Effect of comorbid anxiety on treatment response in bipolar depression.
BACKGROUND
This secondary analysis from a randomized double-blind study of acute bipolar depression compared olanzapine monotherapy, olanzapine-fluoxetine combination (OFC) and placebo in patients with or without comorbid anxiety.


METHODS
Patients with bipolar disorder and a current depressive episode received olanzapine (5-20 mg/day), OFC (6/25, 6/50, or 12/50 mg/day), or placebo in an 8-week trial. Two populations were defined: comorbid (Hamilton Anxiety Rating Scale, HAM-A > or =18) or non-comorbid (HAM-A <18) anxiety. Changes in Montgomery-Asberg Depression Rating Scale (MADRS) and HAM-A total scores, and rates of response (> or =50% decrease from baseline to endpoint) and remission (MADRS < or =12 or HAM-A < or =7) were analyzed.


RESULTS
Baseline MADRS and YMRS scores were significantly higher in patients with comorbid anxiety relative to those without. Patients without comorbid anxiety were more likely to achieve MADRS response and remission than those with comorbid anxiety (relative risk, RR: 1.21 and 1.29, respectively). Patients with comorbid anxiety had greater rates of response and remission with olanzapine and OFC relative to placebo (response RR:1.45 and 2.14; remission RR:1.96 and 2.32, respectively). Response and remission rates on the HAM-A scale were greater for OFC relative to placebo (RR: 2.00 and 3.20). Weight gain was greater for olanzapine (2.59+/-3.24 kg) and OFC (2.79+/-3.23 kg) relative to placebo, as were baseline to endpoint changes in cholesterol levels (6+/-31 and 10+/-67 mg/dL, respectively).


CONCLUSIONS
Comorbid anxiety symptoms in patients with bipolar depression have a negative impact on treatment outcome. Olanzapine and, to a greater extent, olanzapine-fluoxetine combination were effective in reducing both depressive and anxiety symptoms in these patients. The significantly greater changes in weight, glucose and cholesterol parameters observed in the olanzapine and olanzapine-fluoxetine combination groups should be entered into the risk-benefit assessment in determining appropriate treatment options for these patients.
Tohen
Mauricio
M
Lilly Research Laboratories, Indianapolis, IN 46285, United States. m.tohen@lilly.com
Calabrese
Joseph
J
Vieta
Eduard
E
Bowden
Charles
C
Gonzalez-Pinto
Ana
A
Lin
Daniel
D
Xu
Wen
W
Corya
Sara
S
D000208:Acute Disease; D000328:Adult; D017668:Age of Onset; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000453:epidemiology*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D015897:Comorbidity; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine; D012074:Remission Induction; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine