Fluoxetine versus trazodone: efficacy and activating-sedating effects.
BACKGROUND
The efficacy and safety of fluoxetine (N = 65; median sustained dose, 20 mg/day) and of trazodone (N = 61; median sustained dose, 250 mg/day) were compared in a trial in outpatients with major depressive episode. The incidence and temporal patterns of activation and sedation were also assessed.


METHODS
Men and women who met DSM-III criteria for nonpsychotic major depressive episode (but with a current episode greater than or equal to 4 weeks) and had a 21-item Hamilton Rating Scale for Depression (HAM-D21) score greater than 20 were selected. After single-blind placebo was administered for 1 week, eligible patients were randomized to double-blind fluoxetine or trazodone treatment for up to 6 weeks. Efficacy (HAM-D21, Clinical Global Impressions Scales for Severity and Improvement, Patient Global Impressions Scale for Improvement, Guild Memory Test) and adverse events were evaluated weekly.


RESULTS
The HAM-D21 score improved within both treatment groups (p less than .001). The groups were similar with respect to endpoint mean HAM-D21 improvement. For individual adverse events that developed or worsened during therapy, more fluoxetine-treated patients reported rhinitis and tremor (p less than or equal to .05), while more trazodone-treated patients reported somnolence and dizziness (p less than or equal to .05). More combined events suggesting activation (agitation, anxiety, nervousness, insomnia) were reported with fluoxetine than with trazodone (15.4% vs. 3.3%, p less than or equal to .05), while more combined events suggesting sedation (somnolence, asthenia) were reported with trazodone than with fluoxetine (42.6% vs. 21.5%, p less than or equal to .05). Discontinuation rates for activation and sedation did not differ between treatments. Numerically, more sedation (21.5%) than activation (15.4%) was reported with fluoxetine.


CONCLUSIONS
There was little clinical difference between treatments with regard to efficacy and safety. The occurrence and temporal patterns of activation and sedation differed within and between treatments.
Beasley
C M
CM
Division of Clinical Neurosciences, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind. 46285.
Dornseif
B E
BE
Pultz
J A
JA
Bosomworth
J C
JC
Sayler
M E
ME
D000328:Adult; D017109:Akathisia, Drug-Induced; D000553:Ambulatory Care; D001007:Anxiety / Q000139:chemically induced; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012220:Rhinitis / Q000139:chemically induced; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D014196:Trazodone / Q000009:adverse effects / Q000627:therapeutic use*; D014202:Tremor / Q000139:chemically induced
D010919:Placebos; D005473:Fluoxetine; D014196:Trazodone