Drug development optimization--benzodiazepines.

The benzodiazepines are among the most widely-used of drugs. Sedative effects are common but tend to lessen after a few days, although cognitive effects may persist. Car accidents and falls in the elderly are the most serious practical consequences. On discontinuation, a variety of syndromes are encountered, including relapse, rebound, and withdrawal. Anxiety disorders tend to be remitting and relapsing rather than chronic. Withdrawal follows a characteristic course and symptom pattern, perceptual hypersensitivity being common and distressing. The syndrome is worse after stopping shorter-acting than longer-acting benzodiazepines. Benzodiazepines are prescribed for many different mental and physical conditions, sometimes inappropriately. Chronic use for twelve months or more ranges from 0.5% of the adult population in Sweden through 1.8% in the U.S.A., 3.1% in the U.K., and 6.8% in Belgium. Benzodiazepines differ with respect to elimination half-life and potency. High-potency compounds may be particularly likely to induce sedation, memory disturbance and perhaps dependence. Partial agonists may be less of a problem in these respects. Newer compounds include benzodiazepines with selectivity on one or other of the putative subclasses of receptor, partial inverse agonists and antagonists, compounds acting near the benzodiazepine complex, and new drugs, such as buspirone, believed to act primarily on 5-HT pathways.