The experimental pharmacotherapy of benzodiazepine withdrawal

In many people, long-term benzodiazepine (BZ) use produces dependence with manifestation of withdrawal symptoms after abrupt cessation of BZ treatment. The current therapy of BZ dependence in humans utilizes gradual dose-taper to avoid withdrawal symptoms and supportive psychotherapy to help patients cope with withdrawal reactions. The failure of dose-taper in many patients has triggered intensive animal research to find additional pharmacological treatments. The present article reviews evidence from animal studies on effectiveness of pharmacological treatment for BZ dependence and withdrawal. It explores the risk-benefit profiles of putative therapies for BZ withdrawal, including drugs acting via benzodiazepine receptors, serotonergic and noradrenergic agents, cholecystokinin-B receptor antagonists, calcium channel blockers, N-methyl-D-aspartate (NMDA) antagonists, and other miscellaneous agents.