Off-Label Use of Atypical AntiPsychotics

Drugs are the mainstay for treating serious mental illnesses such as schizophrenia, bipolar disease and severe depression.  Atypical antipsychotics, which were a new generation of drugs with supposedly fewer side effects, have become the agents of choice.  Use of these drugs has grown rapidly, with core use more than doubling between 1995 and 2008, but off-label, or FDA unapproved, uses also doubling during that time.  The danger of off-label use is that the manufacturer has not usually done exhaustive research on the compound for those uses.  Nonetheless, many manufacturers have been accused of encouraging, at least implicitly, the use of their compounds for these unapproved purposes.  The issue is exacerbated by the fact that older people with dementia are a large segment of the population for which these off-label uses occur.  Research published in the Journal of the American Medical Association explores this issue.   (JAMA Article)

The research is a meta-review sponsored by the Agency for Healthcare Research & Quality.  Altogether 162 efficacy trials and 231 adverse event studies were included in the review.  The most common off-label uses were for dementia, anxiety, obsessive-compulsive disorder, eating disorders, depression, substance abuse, personality disorders and insomnia.  For dementia, there appeared to be a small, but statistically significant improvement in global symptoms, but it was not clear that use of atypical antipsychotics was more efficacious than use of the older generation.  For anxiety, there was minimal evidence of benefit for some atypicals, as was the case for obsessive-compulsive disorder.  Most of the other conditions had very limited research and for some, such as substance abuse, the results suggest the atypicals should not be used because there fairly clearly was no benefit.

In elderly patients, the atypicals were associated with a greater risk of death and with the development of other adverse events, including neurological symptoms.  For nonelderly adults, there were also significant risks, including the potential for weight gain.  Overall, the off-label use of these drugs seems to have limited benefit and present some dangers.  One thing that would be helpful is to have studies, including pharmacogenomic studies, that identify more precisely individuals who might benefit from the off-label use of these compounds.  Unfortunately, many physicians are susceptible to drug company marketing or opportunities to increase their own income by more visits from patients.  More oversight may be needed to control potential misuse and patient harm.