Antidepressant Discontinuation Syndromes: Common, Under-Recognised and Not Always Benign

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Discontinuation Symptoms Common...

Discontinuation symptom rates in patients taking older antidepressants can be high, as evidenced by reports of 100% with imipramine, 80% with amitriptyline, 33% with clomipramine and 32% with phenelzine.[1] Abrupt discontinuation of treatment with newer agents such as sertraline,[3] paroxetine,[3,4] and venlafaxine[5] also results in spontaneously reported discontinuation symptoms in at least 1 out of 3 patients. Even higher rates have been documented when patients are specifically asked about symptoms, with one study finding evidence of discontinuation syndromes in 2 out of 3 patients treated with paroxetine and sertraline.[6]

Presumably because of the long half-lives of the parent drug (2 to 4 days) and its active metabolite norfluoxetine (7 to 15 days), fluoxetine appears to be much less likely to be associated with discontinuation symptoms than SSRIs such as paroxetine and sertraline.[1,7] When spontaneous adverse drug reaction reports in the UK (up to March 1993) were analysed, the rate of discontinuation reactions per 1000 prescriptions was 100 times lower with fluoxetine than with paroxetine (0.002 vs 0.3 per 1000, respectively) [see fig. 1].[8] Furthermore, in a double-blind placebo-controlled 'treatment interruption' study, discontinuation of fluoxetine for 5 to 8 days was found to produce fewer adverse events than discontinuation of sertraline or paroxetine for a similar length of time (p ≤ 0.001).[6]


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