Publisher's Synopsis
Antipsychotic medications, widely used for the treatment of schizophrenia and other psychotic disorders, are commonly divided into two classes, reflecting two waves of historical development. The conventional antipsychotics--also called typical antipsychotics, conventional neuroleptics, or dopamine antagonists--first appeared in the 1950s and continued to evolve over subsequent decades, starting with chlorpromazine (Thorazine), and were the first successful pharmacologic treatment for primary psychotic disorders, such as schizophrenia. While they provide treatment for psychotic symptoms - for example reducing the intensity and frequency of auditory hallucinations and delusional beliefs - they also commonly produce movement abnormalities, both acutely and during chronic treatment, arising from the drugs' effects on the neurotransmitter dopamine. These side effects often require additional medications, and in some cases, necessitate antipsychotic dose reduction or discontinuation. Such motor system problems spurred the development of the second generation of antipsychotics, which have come to be known as the "atypical antipsychotics." Currently, the U.S. Food and Drug Administration (FDA)-approved atypical antipsychotics are aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Off-label use of the atypical antipsychotics has been reported for the following conditions: dementia and severe geriatric agitation, depression, obsessive-compulsive disorder, posttraumatic stress disorder, and personality disorders. The purpose of this Evidence Report is to review the evidence supporting such off-label uses of these agents. We were also asked to study the use of the atypical antipsychotics for the management of Tourette's Syndrome and autism in children. The medications considered in this report are those listed above; however, we have excluded clozapine, which has been associated with a potentially fatal disorder of bone-marrow suppression and requires frequent blood tests for safety monitoring. Because of these restrictions, it is rarely used except for schizophrenia that has proven refractive to other treatment. The Key Questions were: Key Question 1. What are the leading off-label uses of atypical antipsychotics in the literature? Key Question 2. What does the evidence show regarding the effectiveness of atypical antipsychotics for off-label indications, such as depression? How do atypical antipsychotic medications compare with other drugs for treating off-label indications? Key Question 3. What subset of the population would potentially benefit from off-label uses? Key Question 4. What are the potential adverse effects and/or complications involved with off-label prescribing of atypical antipsychotics? Key Question 5. What are the appropriate dose and time limit for off-label indications?
