Current Psychiatry

Medication nonadherence is a common problem when treating patients with schizophrenia that can worsen prognosis and lead to sub-optimal treatment outcomes. In this article, we discuss common reasons for nonadherence and describe evidence-based treatments intended to increase adherence and improve outcomes (Box).^1-6

Common reasons for nonadherence

The primary predictor of future nonadherence is a history of nonadherence. It is important to understand patients’ reasons for nonadherence so that practical and evidence-based solutions can be implemented into the treatment plans of individual patients.

The 2009 Expert Consensus Guidelines on Adherence Problems in Patients with Serious and Persistent Mental Illness divided variables related to nonadherence into 3 categories:

• those that lie within the patient (intrinsic)
• those that are related to the patient’s relationship with healthcare providers, family, or caregivers (extrinsic)
• those that are related to the healthcare delivery system (extrinsic).⁷

Among intrinsic variables, studies have shown a correlation between nonadherence and education level, lower socioeconomic status, homelessness, and male sex.⁷ (The Expert Consensus Guidelines considered homelessness to be an intrinsic factor because it was used as a demographic variable in the studies.)

Cognitive and negative symptoms associated with schizophrenia are an intrinsic risk factor for nonadherence because patients might not remember when or how to take medication.⁷ In a study by Freudenreich and co-workers⁸ of 81 outpatients who had a diagnosis of schizophrenia, the presence of negative symptoms predicted a negative attitude toward psychotropic medications. Poor insight might be the result of cognitive dysfunction associated with schizophrenia, and often is due to a lack of awareness of the importance of taking medications.

Limited insight into the need for treatment can be problematic early in the course of the illness when it may be directly related to positive symptoms. Perkins and colleagues⁹ demonstrated that patients recovering from a first psychotic episode who had limited insight into their illness and lacked desire to seek treatment were less adherent with medication. In another study, 5% of psychiatrists surveyed thought that many of their patients with schizophrenia were nonadherent because those patients did not believe that medications were effective or useful.¹⁰

Comorbid substance abuse disorders can contribute to medication nonadherence. In an analysis of 6,731 patients with schizophrenia, Novick and co-workers reported that alcohol dependence and substance abuse in the previous month predicted medication nonadherence.¹¹ Hunt and colleagues demonstrated that, among 99 nonadherent patients with schizophrenia, time to first readmission was shorter for patients with comorbid substance abuse disorders compared with patients who had a diagnosis of schizophrenia only. Over the 4-year study period, the 28 patients who had a dual diagnosis (schizophrenia and substance abuse) accounted for 57% of all hospital readmissions.¹²

Several variables that affect medication adherence are related to the patient’s relationship with healthcare providers, family, caregivers, and the service delivery system.⁷ These include:

• the perceived stigma of being given a diagnosis of a serious mental illness
• adverse effects related to medications
• poor social and family support
• difficulty gaining access to mental health services.^7,10

Societal stigma associated with seeking treatment from a mental health professional may contribute to nonadherence in some patients. In 1 study,¹³ 36% of people surveyed would not want to work closely with a person who has a serious mental illness.

Adverse effects contribute significantly to nonadherence

Limited treatment options (which may be expensive) can make it difficult to manage the adverse effects of antipsychotics. In a cross-sectional survey of 876 patients, investigators reported that: 1) <50% of patients were adherent with medication, and 2) 80% experienced ≥1 side effect that was reported to be “somewhat bothersome” in self-ratings (Table 1).¹⁴ Extrapyramidal symptoms (EPS) and agitation were most strongly associated with nonadherence; weight gain, akathisia, and sexual dysfunction also were associated with nonadherence.¹⁴ This study did not distinguish adverse effects associated with first-generation antipsychotics (FGAs) from those associated with second-generation antipsychotics (SGAs), even though 71.7% of patients studied were taking an SGA.

A meta-analysis by Leucht and co-workers¹⁵ compared 15 antipsychotics (the FGAs haloperidol and chlorpromazine and 13 SGAs) for efficacy and tolerability in schizophrenia. Haloperidol had the highest rate of discontinuation for any

Antipsychotic binding affinities to dopamine 2 (D2), serotonin 2A (5-HT2A), histamine (H1), and other receptors have an impact on a medication’s side-effect profile. Because of individual patient characteristics, you might be faced with choosing a medication that has a lower risk of EPS but a higher risk of weight gain and metabolic complications—or the inverse. Understanding binding affinities, side-effect profiles, and how to minimize or utilize adverse effects (ie, giving a drug that is approved to treat schizophrenia and is associated with weight gain to a patient with schizophrenia who has lost weight) may lead to greater adherence (Table 2¹⁶ and Table 3¹⁷).

Adequate support is essential

The therapeutic alliance plays a key role in patients’ attitudes toward taking medication. Magura and colleagues¹⁸ found that one-third of psychiatric patients (13% of whom had a diagnosis of schizophrenia) reported that their psychiatrist did not spend enough time with them explaining side effects, and felt “rushed.”

Patients with schizophrenia often require access to social support systems provided by family members, friends, and community agencies that provide case management and attendant care services. Patients who are adherent to medication tend to have greater perceived family involvement in medication treatment, and tend to have been raised in a family that had more of a positive attitude toward medication.¹⁹

In our practice, we have observed that recent state and federal budget cuts have resulted in patients having greater difficulty gaining access to case management and attendant care services, which then leads to increased rates of medication nonadherence. Be aware that variables such as limited office hours, financial hardship, and cultural and language barriers can compromise a patient’s ability to seek and continue care.

In the following section, we lay out techniques for improving adherence in patients with schizophrenia.

Employ general and specific strategies to boost adherence

How can you raise medication adherence concerns with patients, keeping in mind that they often overestimate their adherence?

Ask. Some clinicians ask questions such as “Are you taking your medication?”, although a more effective approach might be to ask how the patient is taking his (her) medication. Asking questions such as “When do you take your medication?” and “In the past week, how many doses do you think you missed?” might be more effective ways to inquire about adherence.⁷

The Expert Consensus Guidelines recommend asking patients about medication adherence monthly for those who are stable, doing well, and believed to be adherent. For those who are new to a practice or who are not doing well, inquire about medication adherence at least weekly.⁷

In our practice, patients who are unstable but do not require inpatient hospitalization typically are seen more often in the clinic, or are referred to intensive outpatient or partial hospitalization programs. If an unstable patient is unable to come in for more frequent appointments, we arrange phone conferences between her and her provider. If a patient is not doing well and has a case manager, we often ask that case manager to visit the patient, in person, more often than he (she) would otherwise.

Take a nonjudgmental approach when raising these issues with patients. Questions such as “We all forget to take our medication sometimes; do you?” help to normalize nonadherence, and improve the therapeutic alliance, and might result in the patient being more honest with the clinician.⁷ Because patients may be apprehensive about discussing adverse events, clinicians must be proactive about improving the therapeutic alliance and making patients feel comfortable when discussing sensitive topics. Clinicians should try to convey the idea that, although adherence is a concern, so is quality of life. A clinicians’ willingness to take a flexible approach that is nonpunitive nor authoritarian can aid the therapeutic alliance and improve overall adherence.

Be sensitive to financial, cultural, and language variables that can affect access to care. The Expert Consensus Guidelines recommend asking patients if they can afford their medication. In our practice, we have seen patients with schizophrenia discharged from the hospital only to be readmitted 1 month later because they could not afford to fill their prescriptions.

It is important to have translation services available, in person or by phone, for patients who do not speak English. Furthermore, it is important to understand the limitations that your practice might place on access to care. Ask patients if they have ever had trouble making an appointment when they needed to be seen, or if they called the office with a question and did not receive an answer in a timely fashion; doing so allows you to assess the practice’s ability to meet patients’ needs and helps you build a therapeutic alliance.

Make objective assessments. It is important for practitioners to not base their assessment of medication adherence solely on subjective findings. Asking patients to bring in their medication bottles for pill counts and checking with the patients’ pharmacies for information about refill frequency can provide some objective data. Electronic monitoring systems use microprocessors inserted into bottle caps to record the occurrence and timing of each bottle opening. Studies show that these electronic monitoring systems are the gold standard for determining medication adherence and could be used in cases where it is unclear if the patient is taking his (her) medication.^7,20 Such systems have successfully monitored medication adherence in clinical trials, but their use in clinical practice is complicated by ethical and legal considerations and cost issues.

Simplify the regimen. Using medications with once-daily dosing, for example, can help improve adherence. Pfeiffer and co-workers²¹ found that patients whose medication regimens were changed from once daily to more than once daily experienced a decrease in medication adherence. Conversely, a decrease in dosing frequency was significantly associated with improved adherence. More than once-daily dosing was only weakly associated with poorer adherence among patients already on a stable regimen.

Discussing positive and negative aspects of past medication trials with a patient and inquiring if she prefers a specific medication can be an effective way to build the therapeutic relationship and help with adherence.

Direct patients to psychosocial interventions. These can be broadly classified as:

• educational approaches
• group therapy approaches
• family interventions
• cognitive treatments
• combination approaches.

Psychoeducational approaches have limited effect on improving adherence when delivered to individual patients. However, 1 study showed that psychoeducation was effective at improving adherence when extended to include the patient’s family.²²

Motivational interviewing techniques, behavioral approaches, and family interventions are effective at increasing medication adherence. One study looked at the value of training a patient-identified informant to supervise and administer medication. This person, usually a family member or close support, was responsible for obtaining medication from the pharmacy, administering the medication, and recording adherence. After 1 year, 67% of patients who used an informant were adherent, compared with only 45% in the group that did not have informant support.²² Case managers, attendant care workers, home health nurses, and assertive community treatment (ACT) teams also can participate in this manner; it is important, therefore, for you to be aware of the resources available in your community and to understand your role as patient advocate.

Substance abuse is a strong risk factor for nonadherence among patients with schizophrenia,¹⁸ which makes it important to assess patients for substance use and encourage those who do abuse to seek treatment. Although 1 study showed no correlation between Alcoholics Anonymous (AA) attendance and medication adherence,¹² many AA and Narcotics Anonymous groups do not discuss psychiatric medications during group meetings. Magura and colleagues encouraged the use of “dual focus” groups that involve mental health professionals and addiction treatment specialists discussing mental health and substance abuse issues at the same setting.¹⁸

Prescribe long-acting injectable antipsychotics. Typically, long-acting injectable antipsychotics (LAIs) are reserved for patients who have a history of nonadherence. In a small study (N = 97) comparing LAI risperidone and oral risperidone or oral haloperidol, patients treated with an LAI had significantly fewer all-cause discontinuations (26.0%, compared with 70.2%) at 24 months.²³ The Adherence to Treatment and Therapeutic Strategies in Schizophrenic Patients study examined 1,848 patients with schizophrenia and reached similar findings regarding LAI antipsychotics.²⁴ (Note: Aripiprazole, fluphenazine, haloperidol, olanzapine, and paliperidone also are available in an LAI formulation.)

Bottom Line

Antipsychotic nonadherence in schizophrenia is a major problem for patients, families, and society. Being able to identify patients at risk for nonadherence, understanding the reasons for their nonadherence, and seeking practical solutions to the problem are all the responsibility of the treating physician. Psychoeducation, addressing substance abuse, modifying dosing, and using long-acting injectable antipsychotics may help improve adherence.

Related Resources

• Velligan DI, Weiden PJ, Sajatovic M, et al; Expert Consensus Panel on Adherence Problems in Serious and Persistent Mental Illness. Assessment of adherence problems in patients with serious and persistent mental illness: recommendations from the Expert Consensus Guidelines. J Clin Psychiatry. 2009;70(suppl 4):1-46.
• National Alliance on Mental Illness. www.nami.org.
• Assertive Community Treatment (ACT) Organization. www.actassociation.org.

Drug Brand Names

Aripiprazole • Abilify        Chlorpromazine • Thorazine      Clozapine • Clozaril       Fluphenazine • Permitil    Haloperidol • Haldol                  Iloperidone • Fanapt       Olanzapine • Zyprexa      Paliperidone • Invega               Perphenazine • Trilafon    Quetiapine • Seroquel      Risperidone • Risperdal            Ziprasidone • Geodon

Disclosures

Dr. Macaluso has been the principal investigator for clinical trials for AbbVie, Eisai, Envivo, Janssen, Naurex, and Pfizer. All clinical trial and study contracts and payments were made through the Kansas University Medical Center Research Institute. Dr. McKnight reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Medication nonadherence is a common problem when treating patients with schizophrenia that can worsen prognosis and lead to sub-optimal treatment outcomes. In this article, we discuss common reasons for nonadherence and describe evidence-based treatments intended to increase adherence and improve outcomes (Box).^1-6

Common reasons for nonadherence

The primary predictor of future nonadherence is a history of nonadherence. It is important to understand patients’ reasons for nonadherence so that practical and evidence-based solutions can be implemented into the treatment plans of individual patients.

The 2009 Expert Consensus Guidelines on Adherence Problems in Patients with Serious and Persistent Mental Illness divided variables related to nonadherence into 3 categories:

• those that lie within the patient (intrinsic)
• those that are related to the patient’s relationship with healthcare providers, family, or caregivers (extrinsic)
• those that are related to the healthcare delivery system (extrinsic).⁷

Among intrinsic variables, studies have shown a correlation between nonadherence and education level, lower socioeconomic status, homelessness, and male sex.⁷ (The Expert Consensus Guidelines considered homelessness to be an intrinsic factor because it was used as a demographic variable in the studies.)

Cognitive and negative symptoms associated with schizophrenia are an intrinsic risk factor for nonadherence because patients might not remember when or how to take medication.⁷ In a study by Freudenreich and co-workers⁸ of 81 outpatients who had a diagnosis of schizophrenia, the presence of negative symptoms predicted a negative attitude toward psychotropic medications. Poor insight might be the result of cognitive dysfunction associated with schizophrenia, and often is due to a lack of awareness of the importance of taking medications.

Limited insight into the need for treatment can be problematic early in the course of the illness when it may be directly related to positive symptoms. Perkins and colleagues⁹ demonstrated that patients recovering from a first psychotic episode who had limited insight into their illness and lacked desire to seek treatment were less adherent with medication. In another study, 5% of psychiatrists surveyed thought that many of their patients with schizophrenia were nonadherent because those patients did not believe that medications were effective or useful.¹⁰

Comorbid substance abuse disorders can contribute to medication nonadherence. In an analysis of 6,731 patients with schizophrenia, Novick and co-workers reported that alcohol dependence and substance abuse in the previous month predicted medication nonadherence.¹¹ Hunt and colleagues demonstrated that, among 99 nonadherent patients with schizophrenia, time to first readmission was shorter for patients with comorbid substance abuse disorders compared with patients who had a diagnosis of schizophrenia only. Over the 4-year study period, the 28 patients who had a dual diagnosis (schizophrenia and substance abuse) accounted for 57% of all hospital readmissions.¹²

Several variables that affect medication adherence are related to the patient’s relationship with healthcare providers, family, caregivers, and the service delivery system.⁷ These include:

• the perceived stigma of being given a diagnosis of a serious mental illness
• adverse effects related to medications
• poor social and family support
• difficulty gaining access to mental health services.^7,10

Societal stigma associated with seeking treatment from a mental health professional may contribute to nonadherence in some patients. In 1 study,¹³ 36% of people surveyed would not want to work closely with a person who has a serious mental illness.

Adverse effects contribute significantly to nonadherence

Limited treatment options (which may be expensive) can make it difficult to manage the adverse effects of antipsychotics. In a cross-sectional survey of 876 patients, investigators reported that: 1) <50% of patients were adherent with medication, and 2) 80% experienced ≥1 side effect that was reported to be “somewhat bothersome” in self-ratings (Table 1).¹⁴ Extrapyramidal symptoms (EPS) and agitation were most strongly associated with nonadherence; weight gain, akathisia, and sexual dysfunction also were associated with nonadherence.¹⁴ This study did not distinguish adverse effects associated with first-generation antipsychotics (FGAs) from those associated with second-generation antipsychotics (SGAs), even though 71.7% of patients studied were taking an SGA.

A meta-analysis by Leucht and co-workers¹⁵ compared 15 antipsychotics (the FGAs haloperidol and chlorpromazine and 13 SGAs) for efficacy and tolerability in schizophrenia. Haloperidol had the highest rate of discontinuation for any

Antipsychotic binding affinities to dopamine 2 (D2), serotonin 2A (5-HT2A), histamine (H1), and other receptors have an impact on a medication’s side-effect profile. Because of individual patient characteristics, you might be faced with choosing a medication that has a lower risk of EPS but a higher risk of weight gain and metabolic complications—or the inverse. Understanding binding affinities, side-effect profiles, and how to minimize or utilize adverse effects (ie, giving a drug that is approved to treat schizophrenia and is associated with weight gain to a patient with schizophrenia who has lost weight) may lead to greater adherence (Table 2¹⁶ and Table 3¹⁷).

Adequate support is essential

The therapeutic alliance plays a key role in patients’ attitudes toward taking medication. Magura and colleagues¹⁸ found that one-third of psychiatric patients (13% of whom had a diagnosis of schizophrenia) reported that their psychiatrist did not spend enough time with them explaining side effects, and felt “rushed.”

Patients with schizophrenia often require access to social support systems provided by family members, friends, and community agencies that provide case management and attendant care services. Patients who are adherent to medication tend to have greater perceived family involvement in medication treatment, and tend to have been raised in a family that had more of a positive attitude toward medication.¹⁹

In our practice, we have observed that recent state and federal budget cuts have resulted in patients having greater difficulty gaining access to case management and attendant care services, which then leads to increased rates of medication nonadherence. Be aware that variables such as limited office hours, financial hardship, and cultural and language barriers can compromise a patient’s ability to seek and continue care.

In the following section, we lay out techniques for improving adherence in patients with schizophrenia.

Employ general and specific strategies to boost adherence

How can you raise medication adherence concerns with patients, keeping in mind that they often overestimate their adherence?

Ask. Some clinicians ask questions such as “Are you taking your medication?”, although a more effective approach might be to ask how the patient is taking his (her) medication. Asking questions such as “When do you take your medication?” and “In the past week, how many doses do you think you missed?” might be more effective ways to inquire about adherence.⁷

The Expert Consensus Guidelines recommend asking patients about medication adherence monthly for those who are stable, doing well, and believed to be adherent. For those who are new to a practice or who are not doing well, inquire about medication adherence at least weekly.⁷

In our practice, patients who are unstable but do not require inpatient hospitalization typically are seen more often in the clinic, or are referred to intensive outpatient or partial hospitalization programs. If an unstable patient is unable to come in for more frequent appointments, we arrange phone conferences between her and her provider. If a patient is not doing well and has a case manager, we often ask that case manager to visit the patient, in person, more often than he (she) would otherwise.

Take a nonjudgmental approach when raising these issues with patients. Questions such as “We all forget to take our medication sometimes; do you?” help to normalize nonadherence, and improve the therapeutic alliance, and might result in the patient being more honest with the clinician.⁷ Because patients may be apprehensive about discussing adverse events, clinicians must be proactive about improving the therapeutic alliance and making patients feel comfortable when discussing sensitive topics. Clinicians should try to convey the idea that, although adherence is a concern, so is quality of life. A clinicians’ willingness to take a flexible approach that is nonpunitive nor authoritarian can aid the therapeutic alliance and improve overall adherence.

Be sensitive to financial, cultural, and language variables that can affect access to care. The Expert Consensus Guidelines recommend asking patients if they can afford their medication. In our practice, we have seen patients with schizophrenia discharged from the hospital only to be readmitted 1 month later because they could not afford to fill their prescriptions.

It is important to have translation services available, in person or by phone, for patients who do not speak English. Furthermore, it is important to understand the limitations that your practice might place on access to care. Ask patients if they have ever had trouble making an appointment when they needed to be seen, or if they called the office with a question and did not receive an answer in a timely fashion; doing so allows you to assess the practice’s ability to meet patients’ needs and helps you build a therapeutic alliance.

Make objective assessments. It is important for practitioners to not base their assessment of medication adherence solely on subjective findings. Asking patients to bring in their medication bottles for pill counts and checking with the patients’ pharmacies for information about refill frequency can provide some objective data. Electronic monitoring systems use microprocessors inserted into bottle caps to record the occurrence and timing of each bottle opening. Studies show that these electronic monitoring systems are the gold standard for determining medication adherence and could be used in cases where it is unclear if the patient is taking his (her) medication.^7,20 Such systems have successfully monitored medication adherence in clinical trials, but their use in clinical practice is complicated by ethical and legal considerations and cost issues.

Simplify the regimen. Using medications with once-daily dosing, for example, can help improve adherence. Pfeiffer and co-workers²¹ found that patients whose medication regimens were changed from once daily to more than once daily experienced a decrease in medication adherence. Conversely, a decrease in dosing frequency was significantly associated with improved adherence. More than once-daily dosing was only weakly associated with poorer adherence among patients already on a stable regimen.

Discussing positive and negative aspects of past medication trials with a patient and inquiring if she prefers a specific medication can be an effective way to build the therapeutic relationship and help with adherence.

Direct patients to psychosocial interventions. These can be broadly classified as:

• educational approaches
• group therapy approaches
• family interventions
• cognitive treatments
• combination approaches.

Psychoeducational approaches have limited effect on improving adherence when delivered to individual patients. However, 1 study showed that psychoeducation was effective at improving adherence when extended to include the patient’s family.²²

Motivational interviewing techniques, behavioral approaches, and family interventions are effective at increasing medication adherence. One study looked at the value of training a patient-identified informant to supervise and administer medication. This person, usually a family member or close support, was responsible for obtaining medication from the pharmacy, administering the medication, and recording adherence. After 1 year, 67% of patients who used an informant were adherent, compared with only 45% in the group that did not have informant support.²² Case managers, attendant care workers, home health nurses, and assertive community treatment (ACT) teams also can participate in this manner; it is important, therefore, for you to be aware of the resources available in your community and to understand your role as patient advocate.

Substance abuse is a strong risk factor for nonadherence among patients with schizophrenia,¹⁸ which makes it important to assess patients for substance use and encourage those who do abuse to seek treatment. Although 1 study showed no correlation between Alcoholics Anonymous (AA) attendance and medication adherence,¹² many AA and Narcotics Anonymous groups do not discuss psychiatric medications during group meetings. Magura and colleagues encouraged the use of “dual focus” groups that involve mental health professionals and addiction treatment specialists discussing mental health and substance abuse issues at the same setting.¹⁸

Prescribe long-acting injectable antipsychotics. Typically, long-acting injectable antipsychotics (LAIs) are reserved for patients who have a history of nonadherence. In a small study (N = 97) comparing LAI risperidone and oral risperidone or oral haloperidol, patients treated with an LAI had significantly fewer all-cause discontinuations (26.0%, compared with 70.2%) at 24 months.²³ The Adherence to Treatment and Therapeutic Strategies in Schizophrenic Patients study examined 1,848 patients with schizophrenia and reached similar findings regarding LAI antipsychotics.²⁴ (Note: Aripiprazole, fluphenazine, haloperidol, olanzapine, and paliperidone also are available in an LAI formulation.)

Bottom Line

Antipsychotic nonadherence in schizophrenia is a major problem for patients, families, and society. Being able to identify patients at risk for nonadherence, understanding the reasons for their nonadherence, and seeking practical solutions to the problem are all the responsibility of the treating physician. Psychoeducation, addressing substance abuse, modifying dosing, and using long-acting injectable antipsychotics may help improve adherence.

Related Resources

• Velligan DI, Weiden PJ, Sajatovic M, et al; Expert Consensus Panel on Adherence Problems in Serious and Persistent Mental Illness. Assessment of adherence problems in patients with serious and persistent mental illness: recommendations from the Expert Consensus Guidelines. J Clin Psychiatry. 2009;70(suppl 4):1-46.
• National Alliance on Mental Illness. www.nami.org.
• Assertive Community Treatment (ACT) Organization. www.actassociation.org.

Drug Brand Names

Aripiprazole • Abilify        Chlorpromazine • Thorazine      Clozapine • Clozaril       Fluphenazine • Permitil    Haloperidol • Haldol                  Iloperidone • Fanapt       Olanzapine • Zyprexa      Paliperidone • Invega               Perphenazine • Trilafon    Quetiapine • Seroquel      Risperidone • Risperdal            Ziprasidone • Geodon

Disclosures

Dr. Macaluso has been the principal investigator for clinical trials for AbbVie, Eisai, Envivo, Janssen, Naurex, and Pfizer. All clinical trial and study contracts and payments were made through the Kansas University Medical Center Research Institute. Dr. McKnight reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Medication nonadherence is a common problem when treating patients with schizophrenia that can worsen prognosis and lead to sub-optimal treatment outcomes. In this article, we discuss common reasons for nonadherence and describe evidence-based treatments intended to increase adherence and improve outcomes (Box).^1-6

Common reasons for nonadherence

The primary predictor of future nonadherence is a history of nonadherence. It is important to understand patients’ reasons for nonadherence so that practical and evidence-based solutions can be implemented into the treatment plans of individual patients.

The 2009 Expert Consensus Guidelines on Adherence Problems in Patients with Serious and Persistent Mental Illness divided variables related to nonadherence into 3 categories:

• those that lie within the patient (intrinsic)
• those that are related to the patient’s relationship with healthcare providers, family, or caregivers (extrinsic)
• those that are related to the healthcare delivery system (extrinsic).⁷

Among intrinsic variables, studies have shown a correlation between nonadherence and education level, lower socioeconomic status, homelessness, and male sex.⁷ (The Expert Consensus Guidelines considered homelessness to be an intrinsic factor because it was used as a demographic variable in the studies.)

Cognitive and negative symptoms associated with schizophrenia are an intrinsic risk factor for nonadherence because patients might not remember when or how to take medication.⁷ In a study by Freudenreich and co-workers⁸ of 81 outpatients who had a diagnosis of schizophrenia, the presence of negative symptoms predicted a negative attitude toward psychotropic medications. Poor insight might be the result of cognitive dysfunction associated with schizophrenia, and often is due to a lack of awareness of the importance of taking medications.

Limited insight into the need for treatment can be problematic early in the course of the illness when it may be directly related to positive symptoms. Perkins and colleagues⁹ demonstrated that patients recovering from a first psychotic episode who had limited insight into their illness and lacked desire to seek treatment were less adherent with medication. In another study, 5% of psychiatrists surveyed thought that many of their patients with schizophrenia were nonadherent because those patients did not believe that medications were effective or useful.¹⁰

Comorbid substance abuse disorders can contribute to medication nonadherence. In an analysis of 6,731 patients with schizophrenia, Novick and co-workers reported that alcohol dependence and substance abuse in the previous month predicted medication nonadherence.¹¹ Hunt and colleagues demonstrated that, among 99 nonadherent patients with schizophrenia, time to first readmission was shorter for patients with comorbid substance abuse disorders compared with patients who had a diagnosis of schizophrenia only. Over the 4-year study period, the 28 patients who had a dual diagnosis (schizophrenia and substance abuse) accounted for 57% of all hospital readmissions.¹²

Several variables that affect medication adherence are related to the patient’s relationship with healthcare providers, family, caregivers, and the service delivery system.⁷ These include:

• the perceived stigma of being given a diagnosis of a serious mental illness
• adverse effects related to medications
• poor social and family support
• difficulty gaining access to mental health services.^7,10

Societal stigma associated with seeking treatment from a mental health professional may contribute to nonadherence in some patients. In 1 study,¹³ 36% of people surveyed would not want to work closely with a person who has a serious mental illness.

Adverse effects contribute significantly to nonadherence

Limited treatment options (which may be expensive) can make it difficult to manage the adverse effects of antipsychotics. In a cross-sectional survey of 876 patients, investigators reported that: 1) <50% of patients were adherent with medication, and 2) 80% experienced ≥1 side effect that was reported to be “somewhat bothersome” in self-ratings (Table 1).¹⁴ Extrapyramidal symptoms (EPS) and agitation were most strongly associated with nonadherence; weight gain, akathisia, and sexual dysfunction also were associated with nonadherence.¹⁴ This study did not distinguish adverse effects associated with first-generation antipsychotics (FGAs) from those associated with second-generation antipsychotics (SGAs), even though 71.7% of patients studied were taking an SGA.

A meta-analysis by Leucht and co-workers¹⁵ compared 15 antipsychotics (the FGAs haloperidol and chlorpromazine and 13 SGAs) for efficacy and tolerability in schizophrenia. Haloperidol had the highest rate of discontinuation for any

Antipsychotic binding affinities to dopamine 2 (D2), serotonin 2A (5-HT2A), histamine (H1), and other receptors have an impact on a medication’s side-effect profile. Because of individual patient characteristics, you might be faced with choosing a medication that has a lower risk of EPS but a higher risk of weight gain and metabolic complications—or the inverse. Understanding binding affinities, side-effect profiles, and how to minimize or utilize adverse effects (ie, giving a drug that is approved to treat schizophrenia and is associated with weight gain to a patient with schizophrenia who has lost weight) may lead to greater adherence (Table 2¹⁶ and Table 3¹⁷).

Adequate support is essential

The therapeutic alliance plays a key role in patients’ attitudes toward taking medication. Magura and colleagues¹⁸ found that one-third of psychiatric patients (13% of whom had a diagnosis of schizophrenia) reported that their psychiatrist did not spend enough time with them explaining side effects, and felt “rushed.”

Patients with schizophrenia often require access to social support systems provided by family members, friends, and community agencies that provide case management and attendant care services. Patients who are adherent to medication tend to have greater perceived family involvement in medication treatment, and tend to have been raised in a family that had more of a positive attitude toward medication.¹⁹

In our practice, we have observed that recent state and federal budget cuts have resulted in patients having greater difficulty gaining access to case management and attendant care services, which then leads to increased rates of medication nonadherence. Be aware that variables such as limited office hours, financial hardship, and cultural and language barriers can compromise a patient’s ability to seek and continue care.

In the following section, we lay out techniques for improving adherence in patients with schizophrenia.

Employ general and specific strategies to boost adherence

How can you raise medication adherence concerns with patients, keeping in mind that they often overestimate their adherence?

Ask. Some clinicians ask questions such as “Are you taking your medication?”, although a more effective approach might be to ask how the patient is taking his (her) medication. Asking questions such as “When do you take your medication?” and “In the past week, how many doses do you think you missed?” might be more effective ways to inquire about adherence.⁷

The Expert Consensus Guidelines recommend asking patients about medication adherence monthly for those who are stable, doing well, and believed to be adherent. For those who are new to a practice or who are not doing well, inquire about medication adherence at least weekly.⁷

In our practice, patients who are unstable but do not require inpatient hospitalization typically are seen more often in the clinic, or are referred to intensive outpatient or partial hospitalization programs. If an unstable patient is unable to come in for more frequent appointments, we arrange phone conferences between her and her provider. If a patient is not doing well and has a case manager, we often ask that case manager to visit the patient, in person, more often than he (she) would otherwise.

Take a nonjudgmental approach when raising these issues with patients. Questions such as “We all forget to take our medication sometimes; do you?” help to normalize nonadherence, and improve the therapeutic alliance, and might result in the patient being more honest with the clinician.⁷ Because patients may be apprehensive about discussing adverse events, clinicians must be proactive about improving the therapeutic alliance and making patients feel comfortable when discussing sensitive topics. Clinicians should try to convey the idea that, although adherence is a concern, so is quality of life. A clinicians’ willingness to take a flexible approach that is nonpunitive nor authoritarian can aid the therapeutic alliance and improve overall adherence.

Be sensitive to financial, cultural, and language variables that can affect access to care. The Expert Consensus Guidelines recommend asking patients if they can afford their medication. In our practice, we have seen patients with schizophrenia discharged from the hospital only to be readmitted 1 month later because they could not afford to fill their prescriptions.

It is important to have translation services available, in person or by phone, for patients who do not speak English. Furthermore, it is important to understand the limitations that your practice might place on access to care. Ask patients if they have ever had trouble making an appointment when they needed to be seen, or if they called the office with a question and did not receive an answer in a timely fashion; doing so allows you to assess the practice’s ability to meet patients’ needs and helps you build a therapeutic alliance.

Make objective assessments. It is important for practitioners to not base their assessment of medication adherence solely on subjective findings. Asking patients to bring in their medication bottles for pill counts and checking with the patients’ pharmacies for information about refill frequency can provide some objective data. Electronic monitoring systems use microprocessors inserted into bottle caps to record the occurrence and timing of each bottle opening. Studies show that these electronic monitoring systems are the gold standard for determining medication adherence and could be used in cases where it is unclear if the patient is taking his (her) medication.^7,20 Such systems have successfully monitored medication adherence in clinical trials, but their use in clinical practice is complicated by ethical and legal considerations and cost issues.

Simplify the regimen. Using medications with once-daily dosing, for example, can help improve adherence. Pfeiffer and co-workers²¹ found that patients whose medication regimens were changed from once daily to more than once daily experienced a decrease in medication adherence. Conversely, a decrease in dosing frequency was significantly associated with improved adherence. More than once-daily dosing was only weakly associated with poorer adherence among patients already on a stable regimen.

Discussing positive and negative aspects of past medication trials with a patient and inquiring if she prefers a specific medication can be an effective way to build the therapeutic relationship and help with adherence.

Direct patients to psychosocial interventions. These can be broadly classified as:

• educational approaches
• group therapy approaches
• family interventions
• cognitive treatments
• combination approaches.

Psychoeducational approaches have limited effect on improving adherence when delivered to individual patients. However, 1 study showed that psychoeducation was effective at improving adherence when extended to include the patient’s family.²²

Motivational interviewing techniques, behavioral approaches, and family interventions are effective at increasing medication adherence. One study looked at the value of training a patient-identified informant to supervise and administer medication. This person, usually a family member or close support, was responsible for obtaining medication from the pharmacy, administering the medication, and recording adherence. After 1 year, 67% of patients who used an informant were adherent, compared with only 45% in the group that did not have informant support.²² Case managers, attendant care workers, home health nurses, and assertive community treatment (ACT) teams also can participate in this manner; it is important, therefore, for you to be aware of the resources available in your community and to understand your role as patient advocate.

Substance abuse is a strong risk factor for nonadherence among patients with schizophrenia,¹⁸ which makes it important to assess patients for substance use and encourage those who do abuse to seek treatment. Although 1 study showed no correlation between Alcoholics Anonymous (AA) attendance and medication adherence,¹² many AA and Narcotics Anonymous groups do not discuss psychiatric medications during group meetings. Magura and colleagues encouraged the use of “dual focus” groups that involve mental health professionals and addiction treatment specialists discussing mental health and substance abuse issues at the same setting.¹⁸

Prescribe long-acting injectable antipsychotics. Typically, long-acting injectable antipsychotics (LAIs) are reserved for patients who have a history of nonadherence. In a small study (N = 97) comparing LAI risperidone and oral risperidone or oral haloperidol, patients treated with an LAI had significantly fewer all-cause discontinuations (26.0%, compared with 70.2%) at 24 months.²³ The Adherence to Treatment and Therapeutic Strategies in Schizophrenic Patients study examined 1,848 patients with schizophrenia and reached similar findings regarding LAI antipsychotics.²⁴ (Note: Aripiprazole, fluphenazine, haloperidol, olanzapine, and paliperidone also are available in an LAI formulation.)

Bottom Line

Antipsychotic nonadherence in schizophrenia is a major problem for patients, families, and society. Being able to identify patients at risk for nonadherence, understanding the reasons for their nonadherence, and seeking practical solutions to the problem are all the responsibility of the treating physician. Psychoeducation, addressing substance abuse, modifying dosing, and using long-acting injectable antipsychotics may help improve adherence.

Related Resources

• Velligan DI, Weiden PJ, Sajatovic M, et al; Expert Consensus Panel on Adherence Problems in Serious and Persistent Mental Illness. Assessment of adherence problems in patients with serious and persistent mental illness: recommendations from the Expert Consensus Guidelines. J Clin Psychiatry. 2009;70(suppl 4):1-46.
• National Alliance on Mental Illness. www.nami.org.
• Assertive Community Treatment (ACT) Organization. www.actassociation.org.

Drug Brand Names

Aripiprazole • Abilify        Chlorpromazine • Thorazine      Clozapine • Clozaril       Fluphenazine • Permitil    Haloperidol • Haldol                  Iloperidone • Fanapt       Olanzapine • Zyprexa      Paliperidone • Invega               Perphenazine • Trilafon    Quetiapine • Seroquel      Risperidone • Risperdal            Ziprasidone • Geodon

Disclosures

Dr. Macaluso has been the principal investigator for clinical trials for AbbVie, Eisai, Envivo, Janssen, Naurex, and Pfizer. All clinical trial and study contracts and payments were made through the Kansas University Medical Center Research Institute. Dr. McKnight reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

We thank Dr. Ted Jones for his letter and comments about our article, “Chronic non-cancer pain and substance use disorders: Challenges and strategies” (Current Psychiatry, July 2013, p. 35-41; http://bit.ly/162NTCO). Dr. Jones correctly points out that we referred to the SOAPP-R and not to SOAPP (Current Psychiatry, Comments and Controversies, “Did the authors slip on SOAPP?” October 2013, p. 40; http://bit.ly/18YeV2C). This was an oversight and typing mistake.

However, we cannot agree with Dr. Jones’ comments about the sensitivity of SOAPP as we stated it. Dr. Jones says that we asserted the sensitivity of the tool to be 90%—we wrote, “A survey of 48 patients by Moore et al found the combination of a clinical interview and the Screener and Opioid Assessment for Patient with Pain-Revised (SOAPP-R) is 90% sensitive in detecting CNCP/SUD.”

The text in the article by Moore and colleagues1 states, “Combining the clinical interview with the SOAPP increased sensitivity to 0.90.” We believe that these 2 statements basically say the same thing. Whether the patients might or might not represent a substance use disorder is not clear from the article by Moore and colleagues, and probably is clearer to the authors than to the readers.

We stand corrected regarding the incorrectly presented version of the screening tool, but we believe we were correct when writing about the sensitivity of this tool in combination with a clinical interview.

Mark Juska, MD
Fellow

Richard Balon, MD
Professor
Department of Psychiatry and Behavioral Neurosciences

Department of Anesthesiology
Wayne State University
Detroit, Michigan

Reference
1. Moore TM, Jones T, Browder JH, et al. A comparison of common screening methods for predicting aberrant drug-related behavior among patients receiving opioids for chronic pain management. Pain Med. 2009;10(8):1426-1433.

We thank Dr. Ted Jones for his letter and comments about our article, “Chronic non-cancer pain and substance use disorders: Challenges and strategies” (Current Psychiatry, July 2013, p. 35-41; http://bit.ly/162NTCO). Dr. Jones correctly points out that we referred to the SOAPP-R and not to SOAPP (Current Psychiatry, Comments and Controversies, “Did the authors slip on SOAPP?” October 2013, p. 40; http://bit.ly/18YeV2C). This was an oversight and typing mistake.

However, we cannot agree with Dr. Jones’ comments about the sensitivity of SOAPP as we stated it. Dr. Jones says that we asserted the sensitivity of the tool to be 90%—we wrote, “A survey of 48 patients by Moore et al found the combination of a clinical interview and the Screener and Opioid Assessment for Patient with Pain-Revised (SOAPP-R) is 90% sensitive in detecting CNCP/SUD.”

The text in the article by Moore and colleagues1 states, “Combining the clinical interview with the SOAPP increased sensitivity to 0.90.” We believe that these 2 statements basically say the same thing. Whether the patients might or might not represent a substance use disorder is not clear from the article by Moore and colleagues, and probably is clearer to the authors than to the readers.

We stand corrected regarding the incorrectly presented version of the screening tool, but we believe we were correct when writing about the sensitivity of this tool in combination with a clinical interview.

Mark Juska, MD
Fellow

Richard Balon, MD
Professor
Department of Psychiatry and Behavioral Neurosciences

Department of Anesthesiology
Wayne State University
Detroit, Michigan

Reference
1. Moore TM, Jones T, Browder JH, et al. A comparison of common screening methods for predicting aberrant drug-related behavior among patients receiving opioids for chronic pain management. Pain Med. 2009;10(8):1426-1433.

We thank Dr. Ted Jones for his letter and comments about our article, “Chronic non-cancer pain and substance use disorders: Challenges and strategies” (Current Psychiatry, July 2013, p. 35-41; http://bit.ly/162NTCO). Dr. Jones correctly points out that we referred to the SOAPP-R and not to SOAPP (Current Psychiatry, Comments and Controversies, “Did the authors slip on SOAPP?” October 2013, p. 40; http://bit.ly/18YeV2C). This was an oversight and typing mistake.

However, we cannot agree with Dr. Jones’ comments about the sensitivity of SOAPP as we stated it. Dr. Jones says that we asserted the sensitivity of the tool to be 90%—we wrote, “A survey of 48 patients by Moore et al found the combination of a clinical interview and the Screener and Opioid Assessment for Patient with Pain-Revised (SOAPP-R) is 90% sensitive in detecting CNCP/SUD.”

The text in the article by Moore and colleagues1 states, “Combining the clinical interview with the SOAPP increased sensitivity to 0.90.” We believe that these 2 statements basically say the same thing. Whether the patients might or might not represent a substance use disorder is not clear from the article by Moore and colleagues, and probably is clearer to the authors than to the readers.

We stand corrected regarding the incorrectly presented version of the screening tool, but we believe we were correct when writing about the sensitivity of this tool in combination with a clinical interview.

Mark Juska, MD
Fellow

Richard Balon, MD
Professor
Department of Psychiatry and Behavioral Neurosciences

Department of Anesthesiology
Wayne State University
Detroit, Michigan

Reference
1. Moore TM, Jones T, Browder JH, et al. A comparison of common screening methods for predicting aberrant drug-related behavior among patients receiving opioids for chronic pain management. Pain Med. 2009;10(8):1426-1433.

We read Dr. Nasrallah’s editorial in the September 2013 issue (Current Psychiatry, From the Editor, “A saga of psychiatric serendipities…” September 2013, p. 7-8, 54; http://bit.ly/1dLiqhc) with great interest and excitement.

This is an important topic. When we consider mood disorders, John Cade’s discovery of lithium is another example of serendipity and a good measure of clinical judgment involving a handful of patients.¹ Given that most of these discoveries involve small numbers of patients in studies that do not have a double-blind control methodology, it is disappointing that, in today’s academic world, almost no journals will accept pilot studies or case reports that are not seen as crucial for a breakthroughs or discovery. We want to add our voice to that of Dr. Nasrallah and ask people to rethink this policy, which, ultimately, stifles creativity and the progress of new psychiatric treatments.

Ronald Brenner, MD
Chair

Subramoniam Madhusoodanan, MD
Associate Chair

Department of Psychiatry
St. John’s Episcopal Hospital
Far Rockaway, New York

Reference
1. Cade JF. Lithium salts in the treatment of excitement. Med J Aust. 1949;2(10):349-352.

We read Dr. Nasrallah’s editorial in the September 2013 issue (Current Psychiatry, From the Editor, “A saga of psychiatric serendipities…” September 2013, p. 7-8, 54; http://bit.ly/1dLiqhc) with great interest and excitement.

This is an important topic. When we consider mood disorders, John Cade’s discovery of lithium is another example of serendipity and a good measure of clinical judgment involving a handful of patients.¹ Given that most of these discoveries involve small numbers of patients in studies that do not have a double-blind control methodology, it is disappointing that, in today’s academic world, almost no journals will accept pilot studies or case reports that are not seen as crucial for a breakthroughs or discovery. We want to add our voice to that of Dr. Nasrallah and ask people to rethink this policy, which, ultimately, stifles creativity and the progress of new psychiatric treatments.

Ronald Brenner, MD
Chair

Subramoniam Madhusoodanan, MD
Associate Chair

Department of Psychiatry
St. John’s Episcopal Hospital
Far Rockaway, New York

Reference
1. Cade JF. Lithium salts in the treatment of excitement. Med J Aust. 1949;2(10):349-352.

We read Dr. Nasrallah’s editorial in the September 2013 issue (Current Psychiatry, From the Editor, “A saga of psychiatric serendipities…” September 2013, p. 7-8, 54; http://bit.ly/1dLiqhc) with great interest and excitement.

This is an important topic. When we consider mood disorders, John Cade’s discovery of lithium is another example of serendipity and a good measure of clinical judgment involving a handful of patients.¹ Given that most of these discoveries involve small numbers of patients in studies that do not have a double-blind control methodology, it is disappointing that, in today’s academic world, almost no journals will accept pilot studies or case reports that are not seen as crucial for a breakthroughs or discovery. We want to add our voice to that of Dr. Nasrallah and ask people to rethink this policy, which, ultimately, stifles creativity and the progress of new psychiatric treatments.

Ronald Brenner, MD
Chair

Subramoniam Madhusoodanan, MD
Associate Chair

Department of Psychiatry
St. John’s Episcopal Hospital
Far Rockaway, New York

Reference
1. Cade JF. Lithium salts in the treatment of excitement. Med J Aust. 1949;2(10):349-352.

As physicians, we strive to heal suffering; as psychiatry trainees, we are taught to relieve that suffering through careful assessment, development of rapport, and empathic care. What then of the forensic expert, whose role is to provide the courts with objective assessment of the “defendant,” free of a therapeutic alliance^1,2? Learning to navigate between these different roles is a necessary part of forensic training.²

In my journey to become a forensic psychiatrist equipped to treat adults and youth, I’ve had the good fortune to learn from those who appear to have mastered this balancing act. In this article, I present some of those lessons, with the hope that they will resonate with others—both those who are forensically inclined and those who wish to ease the jolt of being subpoenaed to appear before the court. 

A day spent in the system

One of my earliest forensic experiences occurred during my training at Johns Hopkins, when I worked in the municipal court. I learned several lessons when I was assigned to pre-screen a defendant for competency to stand trial³ and criminal responsibility,⁴  both determined by the court but often informed by forensic evaluation.

Lesson #1: Answer only the question that you have been asked. En route to call for the defendant, I scanned my “how-to” guides and was relieved to learn that I was not to serve as decision-maker or treating clinician.⁵ I realized that I was not being asked to determine guilt or even give treatment recommendations; having a circumscribed task made that first evaluation less overwhelming. Learning to answer only the question you are being asked is a valuable lesson—one that ought to be remembered by those preparing for forensic evaluations and court testimony.

Lesson #2: There is a place for role induction. Entering a nearly empty office at municipal court, I sat behind a large metal desk and waited for the defendant. When he arrived, dressed in orange and escorted by the armed court officer, I rose to my feet awkwardly. I thought that I should shake hands with him, but stopped my hand in mid-air when I saw his handcuffed wrists.

As the guard knelt to chain the defendant’s ankle shackle to the floor, I waited patiently. Once the guard was outside, I introduced myself and read from my script. I explained the purpose of the evaluation and informed him that, unlike a
physician-patient relationship, this evaluation would not be confidential and would be shared with the court in a written report. Although the content of this introductory segment was in stark contrast to my usual patient encounters, this role induction⁶ was not. The purpose of role induction in a forensic setting is not to affect prognosis, yet such explanation is necessary to maintain ethical boundaries.¹

Lesson #3: Know your phenomenology. Proceeding with the evaluation, I inquired about aspects of the defendant’s life. I attempted to assess his knowledge of the charges against him and how the court works,³ and obtained his account of the reported criminal events.⁴ Having an interest in psychotic illness and an appreciation for Jaspers’ descriptions of psychiatric phenomenology,⁷ I confidently delved into questions about the source, number, quality, and content of the voices he reported hearing.

Although not fail-proof, knowledge of phenomenology is necessary to discern whether reported symptoms should be trusted.^8,9 In his writings¹⁰ and during my brief mentorship by him, Phillip Resnick, MD, stressed the importance of being able to detect malingering through knowledge of classic phenomenology and by maintaining a healthy level of suspicion. 

Lesson #4: Impartiality is difficult but necessary. I concluded the interview, thanked the defendant, and asked if he had any questions. He declined. I motioned for the court officer to enter the room, unshackle the defendant from the floor, and escort him out. Exiting the room, I turned off the lights and shut the heavy door. The coldness of the physical environment seemed a metaphor for how I felt during the evaluation: In seeking the “truth,”¹¹ had I lost a vital humanistic element? 

Performing that early assessment, I felt as if such work challenged the reason I had decided to enter the medical profession. I struggled to see how such objective work contributed to relieving human suffering.

Now, only slightly more seasoned in this trade, I have a better appreciation for this necessarily impartial work. Although the role of the treating provider and the role of the forensic evaluator are distinct,¹² both can be rewarding and both provide a valuable service.

Service in the name of Justice

I believe that, by presenting assessments free of bias, one can further the goal of justice: Forensic psychiatry provides the courts with the means to better understand and gain access to the mental health system. The task seemed daunting at first; now, I welcome opportunities to make such contributions to the fair and just treatment of all people.

Disclosure

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

As physicians, we strive to heal suffering; as psychiatry trainees, we are taught to relieve that suffering through careful assessment, development of rapport, and empathic care. What then of the forensic expert, whose role is to provide the courts with objective assessment of the “defendant,” free of a therapeutic alliance^1,2? Learning to navigate between these different roles is a necessary part of forensic training.²

In my journey to become a forensic psychiatrist equipped to treat adults and youth, I’ve had the good fortune to learn from those who appear to have mastered this balancing act. In this article, I present some of those lessons, with the hope that they will resonate with others—both those who are forensically inclined and those who wish to ease the jolt of being subpoenaed to appear before the court. 

A day spent in the system

One of my earliest forensic experiences occurred during my training at Johns Hopkins, when I worked in the municipal court. I learned several lessons when I was assigned to pre-screen a defendant for competency to stand trial³ and criminal responsibility,⁴  both determined by the court but often informed by forensic evaluation.

Lesson #1: Answer only the question that you have been asked. En route to call for the defendant, I scanned my “how-to” guides and was relieved to learn that I was not to serve as decision-maker or treating clinician.⁵ I realized that I was not being asked to determine guilt or even give treatment recommendations; having a circumscribed task made that first evaluation less overwhelming. Learning to answer only the question you are being asked is a valuable lesson—one that ought to be remembered by those preparing for forensic evaluations and court testimony.

Lesson #2: There is a place for role induction. Entering a nearly empty office at municipal court, I sat behind a large metal desk and waited for the defendant. When he arrived, dressed in orange and escorted by the armed court officer, I rose to my feet awkwardly. I thought that I should shake hands with him, but stopped my hand in mid-air when I saw his handcuffed wrists.

As the guard knelt to chain the defendant’s ankle shackle to the floor, I waited patiently. Once the guard was outside, I introduced myself and read from my script. I explained the purpose of the evaluation and informed him that, unlike a
physician-patient relationship, this evaluation would not be confidential and would be shared with the court in a written report. Although the content of this introductory segment was in stark contrast to my usual patient encounters, this role induction⁶ was not. The purpose of role induction in a forensic setting is not to affect prognosis, yet such explanation is necessary to maintain ethical boundaries.¹

Lesson #3: Know your phenomenology. Proceeding with the evaluation, I inquired about aspects of the defendant’s life. I attempted to assess his knowledge of the charges against him and how the court works,³ and obtained his account of the reported criminal events.⁴ Having an interest in psychotic illness and an appreciation for Jaspers’ descriptions of psychiatric phenomenology,⁷ I confidently delved into questions about the source, number, quality, and content of the voices he reported hearing.

Although not fail-proof, knowledge of phenomenology is necessary to discern whether reported symptoms should be trusted.^8,9 In his writings¹⁰ and during my brief mentorship by him, Phillip Resnick, MD, stressed the importance of being able to detect malingering through knowledge of classic phenomenology and by maintaining a healthy level of suspicion. 

Lesson #4: Impartiality is difficult but necessary. I concluded the interview, thanked the defendant, and asked if he had any questions. He declined. I motioned for the court officer to enter the room, unshackle the defendant from the floor, and escort him out. Exiting the room, I turned off the lights and shut the heavy door. The coldness of the physical environment seemed a metaphor for how I felt during the evaluation: In seeking the “truth,”¹¹ had I lost a vital humanistic element? 

Performing that early assessment, I felt as if such work challenged the reason I had decided to enter the medical profession. I struggled to see how such objective work contributed to relieving human suffering.

Now, only slightly more seasoned in this trade, I have a better appreciation for this necessarily impartial work. Although the role of the treating provider and the role of the forensic evaluator are distinct,¹² both can be rewarding and both provide a valuable service.

Service in the name of Justice

I believe that, by presenting assessments free of bias, one can further the goal of justice: Forensic psychiatry provides the courts with the means to better understand and gain access to the mental health system. The task seemed daunting at first; now, I welcome opportunities to make such contributions to the fair and just treatment of all people.

Disclosure

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

As physicians, we strive to heal suffering; as psychiatry trainees, we are taught to relieve that suffering through careful assessment, development of rapport, and empathic care. What then of the forensic expert, whose role is to provide the courts with objective assessment of the “defendant,” free of a therapeutic alliance^1,2? Learning to navigate between these different roles is a necessary part of forensic training.²

In my journey to become a forensic psychiatrist equipped to treat adults and youth, I’ve had the good fortune to learn from those who appear to have mastered this balancing act. In this article, I present some of those lessons, with the hope that they will resonate with others—both those who are forensically inclined and those who wish to ease the jolt of being subpoenaed to appear before the court. 

A day spent in the system

One of my earliest forensic experiences occurred during my training at Johns Hopkins, when I worked in the municipal court. I learned several lessons when I was assigned to pre-screen a defendant for competency to stand trial³ and criminal responsibility,⁴  both determined by the court but often informed by forensic evaluation.

Lesson #1: Answer only the question that you have been asked. En route to call for the defendant, I scanned my “how-to” guides and was relieved to learn that I was not to serve as decision-maker or treating clinician.⁵ I realized that I was not being asked to determine guilt or even give treatment recommendations; having a circumscribed task made that first evaluation less overwhelming. Learning to answer only the question you are being asked is a valuable lesson—one that ought to be remembered by those preparing for forensic evaluations and court testimony.

Lesson #2: There is a place for role induction. Entering a nearly empty office at municipal court, I sat behind a large metal desk and waited for the defendant. When he arrived, dressed in orange and escorted by the armed court officer, I rose to my feet awkwardly. I thought that I should shake hands with him, but stopped my hand in mid-air when I saw his handcuffed wrists.

As the guard knelt to chain the defendant’s ankle shackle to the floor, I waited patiently. Once the guard was outside, I introduced myself and read from my script. I explained the purpose of the evaluation and informed him that, unlike a
physician-patient relationship, this evaluation would not be confidential and would be shared with the court in a written report. Although the content of this introductory segment was in stark contrast to my usual patient encounters, this role induction⁶ was not. The purpose of role induction in a forensic setting is not to affect prognosis, yet such explanation is necessary to maintain ethical boundaries.¹

Lesson #3: Know your phenomenology. Proceeding with the evaluation, I inquired about aspects of the defendant’s life. I attempted to assess his knowledge of the charges against him and how the court works,³ and obtained his account of the reported criminal events.⁴ Having an interest in psychotic illness and an appreciation for Jaspers’ descriptions of psychiatric phenomenology,⁷ I confidently delved into questions about the source, number, quality, and content of the voices he reported hearing.

Although not fail-proof, knowledge of phenomenology is necessary to discern whether reported symptoms should be trusted.^8,9 In his writings¹⁰ and during my brief mentorship by him, Phillip Resnick, MD, stressed the importance of being able to detect malingering through knowledge of classic phenomenology and by maintaining a healthy level of suspicion. 

Lesson #4: Impartiality is difficult but necessary. I concluded the interview, thanked the defendant, and asked if he had any questions. He declined. I motioned for the court officer to enter the room, unshackle the defendant from the floor, and escort him out. Exiting the room, I turned off the lights and shut the heavy door. The coldness of the physical environment seemed a metaphor for how I felt during the evaluation: In seeking the “truth,”¹¹ had I lost a vital humanistic element? 

Performing that early assessment, I felt as if such work challenged the reason I had decided to enter the medical profession. I struggled to see how such objective work contributed to relieving human suffering.

Now, only slightly more seasoned in this trade, I have a better appreciation for this necessarily impartial work. Although the role of the treating provider and the role of the forensic evaluator are distinct,¹² both can be rewarding and both provide a valuable service.

Service in the name of Justice

I believe that, by presenting assessments free of bias, one can further the goal of justice: Forensic psychiatry provides the courts with the means to better understand and gain access to the mental health system. The task seemed daunting at first; now, I welcome opportunities to make such contributions to the fair and just treatment of all people.

Disclosure

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

There are a lack of research on, and strategies for dealing with, an insufficient response to antipsychotics. Treatment often is guided by what is described in published case reports or anecdotal evidence, rather than the findings of systematic studies.

We propose that a patient be considered “difficult-to-treat” or “treatment-resistant” after experiencing limited or negative responses to 3 different antipsychotics—with ≥1 being a second-generation antipsychotic (SGA)—that the patient has taken for at least 6 to 8 weeks at the maximum recommended dosage. Furthermore, switching to clozapine is an important strategy; do not consider it solely a last resort.

These 6 ‘D’s can remind you of other problems to consider when evaluating a treatment-resistant patient.

Diagnosis. Is the diagnosis, including the presence of comorbid conditions, accurate? Are significant psychosocial stressors undermining treatment response? Treat any comorbid conditions and consider instituting adjunctive psychosocial interventions, including cognitive-behavioral therapy.

Dosage. Have the patient try the maximum recommended dosage if he (she) can tolerate it. Equivalent dosages of antipsychotics are shown in the Table,^1,2 and can guide off-label use of higher dosages. Research does not support use of chlorpromazine equivalents >1,000 mg/d, and usually should not be employed. If using a higher than normal dosage, perform an ECG before the increase.³

Beneficial and adverse effects should be monitored carefully. Reduce the dosage after 3 months if the risk-benefit ratio does not justify the higher dosage.³

Duration. Try a treatment for at least 6 weeks at the maximum tolerated
dosage—even extending it to 12 weeks—before considering abandoning it because of insufficient response.

Drug interactions. Use a drug interaction tool to ensure drug-drug interactions are not reducing antipsychotic levels. A recent increase in smoking or decrease in caffeine intake can reduce the blood level of olanzapine and clozapine.⁴ Ultra-rapid metabolizers of cytochrome P450 isoenzymes may have a lower blood level of antipsychotic.

Consider pharmacogenetic testing in patients in whom you observe an unexpected lack of efficacy or adverse effects at customary dosages.

Double up. You might need to add another medication to the antipsychotic. Symptoms might help determine which medication to add:

• a combination of an SGA and a first-generation antipsychotic may be more effective than antipsychotic monotherapy⁵
• for prominent negative symptoms, consider using 2 SGAs of different potency together. Use caution when prescribing ziprasidone with another antipsychotic because this could prolong the QTc interval
• if a mood stabilizer is appropriate, consider lamotrigine because of its possible potentiating effect on SGAs⁶
• benzodiazepines can be used to reduce agitation or anxiety but are ineffective for psychosis.⁷

Drug levels. Measurement of the blood level of the drug is most useful when administering clozapine; focus on the clozapine, not on the norclozapine level that also is reported. Ensure a clozapine level of 350 to 600 ng/mL.

Therapeutic levels have been established for most antipsychotics (Table).^1,2 Occasionally, knowing these levels can be helpful in evaluating patients for potential problems with absorption and metabolism of the drug, and with nonadherence.

Disclosures

Drs. Faden and Pinninti report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Mago receives grant/research support from Bristol-Myers Squibb, Forest Institute, Genomind, and Shire.

There are a lack of research on, and strategies for dealing with, an insufficient response to antipsychotics. Treatment often is guided by what is described in published case reports or anecdotal evidence, rather than the findings of systematic studies.

We propose that a patient be considered “difficult-to-treat” or “treatment-resistant” after experiencing limited or negative responses to 3 different antipsychotics—with ≥1 being a second-generation antipsychotic (SGA)—that the patient has taken for at least 6 to 8 weeks at the maximum recommended dosage. Furthermore, switching to clozapine is an important strategy; do not consider it solely a last resort.

These 6 ‘D’s can remind you of other problems to consider when evaluating a treatment-resistant patient.

Diagnosis. Is the diagnosis, including the presence of comorbid conditions, accurate? Are significant psychosocial stressors undermining treatment response? Treat any comorbid conditions and consider instituting adjunctive psychosocial interventions, including cognitive-behavioral therapy.

Dosage. Have the patient try the maximum recommended dosage if he (she) can tolerate it. Equivalent dosages of antipsychotics are shown in the Table,^1,2 and can guide off-label use of higher dosages. Research does not support use of chlorpromazine equivalents >1,000 mg/d, and usually should not be employed. If using a higher than normal dosage, perform an ECG before the increase.³

Beneficial and adverse effects should be monitored carefully. Reduce the dosage after 3 months if the risk-benefit ratio does not justify the higher dosage.³

Duration. Try a treatment for at least 6 weeks at the maximum tolerated
dosage—even extending it to 12 weeks—before considering abandoning it because of insufficient response.

Drug interactions. Use a drug interaction tool to ensure drug-drug interactions are not reducing antipsychotic levels. A recent increase in smoking or decrease in caffeine intake can reduce the blood level of olanzapine and clozapine.⁴ Ultra-rapid metabolizers of cytochrome P450 isoenzymes may have a lower blood level of antipsychotic.

Consider pharmacogenetic testing in patients in whom you observe an unexpected lack of efficacy or adverse effects at customary dosages.

Double up. You might need to add another medication to the antipsychotic. Symptoms might help determine which medication to add:

• a combination of an SGA and a first-generation antipsychotic may be more effective than antipsychotic monotherapy⁵
• for prominent negative symptoms, consider using 2 SGAs of different potency together. Use caution when prescribing ziprasidone with another antipsychotic because this could prolong the QTc interval
• if a mood stabilizer is appropriate, consider lamotrigine because of its possible potentiating effect on SGAs⁶
• benzodiazepines can be used to reduce agitation or anxiety but are ineffective for psychosis.⁷

Drug levels. Measurement of the blood level of the drug is most useful when administering clozapine; focus on the clozapine, not on the norclozapine level that also is reported. Ensure a clozapine level of 350 to 600 ng/mL.

Therapeutic levels have been established for most antipsychotics (Table).^1,2 Occasionally, knowing these levels can be helpful in evaluating patients for potential problems with absorption and metabolism of the drug, and with nonadherence.

Disclosures

Drs. Faden and Pinninti report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Mago receives grant/research support from Bristol-Myers Squibb, Forest Institute, Genomind, and Shire.

There are a lack of research on, and strategies for dealing with, an insufficient response to antipsychotics. Treatment often is guided by what is described in published case reports or anecdotal evidence, rather than the findings of systematic studies.

We propose that a patient be considered “difficult-to-treat” or “treatment-resistant” after experiencing limited or negative responses to 3 different antipsychotics—with ≥1 being a second-generation antipsychotic (SGA)—that the patient has taken for at least 6 to 8 weeks at the maximum recommended dosage. Furthermore, switching to clozapine is an important strategy; do not consider it solely a last resort.

These 6 ‘D’s can remind you of other problems to consider when evaluating a treatment-resistant patient.

Diagnosis. Is the diagnosis, including the presence of comorbid conditions, accurate? Are significant psychosocial stressors undermining treatment response? Treat any comorbid conditions and consider instituting adjunctive psychosocial interventions, including cognitive-behavioral therapy.

Dosage. Have the patient try the maximum recommended dosage if he (she) can tolerate it. Equivalent dosages of antipsychotics are shown in the Table,^1,2 and can guide off-label use of higher dosages. Research does not support use of chlorpromazine equivalents >1,000 mg/d, and usually should not be employed. If using a higher than normal dosage, perform an ECG before the increase.³

Beneficial and adverse effects should be monitored carefully. Reduce the dosage after 3 months if the risk-benefit ratio does not justify the higher dosage.³

Duration. Try a treatment for at least 6 weeks at the maximum tolerated
dosage—even extending it to 12 weeks—before considering abandoning it because of insufficient response.

Drug interactions. Use a drug interaction tool to ensure drug-drug interactions are not reducing antipsychotic levels. A recent increase in smoking or decrease in caffeine intake can reduce the blood level of olanzapine and clozapine.⁴ Ultra-rapid metabolizers of cytochrome P450 isoenzymes may have a lower blood level of antipsychotic.

Consider pharmacogenetic testing in patients in whom you observe an unexpected lack of efficacy or adverse effects at customary dosages.

Double up. You might need to add another medication to the antipsychotic. Symptoms might help determine which medication to add:

• a combination of an SGA and a first-generation antipsychotic may be more effective than antipsychotic monotherapy⁵
• for prominent negative symptoms, consider using 2 SGAs of different potency together. Use caution when prescribing ziprasidone with another antipsychotic because this could prolong the QTc interval
• if a mood stabilizer is appropriate, consider lamotrigine because of its possible potentiating effect on SGAs⁶
• benzodiazepines can be used to reduce agitation or anxiety but are ineffective for psychosis.⁷

Drug levels. Measurement of the blood level of the drug is most useful when administering clozapine; focus on the clozapine, not on the norclozapine level that also is reported. Ensure a clozapine level of 350 to 600 ng/mL.

Therapeutic levels have been established for most antipsychotics (Table).^1,2 Occasionally, knowing these levels can be helpful in evaluating patients for potential problems with absorption and metabolism of the drug, and with nonadherence.

Disclosures

Drs. Faden and Pinninti report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Mago receives grant/research support from Bristol-Myers Squibb, Forest Institute, Genomind, and Shire.