Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial.
BACKGROUND
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.


METHODS
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.
Rosenbaum
J F
JF
Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114, USA.
Fava
M
M
Hoog
S L
SL
Ascroft
R C
RC
Krebs
W B
WB
D015057:1-Naphthylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D003866:Depressive Disorder / Q000175:diagnosis / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010919:Placebos; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000493:pharmacokinetics / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D020280:Sertraline; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D011795:Surveys and Questionnaires
D015057:1-Naphthylamine; D005473:Fluoxetine; D017374:Paroxetine; D010919:Placebos; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline