior residents, we’re too pressed for time to reflect and are focused on mastering clinical skills.

New tool to measure success in residency
The Accreditation Council for Graduate Medical Education (ACGME) recently released the “Milestones Project,”¹ a thor­ough evaluation system for residency pro­grams to apply to their trainees. This is a great effort to push for more field-specific evaluation measures among the specialties.

In psychiatry, subjects now considered when evaluating a resident’s progress and preparedness for promotion include com­petence in applied neuroscience; the prac­titioner’s emotional response to patients’ problems; and regulatory compliance. Ways doctors learn are changing: Emphasis is now on problem-based learning.² Patient safety is a priority; to respect that, we are betting strongly on the physician’s aptitude to provide good care by decreasing burn­out.³ I am pleased to learn that there are ongoing efforts to improve the way we pre­pare psychiatrists.

In line with ACGME practices, residency programs also need to continue revisiting their didactic curricula to include innova­tive, emerging topics. Social media, the antipsychiatry movement, Internet forums, opinionated bloggers, and public figures gone viral—these are some current issues that shouldn’t be ignored during training just because they aren’t discussed in texts or academic journals. Programs that teach and stimulate the inclusion of social sci­ences and critical thinking should yield bet­ter, more holistic psychiatrists.⁴

For me, these avenues of study have made a huge difference. I feel incredibly grateful for the opportunities that my resi­dency program has provided to me as a psychiatrist-in-training, including a year-long course that touches on novel topics, a weekly process group for all residents, and a broad support network to depend on when personal matters arise.

Mentoring: Invaluable part of the process
As part of the journey through residency, we have the opportunity to work alongside renowned academic psychiatrists, most of who also happen to be amazing people. Mentoring has incredible value at this stage of professional development; don’t shy from taking advantage of that opportunity!

Mentors help us make more informed decisions about our career path. I love hear­ing the personal stories that my attending physicians tell. On hectic days, when we are beleaguered by managed care and elec­tronic health records, those stories touch us in ways that abstract learning cannot. Internalizing our role models is a conscious and an unconscious element of the process of becoming a psychiatrist.

About that process: It’s far from perfect, always changing, and only the start of our mastery over the tough but rewarding daily tasks of listening… reflecting… prescribing, and, well, saving lives.


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

Methamphetamine and other amphetamine-type stimulants are the world’s second most widely used group of illicit substances (after Cannabis), with prevalence of abuse varying by region and by locales within nations. As prescription use of stimulants has grown dramatically in recent years, so has abuse of these substances.

Given the widespread and growing misuse of amphetamine-type stimulants (Box,^1-3), clinicians are faced with the need to learn how to recognize and manage methamphetamine abuse. Both pre­scribed and non-prescribed uses of stimulants present complex chal­lenges; in this article, we examine effects, manifestations, and current evidence-based behavioral and medical treatments of methamphet­amine misuse and abuse, and look ahead to investigational therapies that hold promise for improving the limited existing approaches to management.

Effects and manifestations of methamphetamine use
Different routes of administration produce different consequences, in terms of medical comorbidity and propensity to induce addiction. Smoked or injected, methamphetamine enters the brain in seconds; snorted or taken by mouth, the drug produces its effects in several min­utes and a half hour, respectively.

Rapid uptake and effects of methamphetamine result from its ability to cross the blood−brain barrier. Its primary effects are caused by inhibi­tion of dopamine storage and release of intracellular dopamine.

Methamphetamine stimulates the CNS and the cardiovascular sys­tem through release of dopamine and norepinephrine, which increases blood pressure, body temperature, and heart rate, and, occasionally, induces arrhythmia that can contribute to heart attack and stroke. Users experience euphoria, hypervigilance, suppressed appetite, and increased libido.

Binge use is common to sustain eupho­ria and other reinforcing effects, which subside with rapidly developing tolerance. After days of repeated dosing, elevated methamphetamine blood levels can lead to mood disturbances, repetitive motor activities, and psychotic symptoms such as hallucinations, delusions, and paranoia. Acute psychosis can bring on violence and other injurious behaviors that involve law enforcement and emergency medical services.

When methamphetamine is used over months or years, health consequences include anorexia, tremor, so-called meth mouth (broken teeth, infections, cavities, burns), insomnia, panic attacks, confusion, depression, irritability, and impaired mem­ory and other cognitive processes.

Treating methamphetamine intoxication and withdrawal
At initial clinical contact with a person who abuses methamphetamine, practitio­ners may face several acute consequences requiring attention. Prominent among pre­senting conditions, especially during acute intoxication, are agitation, anxiety, and psy­chotic symptoms, which may improve by providing the patient with calming reassur­ance in a quiet space. In more severe cases, a benzodiazepine, antipsychotic, or both might be indicated^4,5 (Table 1).

Methamphetamine withdrawal is char­acterized by anxiety, depression, and insom­nia. These symptoms generally resolve in a matter of days after the start of withdrawal without pharmacotherapy. In some cases, depression or psychosis becomes chronic, as a result of methamphetamine use itself6 or as an emergent concomitant psychiatric condition.

A sedative-hypnotic medication or an anxiolytic can be used as necessary to ame­liorate insomnia or anxiety, respectively. Prolonged depression can be treated with an antidepressant. An antipsychotic might be indicated for long-term management of patients who have persistent psychosis.

Therapy for methamphetamine abuse
Treatment of methamphetamine abuse— with the goal of stopping drug use—is a complicated matter on 2 counts:
   • No medications are FDA-approved for treating methamphetamine addiction.
   • There are no accepted substitution medications (ie, stimulants that can be used in place of methamphetamine, as is avail­able for opioid addiction).

Pharmacotherapeutic possibilities. The rationale for considering replacement phar­macotherapy is that psychostimulants can counter the cravings, dysphoria, and fatigue produced by methamphetamine withdrawal and can alleviate methamphetamine-related cognitive impairment. Although dextro­amphetamine and other psychostimu­lants have been evaluated in small trials as replacement medication, most countries are reluctant to consider their use, because of the potential for abuse and accompanying liability.

After decades of medication research, several drugs have shown promise for reducing methamphetamine abuse, although results have not been robust (Table 2):
   • Bupropion has shown benefit in reduc­ing methamphetamine use among users with less severe addiction.^7,8
   • Methylphenidate, a psychostimulant FDA-approved for attention-deficit/hyper­activity disorder, was found to reduce methamphetamine use compared with pla­cebo in a European sample of amphetamine injectors who had attained abstinence in a residential program.⁹ Those results were not replicated in a recent study by Miles et al, however.¹⁰ A study with a more clinically realistic approach (ie, not requiring daily clinic attendance, as in the Miles trial) vs placebo for methamphetamine abuse was recently published, with promising results that require confirmation in further study.¹¹
   • Mirtazapine, an antidepressant, has demonstrated efficacy in reducing metham­phetamine use compared with placebo.¹²
   • Modafinil, another medication with stimulant properties, reduced metham­phetamine use in a subgroup analysis of heavy users, compared with placebo.¹³
   • Dextroamphetamine, 60 mg/d, showed no difference in reducing methamphet­amine compared with placebo, but did diminish cravings and withdrawal symptoms.¹⁴

Many medications have yielded negligi­ble results in studies: selegiline, baclofen, ser­traline, topiramate, gabapentin, rivastigmine, risperidone, and ondansetron.¹⁶ Recent eval­uation of disulfiram, vigabatrin, and lobeline also has yielded inconsistent findings.¹⁷

No drug has proved effective for pre­venting relapse; research continues, focus­ing on several types of compounds that target various mechanisms: the dopamine system, the opioid system (by way of the γ-aminobutyric acid inhibitory system), and cortico-limbic reward circuitry.

Once-monthly injectable naltrexone has potential for ameliorating craving and relapse by modulating the opioid receptor system. However, the drug has not been adequately explored in generalizable set­tings of methamphetamine users.

Trials of oral naltrexone in Sweden have shown encouraging results, includ­ing reduced subjective effects and amphet­amine use in open-label trials^18,19; results were replicated in a subsequent placebo-controlled trial.²⁰ In an unpublished study, however, no differences in amphetamine use were found among users randomized to depot naltrexone or placebo.²¹

Depot naltrexone with assured dos­ing might have a role in treating metham­phetamine abuse, however; a combination of depot naltrexone and oral bupropion is being examined in a National Institute on Drug Abuse Clinical Trials Networks study that commenced in 2013. Pairing medica­tions that have different mechanistic targets might work toward promoting cessation of methamphetamine abuse and reducing relapse once patients are abstinent.

In an early phase of research, but show­ing promise based on their ability to target different systems, are:  
   • N-acetylcysteine, modulator of the glutamate system  
   • D3 antagonists and partial agonists²²  
   • varenicline.²³

Potential “vaccines” against metham­phetamine are in preclinical development, including use of a protein carrier or other immune-stimulating molecule to create antibodies that bind methamphetamine in the bloodstream and block its psychoactive effects.^24,25

Sigma receptor effects are being studied in rodents as potential targets to mitigate effects of methamphetamine. The ligand AZ66, a sigma receptor antagonist, has demonstrated efficacy in reducing meth­amphetamine-induced cognitive impair­ment—suggesting that the sigma receptor has a potential role in ameliorating meth­amphetamine-related neurotoxicity.²⁶

Psychosocial and behavioral interven­tions. Among the non-drug treatments that have demonstrated efficacy for treat­ing methamphetamine abuse, cognitive-behavioral therapy (CBT) and contingency management (CM) have been most widely studied and applied in treatment settings.

CBT involves individual or group coun­seling that focuses on relapse prevention skills, including identification of relapse triggers, strategies to diminish cravings, and engagement in alternative non-drug activities^27,28 (Table 3).

CM, which is based on positive rein­forcement, offers tangible reinforcers, or rewards, for behaviors (eg, clinic atten­dance, providing a drug-free urine sam­ple) according to guidelines set by the practitioner. CM-based interventions are the most reliably documented approaches for treating methamphetamine abuse,^29,30 but their utility might prove to be most efficient in combination with medication— once suitable pharmacotherapeutic options emerge.

Although CBT and CM remain accepted standard treatments for methamphetamine abuse, outcomes are suboptimal.²⁷ Both interventions have a high rate of dropout during the first month of treatment and a >50% relapse rate 6 to 19 months after treat­ment ends.^31-33

As with treatment of other substance use disorders, patients who abuse methamphet­amine can benefit from residential treatment in a drug-free setting for ≥30 days.³⁴ In the residential approach, removing access to drugs, drug cues, and drug-using acquain­tances combined with group and individ­ual counseling reaches an inevitable end: discharge into the community. Then the patient’s battle to avoid relapse begins.

Because cognitive impairment is com­mon among patients who abuse metham­phetamine, even after they stop using,³⁵ researchers have examined the potential for increasing participation in psychosocial interventions such as CBT by using medica­tions that might have potential to increase cognitive function, such as modafinil.³⁶ Increased attention and concentration afforded by medication could enhance effi­cacy of CBT. Results of trials and new drug development have been mixed³⁷; no clear candidate for preventing relapse through any of the putative mechanisms of action has emerged.

Relapse is a problematic target for treatment
Ending methamphetamine abuse and sus­taining abstinence from stimulants require a change in the cognitive associations that have been laid down in a drug user’s memory. Relapse occurs because of recalled memories that can be cued, or triggered, by internal or external stimuli. Eliminating drug memories, perhaps assisted by medi­cations such as d-cycloserine (an antago­nist of the N-methyl-d-aspartate receptor), could be useful for suppressing the inclina­tion to relapse.

Last, alternative, non-drug forms of cog­nitive amendment have shown efficacy in preventing relapse: for example, incorpo­rating mindfulness meditation, which has shown promise in managing craving for methamphetamine and decreasing reactiv­ity to environmental cues for drug use.³⁸

Bottom Line
Practitioners who work in emergency, inpatient, and outpatient settings will be called on more and more to treat acute stimulant intoxication and withdrawal, stimulant-induced psychosis, and methamphetamine abuse. Few evidence-based treatments and no FDA-approved medications are available to treat this addiction; many drugs and a few psychotherapeutic techniques have shown promise. Ongoing research promises to deliver medical and behavioral interventions to help patients quit using methamphetamine.

Related Resources
• Karch SB, Drummer O. Karch’s pathology of drug abuse, fifth ed. Boca Raton, FL: CRC Press/Taylor & David; 2013.
• Roll J, Rawson RA, Ling W, eds. Methamphetamine addic­tion: from basic science to treatment. New York, NY: Guilford Press; 2009.
• Sheff D. Beautiful boy: a father’s journey through his son’s addiction. New York, NY: Houghton Mifflin Harcourt Publishing Company; 2008.
• Sheff N. Tweak: growing up on methamphetamines. New York, NY: Antheneum Books for Young Readers; 2007.
• National Institute on Drug Abuse. Drugs of abuse. www. drugabuse.gov/drugs-abuse/methamphetamine.

Drug Brand Names
Baclofen • Lioresal                                Naltrexone (depot) • Vivitrol
Bupropion • Wellbutrin                          Naltrexone (oral) • ReVia
D-cycloserine • Seromycin                     Ondansetron • Zofran
Dexreoamphetaime • Adderall                Risperidone • Risperadal
Disulfiram • Antabuse                            Rivastigimine • Exelon
Gabapentin • Neurontin                          Selegiline• EMSAM
Methylphenidate  •  Ritalin                      Sertraline • Zoloft
Mirtazapine •  Remeron                          Topiramate • Topamax
Modafinil • Provigil                                 Varenicline • Chantix
 N-acetylcysteine • Mucomyst                 Vigabatrin • Sabril

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

Methamphetamine and other amphetamine-type stimulants are the world’s second most widely used group of illicit substances (after Cannabis), with prevalence of abuse varying by region and by locales within nations. As prescription use of stimulants has grown dramatically in recent years, so has abuse of these substances.

Given the widespread and growing misuse of amphetamine-type stimulants (Box,^1-3), clinicians are faced with the need to learn how to recognize and manage methamphetamine abuse. Both pre­scribed and non-prescribed uses of stimulants present complex chal­lenges; in this article, we examine effects, manifestations, and current evidence-based behavioral and medical treatments of methamphet­amine misuse and abuse, and look ahead to investigational therapies that hold promise for improving the limited existing approaches to management.

Effects and manifestations of methamphetamine use
Different routes of administration produce different consequences, in terms of medical comorbidity and propensity to induce addiction. Smoked or injected, methamphetamine enters the brain in seconds; snorted or taken by mouth, the drug produces its effects in several min­utes and a half hour, respectively.

Rapid uptake and effects of methamphetamine result from its ability to cross the blood−brain barrier. Its primary effects are caused by inhibi­tion of dopamine storage and release of intracellular dopamine.

Methamphetamine stimulates the CNS and the cardiovascular sys­tem through release of dopamine and norepinephrine, which increases blood pressure, body temperature, and heart rate, and, occasionally, induces arrhythmia that can contribute to heart attack and stroke. Users experience euphoria, hypervigilance, suppressed appetite, and increased libido.

Binge use is common to sustain eupho­ria and other reinforcing effects, which subside with rapidly developing tolerance. After days of repeated dosing, elevated methamphetamine blood levels can lead to mood disturbances, repetitive motor activities, and psychotic symptoms such as hallucinations, delusions, and paranoia. Acute psychosis can bring on violence and other injurious behaviors that involve law enforcement and emergency medical services.

When methamphetamine is used over months or years, health consequences include anorexia, tremor, so-called meth mouth (broken teeth, infections, cavities, burns), insomnia, panic attacks, confusion, depression, irritability, and impaired mem­ory and other cognitive processes.

Treating methamphetamine intoxication and withdrawal
At initial clinical contact with a person who abuses methamphetamine, practitio­ners may face several acute consequences requiring attention. Prominent among pre­senting conditions, especially during acute intoxication, are agitation, anxiety, and psy­chotic symptoms, which may improve by providing the patient with calming reassur­ance in a quiet space. In more severe cases, a benzodiazepine, antipsychotic, or both might be indicated^4,5 (Table 1).

Methamphetamine withdrawal is char­acterized by anxiety, depression, and insom­nia. These symptoms generally resolve in a matter of days after the start of withdrawal without pharmacotherapy. In some cases, depression or psychosis becomes chronic, as a result of methamphetamine use itself6 or as an emergent concomitant psychiatric condition.

A sedative-hypnotic medication or an anxiolytic can be used as necessary to ame­liorate insomnia or anxiety, respectively. Prolonged depression can be treated with an antidepressant. An antipsychotic might be indicated for long-term management of patients who have persistent psychosis.

Therapy for methamphetamine abuse
Treatment of methamphetamine abuse— with the goal of stopping drug use—is a complicated matter on 2 counts:
   • No medications are FDA-approved for treating methamphetamine addiction.
   • There are no accepted substitution medications (ie, stimulants that can be used in place of methamphetamine, as is avail­able for opioid addiction).

Pharmacotherapeutic possibilities. The rationale for considering replacement phar­macotherapy is that psychostimulants can counter the cravings, dysphoria, and fatigue produced by methamphetamine withdrawal and can alleviate methamphetamine-related cognitive impairment. Although dextro­amphetamine and other psychostimu­lants have been evaluated in small trials as replacement medication, most countries are reluctant to consider their use, because of the potential for abuse and accompanying liability.

After decades of medication research, several drugs have shown promise for reducing methamphetamine abuse, although results have not been robust (Table 2):
   • Bupropion has shown benefit in reduc­ing methamphetamine use among users with less severe addiction.^7,8
   • Methylphenidate, a psychostimulant FDA-approved for attention-deficit/hyper­activity disorder, was found to reduce methamphetamine use compared with pla­cebo in a European sample of amphetamine injectors who had attained abstinence in a residential program.⁹ Those results were not replicated in a recent study by Miles et al, however.¹⁰ A study with a more clinically realistic approach (ie, not requiring daily clinic attendance, as in the Miles trial) vs placebo for methamphetamine abuse was recently published, with promising results that require confirmation in further study.¹¹
   • Mirtazapine, an antidepressant, has demonstrated efficacy in reducing metham­phetamine use compared with placebo.¹²
   • Modafinil, another medication with stimulant properties, reduced metham­phetamine use in a subgroup analysis of heavy users, compared with placebo.¹³
   • Dextroamphetamine, 60 mg/d, showed no difference in reducing methamphet­amine compared with placebo, but did diminish cravings and withdrawal symptoms.¹⁴

Many medications have yielded negligi­ble results in studies: selegiline, baclofen, ser­traline, topiramate, gabapentin, rivastigmine, risperidone, and ondansetron.¹⁶ Recent eval­uation of disulfiram, vigabatrin, and lobeline also has yielded inconsistent findings.¹⁷

No drug has proved effective for pre­venting relapse; research continues, focus­ing on several types of compounds that target various mechanisms: the dopamine system, the opioid system (by way of the γ-aminobutyric acid inhibitory system), and cortico-limbic reward circuitry.

Once-monthly injectable naltrexone has potential for ameliorating craving and relapse by modulating the opioid receptor system. However, the drug has not been adequately explored in generalizable set­tings of methamphetamine users.

Trials of oral naltrexone in Sweden have shown encouraging results, includ­ing reduced subjective effects and amphet­amine use in open-label trials^18,19; results were replicated in a subsequent placebo-controlled trial.²⁰ In an unpublished study, however, no differences in amphetamine use were found among users randomized to depot naltrexone or placebo.²¹

Depot naltrexone with assured dos­ing might have a role in treating metham­phetamine abuse, however; a combination of depot naltrexone and oral bupropion is being examined in a National Institute on Drug Abuse Clinical Trials Networks study that commenced in 2013. Pairing medica­tions that have different mechanistic targets might work toward promoting cessation of methamphetamine abuse and reducing relapse once patients are abstinent.

In an early phase of research, but show­ing promise based on their ability to target different systems, are:  
   • N-acetylcysteine, modulator of the glutamate system  
   • D3 antagonists and partial agonists²²  
   • varenicline.²³

Potential “vaccines” against metham­phetamine are in preclinical development, including use of a protein carrier or other immune-stimulating molecule to create antibodies that bind methamphetamine in the bloodstream and block its psychoactive effects.^24,25

Sigma receptor effects are being studied in rodents as potential targets to mitigate effects of methamphetamine. The ligand AZ66, a sigma receptor antagonist, has demonstrated efficacy in reducing meth­amphetamine-induced cognitive impair­ment—suggesting that the sigma receptor has a potential role in ameliorating meth­amphetamine-related neurotoxicity.²⁶

Psychosocial and behavioral interven­tions. Among the non-drug treatments that have demonstrated efficacy for treat­ing methamphetamine abuse, cognitive-behavioral therapy (CBT) and contingency management (CM) have been most widely studied and applied in treatment settings.

CBT involves individual or group coun­seling that focuses on relapse prevention skills, including identification of relapse triggers, strategies to diminish cravings, and engagement in alternative non-drug activities^27,28 (Table 3).

CM, which is based on positive rein­forcement, offers tangible reinforcers, or rewards, for behaviors (eg, clinic atten­dance, providing a drug-free urine sam­ple) according to guidelines set by the practitioner. CM-based interventions are the most reliably documented approaches for treating methamphetamine abuse,^29,30 but their utility might prove to be most efficient in combination with medication— once suitable pharmacotherapeutic options emerge.

Although CBT and CM remain accepted standard treatments for methamphetamine abuse, outcomes are suboptimal.²⁷ Both interventions have a high rate of dropout during the first month of treatment and a >50% relapse rate 6 to 19 months after treat­ment ends.^31-33

As with treatment of other substance use disorders, patients who abuse methamphet­amine can benefit from residential treatment in a drug-free setting for ≥30 days.³⁴ In the residential approach, removing access to drugs, drug cues, and drug-using acquain­tances combined with group and individ­ual counseling reaches an inevitable end: discharge into the community. Then the patient’s battle to avoid relapse begins.

Because cognitive impairment is com­mon among patients who abuse metham­phetamine, even after they stop using,³⁵ researchers have examined the potential for increasing participation in psychosocial interventions such as CBT by using medica­tions that might have potential to increase cognitive function, such as modafinil.³⁶ Increased attention and concentration afforded by medication could enhance effi­cacy of CBT. Results of trials and new drug development have been mixed³⁷; no clear candidate for preventing relapse through any of the putative mechanisms of action has emerged.

Relapse is a problematic target for treatment
Ending methamphetamine abuse and sus­taining abstinence from stimulants require a change in the cognitive associations that have been laid down in a drug user’s memory. Relapse occurs because of recalled memories that can be cued, or triggered, by internal or external stimuli. Eliminating drug memories, perhaps assisted by medi­cations such as d-cycloserine (an antago­nist of the N-methyl-d-aspartate receptor), could be useful for suppressing the inclina­tion to relapse.

Last, alternative, non-drug forms of cog­nitive amendment have shown efficacy in preventing relapse: for example, incorpo­rating mindfulness meditation, which has shown promise in managing craving for methamphetamine and decreasing reactiv­ity to environmental cues for drug use.³⁸

Bottom Line
Practitioners who work in emergency, inpatient, and outpatient settings will be called on more and more to treat acute stimulant intoxication and withdrawal, stimulant-induced psychosis, and methamphetamine abuse. Few evidence-based treatments and no FDA-approved medications are available to treat this addiction; many drugs and a few psychotherapeutic techniques have shown promise. Ongoing research promises to deliver medical and behavioral interventions to help patients quit using methamphetamine.

Related Resources
• Karch SB, Drummer O. Karch’s pathology of drug abuse, fifth ed. Boca Raton, FL: CRC Press/Taylor & David; 2013.
• Roll J, Rawson RA, Ling W, eds. Methamphetamine addic­tion: from basic science to treatment. New York, NY: Guilford Press; 2009.
• Sheff D. Beautiful boy: a father’s journey through his son’s addiction. New York, NY: Houghton Mifflin Harcourt Publishing Company; 2008.
• Sheff N. Tweak: growing up on methamphetamines. New York, NY: Antheneum Books for Young Readers; 2007.
• National Institute on Drug Abuse. Drugs of abuse. www. drugabuse.gov/drugs-abuse/methamphetamine.

Drug Brand Names
Baclofen • Lioresal                                Naltrexone (depot) • Vivitrol
Bupropion • Wellbutrin                          Naltrexone (oral) • ReVia
D-cycloserine • Seromycin                     Ondansetron • Zofran
Dexreoamphetaime • Adderall                Risperidone • Risperadal
Disulfiram • Antabuse                            Rivastigimine • Exelon
Gabapentin • Neurontin                          Selegiline• EMSAM
Methylphenidate  •  Ritalin                      Sertraline • Zoloft
Mirtazapine •  Remeron                          Topiramate • Topamax
Modafinil • Provigil                                 Varenicline • Chantix
 N-acetylcysteine • Mucomyst                 Vigabatrin • Sabril

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

Methamphetamine and other amphetamine-type stimulants are the world’s second most widely used group of illicit substances (after Cannabis), with prevalence of abuse varying by region and by locales within nations. As prescription use of stimulants has grown dramatically in recent years, so has abuse of these substances.

Given the widespread and growing misuse of amphetamine-type stimulants (Box,^1-3), clinicians are faced with the need to learn how to recognize and manage methamphetamine abuse. Both pre­scribed and non-prescribed uses of stimulants present complex chal­lenges; in this article, we examine effects, manifestations, and current evidence-based behavioral and medical treatments of methamphet­amine misuse and abuse, and look ahead to investigational therapies that hold promise for improving the limited existing approaches to management.

Effects and manifestations of methamphetamine use
Different routes of administration produce different consequences, in terms of medical comorbidity and propensity to induce addiction. Smoked or injected, methamphetamine enters the brain in seconds; snorted or taken by mouth, the drug produces its effects in several min­utes and a half hour, respectively.

Rapid uptake and effects of methamphetamine result from its ability to cross the blood−brain barrier. Its primary effects are caused by inhibi­tion of dopamine storage and release of intracellular dopamine.

Methamphetamine stimulates the CNS and the cardiovascular sys­tem through release of dopamine and norepinephrine, which increases blood pressure, body temperature, and heart rate, and, occasionally, induces arrhythmia that can contribute to heart attack and stroke. Users experience euphoria, hypervigilance, suppressed appetite, and increased libido.

Binge use is common to sustain eupho­ria and other reinforcing effects, which subside with rapidly developing tolerance. After days of repeated dosing, elevated methamphetamine blood levels can lead to mood disturbances, repetitive motor activities, and psychotic symptoms such as hallucinations, delusions, and paranoia. Acute psychosis can bring on violence and other injurious behaviors that involve law enforcement and emergency medical services.

When methamphetamine is used over months or years, health consequences include anorexia, tremor, so-called meth mouth (broken teeth, infections, cavities, burns), insomnia, panic attacks, confusion, depression, irritability, and impaired mem­ory and other cognitive processes.

Treating methamphetamine intoxication and withdrawal
At initial clinical contact with a person who abuses methamphetamine, practitio­ners may face several acute consequences requiring attention. Prominent among pre­senting conditions, especially during acute intoxication, are agitation, anxiety, and psy­chotic symptoms, which may improve by providing the patient with calming reassur­ance in a quiet space. In more severe cases, a benzodiazepine, antipsychotic, or both might be indicated^4,5 (Table 1).

Methamphetamine withdrawal is char­acterized by anxiety, depression, and insom­nia. These symptoms generally resolve in a matter of days after the start of withdrawal without pharmacotherapy. In some cases, depression or psychosis becomes chronic, as a result of methamphetamine use itself6 or as an emergent concomitant psychiatric condition.

A sedative-hypnotic medication or an anxiolytic can be used as necessary to ame­liorate insomnia or anxiety, respectively. Prolonged depression can be treated with an antidepressant. An antipsychotic might be indicated for long-term management of patients who have persistent psychosis.

Therapy for methamphetamine abuse
Treatment of methamphetamine abuse— with the goal of stopping drug use—is a complicated matter on 2 counts:
   • No medications are FDA-approved for treating methamphetamine addiction.
   • There are no accepted substitution medications (ie, stimulants that can be used in place of methamphetamine, as is avail­able for opioid addiction).

Pharmacotherapeutic possibilities. The rationale for considering replacement phar­macotherapy is that psychostimulants can counter the cravings, dysphoria, and fatigue produced by methamphetamine withdrawal and can alleviate methamphetamine-related cognitive impairment. Although dextro­amphetamine and other psychostimu­lants have been evaluated in small trials as replacement medication, most countries are reluctant to consider their use, because of the potential for abuse and accompanying liability.

After decades of medication research, several drugs have shown promise for reducing methamphetamine abuse, although results have not been robust (Table 2):
   • Bupropion has shown benefit in reduc­ing methamphetamine use among users with less severe addiction.^7,8
   • Methylphenidate, a psychostimulant FDA-approved for attention-deficit/hyper­activity disorder, was found to reduce methamphetamine use compared with pla­cebo in a European sample of amphetamine injectors who had attained abstinence in a residential program.⁹ Those results were not replicated in a recent study by Miles et al, however.¹⁰ A study with a more clinically realistic approach (ie, not requiring daily clinic attendance, as in the Miles trial) vs placebo for methamphetamine abuse was recently published, with promising results that require confirmation in further study.¹¹
   • Mirtazapine, an antidepressant, has demonstrated efficacy in reducing metham­phetamine use compared with placebo.¹²
   • Modafinil, another medication with stimulant properties, reduced metham­phetamine use in a subgroup analysis of heavy users, compared with placebo.¹³
   • Dextroamphetamine, 60 mg/d, showed no difference in reducing methamphet­amine compared with placebo, but did diminish cravings and withdrawal symptoms.¹⁴

Many medications have yielded negligi­ble results in studies: selegiline, baclofen, ser­traline, topiramate, gabapentin, rivastigmine, risperidone, and ondansetron.¹⁶ Recent eval­uation of disulfiram, vigabatrin, and lobeline also has yielded inconsistent findings.¹⁷

No drug has proved effective for pre­venting relapse; research continues, focus­ing on several types of compounds that target various mechanisms: the dopamine system, the opioid system (by way of the γ-aminobutyric acid inhibitory system), and cortico-limbic reward circuitry.

Once-monthly injectable naltrexone has potential for ameliorating craving and relapse by modulating the opioid receptor system. However, the drug has not been adequately explored in generalizable set­tings of methamphetamine users.

Trials of oral naltrexone in Sweden have shown encouraging results, includ­ing reduced subjective effects and amphet­amine use in open-label trials^18,19; results were replicated in a subsequent placebo-controlled trial.²⁰ In an unpublished study, however, no differences in amphetamine use were found among users randomized to depot naltrexone or placebo.²¹

Depot naltrexone with assured dos­ing might have a role in treating metham­phetamine abuse, however; a combination of depot naltrexone and oral bupropion is being examined in a National Institute on Drug Abuse Clinical Trials Networks study that commenced in 2013. Pairing medica­tions that have different mechanistic targets might work toward promoting cessation of methamphetamine abuse and reducing relapse once patients are abstinent.

In an early phase of research, but show­ing promise based on their ability to target different systems, are:  
   • N-acetylcysteine, modulator of the glutamate system  
   • D3 antagonists and partial agonists²²  
   • varenicline.²³

Potential “vaccines” against metham­phetamine are in preclinical development, including use of a protein carrier or other immune-stimulating molecule to create antibodies that bind methamphetamine in the bloodstream and block its psychoactive effects.^24,25

Sigma receptor effects are being studied in rodents as potential targets to mitigate effects of methamphetamine. The ligand AZ66, a sigma receptor antagonist, has demonstrated efficacy in reducing meth­amphetamine-induced cognitive impair­ment—suggesting that the sigma receptor has a potential role in ameliorating meth­amphetamine-related neurotoxicity.²⁶

Psychosocial and behavioral interven­tions. Among the non-drug treatments that have demonstrated efficacy for treat­ing methamphetamine abuse, cognitive-behavioral therapy (CBT) and contingency management (CM) have been most widely studied and applied in treatment settings.

CBT involves individual or group coun­seling that focuses on relapse prevention skills, including identification of relapse triggers, strategies to diminish cravings, and engagement in alternative non-drug activities^27,28 (Table 3).

CM, which is based on positive rein­forcement, offers tangible reinforcers, or rewards, for behaviors (eg, clinic atten­dance, providing a drug-free urine sam­ple) according to guidelines set by the practitioner. CM-based interventions are the most reliably documented approaches for treating methamphetamine abuse,^29,30 but their utility might prove to be most efficient in combination with medication— once suitable pharmacotherapeutic options emerge.

Although CBT and CM remain accepted standard treatments for methamphetamine abuse, outcomes are suboptimal.²⁷ Both interventions have a high rate of dropout during the first month of treatment and a >50% relapse rate 6 to 19 months after treat­ment ends.^31-33

As with treatment of other substance use disorders, patients who abuse methamphet­amine can benefit from residential treatment in a drug-free setting for ≥30 days.³⁴ In the residential approach, removing access to drugs, drug cues, and drug-using acquain­tances combined with group and individ­ual counseling reaches an inevitable end: discharge into the community. Then the patient’s battle to avoid relapse begins.

Because cognitive impairment is com­mon among patients who abuse metham­phetamine, even after they stop using,³⁵ researchers have examined the potential for increasing participation in psychosocial interventions such as CBT by using medica­tions that might have potential to increase cognitive function, such as modafinil.³⁶ Increased attention and concentration afforded by medication could enhance effi­cacy of CBT. Results of trials and new drug development have been mixed³⁷; no clear candidate for preventing relapse through any of the putative mechanisms of action has emerged.

Relapse is a problematic target for treatment
Ending methamphetamine abuse and sus­taining abstinence from stimulants require a change in the cognitive associations that have been laid down in a drug user’s memory. Relapse occurs because of recalled memories that can be cued, or triggered, by internal or external stimuli. Eliminating drug memories, perhaps assisted by medi­cations such as d-cycloserine (an antago­nist of the N-methyl-d-aspartate receptor), could be useful for suppressing the inclina­tion to relapse.

Last, alternative, non-drug forms of cog­nitive amendment have shown efficacy in preventing relapse: for example, incorpo­rating mindfulness meditation, which has shown promise in managing craving for methamphetamine and decreasing reactiv­ity to environmental cues for drug use.³⁸

Bottom Line
Practitioners who work in emergency, inpatient, and outpatient settings will be called on more and more to treat acute stimulant intoxication and withdrawal, stimulant-induced psychosis, and methamphetamine abuse. Few evidence-based treatments and no FDA-approved medications are available to treat this addiction; many drugs and a few psychotherapeutic techniques have shown promise. Ongoing research promises to deliver medical and behavioral interventions to help patients quit using methamphetamine.

Related Resources
• Karch SB, Drummer O. Karch’s pathology of drug abuse, fifth ed. Boca Raton, FL: CRC Press/Taylor & David; 2013.
• Roll J, Rawson RA, Ling W, eds. Methamphetamine addic­tion: from basic science to treatment. New York, NY: Guilford Press; 2009.
• Sheff D. Beautiful boy: a father’s journey through his son’s addiction. New York, NY: Houghton Mifflin Harcourt Publishing Company; 2008.
• Sheff N. Tweak: growing up on methamphetamines. New York, NY: Antheneum Books for Young Readers; 2007.
• National Institute on Drug Abuse. Drugs of abuse. www. drugabuse.gov/drugs-abuse/methamphetamine.

Drug Brand Names
Baclofen • Lioresal                                Naltrexone (depot) • Vivitrol
Bupropion • Wellbutrin                          Naltrexone (oral) • ReVia
D-cycloserine • Seromycin                     Ondansetron • Zofran
Dexreoamphetaime • Adderall                Risperidone • Risperadal
Disulfiram • Antabuse                            Rivastigimine • Exelon
Gabapentin • Neurontin                          Selegiline• EMSAM
Methylphenidate  •  Ritalin                      Sertraline • Zoloft
Mirtazapine •  Remeron                          Topiramate • Topamax
Modafinil • Provigil                                 Varenicline • Chantix
 N-acetylcysteine • Mucomyst                 Vigabatrin • Sabril

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

The no-show rate is high in ambulatory psychiatric clinics, especially those associated with academic medical institutions, which usually accept all public insurance providers and do not maintain a strict rule by which patients are charged a penalty when they fail to keep a scheduled appointment—a policy that, to the contrary, is customary in private practice. The University of Texas (UT) Health Sciences Center at Houston is primarily an academic medical center with resident-managed, faculty-supervised clinics that provide care to a large volume of patients.

At the UT clinics, we have struggled with a high no-show rate, and were challenged to reduce that rate. Our study of the problem, formulation and application of strat­egies to reduce that rate, and a discussion of our results are provided here for the benefit of psychiatric clinicians who struggle with this problem, to the detriment of their patients’ health and the financial well-being of the practice.

For patients who have a severe psychiatric illness, such as schizophrenia or bipolar disorder, 60% to 70% of the direct cost of their care is attributable to inpatient services.^1,2 Poor medication adherence is a critical factor: It results in exacerbation of symptoms, relapse, and hospitalization. The matter is compounded by patients’ failure to show up for scheduled follow-up appointments.

Studies show that failure to attend routinely scheduled outpatient appointments increases the risk of hospitaliza­tion. Recent research has shown that, among all causes of hospitalization, length of stay and relapse hospitalization are increased in patients with low adherence to their treatment regimen.³ Patients who miss an appoint­ment also are more unwell and more func­tionally impaired—also contributing to a higher risk and rate of rehospitalization.^4,5

To begin to address the problem at UT, we acknowledged that an elevated no-show rate is linked to medication nonadherence, increased risk of re-hospitalization, and increased costs associated with poor care.

Impact of nonadherence
Significant evidence supports the efficacy of antipsychotic medications for treating schizophrenia, of course,⁶ but that success story is undermined by the mean rate of medication nonadherence among schizo­phrenia patients, which can be as high as 49% in studies.⁷ (The actual rate might be higher because those studies do not account for persons who refuse treatment or drop out.)

Nonadherence increases the risk of relapse 3.7-fold, compared with what is seen in patients who adhere to treatment.⁸ Nonadherence to a medication regimen also can increase patients’ risk of engaging in assault and other dangerous behaviors, especially during periods of psychosis.⁸ Variables consistently associated with nonadherence include poor insight, nega­tive attitude or subjective response toward medication, previous nonadherence, sub­stance abuse, shorter duration of illness, inadequate discharge planning or after-care environment, and poorer therapeutic alliance.^7,8

Investigation of medication adher­ence in bipolar disorder suggests that 1 in 3 patients fail to take at least 30% of their medication.⁹ In such patients, medi­cation nonadherence can lead to mania, depression, hospital readmission, sui­cide, increased substance abuse, and nonresponse to treatment.^10,11

Depression also is associated with an increased rate of health care utilization and severe limitation in daily functioning.¹² Compared with non-depressed patients, depressed patients are 3 times more likely to be nonadherent with medical treatment recommendations.¹³ Estimates of medi­cation nonadherence for unipolar and bipolar disorders range from 10% to 60% (median, 40%). This prevalence has not changed significantly with the introduc­tion of new medications._¹⁴

Our literature review of research devoted to reducing no-shows found that few stud­ies have explored this critical treatment con­cern. The no-show rate was higher among younger patients and slightly higher among women, but varied by diagno­sis.¹⁵ The most common reason psychiatric patients gave for missing an appointment  was “forgetting”—a response heard twice as often among no-show patients in psy­chiatry than in other specialties.⁴

Little has been tried to solve the prob­lem. Often, community mental health centers and private practices double-book appointments. Double-booking is intended to reduce the financial burden on the prac­tice when a patient misses an appointment. This approach fails to address nonadher­ence or the poor care that usually results when a patient misses regular outpatient appointments.

Several methods have been employed to improve adherence, such as electronic pill dispensing.¹⁶ Increasing medication adher­ence appears to be a key factor in improv­ing quality-of-life measures in patients with schizophrenia.⁶

The UT project
Methods. This project was completed at the ambulatory psychiatry clinic at the UT Medical School at Houston. The clinic staff comprises residents and faculty members who provide outpatient care. During the study period, the clinic was scheduling as many as 800 office visits a month, includ­ing a mix of new and follow-up appoint­ments. Two weeks’ retrospective data revealed a no-show rate of 31%.

For the project, we defined no-show rate as the total number of patients who missed an appointment or canceled fewer than 24 hours before the scheduled time, divided by the total number of patients scheduled that day.

Table 1 demonstrates the no-show rate calculations for 1 of the weeks preceding the start of the project. Given approxi­mately 800 patient appointments a month, a 31% no-show rate meant that, first, 248 patients failed to receive recommended care and, second, 248 appointment slots were wasted.

We agreed that our current no-show rate of 31% was too high.

We then formed a team of residents, fac­ulty members, therapists, front office staff, an office manager, and an office nurse. We explored and hypothesized what could be contributing to the high no-show rate (Table 2).

By implementing these changes, we aimed to reduce the no-show rate to 20%.

Results. We were able to reduce the no-show rate from a documented average of 31% to an average of 12% during the study period after implementing all the pro­posed changes in the outpatient clinics.

We calculated the no-show rate (as shown in Table 1 for May 2013), then collected the daily no-show rate from June to September 2013 (Figure). With these calculations, we demonstrated a reduction in the no-show rate to 12%. Because of the time and effort required, we reduced data collection from daily to weekly, beginning in September.

Keeping the no-show rate low required consistent effort and monitoring of the newly implemented procedures because even a slight change, such as failure to make reminder calls, resulted in a sudden increase in the no-show rate (that was the case in October of the study period, when we were short-staffed and could not call every patient). Patients told us that it was difficult to ignore a personal call; if they were not planning to keep the appoint­ment, the call allowed them to reschedule on the spot.

We also made sure that current no-show rates were posted in common areas, visible to team members every day.

Discussion
We attempted a literature review of research exploring approaches to reduc­ing the no-show rate but found few studies that explored this critical concern in patient treatment.¹⁵ Some data suggested that, in the setting studied, the no-show rate:
   • was higher among younger patients (age 20 to 39) than older ones (age 60 to 79)
   • was slightly higher in women than in men
   • varied by diagnosis.

We found a paucity of data regarding interventions that can reduce the no-show rate.

Among the changes we made, the one that had the greatest impact was person­alized appointment reminder calls, as evi­denced by our patients’ reports and the increase in the no-show rate when per­sonal calls were not made.

We also realized that, although we had several departmental policies in place regarding appointments, they were not being followed. Raising awareness among team members and their patients also was an effective deterrent to a no-show for an appointment. For example, patients were informed that 3 consecutive no-shows could lead to termination of care. Often, they reacted with surprise to this caution but also voiced a desire to improve their attendance to avoid such an outcome.

We found that establishing common operational definitions is important. It also was important to have a cohesive team, with every member agreeing on goals and changes to operational policies that needed to be implemented. Support from the department chair and the administra­tion, we learned, is vital to the success of such an intervention.

A note about limitations. The goal of the project was limited to reducing the no-show rate. We demonstrated that this is possible among patients who have a severe mental ill­ness, and that reducing the associated waste of time and resources can improve finances in an academic department of psychiatry. We would need additional measures, however, to quantify medication adherence and hos­pitalization; a larger, more inclusive project is needed to demonstrate that reducing the no-show rate reduces the symptomatic bur­den of psychiatric illness.

Comments in conclusion
This project was designed and conducted as a required part of a Clinical Safety and Effectiveness Program at Memorial Hermann Texas Medical Center and the UT Medical School at Houston.¹⁷ Although there was initial hesitancy about attempt­ing to reduce the no-show rate in a chroni­cally mentally ill population, the success of this project—indeed, it surpassed its proposed goals—demonstrates that opera­tional changes in any clinic can reduce the no-show rate. It also is important to main­tain operational changes, however; with­out consistent effort, desired results cannot be sustained.

Last, it is possible to replicate the meth­odology of this project and thereby attempt to reduce the no-show rate in other divi­sions of medicine that offer care to chroni­cally ill patients, such as pediatrics and family medicine.

Bottom Line
Failure to attend routinely scheduled outpatient appointments increases a patient’s functional impairment and risk of hospitalization. Patient education, appointment reminder phone calls, revised policies and procedures, and transparency regarding the no-show rate can reduce the number of missed appointments and improve patient outcomes.

Related Resources
• Mitchell AJ, Selmes T. Why don’t patients attend their ap­pointments? Maintaining engagement with psychiatric ser­vices. Advances in Psychiatric Treatment. 2007;13:423-434.
• Molfenter T. Reducing appointment no-shows: going from theory to practice. Subst Use Misuse. 2013;48(9):743-749.
• Williston MA, Block-Lerner J, Wolanin A, et al. Brief acceptance-based intervention for increasing intake attendance at a com­munity mental health center. Psychol Serv. 2014;11(3):324-332.

Disclosure
Dr. Gajwani receives grant or research support from the National Institute on Mental Health, the National Institute of Drug Abuse, The Stanley Foundation, and Forest Laboratories, Inc. He is a member of the speakers’ bureau of AstraZeneca, Merck, Otsuka America Pharmaceutical, and Sunovion Pharmaceuticals.

The no-show rate is high in ambulatory psychiatric clinics, especially those associated with academic medical institutions, which usually accept all public insurance providers and do not maintain a strict rule by which patients are charged a penalty when they fail to keep a scheduled appointment—a policy that, to the contrary, is customary in private practice. The University of Texas (UT) Health Sciences Center at Houston is primarily an academic medical center with resident-managed, faculty-supervised clinics that provide care to a large volume of patients.

At the UT clinics, we have struggled with a high no-show rate, and were challenged to reduce that rate. Our study of the problem, formulation and application of strat­egies to reduce that rate, and a discussion of our results are provided here for the benefit of psychiatric clinicians who struggle with this problem, to the detriment of their patients’ health and the financial well-being of the practice.

For patients who have a severe psychiatric illness, such as schizophrenia or bipolar disorder, 60% to 70% of the direct cost of their care is attributable to inpatient services.^1,2 Poor medication adherence is a critical factor: It results in exacerbation of symptoms, relapse, and hospitalization. The matter is compounded by patients’ failure to show up for scheduled follow-up appointments.

Studies show that failure to attend routinely scheduled outpatient appointments increases the risk of hospitaliza­tion. Recent research has shown that, among all causes of hospitalization, length of stay and relapse hospitalization are increased in patients with low adherence to their treatment regimen.³ Patients who miss an appoint­ment also are more unwell and more func­tionally impaired—also contributing to a higher risk and rate of rehospitalization.^4,5

To begin to address the problem at UT, we acknowledged that an elevated no-show rate is linked to medication nonadherence, increased risk of re-hospitalization, and increased costs associated with poor care.

Impact of nonadherence
Significant evidence supports the efficacy of antipsychotic medications for treating schizophrenia, of course,⁶ but that success story is undermined by the mean rate of medication nonadherence among schizo­phrenia patients, which can be as high as 49% in studies.⁷ (The actual rate might be higher because those studies do not account for persons who refuse treatment or drop out.)

Nonadherence increases the risk of relapse 3.7-fold, compared with what is seen in patients who adhere to treatment.⁸ Nonadherence to a medication regimen also can increase patients’ risk of engaging in assault and other dangerous behaviors, especially during periods of psychosis.⁸ Variables consistently associated with nonadherence include poor insight, nega­tive attitude or subjective response toward medication, previous nonadherence, sub­stance abuse, shorter duration of illness, inadequate discharge planning or after-care environment, and poorer therapeutic alliance.^7,8

Investigation of medication adher­ence in bipolar disorder suggests that 1 in 3 patients fail to take at least 30% of their medication.⁹ In such patients, medi­cation nonadherence can lead to mania, depression, hospital readmission, sui­cide, increased substance abuse, and nonresponse to treatment.^10,11

Depression also is associated with an increased rate of health care utilization and severe limitation in daily functioning.¹² Compared with non-depressed patients, depressed patients are 3 times more likely to be nonadherent with medical treatment recommendations.¹³ Estimates of medi­cation nonadherence for unipolar and bipolar disorders range from 10% to 60% (median, 40%). This prevalence has not changed significantly with the introduc­tion of new medications._¹⁴

Our literature review of research devoted to reducing no-shows found that few stud­ies have explored this critical treatment con­cern. The no-show rate was higher among younger patients and slightly higher among women, but varied by diagno­sis.¹⁵ The most common reason psychiatric patients gave for missing an appointment  was “forgetting”—a response heard twice as often among no-show patients in psy­chiatry than in other specialties.⁴

Little has been tried to solve the prob­lem. Often, community mental health centers and private practices double-book appointments. Double-booking is intended to reduce the financial burden on the prac­tice when a patient misses an appointment. This approach fails to address nonadher­ence or the poor care that usually results when a patient misses regular outpatient appointments.

Several methods have been employed to improve adherence, such as electronic pill dispensing.¹⁶ Increasing medication adher­ence appears to be a key factor in improv­ing quality-of-life measures in patients with schizophrenia.⁶

The UT project
Methods. This project was completed at the ambulatory psychiatry clinic at the UT Medical School at Houston. The clinic staff comprises residents and faculty members who provide outpatient care. During the study period, the clinic was scheduling as many as 800 office visits a month, includ­ing a mix of new and follow-up appoint­ments. Two weeks’ retrospective data revealed a no-show rate of 31%.

For the project, we defined no-show rate as the total number of patients who missed an appointment or canceled fewer than 24 hours before the scheduled time, divided by the total number of patients scheduled that day.

Table 1 demonstrates the no-show rate calculations for 1 of the weeks preceding the start of the project. Given approxi­mately 800 patient appointments a month, a 31% no-show rate meant that, first, 248 patients failed to receive recommended care and, second, 248 appointment slots were wasted.

We agreed that our current no-show rate of 31% was too high.

We then formed a team of residents, fac­ulty members, therapists, front office staff, an office manager, and an office nurse. We explored and hypothesized what could be contributing to the high no-show rate (Table 2).

By implementing these changes, we aimed to reduce the no-show rate to 20%.

Results. We were able to reduce the no-show rate from a documented average of 31% to an average of 12% during the study period after implementing all the pro­posed changes in the outpatient clinics.

We calculated the no-show rate (as shown in Table 1 for May 2013), then collected the daily no-show rate from June to September 2013 (Figure). With these calculations, we demonstrated a reduction in the no-show rate to 12%. Because of the time and effort required, we reduced data collection from daily to weekly, beginning in September.

Keeping the no-show rate low required consistent effort and monitoring of the newly implemented procedures because even a slight change, such as failure to make reminder calls, resulted in a sudden increase in the no-show rate (that was the case in October of the study period, when we were short-staffed and could not call every patient). Patients told us that it was difficult to ignore a personal call; if they were not planning to keep the appoint­ment, the call allowed them to reschedule on the spot.

We also made sure that current no-show rates were posted in common areas, visible to team members every day.

Discussion
We attempted a literature review of research exploring approaches to reduc­ing the no-show rate but found few studies that explored this critical concern in patient treatment.¹⁵ Some data suggested that, in the setting studied, the no-show rate:
   • was higher among younger patients (age 20 to 39) than older ones (age 60 to 79)
   • was slightly higher in women than in men
   • varied by diagnosis.

We found a paucity of data regarding interventions that can reduce the no-show rate.

Among the changes we made, the one that had the greatest impact was person­alized appointment reminder calls, as evi­denced by our patients’ reports and the increase in the no-show rate when per­sonal calls were not made.

We also realized that, although we had several departmental policies in place regarding appointments, they were not being followed. Raising awareness among team members and their patients also was an effective deterrent to a no-show for an appointment. For example, patients were informed that 3 consecutive no-shows could lead to termination of care. Often, they reacted with surprise to this caution but also voiced a desire to improve their attendance to avoid such an outcome.

We found that establishing common operational definitions is important. It also was important to have a cohesive team, with every member agreeing on goals and changes to operational policies that needed to be implemented. Support from the department chair and the administra­tion, we learned, is vital to the success of such an intervention.

A note about limitations. The goal of the project was limited to reducing the no-show rate. We demonstrated that this is possible among patients who have a severe mental ill­ness, and that reducing the associated waste of time and resources can improve finances in an academic department of psychiatry. We would need additional measures, however, to quantify medication adherence and hos­pitalization; a larger, more inclusive project is needed to demonstrate that reducing the no-show rate reduces the symptomatic bur­den of psychiatric illness.

Comments in conclusion
This project was designed and conducted as a required part of a Clinical Safety and Effectiveness Program at Memorial Hermann Texas Medical Center and the UT Medical School at Houston.¹⁷ Although there was initial hesitancy about attempt­ing to reduce the no-show rate in a chroni­cally mentally ill population, the success of this project—indeed, it surpassed its proposed goals—demonstrates that opera­tional changes in any clinic can reduce the no-show rate. It also is important to main­tain operational changes, however; with­out consistent effort, desired results cannot be sustained.

Last, it is possible to replicate the meth­odology of this project and thereby attempt to reduce the no-show rate in other divi­sions of medicine that offer care to chroni­cally ill patients, such as pediatrics and family medicine.

Bottom Line
Failure to attend routinely scheduled outpatient appointments increases a patient’s functional impairment and risk of hospitalization. Patient education, appointment reminder phone calls, revised policies and procedures, and transparency regarding the no-show rate can reduce the number of missed appointments and improve patient outcomes.

Related Resources
• Mitchell AJ, Selmes T. Why don’t patients attend their ap­pointments? Maintaining engagement with psychiatric ser­vices. Advances in Psychiatric Treatment. 2007;13:423-434.
• Molfenter T. Reducing appointment no-shows: going from theory to practice. Subst Use Misuse. 2013;48(9):743-749.
• Williston MA, Block-Lerner J, Wolanin A, et al. Brief acceptance-based intervention for increasing intake attendance at a com­munity mental health center. Psychol Serv. 2014;11(3):324-332.

Disclosure
Dr. Gajwani receives grant or research support from the National Institute on Mental Health, the National Institute of Drug Abuse, The Stanley Foundation, and Forest Laboratories, Inc. He is a member of the speakers’ bureau of AstraZeneca, Merck, Otsuka America Pharmaceutical, and Sunovion Pharmaceuticals.

The no-show rate is high in ambulatory psychiatric clinics, especially those associated with academic medical institutions, which usually accept all public insurance providers and do not maintain a strict rule by which patients are charged a penalty when they fail to keep a scheduled appointment—a policy that, to the contrary, is customary in private practice. The University of Texas (UT) Health Sciences Center at Houston is primarily an academic medical center with resident-managed, faculty-supervised clinics that provide care to a large volume of patients.

At the UT clinics, we have struggled with a high no-show rate, and were challenged to reduce that rate. Our study of the problem, formulation and application of strat­egies to reduce that rate, and a discussion of our results are provided here for the benefit of psychiatric clinicians who struggle with this problem, to the detriment of their patients’ health and the financial well-being of the practice.

For patients who have a severe psychiatric illness, such as schizophrenia or bipolar disorder, 60% to 70% of the direct cost of their care is attributable to inpatient services.^1,2 Poor medication adherence is a critical factor: It results in exacerbation of symptoms, relapse, and hospitalization. The matter is compounded by patients’ failure to show up for scheduled follow-up appointments.

Studies show that failure to attend routinely scheduled outpatient appointments increases the risk of hospitaliza­tion. Recent research has shown that, among all causes of hospitalization, length of stay and relapse hospitalization are increased in patients with low adherence to their treatment regimen.³ Patients who miss an appoint­ment also are more unwell and more func­tionally impaired—also contributing to a higher risk and rate of rehospitalization.^4,5

To begin to address the problem at UT, we acknowledged that an elevated no-show rate is linked to medication nonadherence, increased risk of re-hospitalization, and increased costs associated with poor care.

Impact of nonadherence
Significant evidence supports the efficacy of antipsychotic medications for treating schizophrenia, of course,⁶ but that success story is undermined by the mean rate of medication nonadherence among schizo­phrenia patients, which can be as high as 49% in studies.⁷ (The actual rate might be higher because those studies do not account for persons who refuse treatment or drop out.)

Nonadherence increases the risk of relapse 3.7-fold, compared with what is seen in patients who adhere to treatment.⁸ Nonadherence to a medication regimen also can increase patients’ risk of engaging in assault and other dangerous behaviors, especially during periods of psychosis.⁸ Variables consistently associated with nonadherence include poor insight, nega­tive attitude or subjective response toward medication, previous nonadherence, sub­stance abuse, shorter duration of illness, inadequate discharge planning or after-care environment, and poorer therapeutic alliance.^7,8

Investigation of medication adher­ence in bipolar disorder suggests that 1 in 3 patients fail to take at least 30% of their medication.⁹ In such patients, medi­cation nonadherence can lead to mania, depression, hospital readmission, sui­cide, increased substance abuse, and nonresponse to treatment.^10,11

Depression also is associated with an increased rate of health care utilization and severe limitation in daily functioning.¹² Compared with non-depressed patients, depressed patients are 3 times more likely to be nonadherent with medical treatment recommendations.¹³ Estimates of medi­cation nonadherence for unipolar and bipolar disorders range from 10% to 60% (median, 40%). This prevalence has not changed significantly with the introduc­tion of new medications._¹⁴

Our literature review of research devoted to reducing no-shows found that few stud­ies have explored this critical treatment con­cern. The no-show rate was higher among younger patients and slightly higher among women, but varied by diagno­sis.¹⁵ The most common reason psychiatric patients gave for missing an appointment  was “forgetting”—a response heard twice as often among no-show patients in psy­chiatry than in other specialties.⁴

Little has been tried to solve the prob­lem. Often, community mental health centers and private practices double-book appointments. Double-booking is intended to reduce the financial burden on the prac­tice when a patient misses an appointment. This approach fails to address nonadher­ence or the poor care that usually results when a patient misses regular outpatient appointments.

Several methods have been employed to improve adherence, such as electronic pill dispensing.¹⁶ Increasing medication adher­ence appears to be a key factor in improv­ing quality-of-life measures in patients with schizophrenia.⁶

The UT project
Methods. This project was completed at the ambulatory psychiatry clinic at the UT Medical School at Houston. The clinic staff comprises residents and faculty members who provide outpatient care. During the study period, the clinic was scheduling as many as 800 office visits a month, includ­ing a mix of new and follow-up appoint­ments. Two weeks’ retrospective data revealed a no-show rate of 31%.

For the project, we defined no-show rate as the total number of patients who missed an appointment or canceled fewer than 24 hours before the scheduled time, divided by the total number of patients scheduled that day.

Table 1 demonstrates the no-show rate calculations for 1 of the weeks preceding the start of the project. Given approxi­mately 800 patient appointments a month, a 31% no-show rate meant that, first, 248 patients failed to receive recommended care and, second, 248 appointment slots were wasted.

We agreed that our current no-show rate of 31% was too high.

We then formed a team of residents, fac­ulty members, therapists, front office staff, an office manager, and an office nurse. We explored and hypothesized what could be contributing to the high no-show rate (Table 2).

By implementing these changes, we aimed to reduce the no-show rate to 20%.

Results. We were able to reduce the no-show rate from a documented average of 31% to an average of 12% during the study period after implementing all the pro­posed changes in the outpatient clinics.

We calculated the no-show rate (as shown in Table 1 for May 2013), then collected the daily no-show rate from June to September 2013 (Figure). With these calculations, we demonstrated a reduction in the no-show rate to 12%. Because of the time and effort required, we reduced data collection from daily to weekly, beginning in September.

Keeping the no-show rate low required consistent effort and monitoring of the newly implemented procedures because even a slight change, such as failure to make reminder calls, resulted in a sudden increase in the no-show rate (that was the case in October of the study period, when we were short-staffed and could not call every patient). Patients told us that it was difficult to ignore a personal call; if they were not planning to keep the appoint­ment, the call allowed them to reschedule on the spot.

We also made sure that current no-show rates were posted in common areas, visible to team members every day.

Discussion
We attempted a literature review of research exploring approaches to reduc­ing the no-show rate but found few studies that explored this critical concern in patient treatment.¹⁵ Some data suggested that, in the setting studied, the no-show rate:
   • was higher among younger patients (age 20 to 39) than older ones (age 60 to 79)
   • was slightly higher in women than in men
   • varied by diagnosis.

We found a paucity of data regarding interventions that can reduce the no-show rate.

Among the changes we made, the one that had the greatest impact was person­alized appointment reminder calls, as evi­denced by our patients’ reports and the increase in the no-show rate when per­sonal calls were not made.

We also realized that, although we had several departmental policies in place regarding appointments, they were not being followed. Raising awareness among team members and their patients also was an effective deterrent to a no-show for an appointment. For example, patients were informed that 3 consecutive no-shows could lead to termination of care. Often, they reacted with surprise to this caution but also voiced a desire to improve their attendance to avoid such an outcome.

We found that establishing common operational definitions is important. It also was important to have a cohesive team, with every member agreeing on goals and changes to operational policies that needed to be implemented. Support from the department chair and the administra­tion, we learned, is vital to the success of such an intervention.

A note about limitations. The goal of the project was limited to reducing the no-show rate. We demonstrated that this is possible among patients who have a severe mental ill­ness, and that reducing the associated waste of time and resources can improve finances in an academic department of psychiatry. We would need additional measures, however, to quantify medication adherence and hos­pitalization; a larger, more inclusive project is needed to demonstrate that reducing the no-show rate reduces the symptomatic bur­den of psychiatric illness.

Comments in conclusion
This project was designed and conducted as a required part of a Clinical Safety and Effectiveness Program at Memorial Hermann Texas Medical Center and the UT Medical School at Houston.¹⁷ Although there was initial hesitancy about attempt­ing to reduce the no-show rate in a chroni­cally mentally ill population, the success of this project—indeed, it surpassed its proposed goals—demonstrates that opera­tional changes in any clinic can reduce the no-show rate. It also is important to main­tain operational changes, however; with­out consistent effort, desired results cannot be sustained.

Last, it is possible to replicate the meth­odology of this project and thereby attempt to reduce the no-show rate in other divi­sions of medicine that offer care to chroni­cally ill patients, such as pediatrics and family medicine.

Bottom Line
Failure to attend routinely scheduled outpatient appointments increases a patient’s functional impairment and risk of hospitalization. Patient education, appointment reminder phone calls, revised policies and procedures, and transparency regarding the no-show rate can reduce the number of missed appointments and improve patient outcomes.

Related Resources
• Mitchell AJ, Selmes T. Why don’t patients attend their ap­pointments? Maintaining engagement with psychiatric ser­vices. Advances in Psychiatric Treatment. 2007;13:423-434.
• Molfenter T. Reducing appointment no-shows: going from theory to practice. Subst Use Misuse. 2013;48(9):743-749.
• Williston MA, Block-Lerner J, Wolanin A, et al. Brief acceptance-based intervention for increasing intake attendance at a com­munity mental health center. Psychol Serv. 2014;11(3):324-332.

Disclosure
Dr. Gajwani receives grant or research support from the National Institute on Mental Health, the National Institute of Drug Abuse, The Stanley Foundation, and Forest Laboratories, Inc. He is a member of the speakers’ bureau of AstraZeneca, Merck, Otsuka America Pharmaceutical, and Sunovion Pharmaceuticals.