Long-term olanzapine therapy in the treatment of bipolar I disorder: an open-label continuation phase study.
BACKGROUND
Olanzapine has demonstrated efficacy in the treatment of acute mania in 2 double-blind, placebo-controlled trials. We describe the results of the open-label extension from one of these trials.


METHODS
In a 3-week, double-blind study of patients with DSM-IV bipolar I disorder, olanzapine was superior to placebo for the treatment of acute manic symptoms. Of the 139 patients who entered the double-blind phase of the 3-week study, 113 patients continued into the 49-week open-label extension. Efficacy measurements including the Young Mania Rating Scale (YMRS), the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Clinical Global Impressions scale-Bipolar Version, and the Positive and Negative Syndrome Scale and safety measurements including the Simpson-Angus scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale were completed throughout. The analysis considered all treatment results, starting with the first olanzapine dose. Adjunctive lithium and fluoxetine were allowed during the open-label extension.


RESULTS
The mean length of olanzapine treatment was 6.6 months, with a mean modal dose of 13.9 mg/day. A significant mean improvement in the YMRS total score, baseline to endpoint (-18.01, p < .001), was observed. During treatment, 88.3% of patients experienced a remission of manic symptoms (YMRS total score < or =12), and only 25.5% subsequently relapsed (YMRS total score > or = 15). Significant improvement in HAM-D-21 scores was observed (p < .001). Forty-one percent of patients were maintained on olanzapine monotherapy. The most common treatment-emergent adverse events reported were somnolence (46.0%), depression (38.9%), and weight gain (36.3%).


CONCLUSIONS
During up to 1 year of olanzapine therapy, either as monotherapy or in combination with lithium and/or fluoxetine, patients with bipolar disorder demonstrated significant improvement in mania and depression symptoms with a favorable safety profile. Further double-blind, controlled studies are needed to confirm these results.
Sanger
T M
TM
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Ind 46285, USA.
Grundy
S L
SL
Gibson
P J
PJ
Namjoshi
M A
MA
Greaney
M G
MG
Tohen
M F
MF
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003866:Depressive Disorder / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D012890:Sleep / Q000187:drug effects; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
D014150:Antipsychotic Agents; D010919:Placebos; D005473:Fluoxetine; D001569:Benzodiazepines; D010890:Pirenzepine; D008094:Lithium; D000077152:Olanzapine