Combining lamotrigine with quetiapine improves the treatment of depressive symptoms in patients with bipolar disorder, with the benefits maintained for at least a year, show findings from the CEQUEL trial.
Scores on the Quick Inventory of Depressive Symptomatology–self report version 16 (QIDS-SR16) at 12 weeks were, on average, 1.73 points lower among 101 moderately depressed bipolar patients randomly assigned to receive lamotrigine (25 mg/day titrated to 200 mg/day) in addition to quetiapine, compared with 101 assigned to receive add-on placebo.
By 52 weeks, the difference was significant at an average of 2.69 points lower for those taking add-on lamotrigine, after taking into account age, bipolar disorder type and dose of quetiapine (< or ≥300 mg/day), the researchers led by John Geddes (University of Oxford, UK) report in The Lancet Psychiatry.
They also found that significantly more patients taking lamotrigine plus quetiapine were in remission at 12 weeks (31 vs 16%) and 52 weeks (36 vs 13%), with relative risks of 2.11 and 3.73, respectively.
Discussing the findings in a related comment, Gin Malhi (University of Sydney, New South Wales, Australia) says: “[T]he investigators skillfully take advantage of the synergy between quetiapine and lamotrigine that arises from their differing, but complementary, mechanisms of action and the separate timescales over which they exert their effects.”
He explains that quetiapine is often given in the short term to ameliorate acute symptoms, whereas lamotrigine is more effective over the longer term. The drug is therefore able to “achieve a therapeutic level and exert its actions under the initial cover of the antipsychotic, which can then be gradually tapered and withdrawn”, he writes.