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Published in: Trials 1/2019

Open Access 01-12-2019 | Affective Disorder | Research

A randomized controlled trial comparing lithium plus valproic acid versus lithium plus carbamazepine in young patients with type 1 bipolar disorder: the LICAVAL study

Authors: Giovani Missio, Doris Hupfeld Moreno, Frederico Navas Demetrio, Marcio Gerhardt Soeiro-de-Souza, Fernando dos Santos Fernandes, Vivian Boschesi Barros, Ricardo Alberto Moreno

Published in: Trials | Issue 1/2019

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Abstract

Background

Treatment of bipolar disorder (BD) usually requires drug combinations. Combinations of lithium plus valproic acid (Li/VPA) and lithium plus carbamazepine (Li/CBZ) are used in clinical practice but were not previously compared in a head-to-head trial.

Objective

The objective of this trial was to compare the efficacy and tolerability of Li/VPA versus Li/CBZ in treating type 1 BD in any phase of illness in young individuals.

Methods

LICAVAL was a randomized, unicenter, open-label, parallel-group trial that was conducted from January 2009 to December 2012 in a tertiary hospital in São Paulo, Brazil. Participants were between 18 and 35 years old and were followed up for 2 years. Our primary outcome was the number of participants achieving/maintaining response and remission during the acute and maintenance phases of BD treatment, respectively. Other outcomes assessed were symptom severity and adverse events throughout the study. In the analysis of the primary outcome, we compared groups by using a two-way repeated measures analysis of variance and estimated effect sizes by using Cohen’s d.

Results

Of our 64 participants, 36 were allocated to Li/VPA and 28 to Li/CBZ. Our sample was composed predominantly of females (66.6%) and the average age was 27.8 years. A total of 27 (45.0%) participants had depression, 17 (28.3%) had mania/hypomania, and 16 (26.7%) had a mixed state. We found no between-group differences in CGI-BP (Clinical Global Impression Scale modified for use in bipolar disorder) scores (P = 0.326) or in any other outcome. Side effects differed significantly between groups only in the first week of treatment (P = 0.021), and there were more side effects in the Li/VPA group. Also, the Li/VPA group gained weight (+2.1 kg) whereas the Li/CBZ group presented slight weight loss (−0.2 kg).

Conclusion

Our study suggests that Li/VPA and Li/CBZ have similar efficacy and tolerability in BD but that Li/CBZ might have metabolic advantages in the long term.

Trial registration

ClinicalTrials.gov identifier: NCT00976794. Registered on September 9, 2009.
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Metadata
Title
A randomized controlled trial comparing lithium plus valproic acid versus lithium plus carbamazepine in young patients with type 1 bipolar disorder: the LICAVAL study
Authors
Giovani Missio
Doris Hupfeld Moreno
Frederico Navas Demetrio
Marcio Gerhardt Soeiro-de-Souza
Fernando dos Santos Fernandes
Vivian Boschesi Barros
Ricardo Alberto Moreno
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Trials / Issue 1/2019
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-019-3655-2

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