Benzodiazepines in schizophrenia.

Benzodiazepines have a checkered history in the United States; public and professional attitudes about them have ranged from their being wonder drugs in the 1970s to being virtually purged from many formularies as addictive and dangerous in the 1980s. The attitude today is that they are useful for specific indications. In the last 20 years they have been investigated as adjunctive agents to conventional antipsychotic drugs in the treatment of schizophrenia. Benzodiazepines may be effective in schizophrenia because stress is one mediator of relapse in these patients. In addition, inhibition of dopamine neurotransmission through gamma-aminobutyric acid-enhancing activity may provide a direct antipsychotic effect. As monotherapy or adjuncts to antipsychotic agents, benzodiazepines produced antipsychotic effects in schizophrenia in approximately 50% of controlled trials. Although there is no particular benzodiazepine of choice, low-potency compounds with long elimination half-lives are recommended. Adverse effects of concern include sedation and cognitive impairment, behavioral disinhibition, exacerbation of psychotic symptoms, and the potential for dependence, withdrawal, and abuse. The recent arrival of atypical antipsychotic drugs has significantly slowed research and interest in benzodiazepines in schizophrenia beyond their initial beneficial sedative effects for acute psychotic episodes.