Current Psychiatry

Psychiatrists occasionally encounter a case of folie à deux, where 2 persons share the same false belief. Paradoxically, it is more common for a large number of people to share a false belief (folie en masse) and uphold it as fact because the idea appears enticingly valid as an “explanation” for a problem or event.

“Conspiracy theories” abound in our society and yet conspiracy theory advocates would express shock and disdain at the infamous event when 918 followers of Jim Jones drank cyanide-laced Kool-Aid because they believed their leader’s irrational ideas. Apart from recognizable cults—some of whom claim to have their own “solutions” for mental illness—many ordinary people uphold beliefs that are not supported by evidence but widely “accepted” as true:

Persons with psychosis are dangerous. This incorrect belief was prevalent before the tragic events at Virginia Tech and Tucson, AZ (remember the “Son of Sam” in New York?) and was reinforced by them. Clinicians know that, similar to the general population, only a small proportion of persons suffering from a psychotic illness exhibit violent behavior. In fact, their illness renders them more likely to be victims than perpetrators of crime.

Atypical antipsychotics are associated with high weight gain, but older neuroleptics are not. Many psychiatrists uphold this clinical mantra and believe that older antipsychotics, such as haloperidol, which cause a lot of movement disorders, are associated with minimal weight gain. Most also believe that some atypicals are weight-neutral compared with other atypicals. The evidence from the European First Episode Schizophrenia Trial (EUFEST) debunked both beliefs by finding substantial weight gain with all antipsychotic drugs, old or new, after 1 year of treatment with haloperidol and several atypicals ( Table ).¹ Neither old antipsychotics, such as haloperidol, nor metabolically “benign” atypicals, such as ziprasidone, are exceptions. Yet this belief likely will persist.

Table 1

Weight gain with antipsychotics: EUFEST results

The U. S. obesity epidemic is caused by too much fast food and too little exercise. This widely accepted explanation sounds like a no-brainer. However, by taking a “big-picture” view, a recent study² pointed to completely different reasons for rising obesity in the United States. Researchers found that other species such as rats and mice (rarely seen waiting in line at McDonald’s) experienced dramatic per-decade increases in obesity rates over the past 50 years, including 38% in pet cats, 34% in chimpanzees in research labs, 21% in alley rats, and 12% in government lab mice. Only pet dogs escaped the escalating obesity rates with 3% per decade. Alternate explanations for rising obesity include less sleep, which increases ghrelin (an appetite-stimulating hormone) and decreases leptin (a satiety hormone); proliferation of fat cells from chemicals such as bisphenol A; central heating (less burning of calories) and air conditioning (prevents the appetite-suppressing heat of summer); infections such as adenoviruses that can cause obesity in animals; and changes in gut bacteria, some of which increase caloric extraction from food.

Many false beliefs have been adopted by a large proportion of the general population. This tendency for folie en masse is consistent with studies that show pre-psychotic thinking is found in more than half of the general population, suggesting a continuum between psychosis proneness and clinical psychosis.³ This raises the question: could psychosis proneness mean that the brain can produce its own “endogenous” Kool-Aid?

Psychiatrists occasionally encounter a case of folie à deux, where 2 persons share the same false belief. Paradoxically, it is more common for a large number of people to share a false belief (folie en masse) and uphold it as fact because the idea appears enticingly valid as an “explanation” for a problem or event.

“Conspiracy theories” abound in our society and yet conspiracy theory advocates would express shock and disdain at the infamous event when 918 followers of Jim Jones drank cyanide-laced Kool-Aid because they believed their leader’s irrational ideas. Apart from recognizable cults—some of whom claim to have their own “solutions” for mental illness—many ordinary people uphold beliefs that are not supported by evidence but widely “accepted” as true:

Persons with psychosis are dangerous. This incorrect belief was prevalent before the tragic events at Virginia Tech and Tucson, AZ (remember the “Son of Sam” in New York?) and was reinforced by them. Clinicians know that, similar to the general population, only a small proportion of persons suffering from a psychotic illness exhibit violent behavior. In fact, their illness renders them more likely to be victims than perpetrators of crime.

Atypical antipsychotics are associated with high weight gain, but older neuroleptics are not. Many psychiatrists uphold this clinical mantra and believe that older antipsychotics, such as haloperidol, which cause a lot of movement disorders, are associated with minimal weight gain. Most also believe that some atypicals are weight-neutral compared with other atypicals. The evidence from the European First Episode Schizophrenia Trial (EUFEST) debunked both beliefs by finding substantial weight gain with all antipsychotic drugs, old or new, after 1 year of treatment with haloperidol and several atypicals ( Table ).¹ Neither old antipsychotics, such as haloperidol, nor metabolically “benign” atypicals, such as ziprasidone, are exceptions. Yet this belief likely will persist.

Table 1

Weight gain with antipsychotics: EUFEST results

The U. S. obesity epidemic is caused by too much fast food and too little exercise. This widely accepted explanation sounds like a no-brainer. However, by taking a “big-picture” view, a recent study² pointed to completely different reasons for rising obesity in the United States. Researchers found that other species such as rats and mice (rarely seen waiting in line at McDonald’s) experienced dramatic per-decade increases in obesity rates over the past 50 years, including 38% in pet cats, 34% in chimpanzees in research labs, 21% in alley rats, and 12% in government lab mice. Only pet dogs escaped the escalating obesity rates with 3% per decade. Alternate explanations for rising obesity include less sleep, which increases ghrelin (an appetite-stimulating hormone) and decreases leptin (a satiety hormone); proliferation of fat cells from chemicals such as bisphenol A; central heating (less burning of calories) and air conditioning (prevents the appetite-suppressing heat of summer); infections such as adenoviruses that can cause obesity in animals; and changes in gut bacteria, some of which increase caloric extraction from food.

Many false beliefs have been adopted by a large proportion of the general population. This tendency for folie en masse is consistent with studies that show pre-psychotic thinking is found in more than half of the general population, suggesting a continuum between psychosis proneness and clinical psychosis.³ This raises the question: could psychosis proneness mean that the brain can produce its own “endogenous” Kool-Aid?

Psychiatrists occasionally encounter a case of folie à deux, where 2 persons share the same false belief. Paradoxically, it is more common for a large number of people to share a false belief (folie en masse) and uphold it as fact because the idea appears enticingly valid as an “explanation” for a problem or event.

“Conspiracy theories” abound in our society and yet conspiracy theory advocates would express shock and disdain at the infamous event when 918 followers of Jim Jones drank cyanide-laced Kool-Aid because they believed their leader’s irrational ideas. Apart from recognizable cults—some of whom claim to have their own “solutions” for mental illness—many ordinary people uphold beliefs that are not supported by evidence but widely “accepted” as true:

Persons with psychosis are dangerous. This incorrect belief was prevalent before the tragic events at Virginia Tech and Tucson, AZ (remember the “Son of Sam” in New York?) and was reinforced by them. Clinicians know that, similar to the general population, only a small proportion of persons suffering from a psychotic illness exhibit violent behavior. In fact, their illness renders them more likely to be victims than perpetrators of crime.

Atypical antipsychotics are associated with high weight gain, but older neuroleptics are not. Many psychiatrists uphold this clinical mantra and believe that older antipsychotics, such as haloperidol, which cause a lot of movement disorders, are associated with minimal weight gain. Most also believe that some atypicals are weight-neutral compared with other atypicals. The evidence from the European First Episode Schizophrenia Trial (EUFEST) debunked both beliefs by finding substantial weight gain with all antipsychotic drugs, old or new, after 1 year of treatment with haloperidol and several atypicals ( Table ).¹ Neither old antipsychotics, such as haloperidol, nor metabolically “benign” atypicals, such as ziprasidone, are exceptions. Yet this belief likely will persist.

Table 1

Weight gain with antipsychotics: EUFEST results

The U. S. obesity epidemic is caused by too much fast food and too little exercise. This widely accepted explanation sounds like a no-brainer. However, by taking a “big-picture” view, a recent study² pointed to completely different reasons for rising obesity in the United States. Researchers found that other species such as rats and mice (rarely seen waiting in line at McDonald’s) experienced dramatic per-decade increases in obesity rates over the past 50 years, including 38% in pet cats, 34% in chimpanzees in research labs, 21% in alley rats, and 12% in government lab mice. Only pet dogs escaped the escalating obesity rates with 3% per decade. Alternate explanations for rising obesity include less sleep, which increases ghrelin (an appetite-stimulating hormone) and decreases leptin (a satiety hormone); proliferation of fat cells from chemicals such as bisphenol A; central heating (less burning of calories) and air conditioning (prevents the appetite-suppressing heat of summer); infections such as adenoviruses that can cause obesity in animals; and changes in gut bacteria, some of which increase caloric extraction from food.

Many false beliefs have been adopted by a large proportion of the general population. This tendency for folie en masse is consistent with studies that show pre-psychotic thinking is found in more than half of the general population, suggesting a continuum between psychosis proneness and clinical psychosis.³ This raises the question: could psychosis proneness mean that the brain can produce its own “endogenous” Kool-Aid?

Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/adapting-dialectical-behavior-therapy.html#comments

Treating suicidal adolescents is fraught with challenges. Antidepressants may be associated with increased suicidal ideation in adolescents,^1-3 although some data suggest that increased adolescent suicide rates are correlated with decreases in antidepressant prescribing.⁴ Adolescents hospitalized after a suicide attempt are likely to attempt suicide again after they are discharged.^5,6 Such patients might not attend outpatient psychotherapy; a study of 167 adolescents discharged after a suicide attempt found that 26% never attended follow-up appointments and 11% went once.⁷

Emerging research supports the effectiveness of dialectical behavior therapy (DBT) for suicidal adolescents. DBT is a form of cognitive-behavioral therapy that combines individual therapy, skills training, and telephone coaching and is implemented by a therapist consultation team that meets weekly. This article reviews evidence supporting the efficacy of DBT for suicidal adolescents and describes principles of outpatient DBT for these patients as developed by Miller et al.⁸

Evidence of DBT’s effectiveness

A review of DBT research found strong evidence for DBT’s effectiveness for suicidal adults.⁹ Recently, DBT has been adapted to treat adolescents with suicidal behavior and nonsuicidal self-injury (NSSI).^10-15

In a nonrandomized trial, Rathus and Miller¹⁰ compared 29 suicidal adolescent outpatients receiving DBT with 82 participants receiving treatment as usual (TAU). Patients were assigned to DBT if they had a suicide attempt in the previous 16 weeks and ≥3 borderline personality disorder (BPD) features or to TAU if they met only 1 of those conditions. Patients in the DBT group had more axis I disorders and pretreatment hospitalizations than the TAU group. Compared with those receiving TAU, patients treated with DBT had fewer hospitalizations (13% in TAU vs 0% in DBT) and a lower dropout rate (60% in TAU vs 38% in DBT). The DBT group experienced significant reductions in suicidal ideation, BPD symptoms, and general psychiatric symptoms. There was 1 suicide attempt in the DBT group vs 7 attempts in the TAU group; however, this difference was not statistically significant.

Woodberry and Popenoe¹¹ examined the use of DBT for suicidal adolescents and their families in a community outpatient clinic. Adolescents reported reductions in overall symptoms, depression, anger, dissociative symptoms, and urges for intentional self-injury. Parents reported reductions in their children’s problem behaviors and in their own depressive symptoms. In a study of DBT in 16 adolescent females with chronic intentional self-injury, patients reported significant reductions in incidents of intentional self-injury, depression, and hopelessness, and increases in overall functioning.¹²

Three studies have examined using DBT for suicidal adolescents in residential facilities. In a pilot study, Katz et al¹³ compared DBT with TAU for 62 suicidal adolescent inpatients. At 1-year follow-up, both groups experienced significant reductions in suicidal ideation, NSSI, and depression. However, compared with those who received TAU, DBT patients had fewer behavioral problems during hospitalization. Sunseri¹⁴ used DBT to treat adolescent females in residential treatment. After DBT was implemented, residents were hospitalized because of NSSI and suicidality for fewer days than before DBT. Trupin et al¹⁵ taught DBT to staff who worked with female adolescent offenders at a juvenile rehabilitation facility. After the staff implemented DBT, the rates of problem behaviors and punishment by staff decreased on 1 unit; there were no behavior or punishment changes on another unit.

Theoretical foundations

Biosocial theory. The problems DBT treats in suicidal adolescents include emotion dysregulation, interpersonal conflict, impulsivity, cognitive dysregulation, and self-dysregulation.⁸ The biosocial theory postulates that these problems are the result of the transaction, or reciprocal relationship, between biologic predispositions and an invalidating environment. The biosocial theory suggests 3 biologic characteristics often are found among suicidal adolescents:

• high emotional sensitivity
• high extremity in reactions
• a slow return to baseline after experiencing a surge in affect.⁸

Although these characteristics indicate higher emotionality, they are not sufficient to account for suicidal adolescents’ difficulties. Problems arise when individuals with these biologic characteristics are raised in an invalidating environment, where the adolescent does not learn how to regulate emotions. Common characteristics of invalidating environments and their effects on adolescents are described in Table 1 .⁸

Treatment theory. DBT for suicidal adolescents focuses on a synthesis between 2 seemingly opposite treatment strategies: change and acceptance. The change focus is derived from behavioral science, and treatment incorporates standard behavior therapy practices, including chain analysis (described below), skills training, contingency management, and exposure.

The acceptance focus draws upon principles of Zen and other Eastern spiritual traditions. Therapists teach patients to accept reality as it is in this moment, without judgment. A key extension of this acceptance is the use of validation—radical acceptance and acknowledgement that all behavior has validity and understandability. DBT therapists strive to use 6 levels of validation with their patients ( Table 2 ),¹⁶ which often is a critical strategy for adolescents who reside in an invalidating environment.

DBT attempts to synthesize the acceptance-based Zen tradition with the change-based strategies of behavioral science through a dialectical philosophy. A fundamental postulate of dialectical philosophy is that a tension occurs when an initial truth or thesis is opposed by an apparently contradictory truth or antithesis.⁸ DBT therapists work with adolescents to find a synthesis that is the “middle path, “ which includes the truth in both positions as well as what is left out of both. For an example of how this might work for an adolescent patient with NSSI, visit this article at CurrentPsychiatry.com.

Table 1

Characteristics of an invalidating environment

Table 2

6 levels of validation employed by DBT therapists

How DBT works

DBT serves 5 functions. It enhances patient capabilities, increases patient motivation, structures the environment to increase the likelihood of success, works to assure generalization from therapy to the natural environment, and enhances therapists’ capabilities and motivation to treat patients effectively.⁸ Outpatient DBT for suicidal adolescents uses 4 modes of treatment:

• weekly individual therapy
• weekly skills training
• telephone coaching
• weekly therapist consultation team meetings.⁸

Although Linehan’s original research with adults was based on a 1-year treatment model,¹⁷ treatment lasts 12 to 16 weeks in the adolescent DBT model designed and studied by Miller et al.⁸ Treatment for adolescents is shorter because research indicates that suicidal adolescents frequently fail to complete longer courses of therapy.¹⁸

Individual therapy. The rank-ordered targets of individual therapy in the first stage of DBT are to:

1. eliminate life-threatening behavior, including NSSI
2. stop therapy-interfering behaviors (eg, not showing up to sessions)
3. change behaviors that interfere with the adolescent’s quality of life (eg, substance abuse)
4. enhance the adolescent’s use of skills.⁸

The individual therapist sets treatment goals in accord with these targets, monitors progress, integrates all modes of therapy, and balances acceptance and validation of the patient with being a catalyst for change. Family members may be included in therapy sessions when family problems emerge as the highest priority.

DBT therapists use chain analysis—which is a process of assessing the series of events, link by link, that lead from a prompting event to a problem behavior (eg, suicide attempt)—to assess problematic behavior and identify methods of change.⁸ The therapist and patient use this process to develop alternative behaviors for the patient to use to reach a more effective outcome.

DBT therapists also ask adolescents to fill out a daily diary card that tracks targeted behaviors, including NSSI, suicidal urges, and important emotions. The diary card helps the therapist determine what needs to be targeted in therapy, increases mindfulness and understanding of problem behaviors, and helps change targeted behavior.

Skills training addresses skills deficits believed to be causing the suicidal adolescent’s problems. DBT systematically teaches 5 skill sets:

• emotional regulation
• mindfulness
• interpersonal effectiveness
• distress tolerance
• “walking the middle path. “⁸

These skills are designed to treat specific problems common among suicidal adolescents and their families. For example, suicidal adolescents often experience a spike in emotions that leads to urges for ineffective behavior, such as attempting suicide or attacking another person. Table 3 provides steps that teach “opposite action, “ which can reduce ineffective emotions and problematic urges associated with these emotions. Table 4 provides mindfulness practices that can help patients address problems such as mindlessness and avoiding the present moment. Although adolescent DBT skills training is similar to that in adults, Table 5 describes key differences.

Table 3

Teaching adolescents ‘opposite action’

Table 4

Mindfulness practices: Teach adolescents to live in the present moment

Table 5

Adapting DBT skills training for adolescents

Telephone consultation. The purpose of brief (5 to 15 minutes) telephone consultations between a patient and therapist is to:

• enhance the likelihood of effective behavior
• coach the use of skills
• decrease the likelihood of problematic behaviors.

DBT telephone consultation for adults differs from that for suicidal adolescents. In DBT for adults, if a patient engages in NSSI or suicidal behavior, there is no telephone contact for 24 hours. This rule aims to avoid reinforcing the behavior with additional contact. However, this rule does not apply to adolescents because restricting adolescents’ access to resources for managing the aftereffects of self-harm could increase their risk of injury or death. Nonetheless, adolescents are strongly encouraged to use telephone coaching before rather than after self-harm. A second difference is that in DBT for adolescents, telephone coaching is offered to parents to help them use skills in the home. To avoid complications with dual relationships, the parents’ telephone coach should not be the adolescent’s individual therapist.

Consultation team meetings. The consultation team meets weekly to increase therapists’ capabilities and motivation.

Therapists who treat suicidal adolescents often have a high degree of burnout, which leads to ineffective treatment and/or quitting.⁸ The team provides support, engages in problem-solving, and helps therapists adhere to the treatment model to improve effectiveness. Clinicians interested in participating a consultation team may review http://behavioraltech.org/resources/crd.cfm for a directory of existing DBT programs. Those interested in starting a consultation team may explore training programs such as those offered at www.behavioraltech.org.

Related Resources

• Lynch TR, Trost WT, Salsman N, et al. Dialectical behavior therapy for borderline personality disorder. Annu Rev Clin Psychol. 2007; 3: 181-205.
• Miller A, Rathus JH, Linehan MM. Dialectical behavior therapy with suicidal adolescents. New York, NY: The Guilford Press; 2007.
• Rathus JH, Miller AL. Dialectical behavior therapy adapted for suicidal adolescents. Suicide Life Threat Behav. 2002; 32(2): 146-157.

Disclosure

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

Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/adapting-dialectical-behavior-therapy.html#comments

Treating suicidal adolescents is fraught with challenges. Antidepressants may be associated with increased suicidal ideation in adolescents,^1-3 although some data suggest that increased adolescent suicide rates are correlated with decreases in antidepressant prescribing.⁴ Adolescents hospitalized after a suicide attempt are likely to attempt suicide again after they are discharged.^5,6 Such patients might not attend outpatient psychotherapy; a study of 167 adolescents discharged after a suicide attempt found that 26% never attended follow-up appointments and 11% went once.⁷

Emerging research supports the effectiveness of dialectical behavior therapy (DBT) for suicidal adolescents. DBT is a form of cognitive-behavioral therapy that combines individual therapy, skills training, and telephone coaching and is implemented by a therapist consultation team that meets weekly. This article reviews evidence supporting the efficacy of DBT for suicidal adolescents and describes principles of outpatient DBT for these patients as developed by Miller et al.⁸

Evidence of DBT’s effectiveness

A review of DBT research found strong evidence for DBT’s effectiveness for suicidal adults.⁹ Recently, DBT has been adapted to treat adolescents with suicidal behavior and nonsuicidal self-injury (NSSI).^10-15

In a nonrandomized trial, Rathus and Miller¹⁰ compared 29 suicidal adolescent outpatients receiving DBT with 82 participants receiving treatment as usual (TAU). Patients were assigned to DBT if they had a suicide attempt in the previous 16 weeks and ≥3 borderline personality disorder (BPD) features or to TAU if they met only 1 of those conditions. Patients in the DBT group had more axis I disorders and pretreatment hospitalizations than the TAU group. Compared with those receiving TAU, patients treated with DBT had fewer hospitalizations (13% in TAU vs 0% in DBT) and a lower dropout rate (60% in TAU vs 38% in DBT). The DBT group experienced significant reductions in suicidal ideation, BPD symptoms, and general psychiatric symptoms. There was 1 suicide attempt in the DBT group vs 7 attempts in the TAU group; however, this difference was not statistically significant.

Woodberry and Popenoe¹¹ examined the use of DBT for suicidal adolescents and their families in a community outpatient clinic. Adolescents reported reductions in overall symptoms, depression, anger, dissociative symptoms, and urges for intentional self-injury. Parents reported reductions in their children’s problem behaviors and in their own depressive symptoms. In a study of DBT in 16 adolescent females with chronic intentional self-injury, patients reported significant reductions in incidents of intentional self-injury, depression, and hopelessness, and increases in overall functioning.¹²

Three studies have examined using DBT for suicidal adolescents in residential facilities. In a pilot study, Katz et al¹³ compared DBT with TAU for 62 suicidal adolescent inpatients. At 1-year follow-up, both groups experienced significant reductions in suicidal ideation, NSSI, and depression. However, compared with those who received TAU, DBT patients had fewer behavioral problems during hospitalization. Sunseri¹⁴ used DBT to treat adolescent females in residential treatment. After DBT was implemented, residents were hospitalized because of NSSI and suicidality for fewer days than before DBT. Trupin et al¹⁵ taught DBT to staff who worked with female adolescent offenders at a juvenile rehabilitation facility. After the staff implemented DBT, the rates of problem behaviors and punishment by staff decreased on 1 unit; there were no behavior or punishment changes on another unit.

Theoretical foundations

Biosocial theory. The problems DBT treats in suicidal adolescents include emotion dysregulation, interpersonal conflict, impulsivity, cognitive dysregulation, and self-dysregulation.⁸ The biosocial theory postulates that these problems are the result of the transaction, or reciprocal relationship, between biologic predispositions and an invalidating environment. The biosocial theory suggests 3 biologic characteristics often are found among suicidal adolescents:

• high emotional sensitivity
• high extremity in reactions
• a slow return to baseline after experiencing a surge in affect.⁸

Although these characteristics indicate higher emotionality, they are not sufficient to account for suicidal adolescents’ difficulties. Problems arise when individuals with these biologic characteristics are raised in an invalidating environment, where the adolescent does not learn how to regulate emotions. Common characteristics of invalidating environments and their effects on adolescents are described in Table 1 .⁸

Treatment theory. DBT for suicidal adolescents focuses on a synthesis between 2 seemingly opposite treatment strategies: change and acceptance. The change focus is derived from behavioral science, and treatment incorporates standard behavior therapy practices, including chain analysis (described below), skills training, contingency management, and exposure.

The acceptance focus draws upon principles of Zen and other Eastern spiritual traditions. Therapists teach patients to accept reality as it is in this moment, without judgment. A key extension of this acceptance is the use of validation—radical acceptance and acknowledgement that all behavior has validity and understandability. DBT therapists strive to use 6 levels of validation with their patients ( Table 2 ),¹⁶ which often is a critical strategy for adolescents who reside in an invalidating environment.

DBT attempts to synthesize the acceptance-based Zen tradition with the change-based strategies of behavioral science through a dialectical philosophy. A fundamental postulate of dialectical philosophy is that a tension occurs when an initial truth or thesis is opposed by an apparently contradictory truth or antithesis.⁸ DBT therapists work with adolescents to find a synthesis that is the “middle path, “ which includes the truth in both positions as well as what is left out of both. For an example of how this might work for an adolescent patient with NSSI, visit this article at CurrentPsychiatry.com.

Table 1

Characteristics of an invalidating environment

Table 2

6 levels of validation employed by DBT therapists

How DBT works

DBT serves 5 functions. It enhances patient capabilities, increases patient motivation, structures the environment to increase the likelihood of success, works to assure generalization from therapy to the natural environment, and enhances therapists’ capabilities and motivation to treat patients effectively.⁸ Outpatient DBT for suicidal adolescents uses 4 modes of treatment:

• weekly individual therapy
• weekly skills training
• telephone coaching
• weekly therapist consultation team meetings.⁸

Although Linehan’s original research with adults was based on a 1-year treatment model,¹⁷ treatment lasts 12 to 16 weeks in the adolescent DBT model designed and studied by Miller et al.⁸ Treatment for adolescents is shorter because research indicates that suicidal adolescents frequently fail to complete longer courses of therapy.¹⁸

Individual therapy. The rank-ordered targets of individual therapy in the first stage of DBT are to:

1. eliminate life-threatening behavior, including NSSI
2. stop therapy-interfering behaviors (eg, not showing up to sessions)
3. change behaviors that interfere with the adolescent’s quality of life (eg, substance abuse)
4. enhance the adolescent’s use of skills.⁸

The individual therapist sets treatment goals in accord with these targets, monitors progress, integrates all modes of therapy, and balances acceptance and validation of the patient with being a catalyst for change. Family members may be included in therapy sessions when family problems emerge as the highest priority.

DBT therapists use chain analysis—which is a process of assessing the series of events, link by link, that lead from a prompting event to a problem behavior (eg, suicide attempt)—to assess problematic behavior and identify methods of change.⁸ The therapist and patient use this process to develop alternative behaviors for the patient to use to reach a more effective outcome.

DBT therapists also ask adolescents to fill out a daily diary card that tracks targeted behaviors, including NSSI, suicidal urges, and important emotions. The diary card helps the therapist determine what needs to be targeted in therapy, increases mindfulness and understanding of problem behaviors, and helps change targeted behavior.

Skills training addresses skills deficits believed to be causing the suicidal adolescent’s problems. DBT systematically teaches 5 skill sets:

• emotional regulation
• mindfulness
• interpersonal effectiveness
• distress tolerance
• “walking the middle path. “⁸

These skills are designed to treat specific problems common among suicidal adolescents and their families. For example, suicidal adolescents often experience a spike in emotions that leads to urges for ineffective behavior, such as attempting suicide or attacking another person. Table 3 provides steps that teach “opposite action, “ which can reduce ineffective emotions and problematic urges associated with these emotions. Table 4 provides mindfulness practices that can help patients address problems such as mindlessness and avoiding the present moment. Although adolescent DBT skills training is similar to that in adults, Table 5 describes key differences.

Table 3

Teaching adolescents ‘opposite action’

Table 4

Mindfulness practices: Teach adolescents to live in the present moment

Table 5

Adapting DBT skills training for adolescents

Telephone consultation. The purpose of brief (5 to 15 minutes) telephone consultations between a patient and therapist is to:

• enhance the likelihood of effective behavior
• coach the use of skills
• decrease the likelihood of problematic behaviors.

DBT telephone consultation for adults differs from that for suicidal adolescents. In DBT for adults, if a patient engages in NSSI or suicidal behavior, there is no telephone contact for 24 hours. This rule aims to avoid reinforcing the behavior with additional contact. However, this rule does not apply to adolescents because restricting adolescents’ access to resources for managing the aftereffects of self-harm could increase their risk of injury or death. Nonetheless, adolescents are strongly encouraged to use telephone coaching before rather than after self-harm. A second difference is that in DBT for adolescents, telephone coaching is offered to parents to help them use skills in the home. To avoid complications with dual relationships, the parents’ telephone coach should not be the adolescent’s individual therapist.

Consultation team meetings. The consultation team meets weekly to increase therapists’ capabilities and motivation.

Therapists who treat suicidal adolescents often have a high degree of burnout, which leads to ineffective treatment and/or quitting.⁸ The team provides support, engages in problem-solving, and helps therapists adhere to the treatment model to improve effectiveness. Clinicians interested in participating a consultation team may review http://behavioraltech.org/resources/crd.cfm for a directory of existing DBT programs. Those interested in starting a consultation team may explore training programs such as those offered at www.behavioraltech.org.

Related Resources

• Lynch TR, Trost WT, Salsman N, et al. Dialectical behavior therapy for borderline personality disorder. Annu Rev Clin Psychol. 2007; 3: 181-205.
• Miller A, Rathus JH, Linehan MM. Dialectical behavior therapy with suicidal adolescents. New York, NY: The Guilford Press; 2007.
• Rathus JH, Miller AL. Dialectical behavior therapy adapted for suicidal adolescents. Suicide Life Threat Behav. 2002; 32(2): 146-157.

Disclosure

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

Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/adapting-dialectical-behavior-therapy.html#comments

Treating suicidal adolescents is fraught with challenges. Antidepressants may be associated with increased suicidal ideation in adolescents,^1-3 although some data suggest that increased adolescent suicide rates are correlated with decreases in antidepressant prescribing.⁴ Adolescents hospitalized after a suicide attempt are likely to attempt suicide again after they are discharged.^5,6 Such patients might not attend outpatient psychotherapy; a study of 167 adolescents discharged after a suicide attempt found that 26% never attended follow-up appointments and 11% went once.⁷

Emerging research supports the effectiveness of dialectical behavior therapy (DBT) for suicidal adolescents. DBT is a form of cognitive-behavioral therapy that combines individual therapy, skills training, and telephone coaching and is implemented by a therapist consultation team that meets weekly. This article reviews evidence supporting the efficacy of DBT for suicidal adolescents and describes principles of outpatient DBT for these patients as developed by Miller et al.⁸

Evidence of DBT’s effectiveness

A review of DBT research found strong evidence for DBT’s effectiveness for suicidal adults.⁹ Recently, DBT has been adapted to treat adolescents with suicidal behavior and nonsuicidal self-injury (NSSI).^10-15

In a nonrandomized trial, Rathus and Miller¹⁰ compared 29 suicidal adolescent outpatients receiving DBT with 82 participants receiving treatment as usual (TAU). Patients were assigned to DBT if they had a suicide attempt in the previous 16 weeks and ≥3 borderline personality disorder (BPD) features or to TAU if they met only 1 of those conditions. Patients in the DBT group had more axis I disorders and pretreatment hospitalizations than the TAU group. Compared with those receiving TAU, patients treated with DBT had fewer hospitalizations (13% in TAU vs 0% in DBT) and a lower dropout rate (60% in TAU vs 38% in DBT). The DBT group experienced significant reductions in suicidal ideation, BPD symptoms, and general psychiatric symptoms. There was 1 suicide attempt in the DBT group vs 7 attempts in the TAU group; however, this difference was not statistically significant.

Woodberry and Popenoe¹¹ examined the use of DBT for suicidal adolescents and their families in a community outpatient clinic. Adolescents reported reductions in overall symptoms, depression, anger, dissociative symptoms, and urges for intentional self-injury. Parents reported reductions in their children’s problem behaviors and in their own depressive symptoms. In a study of DBT in 16 adolescent females with chronic intentional self-injury, patients reported significant reductions in incidents of intentional self-injury, depression, and hopelessness, and increases in overall functioning.¹²

Three studies have examined using DBT for suicidal adolescents in residential facilities. In a pilot study, Katz et al¹³ compared DBT with TAU for 62 suicidal adolescent inpatients. At 1-year follow-up, both groups experienced significant reductions in suicidal ideation, NSSI, and depression. However, compared with those who received TAU, DBT patients had fewer behavioral problems during hospitalization. Sunseri¹⁴ used DBT to treat adolescent females in residential treatment. After DBT was implemented, residents were hospitalized because of NSSI and suicidality for fewer days than before DBT. Trupin et al¹⁵ taught DBT to staff who worked with female adolescent offenders at a juvenile rehabilitation facility. After the staff implemented DBT, the rates of problem behaviors and punishment by staff decreased on 1 unit; there were no behavior or punishment changes on another unit.

Theoretical foundations

Biosocial theory. The problems DBT treats in suicidal adolescents include emotion dysregulation, interpersonal conflict, impulsivity, cognitive dysregulation, and self-dysregulation.⁸ The biosocial theory postulates that these problems are the result of the transaction, or reciprocal relationship, between biologic predispositions and an invalidating environment. The biosocial theory suggests 3 biologic characteristics often are found among suicidal adolescents:

• high emotional sensitivity
• high extremity in reactions
• a slow return to baseline after experiencing a surge in affect.⁸

Although these characteristics indicate higher emotionality, they are not sufficient to account for suicidal adolescents’ difficulties. Problems arise when individuals with these biologic characteristics are raised in an invalidating environment, where the adolescent does not learn how to regulate emotions. Common characteristics of invalidating environments and their effects on adolescents are described in Table 1 .⁸

Treatment theory. DBT for suicidal adolescents focuses on a synthesis between 2 seemingly opposite treatment strategies: change and acceptance. The change focus is derived from behavioral science, and treatment incorporates standard behavior therapy practices, including chain analysis (described below), skills training, contingency management, and exposure.

The acceptance focus draws upon principles of Zen and other Eastern spiritual traditions. Therapists teach patients to accept reality as it is in this moment, without judgment. A key extension of this acceptance is the use of validation—radical acceptance and acknowledgement that all behavior has validity and understandability. DBT therapists strive to use 6 levels of validation with their patients ( Table 2 ),¹⁶ which often is a critical strategy for adolescents who reside in an invalidating environment.

DBT attempts to synthesize the acceptance-based Zen tradition with the change-based strategies of behavioral science through a dialectical philosophy. A fundamental postulate of dialectical philosophy is that a tension occurs when an initial truth or thesis is opposed by an apparently contradictory truth or antithesis.⁸ DBT therapists work with adolescents to find a synthesis that is the “middle path, “ which includes the truth in both positions as well as what is left out of both. For an example of how this might work for an adolescent patient with NSSI, visit this article at CurrentPsychiatry.com.

Table 1

Characteristics of an invalidating environment

Table 2

6 levels of validation employed by DBT therapists

How DBT works

DBT serves 5 functions. It enhances patient capabilities, increases patient motivation, structures the environment to increase the likelihood of success, works to assure generalization from therapy to the natural environment, and enhances therapists’ capabilities and motivation to treat patients effectively.⁸ Outpatient DBT for suicidal adolescents uses 4 modes of treatment:

• weekly individual therapy
• weekly skills training
• telephone coaching
• weekly therapist consultation team meetings.⁸

Although Linehan’s original research with adults was based on a 1-year treatment model,¹⁷ treatment lasts 12 to 16 weeks in the adolescent DBT model designed and studied by Miller et al.⁸ Treatment for adolescents is shorter because research indicates that suicidal adolescents frequently fail to complete longer courses of therapy.¹⁸

Individual therapy. The rank-ordered targets of individual therapy in the first stage of DBT are to:

1. eliminate life-threatening behavior, including NSSI
2. stop therapy-interfering behaviors (eg, not showing up to sessions)
3. change behaviors that interfere with the adolescent’s quality of life (eg, substance abuse)
4. enhance the adolescent’s use of skills.⁸

The individual therapist sets treatment goals in accord with these targets, monitors progress, integrates all modes of therapy, and balances acceptance and validation of the patient with being a catalyst for change. Family members may be included in therapy sessions when family problems emerge as the highest priority.

DBT therapists use chain analysis—which is a process of assessing the series of events, link by link, that lead from a prompting event to a problem behavior (eg, suicide attempt)—to assess problematic behavior and identify methods of change.⁸ The therapist and patient use this process to develop alternative behaviors for the patient to use to reach a more effective outcome.

DBT therapists also ask adolescents to fill out a daily diary card that tracks targeted behaviors, including NSSI, suicidal urges, and important emotions. The diary card helps the therapist determine what needs to be targeted in therapy, increases mindfulness and understanding of problem behaviors, and helps change targeted behavior.

Skills training addresses skills deficits believed to be causing the suicidal adolescent’s problems. DBT systematically teaches 5 skill sets:

• emotional regulation
• mindfulness
• interpersonal effectiveness
• distress tolerance
• “walking the middle path. “⁸

These skills are designed to treat specific problems common among suicidal adolescents and their families. For example, suicidal adolescents often experience a spike in emotions that leads to urges for ineffective behavior, such as attempting suicide or attacking another person. Table 3 provides steps that teach “opposite action, “ which can reduce ineffective emotions and problematic urges associated with these emotions. Table 4 provides mindfulness practices that can help patients address problems such as mindlessness and avoiding the present moment. Although adolescent DBT skills training is similar to that in adults, Table 5 describes key differences.

Table 3

Teaching adolescents ‘opposite action’

Table 4

Mindfulness practices: Teach adolescents to live in the present moment

Table 5

Adapting DBT skills training for adolescents

Telephone consultation. The purpose of brief (5 to 15 minutes) telephone consultations between a patient and therapist is to:

• enhance the likelihood of effective behavior
• coach the use of skills
• decrease the likelihood of problematic behaviors.

DBT telephone consultation for adults differs from that for suicidal adolescents. In DBT for adults, if a patient engages in NSSI or suicidal behavior, there is no telephone contact for 24 hours. This rule aims to avoid reinforcing the behavior with additional contact. However, this rule does not apply to adolescents because restricting adolescents’ access to resources for managing the aftereffects of self-harm could increase their risk of injury or death. Nonetheless, adolescents are strongly encouraged to use telephone coaching before rather than after self-harm. A second difference is that in DBT for adolescents, telephone coaching is offered to parents to help them use skills in the home. To avoid complications with dual relationships, the parents’ telephone coach should not be the adolescent’s individual therapist.

Consultation team meetings. The consultation team meets weekly to increase therapists’ capabilities and motivation.

Therapists who treat suicidal adolescents often have a high degree of burnout, which leads to ineffective treatment and/or quitting.⁸ The team provides support, engages in problem-solving, and helps therapists adhere to the treatment model to improve effectiveness. Clinicians interested in participating a consultation team may review http://behavioraltech.org/resources/crd.cfm for a directory of existing DBT programs. Those interested in starting a consultation team may explore training programs such as those offered at www.behavioraltech.org.

Related Resources

• Lynch TR, Trost WT, Salsman N, et al. Dialectical behavior therapy for borderline personality disorder. Annu Rev Clin Psychol. 2007; 3: 181-205.
• Miller A, Rathus JH, Linehan MM. Dialectical behavior therapy with suicidal adolescents. New York, NY: The Guilford Press; 2007.
• Rathus JH, Miller AL. Dialectical behavior therapy adapted for suicidal adolescents. Suicide Life Threat Behav. 2002; 32(2): 146-157.

Disclosure

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

Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/opioid-use-disorder-during-pregnancy.html#comments

For 3 years, your mental health clinic has been treating Ms. J, age 23, for bipolar disorder. She is single, unemployed, lives alone, and receives Social Security disability assistance and financial support from her parents. She has been successfully maintained on aripiprazole, 15 mg/d, and citalopram, 20 mg/d, for 18 months. Six months ago she began to miss therapy sessions and physician visits.

Her parents inform Ms. J’s therapist that she is “snorting oxycontin” with her new boyfriend. At her next visit Ms. J confirms she has been struggling to manage an opioid use disorder for more than 1 year, and requests help.

After you educate her about the diagnosis, pathophysiology, and treatment of opioid addiction, she chooses to include pharmacotherapy as part of her treatment. After informed consent, Ms. J agrees to take buprenorphine and naloxone, meet with her therapist weekly, and attend twice-weekly Narcotics Anonymous (NA) meetings. Over the ensuing months she is gradually inducted onto buprenorphine and naloxone, 12 mg, shows improved insight and motivation, provides negative urine drug screens, and demonstrates increased ability to manage her recovery. Two weeks later Ms. J tells you she may be pregnant but wants to continue buprenorphine and naloxone.

Opioid use disorder (OUD) during pregnancy is among the most difficult clinical scenarios to manage. The prevalence of OUD during pregnancy is largely unknown. However, stigma against pregnant patients with OUD is substantial.¹ This article briefly summarizes identification, assessment, and treatment of OUD during pregnancy. To avoid confusion with the term “physical dependence, “ we will use “opioid use disorder” instead of “opioid dependence. “ The DSM-5 Substance Use Disorders Workgroup recommends combining abuse and dependence into a single disorder of graded clinical severity; however, this has not been finalized.²

Early identification is crucial

Early identification of OUD in pregnant women can be challenging. Self-reports underestimate use³ and shame, fear of prosecution or involvement of child welfare services, and guilt can further erode self-report. Women with OUD may have irregular menses and might not be aware of their pregnancy until several months after conception.⁴ Also, women with OUD who are maintained on opioid agonist therapies may misinterpret early signs of pregnancy—such as fatigue, nausea, vomiting, headaches, and cramps—as withdrawal symptoms and may respond by increasing their opioid dosing, thus exposing their fetus to increased drug levels. Finally, many women with OUD experience amenorrhea as a result of their stressful, unhealthy lifestyle, which may preclude pregnancy despite sexual activity. When these women later enroll in an opioid maintenance program, their endocrine function may return to normal, leading to unexpected pregnancy.⁵

Screening for OUD in pregnant patients has not been well studied. An interviewer’s nonjudgmental, empathic attitude may be more important than the specific questions he or she asks. It may be best to begin with less threatening questions and proceed to more specific questions after developing a therapeutic alliance.⁶

Chasnoff et al⁷ studied >2, 000 Medicaid-eligible pregnant patients from 9 prenatal clinics to identify risk factors for substance use during pregnancy. Alcohol or tobacco use in the month before pregnancy most differentiated current drug or alcohol use from nonuse while pregnant; however, a wide variation in use rates among patients in this study limits the generalizability of these findings. Consider OUD in women with:

• physical examination findings or history that suggests substance use or withdrawal symptoms
  
• positive drug test results for illicit or nonprescribed opioids
  
• aberrant medication-taking behaviors in those receiving prescribed opioids
  
• nicotine or alcohol use in the month before they knew they were pregnant
  
• a history of addiction-related disorders
  
• evidence of diseases associated with drug use, such as human immunodeficiency virus or hepatitis C
  
• poor prenatal care attendance
  
• unexplained fetal growth abnormalities.
  

A combination of interviewing and biologic drug screening may be more effective than either approach alone.¹¹ Drug screening should include opioids typically screened for (morphine, codeine, heroin metabolite) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and synthetics such as fentanyl). Learn your state’s civil mandates regarding drug-using pregnant women, guidelines for addiction treatment, and confidentiality provisions, especially as they relate to drug testing and mandatory reporting. Ideally, patients should be informed of these issues before they undergo drug testing or other procedures. These requirements may vary according to physician specialty or role in providing care.

Diagnosis of opioid dependence is based on DSM-IV-TR criteria; however, the proposed DSM-5 criteria for OUD may better emphasize cautions about including tolerance or withdrawal when diagnosing OUD in the setting of medically supervised and appropriate opioid use.²

Table 1

The ‘4P’s Plus’ screen for substance use during pregnancy

Office management

OUD-specific treatment decreases opioid use and improves birth outcomes¹⁴ ; however, retaining these patients in treatment can be difficult. Addressing social issues— including financial burdens, unstable living conditions, intimate partner violence, transportation difficulties, and limited access to medical and child care—can facilitate treatment.⁵ The Addiction Severity Index version tailored to women and pregnancy¹⁵ examines 7 domains of functioning (drugs, alcohol, psychological, social, medical, legal, and employment), informs treatment planning, quantifies treatment progress, and has predictive validity.¹⁶ Services are more likely to be effective if started during pregnancy as opposed to after delivery. Although detoxification is possible under carefully monitored conditions, many women relapse after detoxifying, and neonatal abstinence syndrome (NAS)—a disorder in which an addicted newborn experiences drug withdrawal—is common. Therefore, the risks of detoxification often outweigh benefits.^5,17,18

Rehabilitation services for the mother can be provided at various levels of care, including outpatient, intensive outpatient, day hospital, residential, and inpatient. Although pregnancy-specific OUD treatment is ideal, it may not be available. Clinicians should attempt to locate services that can incorporate resources for pregnant women. Providing a means for child care during treatment is paramount to compliance. Develop a plan for nonconfrontational counseling, job skills training/education, and ongoing care after delivery (including child care and transportation resources) at the onset of treatment. The length of time maintained in treatment is one of the strongest predictors of abstinence.⁵

Increased education and screening for substance use as the pregnancy approaches term is necessary because patients may mistake early labor for symptoms of opioid withdrawal or worry that delivery room pain management will be inadequate and therefore relapse. Among pregnant women with addiction, preterm labor may be most common in those with OUD.¹²

Table 2

Medical complications common to pregnancy and substance abuse

Obstetric complications in women with addiction disorders

Opioid agonist therapy

Obstetric complications in women with OUD may be related to rapid, frequent fluctuations of opioid blood levels during intoxication and withdrawal. Therefore, the first goal of pharmacotherapy is to reduce physical stress associated with cycling opioid blood levels. Opioid agonist medications can be extremely effective. Opioid agonist treatment for pregnant patients is similar to that of nonpregnant patients but includes pregnancy-specific objectives ( Table 4 ).²⁰

Few anti-relapse medications have been studied in pregnant patients. Pharmacotherapies for OUD include methadone and buprenorphine. In our experience, opioid antagonists such as naltrexone typically would not be considered for pregnant patients because:

• their expected efficacy in reducing relapse in pregnant patients is lower than that of other medications
  
• their expected risk for inducing withdrawal is higher compared with methadone or buprenorphine
  
• research on the use of naltrexone during pregnancy is lacking.
  

Fluctuating blood opioid levels are minimized when methadone dosage is individually determined. Dosages should be based on a woman’s stage of pregnancy, relapse risk, pre-pregnancy methadone dose, experience with methadone, and clinical history. Some women experience lowered methadone blood levels during pregnancy because of increased fluid space, a larger tissue reservoir that can store methadone, and increased drug metabolism by both placenta and fetus. As a result, increased or split (twice daily) dosing may be indicated.^22-24

The few randomized clinical trials comparing methadone with buprenorphine during pregnancy suggest that buprenorphine is not inferior to methadone in safety and discomfort of induction from a short-acting opioid, nor in outcome measures assessing NAS and maternal and neonatal safety.^26,27 Results from the recent Maternal Opioid Treatment: Human Experimental Research project suggest that buprenorphine may have some advantages over methadone in pregnancy. Buprenorphine-maintained neonates may need less morphine, have shorter hospital stays, and require shorter treatment for NAS.²⁸ However, treatment retention may be lower for buprenorphine-maintained mothers; any resultant long-term consequences on maternal and child health are as yet unexplored. These findings require replication.

Methadone and buprenorphine are not interchangeable. Many patients maintained on methadone do not respond optimally to buprenorphine. Clinics that dispense maintenance methadone are required to provide counseling services and random drug testing; these requirements do not apply to physicians who prescribe buprenorphine. Moreover, in our experience buprenorphine at times has been prescribed without close regard to psychosocial issues, adequate random drug testing, or coordination of care with other providers.

In pregnant patients, buprenorphine is preferred over buprenorphine and naloxone to avoid fetal exposure to naloxone, which may cause intrauterine withdrawal and maternal-fetal hormonal changes. To reduce abuse or diversion, patients should undergo drug testing to ensure buprenorphine is present, smaller prescriptions may be provided, and tablets can be counted. Limited data suggests buprenorphine is not teratogenic. Some data show low placental transfer of buprenorphine, thereby limiting fetal exposure and lowering risk for intrauterine growth restriction.²⁹

Table 4

Opioid agonist treatment objectives for addicted patients who are pregnant

Delivery and postnatal care

Compared with those not in treatment, women who are engaged in a multidisciplinary treatment program at the time of delivery demonstrated higher gestational age, increased birth weights, and lower rates of neonatal ICU admissions. They also realized a cost savings of $4, 644 per mother-infant pair.³⁰

During delivery, pain medication should not be withheld solely because a pregnant woman has a history of addiction-related disorders; these women are subject to pain during delivery as much as other women. Avoid using mixed agonists/antagonists such as nalbuphine or butorphanol in women receiving opioid maintenance medication. Labor and delivery pain management for a pregnant patient maintained on opioid agonist therapies is discussed elsewhere in the literature.³¹ Every effort should be made to ensure that the mother remains in treatment through delivery and beyond.

To read about advising women with OUD on the benefits and risks of breastfeeding while receiving opioid agonist maintenance treatment, see the Box below.

CASE CONTINUED: Medication change

Ms. J’s boyfriend has left her and her parents have not readily accepted her pregnancy and need for support. She continues to attend NA meetings and weekly therapy. After educating her about the differences between buprenorphine and buprenorphine and naloxone in relation to risk, benefits, and side effects, you switch Ms. J to buprenorphine, 12 mg/d, while maintaining her on aripiprazole and citalopram. She consents to exchanging information about her medical, mental health, and addiction-related treatment with her primary care provider, who helps locate an obstetrician/gynecologist comfortable with her OUD and buprenorphine. Ms. J’s therapist helps link her with social services agencies to ensure prenatal care, assist with removing barriers to care, and plan for her needs as a parent.

After checking your state’s mandates, you determine you are not required to report Ms. J’s drug testing results. Ms. J’s ongoing drug testing shows the presence of buprenorphine and the absence of other opioids and all drugs of abuse.

Ms. J’s delivery is uncomplicated medically; however, family, financial, and parental role issues remain problematic. Encouraging her involvement in therapy and social services as part of her continued buprenorphine prescribing proves beneficial.

• Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008; 35(3): 245-259.
  
• Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003; 70(suppl 1 ): S87-S101.
  
• Velez M, Jansson LM. The opioid dependent mother and the newborn dyad: nonpharmacologic care. J Addict Med. 2008; 2(3): 113-120.
  

• Aripiprazole • Abilify
  
• Buprenorphine and naloxone •Suboxone
  
• Buprenorphine • Subutex
  
• Butorphanol • Stadol
  
• Citalopram • Celexa
  
• Fentanyl • Duragesic, Sublimaze, others
  
• Methadone • Dolophine
  
• Naloxone • Narcan
  
• Naltrexone • ReVia
  
• Nalbuphine • Nubain
  
• Oxycodone • Oxycontin
  

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

Dr. Fernandez’ time toward this project was funded by the University Hospital/University of Cincinnati Addiction Psychiatry Fellowship Training Program operated by the Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD), Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati and by the Veterans Affairs Medical Center, Cincinnati, OH.

The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs, the United States Government, or Opiate Addiction Recovery Services.

Acknowledgments

The authors wish to thank Kathleen Peak for her administrative assistance and Paul Horn, Professor, Department of Mathematical Sciences and Cincinnati VA, for statistical assistance.

Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/opioid-use-disorder-during-pregnancy.html#comments

For 3 years, your mental health clinic has been treating Ms. J, age 23, for bipolar disorder. She is single, unemployed, lives alone, and receives Social Security disability assistance and financial support from her parents. She has been successfully maintained on aripiprazole, 15 mg/d, and citalopram, 20 mg/d, for 18 months. Six months ago she began to miss therapy sessions and physician visits.

Her parents inform Ms. J’s therapist that she is “snorting oxycontin” with her new boyfriend. At her next visit Ms. J confirms she has been struggling to manage an opioid use disorder for more than 1 year, and requests help.

After you educate her about the diagnosis, pathophysiology, and treatment of opioid addiction, she chooses to include pharmacotherapy as part of her treatment. After informed consent, Ms. J agrees to take buprenorphine and naloxone, meet with her therapist weekly, and attend twice-weekly Narcotics Anonymous (NA) meetings. Over the ensuing months she is gradually inducted onto buprenorphine and naloxone, 12 mg, shows improved insight and motivation, provides negative urine drug screens, and demonstrates increased ability to manage her recovery. Two weeks later Ms. J tells you she may be pregnant but wants to continue buprenorphine and naloxone.

Opioid use disorder (OUD) during pregnancy is among the most difficult clinical scenarios to manage. The prevalence of OUD during pregnancy is largely unknown. However, stigma against pregnant patients with OUD is substantial.¹ This article briefly summarizes identification, assessment, and treatment of OUD during pregnancy. To avoid confusion with the term “physical dependence, “ we will use “opioid use disorder” instead of “opioid dependence. “ The DSM-5 Substance Use Disorders Workgroup recommends combining abuse and dependence into a single disorder of graded clinical severity; however, this has not been finalized.²

Early identification is crucial

Early identification of OUD in pregnant women can be challenging. Self-reports underestimate use³ and shame, fear of prosecution or involvement of child welfare services, and guilt can further erode self-report. Women with OUD may have irregular menses and might not be aware of their pregnancy until several months after conception.⁴ Also, women with OUD who are maintained on opioid agonist therapies may misinterpret early signs of pregnancy—such as fatigue, nausea, vomiting, headaches, and cramps—as withdrawal symptoms and may respond by increasing their opioid dosing, thus exposing their fetus to increased drug levels. Finally, many women with OUD experience amenorrhea as a result of their stressful, unhealthy lifestyle, which may preclude pregnancy despite sexual activity. When these women later enroll in an opioid maintenance program, their endocrine function may return to normal, leading to unexpected pregnancy.⁵

Screening for OUD in pregnant patients has not been well studied. An interviewer’s nonjudgmental, empathic attitude may be more important than the specific questions he or she asks. It may be best to begin with less threatening questions and proceed to more specific questions after developing a therapeutic alliance.⁶

Chasnoff et al⁷ studied >2, 000 Medicaid-eligible pregnant patients from 9 prenatal clinics to identify risk factors for substance use during pregnancy. Alcohol or tobacco use in the month before pregnancy most differentiated current drug or alcohol use from nonuse while pregnant; however, a wide variation in use rates among patients in this study limits the generalizability of these findings. Consider OUD in women with:

• physical examination findings or history that suggests substance use or withdrawal symptoms
  
• positive drug test results for illicit or nonprescribed opioids
  
• aberrant medication-taking behaviors in those receiving prescribed opioids
  
• nicotine or alcohol use in the month before they knew they were pregnant
  
• a history of addiction-related disorders
  
• evidence of diseases associated with drug use, such as human immunodeficiency virus or hepatitis C
  
• poor prenatal care attendance
  
• unexplained fetal growth abnormalities.
  

A combination of interviewing and biologic drug screening may be more effective than either approach alone.¹¹ Drug screening should include opioids typically screened for (morphine, codeine, heroin metabolite) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and synthetics such as fentanyl). Learn your state’s civil mandates regarding drug-using pregnant women, guidelines for addiction treatment, and confidentiality provisions, especially as they relate to drug testing and mandatory reporting. Ideally, patients should be informed of these issues before they undergo drug testing or other procedures. These requirements may vary according to physician specialty or role in providing care.

Diagnosis of opioid dependence is based on DSM-IV-TR criteria; however, the proposed DSM-5 criteria for OUD may better emphasize cautions about including tolerance or withdrawal when diagnosing OUD in the setting of medically supervised and appropriate opioid use.²

Table 1

The ‘4P’s Plus’ screen for substance use during pregnancy

Office management

OUD-specific treatment decreases opioid use and improves birth outcomes¹⁴ ; however, retaining these patients in treatment can be difficult. Addressing social issues— including financial burdens, unstable living conditions, intimate partner violence, transportation difficulties, and limited access to medical and child care—can facilitate treatment.⁵ The Addiction Severity Index version tailored to women and pregnancy¹⁵ examines 7 domains of functioning (drugs, alcohol, psychological, social, medical, legal, and employment), informs treatment planning, quantifies treatment progress, and has predictive validity.¹⁶ Services are more likely to be effective if started during pregnancy as opposed to after delivery. Although detoxification is possible under carefully monitored conditions, many women relapse after detoxifying, and neonatal abstinence syndrome (NAS)—a disorder in which an addicted newborn experiences drug withdrawal—is common. Therefore, the risks of detoxification often outweigh benefits.^5,17,18

Rehabilitation services for the mother can be provided at various levels of care, including outpatient, intensive outpatient, day hospital, residential, and inpatient. Although pregnancy-specific OUD treatment is ideal, it may not be available. Clinicians should attempt to locate services that can incorporate resources for pregnant women. Providing a means for child care during treatment is paramount to compliance. Develop a plan for nonconfrontational counseling, job skills training/education, and ongoing care after delivery (including child care and transportation resources) at the onset of treatment. The length of time maintained in treatment is one of the strongest predictors of abstinence.⁵

Increased education and screening for substance use as the pregnancy approaches term is necessary because patients may mistake early labor for symptoms of opioid withdrawal or worry that delivery room pain management will be inadequate and therefore relapse. Among pregnant women with addiction, preterm labor may be most common in those with OUD.¹²

Table 2

Medical complications common to pregnancy and substance abuse

Obstetric complications in women with addiction disorders

Opioid agonist therapy

Obstetric complications in women with OUD may be related to rapid, frequent fluctuations of opioid blood levels during intoxication and withdrawal. Therefore, the first goal of pharmacotherapy is to reduce physical stress associated with cycling opioid blood levels. Opioid agonist medications can be extremely effective. Opioid agonist treatment for pregnant patients is similar to that of nonpregnant patients but includes pregnancy-specific objectives ( Table 4 ).²⁰

Few anti-relapse medications have been studied in pregnant patients. Pharmacotherapies for OUD include methadone and buprenorphine. In our experience, opioid antagonists such as naltrexone typically would not be considered for pregnant patients because:

• their expected efficacy in reducing relapse in pregnant patients is lower than that of other medications
  
• their expected risk for inducing withdrawal is higher compared with methadone or buprenorphine
  
• research on the use of naltrexone during pregnancy is lacking.
  

Fluctuating blood opioid levels are minimized when methadone dosage is individually determined. Dosages should be based on a woman’s stage of pregnancy, relapse risk, pre-pregnancy methadone dose, experience with methadone, and clinical history. Some women experience lowered methadone blood levels during pregnancy because of increased fluid space, a larger tissue reservoir that can store methadone, and increased drug metabolism by both placenta and fetus. As a result, increased or split (twice daily) dosing may be indicated.^22-24

The few randomized clinical trials comparing methadone with buprenorphine during pregnancy suggest that buprenorphine is not inferior to methadone in safety and discomfort of induction from a short-acting opioid, nor in outcome measures assessing NAS and maternal and neonatal safety.^26,27 Results from the recent Maternal Opioid Treatment: Human Experimental Research project suggest that buprenorphine may have some advantages over methadone in pregnancy. Buprenorphine-maintained neonates may need less morphine, have shorter hospital stays, and require shorter treatment for NAS.²⁸ However, treatment retention may be lower for buprenorphine-maintained mothers; any resultant long-term consequences on maternal and child health are as yet unexplored. These findings require replication.

Methadone and buprenorphine are not interchangeable. Many patients maintained on methadone do not respond optimally to buprenorphine. Clinics that dispense maintenance methadone are required to provide counseling services and random drug testing; these requirements do not apply to physicians who prescribe buprenorphine. Moreover, in our experience buprenorphine at times has been prescribed without close regard to psychosocial issues, adequate random drug testing, or coordination of care with other providers.

In pregnant patients, buprenorphine is preferred over buprenorphine and naloxone to avoid fetal exposure to naloxone, which may cause intrauterine withdrawal and maternal-fetal hormonal changes. To reduce abuse or diversion, patients should undergo drug testing to ensure buprenorphine is present, smaller prescriptions may be provided, and tablets can be counted. Limited data suggests buprenorphine is not teratogenic. Some data show low placental transfer of buprenorphine, thereby limiting fetal exposure and lowering risk for intrauterine growth restriction.²⁹

Table 4

Opioid agonist treatment objectives for addicted patients who are pregnant

Delivery and postnatal care

Compared with those not in treatment, women who are engaged in a multidisciplinary treatment program at the time of delivery demonstrated higher gestational age, increased birth weights, and lower rates of neonatal ICU admissions. They also realized a cost savings of $4, 644 per mother-infant pair.³⁰

During delivery, pain medication should not be withheld solely because a pregnant woman has a history of addiction-related disorders; these women are subject to pain during delivery as much as other women. Avoid using mixed agonists/antagonists such as nalbuphine or butorphanol in women receiving opioid maintenance medication. Labor and delivery pain management for a pregnant patient maintained on opioid agonist therapies is discussed elsewhere in the literature.³¹ Every effort should be made to ensure that the mother remains in treatment through delivery and beyond.

To read about advising women with OUD on the benefits and risks of breastfeeding while receiving opioid agonist maintenance treatment, see the Box below.

CASE CONTINUED: Medication change

Ms. J’s boyfriend has left her and her parents have not readily accepted her pregnancy and need for support. She continues to attend NA meetings and weekly therapy. After educating her about the differences between buprenorphine and buprenorphine and naloxone in relation to risk, benefits, and side effects, you switch Ms. J to buprenorphine, 12 mg/d, while maintaining her on aripiprazole and citalopram. She consents to exchanging information about her medical, mental health, and addiction-related treatment with her primary care provider, who helps locate an obstetrician/gynecologist comfortable with her OUD and buprenorphine. Ms. J’s therapist helps link her with social services agencies to ensure prenatal care, assist with removing barriers to care, and plan for her needs as a parent.

After checking your state’s mandates, you determine you are not required to report Ms. J’s drug testing results. Ms. J’s ongoing drug testing shows the presence of buprenorphine and the absence of other opioids and all drugs of abuse.

Ms. J’s delivery is uncomplicated medically; however, family, financial, and parental role issues remain problematic. Encouraging her involvement in therapy and social services as part of her continued buprenorphine prescribing proves beneficial.

• Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008; 35(3): 245-259.
  
• Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003; 70(suppl 1 ): S87-S101.
  
• Velez M, Jansson LM. The opioid dependent mother and the newborn dyad: nonpharmacologic care. J Addict Med. 2008; 2(3): 113-120.
  

• Aripiprazole • Abilify
  
• Buprenorphine and naloxone •Suboxone
  
• Buprenorphine • Subutex
  
• Butorphanol • Stadol
  
• Citalopram • Celexa
  
• Fentanyl • Duragesic, Sublimaze, others
  
• Methadone • Dolophine
  
• Naloxone • Narcan
  
• Naltrexone • ReVia
  
• Nalbuphine • Nubain
  
• Oxycodone • Oxycontin
  

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

Dr. Fernandez’ time toward this project was funded by the University Hospital/University of Cincinnati Addiction Psychiatry Fellowship Training Program operated by the Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD), Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati and by the Veterans Affairs Medical Center, Cincinnati, OH.

The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs, the United States Government, or Opiate Addiction Recovery Services.

Acknowledgments

The authors wish to thank Kathleen Peak for her administrative assistance and Paul Horn, Professor, Department of Mathematical Sciences and Cincinnati VA, for statistical assistance.

Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/opioid-use-disorder-during-pregnancy.html#comments

For 3 years, your mental health clinic has been treating Ms. J, age 23, for bipolar disorder. She is single, unemployed, lives alone, and receives Social Security disability assistance and financial support from her parents. She has been successfully maintained on aripiprazole, 15 mg/d, and citalopram, 20 mg/d, for 18 months. Six months ago she began to miss therapy sessions and physician visits.

Her parents inform Ms. J’s therapist that she is “snorting oxycontin” with her new boyfriend. At her next visit Ms. J confirms she has been struggling to manage an opioid use disorder for more than 1 year, and requests help.

After you educate her about the diagnosis, pathophysiology, and treatment of opioid addiction, she chooses to include pharmacotherapy as part of her treatment. After informed consent, Ms. J agrees to take buprenorphine and naloxone, meet with her therapist weekly, and attend twice-weekly Narcotics Anonymous (NA) meetings. Over the ensuing months she is gradually inducted onto buprenorphine and naloxone, 12 mg, shows improved insight and motivation, provides negative urine drug screens, and demonstrates increased ability to manage her recovery. Two weeks later Ms. J tells you she may be pregnant but wants to continue buprenorphine and naloxone.

Opioid use disorder (OUD) during pregnancy is among the most difficult clinical scenarios to manage. The prevalence of OUD during pregnancy is largely unknown. However, stigma against pregnant patients with OUD is substantial.¹ This article briefly summarizes identification, assessment, and treatment of OUD during pregnancy. To avoid confusion with the term “physical dependence, “ we will use “opioid use disorder” instead of “opioid dependence. “ The DSM-5 Substance Use Disorders Workgroup recommends combining abuse and dependence into a single disorder of graded clinical severity; however, this has not been finalized.²

Early identification is crucial

Early identification of OUD in pregnant women can be challenging. Self-reports underestimate use³ and shame, fear of prosecution or involvement of child welfare services, and guilt can further erode self-report. Women with OUD may have irregular menses and might not be aware of their pregnancy until several months after conception.⁴ Also, women with OUD who are maintained on opioid agonist therapies may misinterpret early signs of pregnancy—such as fatigue, nausea, vomiting, headaches, and cramps—as withdrawal symptoms and may respond by increasing their opioid dosing, thus exposing their fetus to increased drug levels. Finally, many women with OUD experience amenorrhea as a result of their stressful, unhealthy lifestyle, which may preclude pregnancy despite sexual activity. When these women later enroll in an opioid maintenance program, their endocrine function may return to normal, leading to unexpected pregnancy.⁵

Screening for OUD in pregnant patients has not been well studied. An interviewer’s nonjudgmental, empathic attitude may be more important than the specific questions he or she asks. It may be best to begin with less threatening questions and proceed to more specific questions after developing a therapeutic alliance.⁶

Chasnoff et al⁷ studied >2, 000 Medicaid-eligible pregnant patients from 9 prenatal clinics to identify risk factors for substance use during pregnancy. Alcohol or tobacco use in the month before pregnancy most differentiated current drug or alcohol use from nonuse while pregnant; however, a wide variation in use rates among patients in this study limits the generalizability of these findings. Consider OUD in women with:

• physical examination findings or history that suggests substance use or withdrawal symptoms
  
• positive drug test results for illicit or nonprescribed opioids
  
• aberrant medication-taking behaviors in those receiving prescribed opioids
  
• nicotine or alcohol use in the month before they knew they were pregnant
  
• a history of addiction-related disorders
  
• evidence of diseases associated with drug use, such as human immunodeficiency virus or hepatitis C
  
• poor prenatal care attendance
  
• unexplained fetal growth abnormalities.
  

A combination of interviewing and biologic drug screening may be more effective than either approach alone.¹¹ Drug screening should include opioids typically screened for (morphine, codeine, heroin metabolite) and those for which additional tests may be required (eg, semi-synthetics such as oxycodone and synthetics such as fentanyl). Learn your state’s civil mandates regarding drug-using pregnant women, guidelines for addiction treatment, and confidentiality provisions, especially as they relate to drug testing and mandatory reporting. Ideally, patients should be informed of these issues before they undergo drug testing or other procedures. These requirements may vary according to physician specialty or role in providing care.

Diagnosis of opioid dependence is based on DSM-IV-TR criteria; however, the proposed DSM-5 criteria for OUD may better emphasize cautions about including tolerance or withdrawal when diagnosing OUD in the setting of medically supervised and appropriate opioid use.²

Table 1

The ‘4P’s Plus’ screen for substance use during pregnancy

Office management

OUD-specific treatment decreases opioid use and improves birth outcomes¹⁴ ; however, retaining these patients in treatment can be difficult. Addressing social issues— including financial burdens, unstable living conditions, intimate partner violence, transportation difficulties, and limited access to medical and child care—can facilitate treatment.⁵ The Addiction Severity Index version tailored to women and pregnancy¹⁵ examines 7 domains of functioning (drugs, alcohol, psychological, social, medical, legal, and employment), informs treatment planning, quantifies treatment progress, and has predictive validity.¹⁶ Services are more likely to be effective if started during pregnancy as opposed to after delivery. Although detoxification is possible under carefully monitored conditions, many women relapse after detoxifying, and neonatal abstinence syndrome (NAS)—a disorder in which an addicted newborn experiences drug withdrawal—is common. Therefore, the risks of detoxification often outweigh benefits.^5,17,18

Rehabilitation services for the mother can be provided at various levels of care, including outpatient, intensive outpatient, day hospital, residential, and inpatient. Although pregnancy-specific OUD treatment is ideal, it may not be available. Clinicians should attempt to locate services that can incorporate resources for pregnant women. Providing a means for child care during treatment is paramount to compliance. Develop a plan for nonconfrontational counseling, job skills training/education, and ongoing care after delivery (including child care and transportation resources) at the onset of treatment. The length of time maintained in treatment is one of the strongest predictors of abstinence.⁵

Increased education and screening for substance use as the pregnancy approaches term is necessary because patients may mistake early labor for symptoms of opioid withdrawal or worry that delivery room pain management will be inadequate and therefore relapse. Among pregnant women with addiction, preterm labor may be most common in those with OUD.¹²

Table 2

Medical complications common to pregnancy and substance abuse

Obstetric complications in women with addiction disorders

Opioid agonist therapy

Obstetric complications in women with OUD may be related to rapid, frequent fluctuations of opioid blood levels during intoxication and withdrawal. Therefore, the first goal of pharmacotherapy is to reduce physical stress associated with cycling opioid blood levels. Opioid agonist medications can be extremely effective. Opioid agonist treatment for pregnant patients is similar to that of nonpregnant patients but includes pregnancy-specific objectives ( Table 4 ).²⁰

Few anti-relapse medications have been studied in pregnant patients. Pharmacotherapies for OUD include methadone and buprenorphine. In our experience, opioid antagonists such as naltrexone typically would not be considered for pregnant patients because:

• their expected efficacy in reducing relapse in pregnant patients is lower than that of other medications
  
• their expected risk for inducing withdrawal is higher compared with methadone or buprenorphine
  
• research on the use of naltrexone during pregnancy is lacking.
  

Fluctuating blood opioid levels are minimized when methadone dosage is individually determined. Dosages should be based on a woman’s stage of pregnancy, relapse risk, pre-pregnancy methadone dose, experience with methadone, and clinical history. Some women experience lowered methadone blood levels during pregnancy because of increased fluid space, a larger tissue reservoir that can store methadone, and increased drug metabolism by both placenta and fetus. As a result, increased or split (twice daily) dosing may be indicated.^22-24

The few randomized clinical trials comparing methadone with buprenorphine during pregnancy suggest that buprenorphine is not inferior to methadone in safety and discomfort of induction from a short-acting opioid, nor in outcome measures assessing NAS and maternal and neonatal safety.^26,27 Results from the recent Maternal Opioid Treatment: Human Experimental Research project suggest that buprenorphine may have some advantages over methadone in pregnancy. Buprenorphine-maintained neonates may need less morphine, have shorter hospital stays, and require shorter treatment for NAS.²⁸ However, treatment retention may be lower for buprenorphine-maintained mothers; any resultant long-term consequences on maternal and child health are as yet unexplored. These findings require replication.

Methadone and buprenorphine are not interchangeable. Many patients maintained on methadone do not respond optimally to buprenorphine. Clinics that dispense maintenance methadone are required to provide counseling services and random drug testing; these requirements do not apply to physicians who prescribe buprenorphine. Moreover, in our experience buprenorphine at times has been prescribed without close regard to psychosocial issues, adequate random drug testing, or coordination of care with other providers.

In pregnant patients, buprenorphine is preferred over buprenorphine and naloxone to avoid fetal exposure to naloxone, which may cause intrauterine withdrawal and maternal-fetal hormonal changes. To reduce abuse or diversion, patients should undergo drug testing to ensure buprenorphine is present, smaller prescriptions may be provided, and tablets can be counted. Limited data suggests buprenorphine is not teratogenic. Some data show low placental transfer of buprenorphine, thereby limiting fetal exposure and lowering risk for intrauterine growth restriction.²⁹

Table 4

Opioid agonist treatment objectives for addicted patients who are pregnant

Delivery and postnatal care

Compared with those not in treatment, women who are engaged in a multidisciplinary treatment program at the time of delivery demonstrated higher gestational age, increased birth weights, and lower rates of neonatal ICU admissions. They also realized a cost savings of $4, 644 per mother-infant pair.³⁰

During delivery, pain medication should not be withheld solely because a pregnant woman has a history of addiction-related disorders; these women are subject to pain during delivery as much as other women. Avoid using mixed agonists/antagonists such as nalbuphine or butorphanol in women receiving opioid maintenance medication. Labor and delivery pain management for a pregnant patient maintained on opioid agonist therapies is discussed elsewhere in the literature.³¹ Every effort should be made to ensure that the mother remains in treatment through delivery and beyond.

To read about advising women with OUD on the benefits and risks of breastfeeding while receiving opioid agonist maintenance treatment, see the Box below.

CASE CONTINUED: Medication change

Ms. J’s boyfriend has left her and her parents have not readily accepted her pregnancy and need for support. She continues to attend NA meetings and weekly therapy. After educating her about the differences between buprenorphine and buprenorphine and naloxone in relation to risk, benefits, and side effects, you switch Ms. J to buprenorphine, 12 mg/d, while maintaining her on aripiprazole and citalopram. She consents to exchanging information about her medical, mental health, and addiction-related treatment with her primary care provider, who helps locate an obstetrician/gynecologist comfortable with her OUD and buprenorphine. Ms. J’s therapist helps link her with social services agencies to ensure prenatal care, assist with removing barriers to care, and plan for her needs as a parent.

After checking your state’s mandates, you determine you are not required to report Ms. J’s drug testing results. Ms. J’s ongoing drug testing shows the presence of buprenorphine and the absence of other opioids and all drugs of abuse.

Ms. J’s delivery is uncomplicated medically; however, family, financial, and parental role issues remain problematic. Encouraging her involvement in therapy and social services as part of her continued buprenorphine prescribing proves beneficial.

• Jones HE, Martin PR, Heil SH, et al. Treatment of opioid dependent pregnant women: clinical and research issues. J Subst Abuse Treat. 2008; 35(3): 245-259.
  
• Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003; 70(suppl 1 ): S87-S101.
  
• Velez M, Jansson LM. The opioid dependent mother and the newborn dyad: nonpharmacologic care. J Addict Med. 2008; 2(3): 113-120.
  

• Aripiprazole • Abilify
  
• Buprenorphine and naloxone •Suboxone
  
• Buprenorphine • Subutex
  
• Butorphanol • Stadol
  
• Citalopram • Celexa
  
• Fentanyl • Duragesic, Sublimaze, others
  
• Methadone • Dolophine
  
• Naloxone • Narcan
  
• Naltrexone • ReVia
  
• Nalbuphine • Nubain
  
• Oxycodone • Oxycontin
  

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

Dr. Fernandez’ time toward this project was funded by the University Hospital/University of Cincinnati Addiction Psychiatry Fellowship Training Program operated by the Center for Treatment, Research, and Education in Addictive Disorders (CeTREAD), Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati and by the Veterans Affairs Medical Center, Cincinnati, OH.

The statements in this publication do not necessarily reflect the views or opinions of the Department of Veterans Affairs, the United States Government, or Opiate Addiction Recovery Services.

Acknowledgments

The authors wish to thank Kathleen Peak for her administrative assistance and Paul Horn, Professor, Department of Mathematical Sciences and Cincinnati VA, for statistical assistance.

CASE: Self-surgery

Dr. T (a pseudonym), a middle-aged male surgeon, arrives in the emergency department (ED) by ambulance after vomiting and losing consciousness at his office. Paramedics place him on an involuntary psychiatric hold, which is permitted in California, after learning that he had been performing surgery on himself.

Dr. T has developed medical complications after attempting to repair his own umbilical hernia. He states that the hernia resulted from weakened periumbilical abdominal muscles after multiple abdominal liposuctions, during which he inserted a cannula through the umbilicus. Dr. T initially repaired the hernia 4 months ago, but the wound margins had dehisced. He had performed the procedure at his ambulatory care surgical suite with help from his surgical assistant. Dr. T says he has performed many procedures on himself, including abdominal and chest liposuction, dermal filler injections, and skin laser resurfacing to improve perceived blemishes and remove hair. These procedures often resulted in poor cosmetic outcomes.

The authors’ observations

Clinical interviews confirmed that Dr. T met DSM-IV-TR criteria for BDD (Table 1).¹ He is excessively preoccupied with perceived physical defects, which cause clinically significant distress, and this preoccupation is not better accounted for by another mental disorder.

Although Dr. T denied any psychotic symptoms during clinical interviews and Mini-Mental State Exam assessment, a reported 77% of BDD patients meet criteria for delusional disorder, somatic type (Table 2).^1,2 Both disorders can be diagnosed concurrently if a patient meets criteria for both disorders.¹ Phillips et al³ have suggested that delusional and non-delusional BDD may constitute the same disorder, spanning a continuum of insight. This hypothesis is supported by reports that selective serotonin reuptake inhibitors (SSRIs) work equally well for both BDD variants.⁴

Table 1

DSM-IV-TR criteria for body dysmorphic disorder

Table 2

DSM-IV-TR criteria for delusional disorder

HISTORY: Accomplishment, anxiety

When we ask Dr. T why he operated on himself, he replies that he did not have time to go to another surgeon. He disagrees when we suggest that he feared that his privacy and professional reputation might be compromised. Dr. T states, “Doctors with walking pneumonia prescribe pills for themselves; this is the same in principle” and “There is no law against operating on oneself.” When we ask if he regrets his actions, he says “I was just overconfident. I did them under local anesthesia and I have a high pain tolerance.” He denies enjoying the pain. He reports that his friends and significant other consider him “courageous” for operating on himself. He denies further plans to perform surgery on himself.

Dr. T has no history of psychiatric hospitalizations or suicide attempts. He has a history of “situational anxiety” and over 3 years his general practitioner prescribed unknown dosages of sertraline, alprazolam, and propranolol, but he did not take these medications regularly and denies taking any other medications. Except for impaired judgment, his mental status exam is within normal limits. He has no other medical problems. He denies alcohol or illicit drug use or a desire to harm himself or others. Dr. T states that as a younger man he was an accomplished athlete and is now an avid body builder who exercises daily and is proud of the intensity and rigor of his workouts.

The authors’ observations

Dr. T does not meet DSM-IV-TR criteria for a current mood or anxiety disorder; however, he has taken medications for what he described as “situational anxiety.” This pattern is consistent with data suggesting that BDD patients feel an unusually high degree of stress in their lives.⁵ Crerand et al⁶ found that >60% of BDD patients had a lifetime history of an anxiety disorder.

Dr. T’s history highlights traits often observed in patients with BDD. As is common in men with BDD, he follows a rigorous exercise regimen.⁷ He also was a competitive athlete, and hypercompetitiveness has significant positive correlation with BDD symptoms.⁸ He is preoccupied with excessive body hair, which is more prevalent in men than in women with BDD.⁹ Dr. T’s work required a keen sense of aesthetics, and it has been observed that individuals with BDD have increased aesthetic sensitivity.^10,11

Although many individuals with BDD struggle socially and financially, some BDD patients are successful and quite accomplished. In a study of 156 Pakistani medical students, 5.8% met criteria for BDD.¹² In The broken mirror,¹³ BDD expert Dr. Katharine Phillips describes caring for many high-functioning health care professionals who suffer from BDD, yet “they provide their patients with superb care … many with this disorder are productive, some are very high achievers.”

EVALUATION: Bad scars

Dr. T has multiple surgical scars on his chest and abdomen (Photo), ecchymoses, and tenderness on palpation. His vital signs are within normal limits and he is otherwise medically healthy. Notable laboratory findings include elevated white blood cell count and platelets, and decreased hemoglobin.

A CT scan shows a large hematoma over the anterior abdominal wall extending toward the flanks with extensive subcutaneous emphysema. The peritoneum is intact. These findings raise the medical team’s concern about possible infection and vascular instability. The involuntary psychiatric hold for observation is continued after evaluation in the ED.

Photo Dr. T’s chest and abdomen during presentation to the ED
Note the asymmetry of the nipples and scarring from prior self-surgeries

The authors’ observations

There is a disconnect between Dr. T’s perception of his physical attributes and the treatment team’s observations. He perceives himself as marred by physical defects, while the treatment team sees him as a handsome and attractive person— excluding his scars from self-surgery.

Patients with BDD frequently are concerned about perceived physical defects that objective observers would consider slight or not noticeable. Three-quarters of individuals with BDD seek surgery or other medical treatment for their perceived physical flaws.⁴ Many patients minimize their BDD symptoms and their distress when talking with health care professionals.¹⁴ Approximately 20% of cosmetic surgery patients report ongoing psychiatric treatment at the time of surgery.¹⁵ Eighty-four percent of cosmetic surgeons state they have refused to operate on a patient because of BDD.¹⁶ However, it may be difficult for surgeons to distinguish a “perfectionist” from a patient with BDD.¹⁷ Even “positive” cosmetic surgery outcomes do not ameliorate BDD symptoms because most patients develop new areas of concern. In a small study of patients with minimal defects who requested cosmetic surgery, surgery did not reduce symptoms of BDD, disability, or psychiatric comorbidity in 6 out of 7 patients at 5-year follow up.¹⁸

Specialized medical equipment, such as surgical instruments and dermabrasion or laser hair removal devices, can be purchased on the Internet, which may increase the likelihood of individuals attempting procedures on themselves. Veale¹⁴ published a retrospective case series of patients who were turned down or unable to afford cosmetic surgery who performed self-surgery. These efforts did not lead to the desired effect, and patients continued to be plagued by their original concerns as well as self-inflicted scarring and damage.

Dr. T had the training and resources to perform cosmetic procedures on himself. Unfortunately, these efforts led to disfigurement. Phillips¹³ states that although self-surgery appears infrequently, it reflects the severe emotional pain and desperation felt by some patients with BDD. Self-surgery is associated with an increased rate of serious suicide attempts.¹⁴ Carefully monitor any BDD patient for suicidal ideation, intent, or plans.

TREATMENT: Refuses follow-up

Dr. T is admitted to the medical service and stabilized with IV fluids and antibiotics. The consultation-liaison service followed him during hospitalization. Because repeated interviews do not uncover grave disability or an imminent danger to himself or others, the involuntary psychiatric hold is discontinued. Dr. T declines psychiatric follow-up care, but says he would consider seeing a mental health professional in the future.

The authors’ observations

This case involves challenging ethical, legal, and countertransference issues. One of the first dilemmas the treatment team encountered was the decision to continue the involuntary hold for observation and assessment. The ED physician and psychiatric resident were faced with telling a fellow physician that he had to remain in the hospital despite his adamant desire to leave. Dr. T’s articulate arguments against staying in the hospital were addressed in order to deliver needed medical treatment. The psychiatric, surgical, and internal medicine teams discussed these countertransference concerns extensively during Dr. T’s hospitalization.

Clearly, Dr. T demonstrated poor judgment by operating on himself, and we aimed to ensure that he received appropriate psychiatric follow-up, but it could not be mandated. After intense and strongly debated ethical and legal discussions with the hospital’s ethicists and risk management team, we determined that we could not file a report with the state medical board because there was no evidence of incompetence, malpractice, or imminent risk to patients. A detailed description of these discussions is omitted from this article to preserve Dr. T’s confidentiality. However, Dr. T will have to disclose and explain the involuntary psychiatric hold on his next medical license renewal.

Our decision was influenced by Phillips,¹³ who found that although patients with BDD may have minimal insight into their illness, “their judgment remains intact in areas unrelated to their body image problem. Attention span and memory are well preserved, and physical and neurologic examinations are normal.” Although Dr. T meets criteria for BDD, mental illness in physicians is not synonymous with impairment.¹⁹

BDD treatment options

With medications and psychotherapy, patients with BDD generally have a good prognosis. A recent meta-analysis found that SSRIs and cognitive-behavioral therapy are effective treatments for BDD.²⁰ In general, higher doses of SSRIs are needed to treat BDD compared with depression. Other medications with evidence of efficacy for BDD include the serotonin norepinephrine reuptake inhibitor venlafaxine²¹ and the anticonvulsant levetiracetam.²² However, clinicians often don’t have the opportunity to try these approaches because BDD patients are difficult to engage in treatment, as is evident in Dr. T’s case. Innovative approaches that combine practical and evidence-based strategies have been manualized.²³ These approaches can help clinicians engage BDD patients in treatment and recognize underlying issues of distorted body image.

Related Resources

• BDD Central. www.bddcentral.com.
• Phillips KA. The broken mirror: understanding and treating body dysmorphic disorder. New York, NY: Oxford University Press; 2005.

Drug Brand Names

• Alprazolam • Xanax
• Levetiracetam • Keppra
• Propranolol • Inderal
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosure

Dr. Rapaport receives grant/research support from the National Institute of Mental Health and the National Center for Complementary and Alternative Medicine and is a consultant for Affectis Pharmaceuticals, Methylation Sciences, PAX Pharmaceuticals, and Johnson and Johnson Pharmaceuticals.

Drs. Rafin and Pimstone report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

The authors wish to thank Dr. Kristine Andrade for editorial assistance. We also wish to thank the Institutional Review Board at Cedars-Sinai Medical Center for its review and approval of this case report, and Dr. T for his consent to publish it.

CASE: Self-surgery

Dr. T (a pseudonym), a middle-aged male surgeon, arrives in the emergency department (ED) by ambulance after vomiting and losing consciousness at his office. Paramedics place him on an involuntary psychiatric hold, which is permitted in California, after learning that he had been performing surgery on himself.

Dr. T has developed medical complications after attempting to repair his own umbilical hernia. He states that the hernia resulted from weakened periumbilical abdominal muscles after multiple abdominal liposuctions, during which he inserted a cannula through the umbilicus. Dr. T initially repaired the hernia 4 months ago, but the wound margins had dehisced. He had performed the procedure at his ambulatory care surgical suite with help from his surgical assistant. Dr. T says he has performed many procedures on himself, including abdominal and chest liposuction, dermal filler injections, and skin laser resurfacing to improve perceived blemishes and remove hair. These procedures often resulted in poor cosmetic outcomes.

The authors’ observations

Clinical interviews confirmed that Dr. T met DSM-IV-TR criteria for BDD (Table 1).¹ He is excessively preoccupied with perceived physical defects, which cause clinically significant distress, and this preoccupation is not better accounted for by another mental disorder.

Although Dr. T denied any psychotic symptoms during clinical interviews and Mini-Mental State Exam assessment, a reported 77% of BDD patients meet criteria for delusional disorder, somatic type (Table 2).^1,2 Both disorders can be diagnosed concurrently if a patient meets criteria for both disorders.¹ Phillips et al³ have suggested that delusional and non-delusional BDD may constitute the same disorder, spanning a continuum of insight. This hypothesis is supported by reports that selective serotonin reuptake inhibitors (SSRIs) work equally well for both BDD variants.⁴

Table 1

DSM-IV-TR criteria for body dysmorphic disorder

Table 2

DSM-IV-TR criteria for delusional disorder

HISTORY: Accomplishment, anxiety

When we ask Dr. T why he operated on himself, he replies that he did not have time to go to another surgeon. He disagrees when we suggest that he feared that his privacy and professional reputation might be compromised. Dr. T states, “Doctors with walking pneumonia prescribe pills for themselves; this is the same in principle” and “There is no law against operating on oneself.” When we ask if he regrets his actions, he says “I was just overconfident. I did them under local anesthesia and I have a high pain tolerance.” He denies enjoying the pain. He reports that his friends and significant other consider him “courageous” for operating on himself. He denies further plans to perform surgery on himself.

Dr. T has no history of psychiatric hospitalizations or suicide attempts. He has a history of “situational anxiety” and over 3 years his general practitioner prescribed unknown dosages of sertraline, alprazolam, and propranolol, but he did not take these medications regularly and denies taking any other medications. Except for impaired judgment, his mental status exam is within normal limits. He has no other medical problems. He denies alcohol or illicit drug use or a desire to harm himself or others. Dr. T states that as a younger man he was an accomplished athlete and is now an avid body builder who exercises daily and is proud of the intensity and rigor of his workouts.

The authors’ observations

Dr. T does not meet DSM-IV-TR criteria for a current mood or anxiety disorder; however, he has taken medications for what he described as “situational anxiety.” This pattern is consistent with data suggesting that BDD patients feel an unusually high degree of stress in their lives.⁵ Crerand et al⁶ found that >60% of BDD patients had a lifetime history of an anxiety disorder.

Dr. T’s history highlights traits often observed in patients with BDD. As is common in men with BDD, he follows a rigorous exercise regimen.⁷ He also was a competitive athlete, and hypercompetitiveness has significant positive correlation with BDD symptoms.⁸ He is preoccupied with excessive body hair, which is more prevalent in men than in women with BDD.⁹ Dr. T’s work required a keen sense of aesthetics, and it has been observed that individuals with BDD have increased aesthetic sensitivity.^10,11

Although many individuals with BDD struggle socially and financially, some BDD patients are successful and quite accomplished. In a study of 156 Pakistani medical students, 5.8% met criteria for BDD.¹² In The broken mirror,¹³ BDD expert Dr. Katharine Phillips describes caring for many high-functioning health care professionals who suffer from BDD, yet “they provide their patients with superb care … many with this disorder are productive, some are very high achievers.”

EVALUATION: Bad scars

Dr. T has multiple surgical scars on his chest and abdomen (Photo), ecchymoses, and tenderness on palpation. His vital signs are within normal limits and he is otherwise medically healthy. Notable laboratory findings include elevated white blood cell count and platelets, and decreased hemoglobin.

A CT scan shows a large hematoma over the anterior abdominal wall extending toward the flanks with extensive subcutaneous emphysema. The peritoneum is intact. These findings raise the medical team’s concern about possible infection and vascular instability. The involuntary psychiatric hold for observation is continued after evaluation in the ED.

Photo Dr. T’s chest and abdomen during presentation to the ED
Note the asymmetry of the nipples and scarring from prior self-surgeries

The authors’ observations

There is a disconnect between Dr. T’s perception of his physical attributes and the treatment team’s observations. He perceives himself as marred by physical defects, while the treatment team sees him as a handsome and attractive person— excluding his scars from self-surgery.

Patients with BDD frequently are concerned about perceived physical defects that objective observers would consider slight or not noticeable. Three-quarters of individuals with BDD seek surgery or other medical treatment for their perceived physical flaws.⁴ Many patients minimize their BDD symptoms and their distress when talking with health care professionals.¹⁴ Approximately 20% of cosmetic surgery patients report ongoing psychiatric treatment at the time of surgery.¹⁵ Eighty-four percent of cosmetic surgeons state they have refused to operate on a patient because of BDD.¹⁶ However, it may be difficult for surgeons to distinguish a “perfectionist” from a patient with BDD.¹⁷ Even “positive” cosmetic surgery outcomes do not ameliorate BDD symptoms because most patients develop new areas of concern. In a small study of patients with minimal defects who requested cosmetic surgery, surgery did not reduce symptoms of BDD, disability, or psychiatric comorbidity in 6 out of 7 patients at 5-year follow up.¹⁸

Specialized medical equipment, such as surgical instruments and dermabrasion or laser hair removal devices, can be purchased on the Internet, which may increase the likelihood of individuals attempting procedures on themselves. Veale¹⁴ published a retrospective case series of patients who were turned down or unable to afford cosmetic surgery who performed self-surgery. These efforts did not lead to the desired effect, and patients continued to be plagued by their original concerns as well as self-inflicted scarring and damage.

Dr. T had the training and resources to perform cosmetic procedures on himself. Unfortunately, these efforts led to disfigurement. Phillips¹³ states that although self-surgery appears infrequently, it reflects the severe emotional pain and desperation felt by some patients with BDD. Self-surgery is associated with an increased rate of serious suicide attempts.¹⁴ Carefully monitor any BDD patient for suicidal ideation, intent, or plans.

TREATMENT: Refuses follow-up

Dr. T is admitted to the medical service and stabilized with IV fluids and antibiotics. The consultation-liaison service followed him during hospitalization. Because repeated interviews do not uncover grave disability or an imminent danger to himself or others, the involuntary psychiatric hold is discontinued. Dr. T declines psychiatric follow-up care, but says he would consider seeing a mental health professional in the future.

The authors’ observations

This case involves challenging ethical, legal, and countertransference issues. One of the first dilemmas the treatment team encountered was the decision to continue the involuntary hold for observation and assessment. The ED physician and psychiatric resident were faced with telling a fellow physician that he had to remain in the hospital despite his adamant desire to leave. Dr. T’s articulate arguments against staying in the hospital were addressed in order to deliver needed medical treatment. The psychiatric, surgical, and internal medicine teams discussed these countertransference concerns extensively during Dr. T’s hospitalization.

Clearly, Dr. T demonstrated poor judgment by operating on himself, and we aimed to ensure that he received appropriate psychiatric follow-up, but it could not be mandated. After intense and strongly debated ethical and legal discussions with the hospital’s ethicists and risk management team, we determined that we could not file a report with the state medical board because there was no evidence of incompetence, malpractice, or imminent risk to patients. A detailed description of these discussions is omitted from this article to preserve Dr. T’s confidentiality. However, Dr. T will have to disclose and explain the involuntary psychiatric hold on his next medical license renewal.

Our decision was influenced by Phillips,¹³ who found that although patients with BDD may have minimal insight into their illness, “their judgment remains intact in areas unrelated to their body image problem. Attention span and memory are well preserved, and physical and neurologic examinations are normal.” Although Dr. T meets criteria for BDD, mental illness in physicians is not synonymous with impairment.¹⁹

BDD treatment options

With medications and psychotherapy, patients with BDD generally have a good prognosis. A recent meta-analysis found that SSRIs and cognitive-behavioral therapy are effective treatments for BDD.²⁰ In general, higher doses of SSRIs are needed to treat BDD compared with depression. Other medications with evidence of efficacy for BDD include the serotonin norepinephrine reuptake inhibitor venlafaxine²¹ and the anticonvulsant levetiracetam.²² However, clinicians often don’t have the opportunity to try these approaches because BDD patients are difficult to engage in treatment, as is evident in Dr. T’s case. Innovative approaches that combine practical and evidence-based strategies have been manualized.²³ These approaches can help clinicians engage BDD patients in treatment and recognize underlying issues of distorted body image.

Related Resources

• BDD Central. www.bddcentral.com.
• Phillips KA. The broken mirror: understanding and treating body dysmorphic disorder. New York, NY: Oxford University Press; 2005.

Drug Brand Names

• Alprazolam • Xanax
• Levetiracetam • Keppra
• Propranolol • Inderal
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosure

Dr. Rapaport receives grant/research support from the National Institute of Mental Health and the National Center for Complementary and Alternative Medicine and is a consultant for Affectis Pharmaceuticals, Methylation Sciences, PAX Pharmaceuticals, and Johnson and Johnson Pharmaceuticals.

Drs. Rafin and Pimstone report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

The authors wish to thank Dr. Kristine Andrade for editorial assistance. We also wish to thank the Institutional Review Board at Cedars-Sinai Medical Center for its review and approval of this case report, and Dr. T for his consent to publish it.

CASE: Self-surgery

Dr. T (a pseudonym), a middle-aged male surgeon, arrives in the emergency department (ED) by ambulance after vomiting and losing consciousness at his office. Paramedics place him on an involuntary psychiatric hold, which is permitted in California, after learning that he had been performing surgery on himself.

Dr. T has developed medical complications after attempting to repair his own umbilical hernia. He states that the hernia resulted from weakened periumbilical abdominal muscles after multiple abdominal liposuctions, during which he inserted a cannula through the umbilicus. Dr. T initially repaired the hernia 4 months ago, but the wound margins had dehisced. He had performed the procedure at his ambulatory care surgical suite with help from his surgical assistant. Dr. T says he has performed many procedures on himself, including abdominal and chest liposuction, dermal filler injections, and skin laser resurfacing to improve perceived blemishes and remove hair. These procedures often resulted in poor cosmetic outcomes.

The authors’ observations

Clinical interviews confirmed that Dr. T met DSM-IV-TR criteria for BDD (Table 1).¹ He is excessively preoccupied with perceived physical defects, which cause clinically significant distress, and this preoccupation is not better accounted for by another mental disorder.

Although Dr. T denied any psychotic symptoms during clinical interviews and Mini-Mental State Exam assessment, a reported 77% of BDD patients meet criteria for delusional disorder, somatic type (Table 2).^1,2 Both disorders can be diagnosed concurrently if a patient meets criteria for both disorders.¹ Phillips et al³ have suggested that delusional and non-delusional BDD may constitute the same disorder, spanning a continuum of insight. This hypothesis is supported by reports that selective serotonin reuptake inhibitors (SSRIs) work equally well for both BDD variants.⁴

Table 1

DSM-IV-TR criteria for body dysmorphic disorder

Table 2

DSM-IV-TR criteria for delusional disorder

HISTORY: Accomplishment, anxiety

When we ask Dr. T why he operated on himself, he replies that he did not have time to go to another surgeon. He disagrees when we suggest that he feared that his privacy and professional reputation might be compromised. Dr. T states, “Doctors with walking pneumonia prescribe pills for themselves; this is the same in principle” and “There is no law against operating on oneself.” When we ask if he regrets his actions, he says “I was just overconfident. I did them under local anesthesia and I have a high pain tolerance.” He denies enjoying the pain. He reports that his friends and significant other consider him “courageous” for operating on himself. He denies further plans to perform surgery on himself.

Dr. T has no history of psychiatric hospitalizations or suicide attempts. He has a history of “situational anxiety” and over 3 years his general practitioner prescribed unknown dosages of sertraline, alprazolam, and propranolol, but he did not take these medications regularly and denies taking any other medications. Except for impaired judgment, his mental status exam is within normal limits. He has no other medical problems. He denies alcohol or illicit drug use or a desire to harm himself or others. Dr. T states that as a younger man he was an accomplished athlete and is now an avid body builder who exercises daily and is proud of the intensity and rigor of his workouts.

The authors’ observations

Dr. T does not meet DSM-IV-TR criteria for a current mood or anxiety disorder; however, he has taken medications for what he described as “situational anxiety.” This pattern is consistent with data suggesting that BDD patients feel an unusually high degree of stress in their lives.⁵ Crerand et al⁶ found that >60% of BDD patients had a lifetime history of an anxiety disorder.

Dr. T’s history highlights traits often observed in patients with BDD. As is common in men with BDD, he follows a rigorous exercise regimen.⁷ He also was a competitive athlete, and hypercompetitiveness has significant positive correlation with BDD symptoms.⁸ He is preoccupied with excessive body hair, which is more prevalent in men than in women with BDD.⁹ Dr. T’s work required a keen sense of aesthetics, and it has been observed that individuals with BDD have increased aesthetic sensitivity.^10,11

Although many individuals with BDD struggle socially and financially, some BDD patients are successful and quite accomplished. In a study of 156 Pakistani medical students, 5.8% met criteria for BDD.¹² In The broken mirror,¹³ BDD expert Dr. Katharine Phillips describes caring for many high-functioning health care professionals who suffer from BDD, yet “they provide their patients with superb care … many with this disorder are productive, some are very high achievers.”

EVALUATION: Bad scars

Dr. T has multiple surgical scars on his chest and abdomen (Photo), ecchymoses, and tenderness on palpation. His vital signs are within normal limits and he is otherwise medically healthy. Notable laboratory findings include elevated white blood cell count and platelets, and decreased hemoglobin.

A CT scan shows a large hematoma over the anterior abdominal wall extending toward the flanks with extensive subcutaneous emphysema. The peritoneum is intact. These findings raise the medical team’s concern about possible infection and vascular instability. The involuntary psychiatric hold for observation is continued after evaluation in the ED.

Photo Dr. T’s chest and abdomen during presentation to the ED
Note the asymmetry of the nipples and scarring from prior self-surgeries

The authors’ observations

There is a disconnect between Dr. T’s perception of his physical attributes and the treatment team’s observations. He perceives himself as marred by physical defects, while the treatment team sees him as a handsome and attractive person— excluding his scars from self-surgery.

Patients with BDD frequently are concerned about perceived physical defects that objective observers would consider slight or not noticeable. Three-quarters of individuals with BDD seek surgery or other medical treatment for their perceived physical flaws.⁴ Many patients minimize their BDD symptoms and their distress when talking with health care professionals.¹⁴ Approximately 20% of cosmetic surgery patients report ongoing psychiatric treatment at the time of surgery.¹⁵ Eighty-four percent of cosmetic surgeons state they have refused to operate on a patient because of BDD.¹⁶ However, it may be difficult for surgeons to distinguish a “perfectionist” from a patient with BDD.¹⁷ Even “positive” cosmetic surgery outcomes do not ameliorate BDD symptoms because most patients develop new areas of concern. In a small study of patients with minimal defects who requested cosmetic surgery, surgery did not reduce symptoms of BDD, disability, or psychiatric comorbidity in 6 out of 7 patients at 5-year follow up.¹⁸

Specialized medical equipment, such as surgical instruments and dermabrasion or laser hair removal devices, can be purchased on the Internet, which may increase the likelihood of individuals attempting procedures on themselves. Veale¹⁴ published a retrospective case series of patients who were turned down or unable to afford cosmetic surgery who performed self-surgery. These efforts did not lead to the desired effect, and patients continued to be plagued by their original concerns as well as self-inflicted scarring and damage.

Dr. T had the training and resources to perform cosmetic procedures on himself. Unfortunately, these efforts led to disfigurement. Phillips¹³ states that although self-surgery appears infrequently, it reflects the severe emotional pain and desperation felt by some patients with BDD. Self-surgery is associated with an increased rate of serious suicide attempts.¹⁴ Carefully monitor any BDD patient for suicidal ideation, intent, or plans.

TREATMENT: Refuses follow-up

Dr. T is admitted to the medical service and stabilized with IV fluids and antibiotics. The consultation-liaison service followed him during hospitalization. Because repeated interviews do not uncover grave disability or an imminent danger to himself or others, the involuntary psychiatric hold is discontinued. Dr. T declines psychiatric follow-up care, but says he would consider seeing a mental health professional in the future.

The authors’ observations

This case involves challenging ethical, legal, and countertransference issues. One of the first dilemmas the treatment team encountered was the decision to continue the involuntary hold for observation and assessment. The ED physician and psychiatric resident were faced with telling a fellow physician that he had to remain in the hospital despite his adamant desire to leave. Dr. T’s articulate arguments against staying in the hospital were addressed in order to deliver needed medical treatment. The psychiatric, surgical, and internal medicine teams discussed these countertransference concerns extensively during Dr. T’s hospitalization.

Clearly, Dr. T demonstrated poor judgment by operating on himself, and we aimed to ensure that he received appropriate psychiatric follow-up, but it could not be mandated. After intense and strongly debated ethical and legal discussions with the hospital’s ethicists and risk management team, we determined that we could not file a report with the state medical board because there was no evidence of incompetence, malpractice, or imminent risk to patients. A detailed description of these discussions is omitted from this article to preserve Dr. T’s confidentiality. However, Dr. T will have to disclose and explain the involuntary psychiatric hold on his next medical license renewal.

Our decision was influenced by Phillips,¹³ who found that although patients with BDD may have minimal insight into their illness, “their judgment remains intact in areas unrelated to their body image problem. Attention span and memory are well preserved, and physical and neurologic examinations are normal.” Although Dr. T meets criteria for BDD, mental illness in physicians is not synonymous with impairment.¹⁹

BDD treatment options

With medications and psychotherapy, patients with BDD generally have a good prognosis. A recent meta-analysis found that SSRIs and cognitive-behavioral therapy are effective treatments for BDD.²⁰ In general, higher doses of SSRIs are needed to treat BDD compared with depression. Other medications with evidence of efficacy for BDD include the serotonin norepinephrine reuptake inhibitor venlafaxine²¹ and the anticonvulsant levetiracetam.²² However, clinicians often don’t have the opportunity to try these approaches because BDD patients are difficult to engage in treatment, as is evident in Dr. T’s case. Innovative approaches that combine practical and evidence-based strategies have been manualized.²³ These approaches can help clinicians engage BDD patients in treatment and recognize underlying issues of distorted body image.

Related Resources

• BDD Central. www.bddcentral.com.
• Phillips KA. The broken mirror: understanding and treating body dysmorphic disorder. New York, NY: Oxford University Press; 2005.

Drug Brand Names

• Alprazolam • Xanax
• Levetiracetam • Keppra
• Propranolol • Inderal
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosure

Dr. Rapaport receives grant/research support from the National Institute of Mental Health and the National Center for Complementary and Alternative Medicine and is a consultant for Affectis Pharmaceuticals, Methylation Sciences, PAX Pharmaceuticals, and Johnson and Johnson Pharmaceuticals.

Drs. Rafin and Pimstone report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Acknowledgement

The authors wish to thank Dr. Kristine Andrade for editorial assistance. We also wish to thank the Institutional Review Board at Cedars-Sinai Medical Center for its review and approval of this case report, and Dr. T for his consent to publish it.

I agree with Dr. Henry A. Nasrallah’s commentary, “Are some nonpsychotic psychiatric disorders actually psychotic?” (From the Editor, Current Psychiatry, November 2010, p. 16-19), but I believe the issue is bigger than he states. Let’s start with the fact that psychiatry mostly operates with diagnoses that do not have any tangible biologic underpinning and remain phenomenological descriptions. No one in general medicine would accept a diagnosis of headache or nausea, but we are quite comfortable with anxiety disorder, not otherwise specified (NOS) or intermittent explosive disorder. The list could go on.

Psychiatry is not considered a true medical discipline and we are paying the price. The “old school” of clinical psychiatry operated within a dichotomy of major categories—neurosis or psychosis—and the latter one recognized only 3 diagnostic entities: schizophrenia, manic-depressive disease, and organic disorder. It was a medical classification based on the putative biologic underpinnings of the disease, as in other medical specialties. Since then our psychiatric language became inundated with multiple NOS and descriptive labels in lieu of medical diagnoses.

True, in psychiatry we cannot use ultrasound to diagnose schizoaffective disorder, and we have to use the same method of careful medical interview and history-taking as did many generations of psychiatrists before us. We lack objectivity of the diagnosis but still—hopefully—possess our mental capacity and ability to analyze data and use our clinical experience. We are making some headway in using medical tests such as genetic testing or MRI, but they remain supplemental to our clinical thinking. The analytical part of a psychiatric brain does not seem to be too much in demand or relied upon. DSM classification gives us many choices to pick a label for the occasion regardless of the essence of the disease. The Texas Medication Algorithm Project is supposed to help streamline treatment modules, but it also eliminates the need to think because the perfect recipe is ready at every step. If patients are not getting better—oh well—we followed the protocol.

About Dr. Nasrallah’s article: how much could traditionally non-psychotic conditions be psychotic? We know that multiple neurotransmitters in the brain are engaged in psychiatric diseases. We do not know all of them and have only a partial understanding of their role in pathogenesis, but any psychiatric condition has a list of usual participants—neurotransmitters. Imagine a piano keyboard where one can play a popular song or jazz or Bach using the same keys, depending on the taste and skills of the performer. Our brain probably has the same “keyboard” of neurotransmitters playing different tunes.

The diagnosis of treatment-resistant depression—recently so fashionable and investigated—does not make clinical sense, but responds well to olanzapine and other second-generation antipsychotics (SGAs), which the bravest of us use off-label. Before the SGA era we used haloperidol intravenous drip to treat “resistant depression” and it helped! But before we hooked our patients to a bolus of haloperidol, we talked about the clinical diagnosis and at least tried to outline what we were attempting to treat. Sadly, the art of clinical interview and refining analysis is steadily moving toward extinction.

Our residents are brought up on a combination of traffic rules and basic cookbooks—not even gourmet ones—learning how to use a cookie cutter for any occasion. Residents are taught how to fit patients into a familiar pattern, not how to see in what ways patients are different. During my supervision with recent graduates I heard questions that follow the pattern they were taught—finding the correct and quick recipe and mold by association, not by analysis.

I would to thank Dr. Nasrallah for breaking the box psychiatry was corralled to and provoking our peers to think rather than live in the one-dimensional world of a cookbook.

Irene Abramovich, MD, PhD
Private Practice
New York, NY

I agree with Dr. Henry A. Nasrallah’s commentary, “Are some nonpsychotic psychiatric disorders actually psychotic?” (From the Editor, Current Psychiatry, November 2010, p. 16-19), but I believe the issue is bigger than he states. Let’s start with the fact that psychiatry mostly operates with diagnoses that do not have any tangible biologic underpinning and remain phenomenological descriptions. No one in general medicine would accept a diagnosis of headache or nausea, but we are quite comfortable with anxiety disorder, not otherwise specified (NOS) or intermittent explosive disorder. The list could go on.

Psychiatry is not considered a true medical discipline and we are paying the price. The “old school” of clinical psychiatry operated within a dichotomy of major categories—neurosis or psychosis—and the latter one recognized only 3 diagnostic entities: schizophrenia, manic-depressive disease, and organic disorder. It was a medical classification based on the putative biologic underpinnings of the disease, as in other medical specialties. Since then our psychiatric language became inundated with multiple NOS and descriptive labels in lieu of medical diagnoses.

True, in psychiatry we cannot use ultrasound to diagnose schizoaffective disorder, and we have to use the same method of careful medical interview and history-taking as did many generations of psychiatrists before us. We lack objectivity of the diagnosis but still—hopefully—possess our mental capacity and ability to analyze data and use our clinical experience. We are making some headway in using medical tests such as genetic testing or MRI, but they remain supplemental to our clinical thinking. The analytical part of a psychiatric brain does not seem to be too much in demand or relied upon. DSM classification gives us many choices to pick a label for the occasion regardless of the essence of the disease. The Texas Medication Algorithm Project is supposed to help streamline treatment modules, but it also eliminates the need to think because the perfect recipe is ready at every step. If patients are not getting better—oh well—we followed the protocol.

About Dr. Nasrallah’s article: how much could traditionally non-psychotic conditions be psychotic? We know that multiple neurotransmitters in the brain are engaged in psychiatric diseases. We do not know all of them and have only a partial understanding of their role in pathogenesis, but any psychiatric condition has a list of usual participants—neurotransmitters. Imagine a piano keyboard where one can play a popular song or jazz or Bach using the same keys, depending on the taste and skills of the performer. Our brain probably has the same “keyboard” of neurotransmitters playing different tunes.

The diagnosis of treatment-resistant depression—recently so fashionable and investigated—does not make clinical sense, but responds well to olanzapine and other second-generation antipsychotics (SGAs), which the bravest of us use off-label. Before the SGA era we used haloperidol intravenous drip to treat “resistant depression” and it helped! But before we hooked our patients to a bolus of haloperidol, we talked about the clinical diagnosis and at least tried to outline what we were attempting to treat. Sadly, the art of clinical interview and refining analysis is steadily moving toward extinction.

Our residents are brought up on a combination of traffic rules and basic cookbooks—not even gourmet ones—learning how to use a cookie cutter for any occasion. Residents are taught how to fit patients into a familiar pattern, not how to see in what ways patients are different. During my supervision with recent graduates I heard questions that follow the pattern they were taught—finding the correct and quick recipe and mold by association, not by analysis.

I would to thank Dr. Nasrallah for breaking the box psychiatry was corralled to and provoking our peers to think rather than live in the one-dimensional world of a cookbook.

Irene Abramovich, MD, PhD
Private Practice
New York, NY

I agree with Dr. Henry A. Nasrallah’s commentary, “Are some nonpsychotic psychiatric disorders actually psychotic?” (From the Editor, Current Psychiatry, November 2010, p. 16-19), but I believe the issue is bigger than he states. Let’s start with the fact that psychiatry mostly operates with diagnoses that do not have any tangible biologic underpinning and remain phenomenological descriptions. No one in general medicine would accept a diagnosis of headache or nausea, but we are quite comfortable with anxiety disorder, not otherwise specified (NOS) or intermittent explosive disorder. The list could go on.

Psychiatry is not considered a true medical discipline and we are paying the price. The “old school” of clinical psychiatry operated within a dichotomy of major categories—neurosis or psychosis—and the latter one recognized only 3 diagnostic entities: schizophrenia, manic-depressive disease, and organic disorder. It was a medical classification based on the putative biologic underpinnings of the disease, as in other medical specialties. Since then our psychiatric language became inundated with multiple NOS and descriptive labels in lieu of medical diagnoses.

True, in psychiatry we cannot use ultrasound to diagnose schizoaffective disorder, and we have to use the same method of careful medical interview and history-taking as did many generations of psychiatrists before us. We lack objectivity of the diagnosis but still—hopefully—possess our mental capacity and ability to analyze data and use our clinical experience. We are making some headway in using medical tests such as genetic testing or MRI, but they remain supplemental to our clinical thinking. The analytical part of a psychiatric brain does not seem to be too much in demand or relied upon. DSM classification gives us many choices to pick a label for the occasion regardless of the essence of the disease. The Texas Medication Algorithm Project is supposed to help streamline treatment modules, but it also eliminates the need to think because the perfect recipe is ready at every step. If patients are not getting better—oh well—we followed the protocol.

About Dr. Nasrallah’s article: how much could traditionally non-psychotic conditions be psychotic? We know that multiple neurotransmitters in the brain are engaged in psychiatric diseases. We do not know all of them and have only a partial understanding of their role in pathogenesis, but any psychiatric condition has a list of usual participants—neurotransmitters. Imagine a piano keyboard where one can play a popular song or jazz or Bach using the same keys, depending on the taste and skills of the performer. Our brain probably has the same “keyboard” of neurotransmitters playing different tunes.

The diagnosis of treatment-resistant depression—recently so fashionable and investigated—does not make clinical sense, but responds well to olanzapine and other second-generation antipsychotics (SGAs), which the bravest of us use off-label. Before the SGA era we used haloperidol intravenous drip to treat “resistant depression” and it helped! But before we hooked our patients to a bolus of haloperidol, we talked about the clinical diagnosis and at least tried to outline what we were attempting to treat. Sadly, the art of clinical interview and refining analysis is steadily moving toward extinction.

Our residents are brought up on a combination of traffic rules and basic cookbooks—not even gourmet ones—learning how to use a cookie cutter for any occasion. Residents are taught how to fit patients into a familiar pattern, not how to see in what ways patients are different. During my supervision with recent graduates I heard questions that follow the pattern they were taught—finding the correct and quick recipe and mold by association, not by analysis.

I would to thank Dr. Nasrallah for breaking the box psychiatry was corralled to and provoking our peers to think rather than live in the one-dimensional world of a cookbook.

Irene Abramovich, MD, PhD
Private Practice
New York, NY

In October 2010, the FDA approved a combination of dextromethorphan (DM) and quinidine for the treatment of pseudobulbar affect (PBA)—also called pathological laughing and crying, affective lability, emotional dyscontrol, emotional incontinence, and involuntary emotional expression disorder—in patients with neurologic disorders and brain injuries (Table). Despite receiving an approvable letter in 2006, the compound was not approved at that time because of concerns about the arrhythmogenic potential of quinidine, which prolongs the QT interval. The manufacturer conducted another study using one-third of the previous quinidine dose, which ameliorated this concern and led to approval.

Clinical implications

PBA is manifested by involuntary labile, shallow affect with sudden and unpredictable laughing, crying, or other emotional displays that are not appropriate to the social setting and may not be congruent with the patient’s prevailing mood.¹ Episodes are often paroxysmal and cannot be interrupted voluntarily.² PBA seems to be caused by a loss of descending cortical control of brainstem motor nuclei and possibly the cerebellum, disrupting inhibitory mechanisms and resulting in inappropriate and involuntary emotional display.³ Several studies have demonstrated involvement of subcortical areas, particularly the anterior limb of the internal capsule and the bulbar area. The patho-physiology of PBA may involve excessive release of glutamate by injured neurons, disrupting systems for motor control of emotional expression.^4,5

Table

Dextromethorphan/quinidine: Fast facts

PBA is most common in diseases that interfere bilaterally with the corticohypothalamic and corticobulbar tracts that control voluntary and involuntary faciorespiratory mechanisms. However, PBA occurs in unilateral disease as well. The reported prevalence of PBA is:

• 49% in amyotrophic lateral sclerosis (ALS)
• 18% to 39% in Alzheimer’s disease
• 11% to 34% in stroke
• 10% to 11% in multiple sclerosis (MS) and traumatic brain injury.^6,7

PBA also has been reported in patients with Parkinson’s disease, brain tumors, Wilson’s disease, syphilitic pseudobulbar palsy, and various encephalitides.¹ An estimated 880,000 U.S. patients exhibit PBA.⁸

Previously, there was no FDA-approved treatment for PBA. However, small controlled trials suggest that selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs)— usually in doses lower than those used to treat depression—may effectively reduce symptoms within 2 to 3 days.¹ Although dopaminergic agents such as levodopa and amantadine have shown benefit in open trials, results of controlled studies using objective measurements have not been positive.

How it works

DM is a serotonergic substance that also is an agonist of 1-sigma receptors and a low-affinity, uncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptors, which are important in glutamate signaling, through binding at the phencyclidine site on the NMDA complex.^7,9 The 1-sigma receptor was thought to be an opioid receptor subtype, but unlike opioid receptors it is not blocked by narcotic antagonists and does not have an endogenous ligand. However, the 1-sigma receptor does modulate activity of opioid mu receptors in addition to altering dopamine release and possibly reducing glutamate release.⁹ Sigma receptors are densely distributed in the limbic system and in systems related to motor control of affective expression and seem to be involved in learning, responses to stress, mood regulation, and drug dependence.¹ Because DM preferentially binds to brain regions that regulate emotional expression,¹⁰ it could normalize glutaminergic neurotransmission and other relevant systems in these regions.¹ However, DM’s exact mechanism of action is unknown.

Quinidine is a sodium channel antagonist usually used as a type Ia antiarrhythmic.⁵ DM is subject to extensive first-pass metabolism by cytochrome P (CYP) 450 2D6 to dextrorphan, which after being glucuronidated cannot cross the blood-brain barrier. In doses 10 to 25 times lower than those used to treat cardiac arrhythmias, quinidine inhibits 2D6 and increases DM bioavailability.¹⁰ DM blood levels increase linearly with dose following coadministration with quinidine but are undetectable in most patients given DM alone.^7,9

Efficacy and tolerability

A combination of DM and quinidine (DMQ) reduced Center for Neurologic Study-Lability Scale (CNC-LS) scores and the number of daily PBA episodes in 3 randomized trials.^5,7,10 Visit this article at CurrentPsychiatry.com for a table summarizing these studies.

An 85-day randomized, double-blind, placebo-controlled study of 150 patients with PBA associated with MS found that DM, 30 mg, plus quinidine, 30 mg, (DMQ 30-30) was twice as effective as placebo within a week in reducing CNC-LS scores.¹⁰ DMQ 30-30 patients also had approximately half as many episodes of inappropriate laughing, crying, or combined laughing and crying and a 2-fold greater decrease in pain intensity.¹⁰ Twenty-one percent of DMQ 30-30 patients experienced complete remission—no PBA episodes—compared with 7% of placebo patients. There were no significant differences in QT prolongation between DMQ 30-30 and placebo.

A 3-arm, double-blind, 28-day, phase III multicenter trial of 140 ALS patients with PBA compared DM monotherapy, quinidine monotherapy, and DMQ 30-30.⁵ Compared with either drug alone, DMQ 30-30 showed greater reduction of CNC-LS scores, as well as improved quality of life and quality of relationships scores, with equal benefit in poor and extensive DM metabolizers. However, the control conditions may not have been adequate. Quinidine alone would not be expected to have an effect on PBA, and the DM dose, which was the same in combination and monotherapy, may have been too low to be effective by itself. In support of this hypothesis, the DM plasma level was 18 times higher in patients taking DMQ 30-30 than those taking DM monotherapy.

In a manufacturer-sponsored, multicenter, 12-week randomized trial, 326 patients with ALS or MS and clinically significant PBA were randomly assigned to DM, 30 mg, plus quinidine, 10 mg (DMQ 30-10), DM, 20 mg, plus quinidine, 10 mg (DMQ 20-10), or placebo, each administered twice daily.⁷ Patients with comorbid psychiatric disorders or significant depressive symptoms were excluded. Although daily PBA episodes decreased in all groups, the daily rate of PBA episodes was 47% lower for patients taking DMQ 30-10, and 49% lower with DMQ 20-10 compared with placebo (both P < .001). The mean decrease in the number of daily PBA episodes was 3.9 to 4.1 with active treatment and 3.0 with placebo. Side effects were more common with active drug than placebo and included dizziness, nausea, diarrhea, and urinary tract infection. There were no serious adverse cardiac events and no active drug recipients showed a QTc interval >480 msec or a change from baseline >60 msec.¹¹ Discontinuation rates in this study were lower than in studies of DMQ 30-30. In an open-label extension of 253 patients who completed the double-blind phase and were assigned to DMQ 30-10 for 12 weeks, the incidence of treatment-related adverse events was 28%, with a 5.5% rate of serious adverse events.¹²

Safety

Because the 10 mg dose of quinidine in the approved formulation of DMQ is 10 times lower than the antiarrhythmic dose, substantial ECG changes and adverse cardiac effects with DMQ have not been reported. The most common side effects of DM are nausea, somnolence, dizziness, and headache. Thrombocytopenia, QT prolongation, hepatotoxicity, allergic reactions, and anticholinergic side effects can occur.

In high doses and combined with other substances, DM has been used as a recreational drug. When taken in high doses, adverse effects include nausea, vomiting, malaise, dilated pupils, difficulty urinating, increased urination frequency, fever, tachycardia, loss of appetite, shakiness, seizures, and potentially coma and death. DMQ may have a greater potential for serious adverse effects than DM alone because quinidine increases DM bioavailability and blood levels. The abuse potential of DMQ is not clear.

Psychosis has been reported with higher DM doses. The psychotomimetic effects of phencyclidine (PCP) are related to binding to the PCP site on the NMDA receptor complex—to which DM also binds—with reduced glutamate signaling in information processing systems. Therefore, caution is indicated when prescribing DM to patients with psychosis.

Because DM, a CYP2D6 substrate, is combined with quinidine, a 2D6 inhibitor, administering DMQ with other 2D6 inhibitors could lead to toxicity. When DMQ is combined with SSRIs and similar agents, the serotonergic properties of DM could result in serotonin syndrome, which could be fatal if DM is combined with monoamine oxidase inhibitors.¹⁰ Combinations of DM and acetaminophen and antihistamines can be dangerous at higher doses.¹⁰ Because quinidine is metabolized by CYP3A, inhibitors of this enzyme such as ketoconazole, nefazodone, and grapefruit juice should be avoided. Similarly, inhibition of CYP2D6 by quinidine could raise levels of coadministered 2D6 substrates.

Contraindications. DMQ is contraindicated in patients with:

• heart failure
• prolonged QT interval
• congenital long QT interval
• history of torsades de pointes
• complete atrioventricular (AV) block without implanted pacemakers.¹³

DMQ also is contraindicated in patients at high risk for complete AV block.¹³

Dosing

DMQ is available as a capsule containing DM, 20 mg, and quinidine, 10 mg. The recommended starting dose is 1 capsule by mouth for 7 days, then 1 capsule every 12 hours.

Although DMQ is convenient, its advantage over starting with DM alone and adding a small dose of a non-serotonergic 2D6 inhibitor if DM is not effective remains to be demonstrated. In view of the unknown potential for abuse and toxicity as well as the cost of the proprietary drug ($3,000 to $5,000 a year), it would seem prudent to consider using an SSRI or a TCA first.⁸ These medications also act on 1-sigma receptors,^14,15 which may account in part for their reported benefit.

Related Resource

• Neudexta [package insert]. Aliso Viejo, CA: Avanir Pharmaceuticals; 2010.

Drug Brand Names

• Amantadine • Symmetrel
• Dextromethorphan/quinidine •Nefazodone
• Ketoconazole • Nizoral
• Levodopa • Sinemet
• Neudexta • Serzone
• Quinidine • Quinidex

Disclosures

Dr. Dubovsky receives research support from Biogen Idec, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Otsuka, the Peter and Elizabeth C. Tower Foundation, and Pfizer, Inc.

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

Table 2

Dextromethorphan/quinidine for PBA: Evidence shows efficacy

In October 2010, the FDA approved a combination of dextromethorphan (DM) and quinidine for the treatment of pseudobulbar affect (PBA)—also called pathological laughing and crying, affective lability, emotional dyscontrol, emotional incontinence, and involuntary emotional expression disorder—in patients with neurologic disorders and brain injuries (Table). Despite receiving an approvable letter in 2006, the compound was not approved at that time because of concerns about the arrhythmogenic potential of quinidine, which prolongs the QT interval. The manufacturer conducted another study using one-third of the previous quinidine dose, which ameliorated this concern and led to approval.

Clinical implications

PBA is manifested by involuntary labile, shallow affect with sudden and unpredictable laughing, crying, or other emotional displays that are not appropriate to the social setting and may not be congruent with the patient’s prevailing mood.¹ Episodes are often paroxysmal and cannot be interrupted voluntarily.² PBA seems to be caused by a loss of descending cortical control of brainstem motor nuclei and possibly the cerebellum, disrupting inhibitory mechanisms and resulting in inappropriate and involuntary emotional display.³ Several studies have demonstrated involvement of subcortical areas, particularly the anterior limb of the internal capsule and the bulbar area. The patho-physiology of PBA may involve excessive release of glutamate by injured neurons, disrupting systems for motor control of emotional expression.^4,5

Table

Dextromethorphan/quinidine: Fast facts

PBA is most common in diseases that interfere bilaterally with the corticohypothalamic and corticobulbar tracts that control voluntary and involuntary faciorespiratory mechanisms. However, PBA occurs in unilateral disease as well. The reported prevalence of PBA is:

• 49% in amyotrophic lateral sclerosis (ALS)
• 18% to 39% in Alzheimer’s disease
• 11% to 34% in stroke
• 10% to 11% in multiple sclerosis (MS) and traumatic brain injury.^6,7

PBA also has been reported in patients with Parkinson’s disease, brain tumors, Wilson’s disease, syphilitic pseudobulbar palsy, and various encephalitides.¹ An estimated 880,000 U.S. patients exhibit PBA.⁸

Previously, there was no FDA-approved treatment for PBA. However, small controlled trials suggest that selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs)— usually in doses lower than those used to treat depression—may effectively reduce symptoms within 2 to 3 days.¹ Although dopaminergic agents such as levodopa and amantadine have shown benefit in open trials, results of controlled studies using objective measurements have not been positive.

How it works

DM is a serotonergic substance that also is an agonist of 1-sigma receptors and a low-affinity, uncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptors, which are important in glutamate signaling, through binding at the phencyclidine site on the NMDA complex.^7,9 The 1-sigma receptor was thought to be an opioid receptor subtype, but unlike opioid receptors it is not blocked by narcotic antagonists and does not have an endogenous ligand. However, the 1-sigma receptor does modulate activity of opioid mu receptors in addition to altering dopamine release and possibly reducing glutamate release.⁹ Sigma receptors are densely distributed in the limbic system and in systems related to motor control of affective expression and seem to be involved in learning, responses to stress, mood regulation, and drug dependence.¹ Because DM preferentially binds to brain regions that regulate emotional expression,¹⁰ it could normalize glutaminergic neurotransmission and other relevant systems in these regions.¹ However, DM’s exact mechanism of action is unknown.

Quinidine is a sodium channel antagonist usually used as a type Ia antiarrhythmic.⁵ DM is subject to extensive first-pass metabolism by cytochrome P (CYP) 450 2D6 to dextrorphan, which after being glucuronidated cannot cross the blood-brain barrier. In doses 10 to 25 times lower than those used to treat cardiac arrhythmias, quinidine inhibits 2D6 and increases DM bioavailability.¹⁰ DM blood levels increase linearly with dose following coadministration with quinidine but are undetectable in most patients given DM alone.^7,9

Efficacy and tolerability

A combination of DM and quinidine (DMQ) reduced Center for Neurologic Study-Lability Scale (CNC-LS) scores and the number of daily PBA episodes in 3 randomized trials.^5,7,10 Visit this article at CurrentPsychiatry.com for a table summarizing these studies.

An 85-day randomized, double-blind, placebo-controlled study of 150 patients with PBA associated with MS found that DM, 30 mg, plus quinidine, 30 mg, (DMQ 30-30) was twice as effective as placebo within a week in reducing CNC-LS scores.¹⁰ DMQ 30-30 patients also had approximately half as many episodes of inappropriate laughing, crying, or combined laughing and crying and a 2-fold greater decrease in pain intensity.¹⁰ Twenty-one percent of DMQ 30-30 patients experienced complete remission—no PBA episodes—compared with 7% of placebo patients. There were no significant differences in QT prolongation between DMQ 30-30 and placebo.

A 3-arm, double-blind, 28-day, phase III multicenter trial of 140 ALS patients with PBA compared DM monotherapy, quinidine monotherapy, and DMQ 30-30.⁵ Compared with either drug alone, DMQ 30-30 showed greater reduction of CNC-LS scores, as well as improved quality of life and quality of relationships scores, with equal benefit in poor and extensive DM metabolizers. However, the control conditions may not have been adequate. Quinidine alone would not be expected to have an effect on PBA, and the DM dose, which was the same in combination and monotherapy, may have been too low to be effective by itself. In support of this hypothesis, the DM plasma level was 18 times higher in patients taking DMQ 30-30 than those taking DM monotherapy.

In a manufacturer-sponsored, multicenter, 12-week randomized trial, 326 patients with ALS or MS and clinically significant PBA were randomly assigned to DM, 30 mg, plus quinidine, 10 mg (DMQ 30-10), DM, 20 mg, plus quinidine, 10 mg (DMQ 20-10), or placebo, each administered twice daily.⁷ Patients with comorbid psychiatric disorders or significant depressive symptoms were excluded. Although daily PBA episodes decreased in all groups, the daily rate of PBA episodes was 47% lower for patients taking DMQ 30-10, and 49% lower with DMQ 20-10 compared with placebo (both P < .001). The mean decrease in the number of daily PBA episodes was 3.9 to 4.1 with active treatment and 3.0 with placebo. Side effects were more common with active drug than placebo and included dizziness, nausea, diarrhea, and urinary tract infection. There were no serious adverse cardiac events and no active drug recipients showed a QTc interval >480 msec or a change from baseline >60 msec.¹¹ Discontinuation rates in this study were lower than in studies of DMQ 30-30. In an open-label extension of 253 patients who completed the double-blind phase and were assigned to DMQ 30-10 for 12 weeks, the incidence of treatment-related adverse events was 28%, with a 5.5% rate of serious adverse events.¹²

Safety

Because the 10 mg dose of quinidine in the approved formulation of DMQ is 10 times lower than the antiarrhythmic dose, substantial ECG changes and adverse cardiac effects with DMQ have not been reported. The most common side effects of DM are nausea, somnolence, dizziness, and headache. Thrombocytopenia, QT prolongation, hepatotoxicity, allergic reactions, and anticholinergic side effects can occur.

In high doses and combined with other substances, DM has been used as a recreational drug. When taken in high doses, adverse effects include nausea, vomiting, malaise, dilated pupils, difficulty urinating, increased urination frequency, fever, tachycardia, loss of appetite, shakiness, seizures, and potentially coma and death. DMQ may have a greater potential for serious adverse effects than DM alone because quinidine increases DM bioavailability and blood levels. The abuse potential of DMQ is not clear.

Psychosis has been reported with higher DM doses. The psychotomimetic effects of phencyclidine (PCP) are related to binding to the PCP site on the NMDA receptor complex—to which DM also binds—with reduced glutamate signaling in information processing systems. Therefore, caution is indicated when prescribing DM to patients with psychosis.

Because DM, a CYP2D6 substrate, is combined with quinidine, a 2D6 inhibitor, administering DMQ with other 2D6 inhibitors could lead to toxicity. When DMQ is combined with SSRIs and similar agents, the serotonergic properties of DM could result in serotonin syndrome, which could be fatal if DM is combined with monoamine oxidase inhibitors.¹⁰ Combinations of DM and acetaminophen and antihistamines can be dangerous at higher doses.¹⁰ Because quinidine is metabolized by CYP3A, inhibitors of this enzyme such as ketoconazole, nefazodone, and grapefruit juice should be avoided. Similarly, inhibition of CYP2D6 by quinidine could raise levels of coadministered 2D6 substrates.

Contraindications. DMQ is contraindicated in patients with:

• heart failure
• prolonged QT interval
• congenital long QT interval
• history of torsades de pointes
• complete atrioventricular (AV) block without implanted pacemakers.¹³

DMQ also is contraindicated in patients at high risk for complete AV block.¹³

Dosing

DMQ is available as a capsule containing DM, 20 mg, and quinidine, 10 mg. The recommended starting dose is 1 capsule by mouth for 7 days, then 1 capsule every 12 hours.

Although DMQ is convenient, its advantage over starting with DM alone and adding a small dose of a non-serotonergic 2D6 inhibitor if DM is not effective remains to be demonstrated. In view of the unknown potential for abuse and toxicity as well as the cost of the proprietary drug ($3,000 to $5,000 a year), it would seem prudent to consider using an SSRI or a TCA first.⁸ These medications also act on 1-sigma receptors,^14,15 which may account in part for their reported benefit.

Related Resource

• Neudexta [package insert]. Aliso Viejo, CA: Avanir Pharmaceuticals; 2010.

Drug Brand Names

• Amantadine • Symmetrel
• Dextromethorphan/quinidine •Nefazodone
• Ketoconazole • Nizoral
• Levodopa • Sinemet
• Neudexta • Serzone
• Quinidine • Quinidex

Disclosures

Dr. Dubovsky receives research support from Biogen Idec, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Otsuka, the Peter and Elizabeth C. Tower Foundation, and Pfizer, Inc.

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

Table 2

Dextromethorphan/quinidine for PBA: Evidence shows efficacy

In October 2010, the FDA approved a combination of dextromethorphan (DM) and quinidine for the treatment of pseudobulbar affect (PBA)—also called pathological laughing and crying, affective lability, emotional dyscontrol, emotional incontinence, and involuntary emotional expression disorder—in patients with neurologic disorders and brain injuries (Table). Despite receiving an approvable letter in 2006, the compound was not approved at that time because of concerns about the arrhythmogenic potential of quinidine, which prolongs the QT interval. The manufacturer conducted another study using one-third of the previous quinidine dose, which ameliorated this concern and led to approval.

Clinical implications

PBA is manifested by involuntary labile, shallow affect with sudden and unpredictable laughing, crying, or other emotional displays that are not appropriate to the social setting and may not be congruent with the patient’s prevailing mood.¹ Episodes are often paroxysmal and cannot be interrupted voluntarily.² PBA seems to be caused by a loss of descending cortical control of brainstem motor nuclei and possibly the cerebellum, disrupting inhibitory mechanisms and resulting in inappropriate and involuntary emotional display.³ Several studies have demonstrated involvement of subcortical areas, particularly the anterior limb of the internal capsule and the bulbar area. The patho-physiology of PBA may involve excessive release of glutamate by injured neurons, disrupting systems for motor control of emotional expression.^4,5

Table

Dextromethorphan/quinidine: Fast facts

PBA is most common in diseases that interfere bilaterally with the corticohypothalamic and corticobulbar tracts that control voluntary and involuntary faciorespiratory mechanisms. However, PBA occurs in unilateral disease as well. The reported prevalence of PBA is:

• 49% in amyotrophic lateral sclerosis (ALS)
• 18% to 39% in Alzheimer’s disease
• 11% to 34% in stroke
• 10% to 11% in multiple sclerosis (MS) and traumatic brain injury.^6,7

PBA also has been reported in patients with Parkinson’s disease, brain tumors, Wilson’s disease, syphilitic pseudobulbar palsy, and various encephalitides.¹ An estimated 880,000 U.S. patients exhibit PBA.⁸

Previously, there was no FDA-approved treatment for PBA. However, small controlled trials suggest that selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs)— usually in doses lower than those used to treat depression—may effectively reduce symptoms within 2 to 3 days.¹ Although dopaminergic agents such as levodopa and amantadine have shown benefit in open trials, results of controlled studies using objective measurements have not been positive.

How it works

DM is a serotonergic substance that also is an agonist of 1-sigma receptors and a low-affinity, uncompetitive antagonist of N-methyl-d-aspartate (NMDA) receptors, which are important in glutamate signaling, through binding at the phencyclidine site on the NMDA complex.^7,9 The 1-sigma receptor was thought to be an opioid receptor subtype, but unlike opioid receptors it is not blocked by narcotic antagonists and does not have an endogenous ligand. However, the 1-sigma receptor does modulate activity of opioid mu receptors in addition to altering dopamine release and possibly reducing glutamate release.⁹ Sigma receptors are densely distributed in the limbic system and in systems related to motor control of affective expression and seem to be involved in learning, responses to stress, mood regulation, and drug dependence.¹ Because DM preferentially binds to brain regions that regulate emotional expression,¹⁰ it could normalize glutaminergic neurotransmission and other relevant systems in these regions.¹ However, DM’s exact mechanism of action is unknown.

Quinidine is a sodium channel antagonist usually used as a type Ia antiarrhythmic.⁵ DM is subject to extensive first-pass metabolism by cytochrome P (CYP) 450 2D6 to dextrorphan, which after being glucuronidated cannot cross the blood-brain barrier. In doses 10 to 25 times lower than those used to treat cardiac arrhythmias, quinidine inhibits 2D6 and increases DM bioavailability.¹⁰ DM blood levels increase linearly with dose following coadministration with quinidine but are undetectable in most patients given DM alone.^7,9

Efficacy and tolerability

A combination of DM and quinidine (DMQ) reduced Center for Neurologic Study-Lability Scale (CNC-LS) scores and the number of daily PBA episodes in 3 randomized trials.^5,7,10 Visit this article at CurrentPsychiatry.com for a table summarizing these studies.

An 85-day randomized, double-blind, placebo-controlled study of 150 patients with PBA associated with MS found that DM, 30 mg, plus quinidine, 30 mg, (DMQ 30-30) was twice as effective as placebo within a week in reducing CNC-LS scores.¹⁰ DMQ 30-30 patients also had approximately half as many episodes of inappropriate laughing, crying, or combined laughing and crying and a 2-fold greater decrease in pain intensity.¹⁰ Twenty-one percent of DMQ 30-30 patients experienced complete remission—no PBA episodes—compared with 7% of placebo patients. There were no significant differences in QT prolongation between DMQ 30-30 and placebo.

A 3-arm, double-blind, 28-day, phase III multicenter trial of 140 ALS patients with PBA compared DM monotherapy, quinidine monotherapy, and DMQ 30-30.⁵ Compared with either drug alone, DMQ 30-30 showed greater reduction of CNC-LS scores, as well as improved quality of life and quality of relationships scores, with equal benefit in poor and extensive DM metabolizers. However, the control conditions may not have been adequate. Quinidine alone would not be expected to have an effect on PBA, and the DM dose, which was the same in combination and monotherapy, may have been too low to be effective by itself. In support of this hypothesis, the DM plasma level was 18 times higher in patients taking DMQ 30-30 than those taking DM monotherapy.

In a manufacturer-sponsored, multicenter, 12-week randomized trial, 326 patients with ALS or MS and clinically significant PBA were randomly assigned to DM, 30 mg, plus quinidine, 10 mg (DMQ 30-10), DM, 20 mg, plus quinidine, 10 mg (DMQ 20-10), or placebo, each administered twice daily.⁷ Patients with comorbid psychiatric disorders or significant depressive symptoms were excluded. Although daily PBA episodes decreased in all groups, the daily rate of PBA episodes was 47% lower for patients taking DMQ 30-10, and 49% lower with DMQ 20-10 compared with placebo (both P < .001). The mean decrease in the number of daily PBA episodes was 3.9 to 4.1 with active treatment and 3.0 with placebo. Side effects were more common with active drug than placebo and included dizziness, nausea, diarrhea, and urinary tract infection. There were no serious adverse cardiac events and no active drug recipients showed a QTc interval >480 msec or a change from baseline >60 msec.¹¹ Discontinuation rates in this study were lower than in studies of DMQ 30-30. In an open-label extension of 253 patients who completed the double-blind phase and were assigned to DMQ 30-10 for 12 weeks, the incidence of treatment-related adverse events was 28%, with a 5.5% rate of serious adverse events.¹²

Safety

Because the 10 mg dose of quinidine in the approved formulation of DMQ is 10 times lower than the antiarrhythmic dose, substantial ECG changes and adverse cardiac effects with DMQ have not been reported. The most common side effects of DM are nausea, somnolence, dizziness, and headache. Thrombocytopenia, QT prolongation, hepatotoxicity, allergic reactions, and anticholinergic side effects can occur.

In high doses and combined with other substances, DM has been used as a recreational drug. When taken in high doses, adverse effects include nausea, vomiting, malaise, dilated pupils, difficulty urinating, increased urination frequency, fever, tachycardia, loss of appetite, shakiness, seizures, and potentially coma and death. DMQ may have a greater potential for serious adverse effects than DM alone because quinidine increases DM bioavailability and blood levels. The abuse potential of DMQ is not clear.

Psychosis has been reported with higher DM doses. The psychotomimetic effects of phencyclidine (PCP) are related to binding to the PCP site on the NMDA receptor complex—to which DM also binds—with reduced glutamate signaling in information processing systems. Therefore, caution is indicated when prescribing DM to patients with psychosis.

Because DM, a CYP2D6 substrate, is combined with quinidine, a 2D6 inhibitor, administering DMQ with other 2D6 inhibitors could lead to toxicity. When DMQ is combined with SSRIs and similar agents, the serotonergic properties of DM could result in serotonin syndrome, which could be fatal if DM is combined with monoamine oxidase inhibitors.¹⁰ Combinations of DM and acetaminophen and antihistamines can be dangerous at higher doses.¹⁰ Because quinidine is metabolized by CYP3A, inhibitors of this enzyme such as ketoconazole, nefazodone, and grapefruit juice should be avoided. Similarly, inhibition of CYP2D6 by quinidine could raise levels of coadministered 2D6 substrates.

Contraindications. DMQ is contraindicated in patients with:

• heart failure
• prolonged QT interval
• congenital long QT interval
• history of torsades de pointes
• complete atrioventricular (AV) block without implanted pacemakers.¹³

DMQ also is contraindicated in patients at high risk for complete AV block.¹³

Dosing

DMQ is available as a capsule containing DM, 20 mg, and quinidine, 10 mg. The recommended starting dose is 1 capsule by mouth for 7 days, then 1 capsule every 12 hours.

Although DMQ is convenient, its advantage over starting with DM alone and adding a small dose of a non-serotonergic 2D6 inhibitor if DM is not effective remains to be demonstrated. In view of the unknown potential for abuse and toxicity as well as the cost of the proprietary drug ($3,000 to $5,000 a year), it would seem prudent to consider using an SSRI or a TCA first.⁸ These medications also act on 1-sigma receptors,^14,15 which may account in part for their reported benefit.

Related Resource

• Neudexta [package insert]. Aliso Viejo, CA: Avanir Pharmaceuticals; 2010.

Drug Brand Names

• Amantadine • Symmetrel
• Dextromethorphan/quinidine •Nefazodone
• Ketoconazole • Nizoral
• Levodopa • Sinemet
• Neudexta • Serzone
• Quinidine • Quinidex

Disclosures

Dr. Dubovsky receives research support from Biogen Idec, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Otsuka, the Peter and Elizabeth C. Tower Foundation, and Pfizer, Inc.

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

Table 2

Dextromethorphan/quinidine for PBA: Evidence shows efficacy