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Br J Psychiatry. 2000 Apr;176:363-8.

Interruption of selective serotonin reuptake inhibitor treatment. Double-blind, placebo-controlled trial.

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  • 1Lilly Research Laboratories, Indianapolis, IN 46285, USA.



Abrupt interruption of therapy with selective serotonin reuptake inhibitors (SSRIs) has been associated with somatic and psychological symptoms.


Systematically to assess symptoms and effects on daily functioning related to interruption of SSRI therapy.


Patients treated with fluoxetine, setraline or paroxetine underwent identical five-day periods of treatment interruption and continued active treatment under double-blind, order-randomised conditions, with regular assessment of new symptoms.


Placebo substitution for paroxetine was associated with increases in the number and severity of adverse events following the second missed dose, and increases in functional impairment at five days. Placebo substitution for sertraline resulted in less pronounced changes, while interruption of fluoxetine was not associated with any significant increase in symptomatology.


Abrupt interruption of SSRI treatment can result in a syndrome characterised by specific physical and psychological symptoms. Incidence, timing and severity of symptoms vary among SSRIs in a fashion that appears to be related to plasma elimination characteristics.

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