High-potency benzodiazepines for short-term management of panic disorder: the U.S. experience

Interest in benzodiazepines for treatment of panic attacks followed a report of the success of alprazolam, used for generalized anxiety, in blocking such attacks. Twelve controlled trials and several open studies have substantiated the antipanic and antiphobic activity of alprazolam and concluded it is comparable to but more rapid than antidepressants in its effects and better tolerated. In a controlled trial of clonazepam, alprazolam, and placebo, the two active agents had similar positive effects. Diazepam and lorazepam have been effective in other studies. Clonazepam, with its relatively long half-life, permits less frequent dosing than possible with benzodiazepines with shorter half-lives and more continuous control of anxiety, although around 20% of patients experience unacceptable sedative effects or no reduction in anxiety. In general, benzodiazepines are safe and well tolerated. The most common adverse effects are intoxication, dependence, rebound, withdrawal, hostility, and affective disturbances. Discontinuation of alprazolam is particularly difficult and is sometimes associated with serious rebound and withdrawal symptoms. The morbidity and mortality associated with panic disorder suggest that the benefits of benzodiazepine treatment outweigh its risks.