Benzodiazepines rebound from

Equivalent doses from Chouinard C. Issues in the clinical use of benzodiazepines Potency, withdrawal and rebound. J Qin Psychiatry 2004 65(Suppl 5) 7-12. 

Antidepressants differ from benzodiazepines in the onset and course of their actions (Fig. 2). Most cause an increase in anxiety on initiation of therapy, and anxiolytic effects occur later. In comparative studies, improvement matches that on benzodiazepines after 4 weeks (Rocca et al. 1997). Withdrawal effects, particularly rebound, are less problematic with antidepressants, although stopping treatment is associated with a significant rate of relapse, and a withdrawal syndrome has been described for most of the shorter-acting drugs. 

Another advantage of these agents over even fast-onset, short-duration benzodiazepines such as triazolam is that the binding of nonbenzodiazepines to the benzodiazepine receptor is different from benzodiazepine binding to this receptor, and may exhibit partial agonist properties (Fig. 8—28). Perhaps because of this, rebound insomnia (i.e., insomnia caused by withdrawal of the drug), dependence, withdrawal... 

Rebound may be contrasted with a withdrawal reaction in which stopping the hypnotic is followed by the emergence of new symptoms, not previously experienced by the patient. Muscle tension and pain, loss of appetite and weight, and perceptual changes such as hyperacusis are cardinal features of withdrawal reactions from benzodiazepine-type depressants. 

Frequency of rebound insomnia resulting from discontinuation of benzodiazepine therapy. 

Q10 A major problem associated with benzodiazepines is the development of tolerance, a gradual increase in the dose needed to elicit the therapeutic effect and dependence in chronic use. Following the cessation of treatment, the patient may suffer from rebound anxiety and insomnia. Withdrawal from benzodiazepines also occasionally causes bizarre visual disturbances. 

Although structurally unrelated to the benzodiazepines, these drugs act on the same macromolecular receptor complex but at different sites from the benzodiazepines their effects can be blocked by flumazenil, the receptor antagonist. Those described below are all effective in insomnia, have low propensity for tolerance, rebound insomnia, withdrawal symptoms and abuse potential but there are few data of their effects in long-term studies. 

The toxic effects of an overdosage result from profound central depression and may include coma, respiratory and cardiovascular depression with hypertension, and shock leading to renal failure. Withdrawal of the drug is more frequently a problem with barbiturates than with benzodiazepines. Withdrawal of barbiturates leads to rapid eye movement (REM) sleep rebound and rebound insomnia. 

Zopiclone, the first compound of the cyclopyrrolone class to be marketed, possesses anticonvulsant, anxiolytic, muscle relaxant, and sedative properties. It causes no dependence and no rebound insomnia. Zopiclone interacts with GABA receptors (see Figure 50). It is rapidly absorbed from the GI tract, and with an oral dose of 7.5 mg, it produces a peak-plasma concentration of 50 to 80 )tg/L. Zopiclone becomes metabolized to A-demethylzopiclone (inactive) and zopiclone-iV-oxide (active). Zopiclone exhibits a high affinity for benzodiazepine-binding sites in the cerebral cortex, hippocampus, and cerebellum, but does not interact with the peripheral benzodiazepine-binding sites. 

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