Analyses of treatment-emergent mania with olanzapine/fluoxetine combination in the treatment of bipolar depression.
BACKGROUND
Treatment-emergent mania is a potential risk when patients with bipolar disorder are treated with antidepressant agents. These subanalyses compare treatment-emergent mania rates in bipolar I depressed patients treated with olanzapine, placebo, or olanzapine/fluoxetine combination.


METHODS
In this 8-week, double-blind investigation, patients with bipolar I depression (DSM-IV criteria) (N = 833, baseline Montgomery-Asberg Depression Rating Scale total score > or = 20) were randomly assigned to olanzapine (5-20 mg/day, N = 370), placebo (N = 377), or olanzapine/fluoxetine combination (6/25, 6/50, or 12/50 mg/day; N = 86). Treatment-emergent mania was evaluated with the Young Mania Rating Scale (YMRS), the Clinical Global Impressions-Bipolar Edition (CGI-BP) Severity of Mania scale, and adverse events records.


RESULTS
Overall rates of study discontinuation due to mania were low and not significantly different among the therapy groups (p = .358). Incidence of treatment-emergent mania (defined as a YMRS score < 15 at baseline and > or = 15 at any subsequent visit) did not differ significantly among therapy groups (olanzapine 5.7%, placebo 6.7%, olanzapine/fluoxetine combination 6.4%; p = .861). Subjects receiving olanzapine or olanzapine/fluoxetine combination had greater mean decreases in YMRS scores than those receiving placebo (p < .001 for both). Subjects receiving olanzapine or olanzapine/fluoxetine combination also had greater mean decreases in CGI-BP scores than those receiving placebo (p = .040 and p = .003, respectively).


CONCLUSIONS
These results suggest that olanzapine/fluoxetine combination does not present a greater risk of treatment-emergent mania compared to olanzapine or placebo over 8 weeks of acute treatment for bipolar I depression. Due to the cyclical nature of bipolar disorder, patients taking olanzapine/fluoxetine combination for bipolar depression should still be monitored for signs or symptoms of emerging mania.
Keck
Paul E
PE
Psychopharmacology Research Program, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. paul.keck@ic.edu
Corya
Sara A
SA
Altshuler
Lori L
LL
Ketter
Terence A
TA
McElroy
Susan L
SL
Case
Michael
M
Briggs
Susan D
SD
Tohen
Mauricio
M
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D005473:Fluoxetine; D000077152:Olanzapine; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors