Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126).
BACKGROUND
This study examined the efficacy and safety of quetiapine in combination with lithium or divalproex compared with placebo with lithium or divalproex in the prevention of recurrent mood events in bipolar I patients, most recent episode mania, depression, or mixed.


METHODS
Patients received open-label quetiapine (400-800 mg/day; flexible, divided doses) with lithium or divalproex (target serum concentrations 0.5-1.2 mEq/L and 50-125 microg/mL, respectively) for up to 36 weeks to achieve at least 12 weeks of clinical stability. Patients were subsequently randomized to double-blind treatment with quetiapine (400-800 mg/day) plus lithium/divalproex or placebo plus lithium/divalproex for up to 104 weeks. The primary endpoint was time to recurrence of any mood event.


RESULTS
Treatment with quetiapine in combination with lithium/divalproex significantly increased the time to recurrence of any mood event compared with placebo plus lithium/divalproex. The proportion of patients having a mood event was markedly lower in the quetiapine than in the placebo group (18.5% versus 49.0%). The hazard ratio for time to recurrence of a mood event was 0.28 (P<0.001), a mania event 0.30 (P<0.001), and a depression event 0.26 (P<0.001) corresponding to risk reductions of 72%, 70%, and 74%, respectively. During the randomization phase, the most common adverse events occurring in > or =5% in the quetiapine group were somnolence, nasopharyngitis, and headache. Insomnia was more common in the placebo group. During the randomization phase, there was an increase in weight of 0.5 kg in the quetiapine group and a reduction of 1.9 kg in the placebo group. The incidence and incidence density of a single emergent fasting blood glucose value> or =126 mg/dL was higher with quetiapine than with placebo (9.3% versus 4.1%; 17.6 versus 9.5 patients per 100 patient-years).


CONCLUSIONS
This was an enriched sample of patients with bipolar I disorder responding to treatment with quetiapine plus lithium/divalproex.


CONCLUSIONS
Maintenance treatment with quetiapine in combination with lithium/divalproex significantly increased time to recurrence of any event (mania, depression, or mixed) irrespective of the polarity of the index episode compared with placebo with lithium/divalproex. Long-term treatment with quetiapine was generally well-tolerated. Quetiapine with lithium/divalproex can provide an effective long-term treatment option for bipolar I disorder to prevent recurrences not only of mania but also depression.
Vieta
Eduard
E
Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBER-SAM, Barcelona, Spain. evieta@mclean.harvard.edu <evieta@mclean.harvard.edu>
Suppes
Trisha
T
Eggens
Ivan
I
Persson
Inger
I
Paulsson
Björn
B
Brecher
Martin
M
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology*; D003710:Demography; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D006261:Headache / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D007391:International Cooperation; D016651:Lithium Carbonate / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009304:Nasopharyngitis / Q000139:chemically induced / Q000453:epidemiology; D000069348:Quetiapine Fumarate; D012720:Severity of Illness Index; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced / Q000453:epidemiology; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D016651:Lithium Carbonate; D000069348:Quetiapine Fumarate; D014635:Valproic Acid