Off-Label Use of Antipsychotics Effective for Some Indications
Over the past decade or so, atypical antipsychotic use has exploded, for both FDA approved indications and off-label treatments. A recent meta-analysis examined the efficacy (when compared to placebo), comparative effectiveness (when compared to another medication), and safety of atypicals including risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify), and ziprasidone (Geodon) for a number of off-label uses. Controlled trials comparing off-label treatment with atypical antipsychotics to placebo or to other medications were considered for the review. The researchers used a number of tools to rank the quality of the studies they evaluated.
Here’s how they stacked up, by condition:
Dementia: Researchers examined three measures: improvement in psychosis, improvement in agitation, and total “global” score. Small, but statistically significant effect sizes (ranging from 0.12 to 0.20) were seen with Abilify, Zyprexa, and Risperdal. (Note the caveats in the “side effects” section).
Generalized Anxiety Disorder:Seroquel was associated with a 26% greater likelihood of improvement in symptoms than placebo (an effect size of approximately 0.30). However, researchers considered this evidence “moderate,” because all Seroquel trials examined for this disorder were funded by the drug company and results across studies were inconsistent.
Obsessive Compulsive Disorder: Risperdal was a clear winner—showing a four times greater likelihood of improvement compared to placebo (an effect size of approximately 1.14)—but the studies were quite small and all involved Risperdal augmentation to another drug. Researchers also found that Seroquel augmentation of citalopram (Celexa) was superior to placebo in two studies, and Seroquel augmentation of an SSRI was superior to clomipramine (Anafranil) plus SSRI.
Other Conditions: There was no significant proof that atypical antipsychotics are an effective treatment for eating disorders, PTSD, or substance abuse. There is moderate evidence that Risperdal is effective for personality disorders.
But those dreaded side effects… The atypicals were especially bothersome for elderly patients with dementia. Side effects included increased risk of EPS and urinary tract disorders, plus some cardiovascular symptoms (especially with Zyprexa and Risperdal). When data was pooled from 15 trials, 3.5% of elderly participants assigned an atypical died, compared to 2.3% of those assigned to placebo. The NNH for the increased risk of mortality for the elderly was 87. For the non-elderly, the usual atypical side effects were seen: weight gain, fatigue, sedation, and EPS (Maher AR et al, JAMA 2011;306(12):1359–1369).
TCPR’s Take: Given the combination of a high side effect burden of atypicals, along with the small to moderate effect sizes for off-label uses, we recommend reserving these drugs for psychosis and bipolar disorder—with some consideration in patients with treatment-resistant depression.