A randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder.
OBJECTIVE
To evaluate the antimanic efficacy and safety of paliperidone extended-release (ER) tablets in patients with bipolar I disorder.


METHODS
This study included a 3-week, double-blind, acute treatment phase (paliperidone ER versus placebo, with quetiapine as control), and a 9-week, double-blind, maintenance phase (paliperidone ER versus quetiapine). Patients [n = 493; Young Mania Rating Scale (YMRS) score >or= 20] were randomized (2:2:1) to flexibly dosed paliperidone ER (3-12 mg/day), quetiapine (400-800 mg/day), or placebo for the acute treatment phase. During the maintenance phase, patients assigned to placebo were switched to paliperidone ER but not included in analysis of efficacy.


RESULTS
Paliperidone ER was superior to placebo at the 3-week endpoint {primary outcome; least-squares mean difference in change from baseline in YMRS scores [95% confidence interval (CI)]: -5.5 (-7.57; -3.35); p < 0.001} and noninferior to quetiapine at the 12-week endpoint [least-squares mean difference (95% CI): 1.7 (-0.47; 3.96)]. The median mode dose during the 12-week treatment period was 9 mg for paliperidone ER and 600 mg for quetiapine. The most common (>or= 10%) treatment-emergent adverse events during the 12-week period were: headache (16%), somnolence (10%), and akathisia (10%) for paliperidone ER; somnolence (21%), sedation and dry mouth (17% each), headache (14%), and dizziness (13%) for quetiapine. Body weight increase >or= 7% from baseline to 12-week endpoint was 8% with paliperidone ER and 17% with quetiapine. A higher percentage of paliperidone ER (13.9%) versus quetiapine patients (7.5%) 'switched to depression' at the12-week endpoint.


CONCLUSIONS
Paliperidone ER (3-12 mg/day) was efficacious and tolerable in the treatment of acute mania.
Vieta
Eduard
E
Institute of Neuroscience, University of Barcelona Hospital Clinic, IDIBAPS, CIBERSAM, Barcelona, Spain.
Nuamah
Isaac F
IF
Lim
Pilar
P
Yuen
Eric C
EC
Palumbo
Joseph M
JM
Hough
David W
DW
Berwaerts
Joris
J
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000145:classification / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000627:therapeutic use; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000627:therapeutic use*; D000069348:Quetiapine Fumarate; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D007555:Isoxazoles; D011743:Pyrimidines; D000069348:Quetiapine Fumarate; D000068882:Paliperidone Palmitate