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For some chronic benzodiazepine users, withdrawal can be a long, drawn-out process. A sizable minority, perhaps 10% to 15%^ develop a Apost-withdrawal syndrome,"2 which may linger for months or even years. This syndrome is clearly not a disease entity; it probably represents an amalgam of pharmacological and psychological factors directly and indirectly related to benzodiazepine use. The syndrome includes (1) pharmacological withdrawal symptoms involving the slow reversal of receptor changes directly induced in the brain by benzodiazepines,3,5 and (2) psychological symptoms resulting indirectly from long-term benzodiazepine use, including exposure of poor stress-coping abilities and other personal difficulties. These symptoms merge into a complex clinical picture that may be further complicated by the reappearance of underlying anxiety or depression and possibly also by illunderstood long-term neurological effects of benzodiazepines.4
Thus, the totality of the benzodiazepine withdrawal syndrome is as difficult to define or demarcate as a bout of influenza, which may include the overlapping pathologies of acute viral toxemia, secondary bacterial infection, and prolonged post-viral depression. Nevertheless, an awareness that symptoms may be protracted is important for clinicians supervising benzodiazepine withdrawal; proper management of the post-withdrawal phase can decrease its severity and duration and improve the prospects for eventual recovery.
ACUTE WITHDRAWAL PHASE
The acute "pharmacological" benzodiazepine withdrawal syndrome is classically described as lasting 5 to 28 days, with a peak in severity around 2 weeks post-withdrawal, after which most symptoms return to prewithdrawal levels.6"12 The symptom constellation includes symptoms common to all anxiety states, but some features are unusual and considered to be relatively specific to benzodiazepine withdrawal (Table 1).
However, the duration of this acute phase has probably been underestimated. First, most clinical studies terminate 4 to 8 weeks after withdrawal, and the progress of remaining symptoms is not monitored. Second, most reports do not include the later experience of dropouts, although the reason for dropout is often the continuation of symptoms. Indeed, persistence of high anxiety levels beyond 28 days post-withdrawal is usually interpreted not as a withdrawal effect, but as reemergence of an underlying anxiety state previously controlled by the benzodiazepine12'13 and often results in reinstatement of benzodiazepine treatment. Third, it has been assumed that return to pre-withdrawal symptom levels in those who complete withdrawal represents the end of the withdrawal syndrome.