Long-term antidepressant efficacy and safety of olanzapine/fluoxetine combination: a 76-week open-label study.
BACKGROUND
The olanzapine/fluoxetine combination has demonstrated effectiveness in treatment-resistant depression (TRD). Although this combination is being used by prescribers, this is the first study to examine long-term use. Long-term efficacy and safety were therefore investigated in a group of patients with major depressive disorder (MDD) with and without TRD.


METHODS
560 patients who met DSM-IV diagnostic criteria for MDD were enrolled in this 76-week, open-label study (Feb. 2000-July 2002). The Montgomery-Asberg Depression Rating Scale (MADRS) total score was the primary efficacy measure. Safety was assessed via adverse events, vital signs, laboratory analytes, electrocardiography, and extrapyramidal symptom measures.


RESULTS
MADRS mean total scores decreased 7 points from baseline (31.6 [N = 552]) at 1/2 week of treatment, 11 points at 1 week of treatment, and 18 points at 8 weeks of treatment. This effect was maintained to endpoint with a mean decrease of 22 points at 76 weeks. Response and remission rates for the total sample were high (62% and 56%, respectively), and the relapse rate was low (15%). Response, remission, and relapse rates for TRD patients (N = 145) were 53%, 44%, and 25%, respectively. The most frequently reported adverse events were somnolence, weight gain, dry mouth, increased appetite, and headache. At endpoint, there were no clinically meaningful changes in vital signs, laboratory analytes, or electrocardiography. There were no significant increases on any measure of extrapyramidal symptoms.


CONCLUSIONS
The olanzapine/fluoxetine combination showed rapid, robust, and sustained improvement in depressive symptoms in patients with MDD, including patients with TRD. The long-term safety profile of the combination was similar to that of its component monotherapies.
Corya
Sara A
SA
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. scorya@lilly.com
Andersen
Scott W
SW
Detke
Holland C
HC
Kelly
Linda S
LS
Van Campen
Luann E
LE
Sanger
Todd M
TM
Williamson
Douglas J
DJ
Dubé
Sanjay
S
D000328:Adult; D001569:Benzodiazepines; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D001569:Benzodiazepines; D005473:Fluoxetine; D000077152:Olanzapine; D010890:Pirenzepine; D017367:Selective Serotonin Reuptake Inhibitors