Abstract

Valproate is an effective antimanic agent and is recommended as a first-line medication in the treatment of acute mania. Current evidence based guidelines recommend that valproate should be given as a loading dose as it produces a rapid antimanic and antipsychotic response with minimal side-effects. However, no clear guidelines are available on the appropriate dosing or serum levels of valproate in the continuation or maintenance phase of bipolar disorder. We present 4 clinical cases to hypothesize that the higher doses of valproate, such as those used in the treatment of acute mania, may cause a depressive switch. So consideration should be given to reducing the dose of valproate if a patient develops depressive symptoms following recovery from the manic episode, as a therapeutic strategy. The cases also indicate that relatively lower doses and serum levels of valproate are effective in the maintenance phase compared to those needed in the acute manic phase of bipolar disorder. This is the first set of case series that questions the depressogenic potential of valproate in patients remitting from an acute manic episode. It highlights that different doses and serum levels of valproate may be therapeutic in different phases of bipolar disorder.

Highlights

  • Bipolar disorder is a severe mental illness characterized by recurrent episodes of mania and depression and is associated with high morbidity and mortality

  • We present 4 cases to hypothesize that (a) higher doses of valproate, such as those used in acute mania, may induce a depressive switch following remission from acute mania and (b) relatively lower doses and serum levels of valproate are needed to be effective in the maintenance phase as compared to the manic phase of bipolar disorder (BPD)

  • We observe from all of the four cases that even though the dose of valproate was reduced in the maintenance phase of BPD, there was no recurrence of mania in the threeyear follow-up period, in spite of adding a low dose of antidepressant in Case 1 for a significant period of time

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Summary

Introduction

Bipolar disorder is a severe mental illness characterized by recurrent episodes of mania and depression and is associated with high morbidity and mortality. Valproate is an anticonvulsant that is commonly used in the treatment of bipolar disorder (BPD). The efficacy of valproate has been found to be comparable to lithium in the maintenance phase of BPD based on results from a few randomized controlled trials [7,8,9,10]. The evidence available on either the dosing range or target serum levels of valproate in the continuation or maintenance phase of BPD is poor [16]. We present 4 cases to hypothesize that (a) higher doses of valproate, such as those used in acute mania, may induce a depressive switch following remission from acute mania and (b) relatively lower doses and serum levels of valproate are needed to be effective in the maintenance phase as compared to the manic phase of BPD

Case 1
Case 2
Case 3
Case 4
Discussion
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Conflict of Interests
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