Off-label use of atypical antipsychotics

Controversy surrounds the use of atypical antipsychotics for off-label indications in adults, especially the elderly with dementia. A new meta-analysis reviews the evidence of efficacy of these drugs for various off-label uses. Of more than 12,000 studies considered, 162 were included in the analysis. Drugs reviewed included risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify), ziprasidone (Geodon), asenapine (Saphris), iloperidone (Fanapt), and paliperidone (Invega). For elderly patients with dementia, a small but statistically significant improvement in symptoms such as psychosis, mood alterations, and aggression were seen with aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, quetiapine was the most effective, while for obsessive-compulsive disorder, risperidone was associated with a 3.9 greater likelihood of favorable response, compared with placebo when used with antidepressants. There was no benefit seen with any of the drugs used in treating eating disorders, substance abuse, or insomnia, and only marginal benefit in personality disorders or posttraumatic stress disorder. All of these drugs have a boxed warning regarding increased mortality in elderly patients with dementia and increased risk of suicidality. Increased risk of death was seen in elderly patients with a number needed to harm (NNH) of 87. Also noted was increased risk of stroke, especially with risperidone (NNH = 53), extraparametal symptoms (NNH = 10 for olanzepine, NNH = 20 for risperidone), and urinary tract symptoms (NNH range = 16-36). Weight gain was also a problem in non-elderly adults, particularly with olanzapine (incidence of more than 40%), while akathisia was more common with aripiprazole. Other common side effects included fatigue, sedation, and extrapyramidal symptoms. (JAMA 2011;306:1359-1369).