December 29, 2015
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Lamotrigine, quetiapine combination improves outcomes in bipolar disorder

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Results from a double-blind, randomized, placebo-controlled, parallel group, 2x2 factorial trial indicated adding lamotrigine to quetiapine treatment improved outcomes among individuals with bipolar disorder I or II.

“Lamotrigine is widely used as an antiepileptic. It is an inhibitor of voltage-sensitive sodium channels, and is thought to work by reducing presynaptic release of glutamate, although its mechanism of action in bipolar disorder remains unclear,” John R Geddes, MD, FRCPsych, of the University of Oxford, Warneford Hospital, United Kingdom, and colleagues wrote. “Lamotrigine is now licensed in the USA and the European Union for the prevention of relapse in patients with bipolar type 1 disorder who have predominantly depressive episodes. There has been considerable uncertainly, however, around the efficacy of lamotrigine monotherapy in the acute phase of bipolar depression.”

Researchers randomly assigned 202 individuals with bipolar disorder I or II who required new treatment for a depressive episode to lamotrigine or placebo and to folic acid or placebo. Prior to randomization, study participants, aged 16 years or older, had 7 to 14 days run-in on quetiapine.

Quick Inventory of Depressive Symptomatology-self report version 16 (QIDS-SR16) total scores had a mean difference of –1.73 (95% CI, –3.57 to 0.11; P = .066) at 12 weeks and –2.69 (95% CI, –4.89 to –0.49; P < .017) at 52 weeks for individuals who received lamotrigine vs. placebo.

Folic acid was not superior to placebo, according to researchers.

However, folic acid reduced the effectiveness of lamotrigine at 12 weeks (P = .028).

The mean difference in QIDS-SR16 scores was –4.14 (95% CI, –6.9 to – 1.37; P = .004) for individuals receiving lamotrigine without folic acid, compared with 0.12 (95% CI, –2.58 to 2.82) among those receiving lamotrigine and folic acid.

“CEQUEL confirms the efficacy, in the absence of folic acid, of adding lamotrigine to quetiapine in bipolar depression and that the benefits persist for 52 weeks,” Geddes and colleagues wrote. “These findings complement another independent trial, which showed clinical benefit for lamotrigine combination therapy, although in that case in combination with lithium. Together with the pooled data of lamotrigine vs. placebo, it seems that lamotrigine is an effective treatment in bipolar depression.” – by Amanda Oldt

Disclosure: Geddes reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.