Asenapine in the treatment of acute mania in bipolar I disorder: a randomized, double-blind, placebo-controlled trial.
BACKGROUND
Asenapine is indicated in adults for acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. This randomized, double-blind, placebo-controlled trial assessed the efficacy, safety, and tolerability of asenapine in bipolar I disorder.


METHODS
Adults experiencing manic or mixed episodes were randomized to 3 weeks of flexible-dose treatment with sublingual asenapine (day 1: 10mg BID, 5 or 10mg BID thereafter; n=185), placebo (n=98), or oral olanzapine (day 1: 15 mg QD, 5-20mg QD thereafter; n=205). Primary efficacy, YMRS total score change from baseline to day 21, was assessed using ANCOVA with last observation carried forward.


RESULTS
Mean daily doses were 18.4 mg asenapine and 15.9mg olanzapine. Least squares mean changes in YMRS total score on day 21 were significantly greater with asenapine than placebo (-11.5 vs -7.8; P<0.007), with advantage seen as early as day 2 (-3.2 vs -1.7; P=0.022). Changes with olanzapine on days 2 and 21 also exceeded placebo (both P<0.0001). YMRS response and remission rates with olanzapine, but not asenapine, exceeded those of placebo. Incidence of EPS-related adverse events was 10.3%, 3.1%, and 6.8% with asenapine, placebo, and olanzapine, respectively; incidence of clinically significant weight gain (7.2%; 1.2%; 19.0%). Mean weight change (baseline to endpoint) was 0.9, 0.1, and 2.6 kg with asenapine, placebo, and olanzapine, respectively.


CONCLUSIONS
As this short-term study was designed for comparisons with placebo, any comparisons between asenapine and olanzapine should be interpreted cautiously.


CONCLUSIONS
Asenapine was superior to placebo in reducing YMRS total score and was well tolerated.
McIntyre
Roger S
RS
University of Toronto, Toronto, ON, Canada M5T 2S8. roger.mcintyre@uhn.on.ca
Cohen
Miriam
M
Zhao
Jun
J
Alphs
Larry
L
Macek
Thomas A
TA
Panagides
John
J
D000208:Acute Disease; D000286:Administration, Sublingual; 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 / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003986:Dibenzocycloheptenes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; 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