Asenapine for long-term treatment of bipolar disorder: a double-blind 40-week extension study.
BACKGROUND
Asenapine is approved in the United States for acute treatment of manic or mixed episodes of bipolar I disorder with or without psychotic features. We report the results of long-term treatment with asenapine in patients with bipolar I disorder.


METHODS
Patients completing either of two 3-week efficacy trials and a subsequent 9-week double-blind extension were eligible for this 40-week double-blind extension. Patients in the 3-week trials were randomized to flexible-dose asenapine (5 or 10mg BID), placebo, or olanzapine (5-20mg QD; included for assay sensitivity only). Patients entering the extension phase maintained their preestablished treatment; those originally randomized to placebo received flexible-dose asenapine (placebo/asenapine). Safety and tolerability endpoints included adverse events (AEs), extrapyramidal symptoms, laboratory values, and anthropometric measures. Efficacy, a secondary assessment, was measured as change in Young Mania Rating Scale (YMRS) total score from 3-week trial baseline to week 52 with asenapine or olanzapine; the placebo/asenapine group was assessed for safety only.


RESULTS
Incidence of treatment-emergent AEs was 71.9%, 86.1%, and 79.4% with placebo/asenapine, asenapine, and olanzapine, respectively. The most frequent treatment-emergent AEs were headache and somnolence with placebo/asenapine; insomnia, sedation, and depression with asenapine; and weight gain, somnolence, and sedation with olanzapine. Among observed cases, mean ± SD changes in YMRS total score at week 52 were -28.6 ± 8.1 and -28.2 ± 6.8 for asenapine and olanzapine, respectively.


CONCLUSIONS
The study did not have a long-term placebo group.


CONCLUSIONS
In this 52-week extension in patients with bipolar mania, asenapine was well tolerated and long-term maintenance of efficacy was supported.
McIntyre
Roger S
RS
Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada. roger.mcintyre@uhn.on.ca
Cohen
Miriam
M
Zhao
Jun
J
Alphs
Larry
L
Macek
Thomas A
TA
Panagides
John
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D003986:Dibenzocycloheptenes; D004311:Double-Blind Method; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011594:Psychometrics; D055815:Young Adult
D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D001569:Benzodiazepines; C522667:asenapine; D000077152:Olanzapine