Recent reports describe discontinuation-emergent adverse events upon cessation of selective serotonin reuptake inhibitors including dizziness, insomnia, nervousness, nausea, and agitation. We hypothesized that interruption of fluoxetine treatment would be associated with fewer discontinuation-emergent adverse events than interruption of sertraline or paroxetine treatment, based on fluoxetine’s longer half-life.
In this 4-week study, 242 patients with remitted depression receiving maintenance therapy with open-label fluoxetine, sertraline, or paroxetine for 4 -24 months had their maintenance therapy interrupted with double-blind placebo substitution for 5 -8 days. The Symptom Questionnaire (SQ), the Discontinuation-Emergent Signs and Symptoms checklist, the 28-item Hamilton Depression Rating Scale, and the Montgomery -Asberg Depression Rating Scale were used to assess somatic distress and stability of antidepressant response.
Results: Two hundred twenty patients (91%) completed the study. Following interruption of therapy, fluoxetine-treated patients experienced fewer discontinuation-emergent events than either sertraline-treated or paroxetine-treated patients (p < .001). The mean SQ somatic symptom scale score in fluoxetine-treated patients was significantly lower than that in sertraline-treated and paroxetine-treated patients (p < .001). Fluoxetine-treated patients also experienced less reemergence of depressive symptoms than sertraline-treated or paroxetine-treated patients (p < .001).
Conclusions: Abrupt interruption of antidepressant therapy for 5 -8 days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline, with few symptoms seen with fluoxetine.
Jerrold F. Rosenbaum, Maurizio Fava, Sharon L. Hoog, Richard C. Ascroft and William B. Krebs
Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA (JFR, MF)
U.S. Medical Division, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA (SLH, RCA, WBK)
Received 18 November 1997; revised 18 March 1998; accepted 24 March 1998. Available online 1 December 1998.
Biological Psychiatry, Volume 44, Issue 2, 15 July 1998, Pages 77-87