Long-term anxiolytic therapy: the issue of drug withdrawal

Although widespread use has confirmed their efficacy as anxiolytic agents, the benzodiazepine drugs are indicated only for short-term or intermittent therapy at as low a therapeutic dose as possible because of their liability for causing dependence or abuse. When first introduced, benzodiazepine drugs appeared to be therapeutically equal or superior to barbiturate agents, while causing fewer side effects, being safer in overdose, and producing fewer dependence and abuse problems. Although benzodiazepine drugs have become the most commonly prescribed anxiolytic agents, evidence has emerged that their use in long-term therapy can cause severe withdrawal problems, even when relatively low doses are used or when the drug is discontinued gradually. Based on results from both animal models and clinical investigations, buspirone appears to be as effective in treating anxiety as the benzodiazepine drugs while causing fewer withdrawal problems. Data suggest no appreciable propensity to cause physical dependence or abuse associated with buspirone therapy. The drug demonstrates no cross-tolerance with either the barbiturate agents or the benzodiazepine drugs and seems to be a dysphoriant at high doses rather than a euphoriant. Although buspirone seems to be an appropriate drug for patients requiring longer-term anxiolytic therapy, careful monitoring for withdrawal problems and other adverse side effects is essential as buspirone is introduced to successive markets.