Efficacy, adverse events, and treatment discontinuations in fluoxetine clinical studies of major depression: a meta-analysis of the 20-mg/day dose.
BACKGROUND
The efficacy and safety of fluoxetine in adults with moderate-to-severe major depression are well established. However, most analyses combined dosages (20-80 mg/day) of the compound. We hypothesized that in patients taking 20 mg/day, efficacy would be maintained but the incidence of adverse events would be lower. We present a meta-analysis of efficacy and safety data for fluoxetine, 20 mg/day.


METHODS
Data were from 3 double-blind studies (N = 417) that included patients with moderate-to-severe major depression (DSM-III or DSM-III-R criteria) who received placebo or fixed-dose 20-mg/day treatment with fluoxetine. Efficacy was assessed using the Hamilton Rating Scale for Depression (HAM-D; HAM-D-17 total score and anxiety/somatization, retardation, sleep disturbance, and cognitive disturbance factors) and response and remission rates. Safety assessments included treatment-emergent adverse events, reasons for discontinuation, and adverse events leading to discontinuation. Adverse events were evaluated to determine the emergence of activation and/or sedation.


RESULTS
At 20 mg/day, fluoxetine-treated patients demonstrated significantly greater remission and response rates and mean changes on HAM-D-17 total score and anxiety/somatization, retardation, and cognitive disturbance factor scores than placebo-treated patients (p < .001). The incidence of specific adverse events leading to discontinuation and the frequency of study discontinuations due to adverse events were similar among fluoxetine-treated and placebo-treated patients (6.1% vs. 5.8%, p = .879). Several adverse events (insomnia, asthenia, somnolence, gastroenteritis, decreased libido, chills, and confusion) occurred significantly more frequently among fluoxetine-treated patients. A significant change in sedation, but not activation, occurred in patients in the fluoxetine 20-mg/day group compared with the placebo group.


CONCLUSIONS
These data affirm that fluoxetine at 20 mg/day is efficacious, safe, and of similar activation potential when compared with placebo in patients with major depression.
Beasley
C M
CM
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Ind 46285, USA.
Nilsson
M E
ME
Koke
S C
SC
Gonzales
J S
JS
D000328:Adult; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D010919:Placebos; D012220:Rhinitis / Q000139:chemically induced; D012720:Severity of Illness Index; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D016896:Treatment Outcome
D010919:Placebos; D005473:Fluoxetine