Valproate and Lithium in Maintenance Therapy of Bipolar Affective Disorder
Among the so-called mood stabilizers, drugs commonly used in the therapy of bipolar affective disorder, are valproate and lithium. Canadian authors recently conducted a post hoc analysis of a study aimed at comparing their effectiveness in the maintenance treatment of bipolar I disorder.
Introduction
Bipolar affective disorder (BAD) is a serious mental illness with a prevalence of around 2%. According to symptoms, we distinguish between bipolar affective disorder type I and type II. Bipolar I disorder is characterized by fully developed manic episodes alternating with depressive phases. For bipolar II disorder, longer depressive episodes and hypomanic episodes are typical.
The therapy for bipolar disorder involves a combination of non-pharmacological and pharmacological treatments. The most commonly prescribed medications are lithium, anticonvulsants such as valproate or carbamazepine, and some atypical antipsychotics. For the acute manic and depressive phase, rapid symptom reduction and remission induction are important. Maintenance therapy aims to prevent mood swings into manic and depressive phases. The following study analysis focused on the two mentioned drugs: valproate and lithium.
Lithium and Valproate in BAD Therapy
Lithium is classified as a mood stabilizer and is the drug of choice for preventing mood instability and treating mania. Its efficacy has been proven in monotherapy for the depressive phase, long-term therapy for bipolar disorder, and reducing aggressive behavior in manic patients. Due to its narrow therapeutic window, regular monitoring of serum lithium levels is necessary.
Valproate is an anticonvulsant. Its main psychiatric indications are the treatment of acute manic episodes and, primarily, maintenance monotherapy of bipolar disorder. Compared to lithium, it has a faster onset of action and is the most frequently used mood stabilizer. Like lithium, its levels should be monitored. It has been shown that valproate can cause neural tube defects, so pregnant women should not use it.
The cited post hoc analysis was based on a study aimed at comparing the efficacy of valproate and lithium in mood stabilization during maintenance treatment of bipolar I disorder, either in monotherapy or in combination with an atypical antipsychotic.
Findings from the post hoc Analysis
The authors conducted a post hoc analysis of a randomized double-blind placebo-controlled study. The study lasted 52 weeks and included 159 patients who recently experienced a manic episode during BAD type I treatment and were already in remission. As part of maintenance therapy, patients took valproate or lithium in combination with atypical antipsychotics. Subsequently, the atypical antipsychotics were randomly discontinued at weeks 0, 24, or 52 of follow-up.
No significant differences in efficacy were observed in either manic or depressive episodes during monotherapy with valproate or lithium (hazard ratio [HR] 0.99; 95% confidence interval [CI] 0.66−1.48). Valproate therapy combined with an atypical antipsychotic for 24 weeks showed significantly better effects than valproate monotherapy in preventing both manic and depressive relapses (HR 0.46; 95% CI 0.22−0.97). When patients took lithium and discontinued the atypical antipsychotic at week 24 of the study, greater efficacy was demonstrated in preventing mania compared to lithium monotherapy, but not in preventing depression (HR 0.27; 95% CI 0.09−0.85).
Discussion and Conclusion
Valproate and lithium have significant roles in the treatment of bipolar disorder. The post hoc analysis did not show any substantial difference in their efficacy during the maintenance treatment of BAD type I, whether in monotherapy or in combination with an atypical antipsychotic. If such a difference exists, its non-detection could have been due to the small sample size and the overall study design. Studies with different designs would be appropriate to compare the effectiveness of lithium and valproate.
(vef)
Sources:
1. Kang M. G., Qian H., Keramatian K. et al. Lithium vs valproate in the maintenance treatment of bipolar I disorder: a post-hoc analysis of a randomized double-blind placebo-controlled trial. Aust N Z J Psychiatry 2020; 54 (3): 298−307, doi:10.1177/0004867419894067.
2. Dea L., Tsu L., Gutierrez M. et al. Management of bipolar disorder. US Pharmacist 2016; 41 (11): 34−37.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.