Long-term efficacy of quetiapine in combination with lithium or divalproex on mixed symptoms in bipolar I disorder.
BACKGROUND
To evaluate quetiapine in patients with bipolar I disorder with mixed symptoms.


METHODS
Data from 2 studies (D1447C00126, D1447C00127) were pooled and mixed events analyzed separately. Patients received quetiapine (400-800mg/day) plus lithium/divalproex to achieve ≥12 weeks of clinical stability, followed by double-blind quetiapine (400-800mg/day) or placebo, plus lithium/divalproex, for up to 104 weeks. Primary endpoint was time to first mood event post-randomization.


RESULTS
The ITT population included 1326 patients, of whom 445 had a mixed episode at study entry, 219 received quetiapine plus lithium/divalproex, and 226 received placebo plus lithium/divalproex. Mood events were reported by fewer quetiapine-plus-lithium/divalproex than placebo-plus-lithium/divalproex-treated patients (21.0% vs 54.0%), and included mixed (6.4% vs 22.1%), pure manic (5.0% vs 13.3%), and pure depressed events (9.6% vs 18.6%). Hazard ratios (HR) for time to recurrence were longer for quetiapine plus lithium/divalproex than placebo plus lithium/divalproex for mixed (HR=0.23; 95% CI: 0.13-0.42; p<0.0001), pure manic (HR=0.30; 95% CI: 0.15-0.60; p=0.0007), and pure depressed events (HR=0.38; 95% CI: 0.22-0.64; p=0.0003). No new safety concerns were noted.


CONCLUSIONS
The post hoc nature of the analyses as patients were not randomized according to index symptom status.


CONCLUSIONS
In stable patients with bipolar I disorder, quetiapine plus lithium/divalproex significantly increased time to recurrence of mood events versus placebo in patients with mixed symptoms at study entry and time to occurrence of mixed-mood events in patients with any mood episode at study entry.
Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain. evieta@clinic.ub.es
Eduard
E
Vieta
Trisha
T
Suppes
Birgit
B
Ekholm
Mattias
M
Udd
Urban
U
Gustafsson
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage; D001714:Bipolar Disorder / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000008:administration & dosage*; D008297:Male; D011788:Quality of Life; D000069348:Quetiapine Fumarate; D012008:Recurrence; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage*; D015430:Weight Gain / Q000187:drug effects
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D016651:Lithium Carbonate; D000069348:Quetiapine Fumarate; D014635:Valproic Acid