Analysis Shows Lamotrigine Effective Treating Acute Bipolar Depression


Lamotrigine is currently being used as a maintenance therapy for bipolar disorder.

New research suggests lamotrigine could be a viable option in treating acute bipolar depression.

A team, led by Evyn M. Peters, Department of Psychiatry, University of Saskatchewan, analyzed the efficacy of lamotrigine compared to placebo for the treatment of acute bipolar depression and determined if certain depression scale items were more responsive to lamotrigine treatment.

While lamotrigine has commonly been used to treat bipolar depression, there is not consistent evidence showing the efficacy of the medication.

Inconsistent Previous Lamotrigine Research

In the study, the researchers conducted an item-level analysis of pooled data from 5 randomized placebo-controlled trials testing the medication in 1072 patients with acute bipolar depression. Each patient was treated for 7-10 weeks.

The target dose of lamotrigine is 200 mg per day, with higher doses sometimes required in clinical practice.

In 4 of the 5 trials, patients were treated with 200 mg per day as the maximum dose.

The researchers explained why they thought previous trials yielded inconsistent results.

“Suboptimal dosing could explain the negative results from the monotherapy trials,” the authors wrote. “Another possible explanation for the inconsistent findings is that lamotrigine may be more effective for specific depressive symptoms that were not deliberately assessed in the original trials.”

The trials, while inconsistent, led to the approval of the treatment as a maintenance therapy in bipolar disorder, but not as an acute depression treatment.

The Study

The researchers measured depressive symptoms with the Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale.

“Relying on total depression scale sum scores over targeted assessments of core depressive symptoms may have impeded signal detection in the original trials,” the authors wrote.

The team also compared change scores on individual scale items between the different treatment groups.

The study resulted in statistically significant effects on items assessing depressed mood/sadness, lack of interest/anhedonia, pessimism/guilt, and anergia/fatigue on both scales.

However, they found marked variation in the baseline symptom prevalence, as well as items with higher scores at baseline generally had larger and statistically significant treatment effects.

“The results suggested a significant treatment effect on core symptoms of depression,” the authors wrote. “A floor effect appeared to limit the sensitivity of other scale items. Given the exploratory nature of the analysis, firm conclusions cannot be drawn, although the results were consistent with past research.”


However, the researchers said the study should be duplicated in order to confirm the hypothesis.

“Given the exploratory nature of the analysis, the results need to be considered hypothesis-generating until replicated with additional data,” the authors wrote. “Furthermore, the results may not generalize to broader clinical populations, and only clinician-rated symptom scales were used to measure efficacy.”

The researchers also did not test for interactions with other variables including age and sex. Finally, the use of single items to assess symptoms is another limitation, although it does permit comparison with a significant number of industry-sponsored trials.

The study, “Lamotrigine for acute bipolar depression: An exploratory item-level analysis,” was published online in Brain and Behavior.

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