Off-label use of atypical antipsychotic agents for treatment of insomnia

Despite limited supporting evidence, off-label uses of atypical or second generation antipsychotics (particularly olanzapine, quetiapine, and risperidone) are not uncommon. The off-label use of these agents for the treatment of insomnia is the focus of this review. While atypical antipsychotics are associated with a lower risk of tardive dyskinesia, extrapyramidal side effects, and more favorable effects on cognitive deficits and negative symptomatology in schizophrenic patients compared to typical or first generation antipsychotic agents, they are not without risks. Metabolic adverse effects are particularly problematic with atypical antipsychotics, even at doses lower than those used to treat FDA-approved indications. The receptor affinity profiles of most atypical antipsychotic agents promote sedation. The level of H1-histamine receptor blockade is believed to be most associated with somnolence and sedation. Several studies evaluating the safety and efficacy of the atypical antipsychotics quetiapine, olanzapine, and risperidone for the treatment of insomnia were identified and are summarized in this article.