Self-Assessment Activity: Understanding the Evidence for Off-Label Use of Atypical Antipsychotic Medications

In 2011, the Agency for Healthcare Quality and Research (AHRQ) published a comprehensive report (“Off-Label Use of Atypical Antipsychotics: An Update,” Comparative Effectiveness Review No. 43 [1]) summarizing the evidence for off-label use of antipsychotics for treatment of mental disorders (available at www.effectivehealthcare.ahrq.gov/reports/final.cfm). As described in the report, prescribing of atypical antipsychotics has moved beyond approved indications; however, the effectiveness, benefits, and adverse effects in off-label uses are not well understood. Through a grant from AHRQ, the American Psychiatric Association (APA) developed a FREE multipart CME program to disseminate the conclusions of the AHRQ report and to update clinicians about new developments regarding the evidence.

Our understanding of the evidence continues to evolve. The developers of this program are aware that off-label uses of antipsychotic medications constitute rapidly changing areas in clinical investigation and that new studies and revised Food and Drug Administration (FDA) approvals appear on a regular basis. The material in this program represents the best information available to the developers based on AHRQ reviews and updated literature as of February 2014.

Overall, a class effect of the atypical antipsychotics for each disorder cannot be assumed, and for most atypicals, adequate supporting evidence for either efficacy or comparative effectiveness is still lacking for many indications. The study of the evidence provided in this program will assist the physician in making informed decisions and provide a foundation for discussions with patients about the risks and benefits of this class of medications.

The AHRQ report addressed the following questions.

The task of the AHRQ reviewers was to review off-label use. It is important to note that other established agents as well as psychosocial treatments are available as first line treatments. Table 1 shows how the strength of evidence assessed in the AHRQ report was classified.

Strength of evidence is not the same as the size of the potential effect (i.e., There may be a moderate to high strength of evidence of a beneficial effect, but the size of the effect may be small).

Self-Assessment Activity

Part one of the evidence dissemination program is the self-assessment activity presented as a special feature in this issue of FOCUS. Participants complete a 25-question, multiple-choice self-assessment and assess their strengths and weaknesses regarding their knowledge of evidence for off-label use of atypical antipsychotics. After completing the quiz online at apaeducation.org, participants receive a score report with peer comparison, review the answers and rationales for the quiz, and access links to the AHRQ report and to other important clinical references that describe the evidence for the risks and benefits of these medications.

Look for part 2 of this activity available both at apaeducation.org and also delivered by e-mail as eFocus clinical vignette exercises. After reading a vignette, answer online questions regarding patient management decisions and read the commentary for the best answer choice. You will be able to compare your treatment decisions to those of your peers and receive additional self-assessment CME credit approved by ABPN for MOC part 2. Through completion of this self-assessment and the 10 vignettes that follow, participants will be able to earn up to 25 self-assessment credits for this multipart program.

Self-Assessment

Go to apaeducation.org to complete the self-assessment.

1. Which of the following atypical antipsychotics has moderate strength evidence of efficacy for off-label use as a monotherapy (single-agent) treatment for major depressive disorder (MDD)?

2. What is the conclusion of the AHRQ report about the efficacy of antipsychotic medications as augmenting agents of antidepressants for MDD?

3. When using an atypical antipsychotic agent to augment an antidepressant medication in nonpsychotic unipolar depression, which of the following measures is most likely to be useful for managing side effect(s)?

4. For treatment of patients with PTSD without psychosis, what does the most recent evidence reflected in the Department of Defense (DoD) guideline currently recommend regarding the use of atypical antipsychotics in the treatment of these patients?

5. A 28-year-old female veteran is receiving cognitive-processing therapy for intrusive memories of dead bodies she saw while serving in Afghanistan. When she has these memories, she feels as if she is there, and feels extremely distressed. In addition, she finds herself avoiding public places, and startling easily when approached by her family. She describes herself as “angry” all the time; however, she does feel her sleep, appetite, and energy are normal. After several months of therapy she is less irritable but continues to have the intrusive visions. Which of the following medications has the best evidence for efficacy in treating her symptoms?

6. According to the 2011 AHRQ review, which atypical has the highest level of confidence for effectiveness to support its use in the management of dementia-related agitation?

7. A psychiatry consultation is requested for a 72-year-old nursing home resident with major neurocognitive disorder because of Alzheimer’s disease. In the past, the patient had been violent, injuring both himself and others. Behavioral interventions were tried without success. One year prior, the patient was put on risperidone (1 mg) and showed improvement. An attempt to lower his dose 6 months later resulted in worsening behaviors, and the patient was returned to 1 mg. Since then, there have been no incidents. He also receives hydrochlorothiazide and atenolol for hypertension. His gait is somewhat slow but the nurses insist that this was the case before he was started on risperidone.

A recent pharmacy review questioned the use of antipsychotics for a nonpsychotic patient and informed the Director of Nursing that these drugs are associated with increased mortality in patients with dementia. As a result, the Director of Nursing is requesting an alternative drug. The patient’s family, however, expresses concern over the possibility that the patient’s agitation may return. Which of the following would be the most appropriate recommendation for a psychiatric consultant to give?

8. Which of the following atypical antipsychotics is most likely to cause weight gain in elderly patients?

9. In nonelderly adults (18–64) taking atypical antipsychotic medications, what does the evidence show about antipsychotics and weight gain in this patient group?

10. A 46-year-old woman sees a psychiatrist for ”chronic anxiety.” She has always been an anxious person but has noticed more symptoms in the past 6 months when she returned to the workforce after being home with her children for 10 years. She has difficulty concentrating, and feels on edge at work. She also has difficulty falling asleep and feels fatigued during the day. She says she is not depressed, just “worried all the time.”

She denies any substance use or medical problems. Her physical last year was unremarkable. Which of the following medications would be a first choice to help this patient?

11. In the 2011 AHRQ review, which of the following studied atypical medications has the most evidence for effective treatment of moderate generalized anxiety disorder?

12. What is the best estimate of risk of tardive dyskinesia with atypical antipsychotics compared with typical antipsychotics?

13. A 20-year-old college student is referred to a psychiatrist by the student health service for possible eating disorder. She has lost 30 pounds and now weighs 95 pounds at 5′4”. She says she feels fat and would like to lose more weight. She does not binge or purge, although in high school she once tried using laxatives to lose weight. Her electrolytes and lab tests are all WNL.

What is the next step the psychiatrist should take?

14. For the treatment of patients with eating disorders, what does the evidence show regarding the use of atypical antipsychotics to increase body mass index (BMI) in patients with anorexia nervosa (AN)?

15. What do the data show about efficacy of atypical antipsychotics in the treatment of substance use disorders?

16. A 35-year-old stockbroker is referred to you for treatment of methamphetamine addiction. Which of the following is the most effective treatment for this addiction?

17. A 45-year-old woman complains that she has difficulty falling asleep almost every night. This is a long standing problem but has worsened over the past several months as her job has become more stressful. She watches TV in bed and has been drinking a glass of wine before bed, which seemed to help, but she then began waking up at 2 a.m. and is not able to get back to sleep. What would be the best treatment at this time?

18. Treatment of adolescents and children with atypical antipsychotic medications, including olanzapine, risperidone, quetiapine, and aripiprazole, for psychotic and bipolar disorders was associated with:

19. The AHRQ report reviewed the evidence for atypical antipsychotics in the treatment of Borderline Personality Disorder (BPD). What does the evidence show regarding treatment of Borderline patients with atypical antipsychotics? For which symptoms of BPD do atypical antipsychotics have the best evidence?

20. Which of the following medications would be the first choice for a 10-year-old boy with ADHD and no serious co-occurring disorders?

21. The AHRQ review reported on the effectiveness of atypical antipsychotics as medication augmentation in obsessive compulsive disorder (OCD) as studied in two different experimental designs: one in which specific atypical antipsychotics augment any SRI antidepressant and the other in which they augment citalopram. Some atypical antipsychotics have shown efficacy. When augmenting SRIs, which atypical has the most evidence for effectiveness?

22. According to the 2011 AHRQ review, for elders (≥65 years old) receiving atypical antipsychotic agents for the management of dementia, stroke (CVA) was significantly higher in medication than placebo subjects for which medication?

24. In adults treated with atypical antipsychotics, which of the following atypical antipsychotics has shown the lowest risk of extrapyramidal symptoms?

25. Which of the following is an approved indication for treatment with an atypical for a use other than for psychosis?