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Interruption of selective serotonin reuptake inhibitor treatment

Double-blind, placebo-controlled trial

Lilly Research Laboratories, Indianapolis

MAURIZIO FAVA, MD

Massachusetts General Hospital, Boston

JAY AMSTERDAM, MD

University of Pennsylvania, Philadelphia

JEFFREY APTER, MD

Princeton Biomedical Research, Princeton

PETER LONDBORG, MD

Seattle Clinical Research Center, Seattle

ROY TAMURA, PhD and ROSALINDA G. TEPNER, RPh

Lilly Research Laboratories, Indianapolis

Declaration of interest This work was sponsored by Eli Lilly and Company.

Correspondence: Dr David Michelson, Lilly Research Laboratories, Lilly Corporate Center, Drop Code 2423, Indianapolis, IN 46285, USA. Tel: (317) 277-6443; Fax: (317) 277-3262; e-mail: dmichelson{at}lilly.com

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

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

Method 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.

Results 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.

Conclusions 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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