Onset of antidepressant effect of olanzapine and olanzapine/fluoxetine combination in bipolar depression.
OBJECTIVE
The current analysis investigated the onset of antidepressant effect of olanzapine/fluoxetine combination.


METHODS
Data for these post hoc analyses were obtained from a clinical trial comparing olanzapine, placebo, and olanzapine/fluoxetine combination in bipolar depression (BD). Subjects were 833 patients with a DSM-IV diagnosis of bipolar I disorder, depressed. The Montgomery-Asberg Depression Rating Scale measured depressive symptoms. Multiple analytic methods were applied, including traditional (mean differences) analysis, pattern analysis, survival analysis of sustained response, mixed-effects regression, and area-under-the-curve analysis.


RESULTS
Traditional analysis showed significantly greater improvement in depression scores at week 1 for olanzapine/fluoxetine combination versus placebo (-9.55 versus -5.08, p < 0.001) and for olanzapine versus placebo (-8.31 versus -5.08, p < 0.001). Pattern analysis revealed olanzapine/fluoxetine combination had a significantly greater percentage of early persistent responders than placebo or olanzapine (32.4% versus 12.7%, p < 0.001; and 18.3%, p < 0.05, respectively). Survival analysis showed a significantly shorter time to sustained response for the combination versus placebo (p < 0.001), for olanzapine versus placebo (p = 0.04), and for the combination versus olanzapine (p = 0.03). Mixed-effects regression analysis revealed a significant therapy-by-time interaction (p < 0.001). Early area-under-the-curve analysis revealed a significantly greater percentage of improvement for the combination versus placebo (26.7% versus 13.9%, p < 0.001) and for olanzapine versus placebo (22.0% versus 13.9%, p < 0.001).


CONCLUSIONS
Based on consistent results from related methods of measuring onset, olanzapine/fluoxetine combination demonstrated rapid onset of antidepressant effect (within 7 days) compared to placebo that was sustained over 8 weeks of treatment in a sample of BD patients. Using multiple statistical techniques may help profile a drug's onset of effect.
Dubé
Sanjay
S
Lilly Research Laboratories, Indianapolis, IN 46285, USA. dube_sanjay@lilly.com
Tollefson
Gary D
GD
Thase
Michael E
ME
Briggs
Susan D
SD
Van Campen
Luann E
LE
Case
Michael
M
Tohen
Mauricio
M
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D001714:Bipolar Disorder / Q000188:drug therapy*; D003866:Depressive Disorder / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D000077152:Olanzapine; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D016019:Survival Analysis; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D005473:Fluoxetine; D001569:Benzodiazepines; D000077152:Olanzapine