Depakine Chrono versus Other Valproates in the Treatment of Bipolar Disorder

Introduction

Treatment of bipolar disorder (BD) is challenging due to its recurrent, episodic, and heterogeneous nature. Main goals include the treatment of acute depression, manic episodes, and prevention of depression or mania relapses.

Sodium valproate is an antiepileptic drug commonly used in the acute and chronic management of BD – it is effective both in treating manic episodes and in preventing relapses and is considered a drug of choice along with mood stabilizers and antipsychotics.

The cited study examined the use of the valproate-based drug Depakine Chrono in treating BD compared to other forms of valproate.

Methods, Course, and Study Objectives

This was an open, non-randomized, retrospective study conducted from July 2007 to November 2009. It included men and women (n = 1670) diagnosed with BD according to DSM-IV, initially treated with another form of valproate and then switched to Depakine Chrono for at least 3 months.

The primary objective of the study was to assess the reasons for switching therapy to Depakine Chrono and evaluate the results of this changed therapy after 3 months. The secondary objective was to evaluate the prescribed doses of the drug and the associated additional medication in practice.

In terms of diagnosis, patients presented with BD type I (alternating depressive and fully manic episodes), type II (recurrent depressive and only hypomanic episodes), cyclothymia, and unspecified BD (bipolar disorder not otherwise specified). The mood of patients was assessed when switching therapy to Depakine Chrono from another mood stabilizer. The largest percentage of patients had a depressive mood.

Results

The main reasons for switching therapy included low compliance, side effects, and insufficient efficacy. More than 40% of patients switched therapy for all these reasons combined. 20% switched therapy due to efficacy alone, 7.7% due to compliance, and 6.4% due to side effects.

The dosing of Depakine Chrono varied according to the patient's condition at the time of therapy change, ranging from 150 mg/day to 2000 mg/day. Lower doses were prescribed to patients with cyclothymia and BD II, while higher doses were used for treating BD I. The average dose of the drug decreased from 1042.45 mg to 1032.86 mg over the 3-month therapy period, while the number of doses per day remained almost unchanged.

The study also analyzed the relationships between Depakine Chrono and other antipsychotics (typical and atypical), antidepressants, anxiolytics, hypnotics, or other mood stabilizers. The most common combinations included olanzapine (n = 316), quetiapine (n = 199), amisulpride (n = 199), risperidone (n = 59), sertraline (n = 39), and escitalopram (n = 35).

After 3 months of using Depakine Chrono, the majority of patients achieved significant or mild improvement in the aspects for which they switched therapy (efficacy 80.4%, compliance 64.5%, side effects 47.2%).

Conclusion

The main reasons for switching therapy from other valproates to Depakine Chrono in bipolar disorder are higher efficacy, better compliance, and fewer side effects during treatment. After 3 months of this therapy, improvement in the mentioned aspects was high to moderate, likely leading to a reduction in the average daily dose of this medication. However, since this study was uncontrolled, non-randomized, retrospective, and lacked scales evaluating the effect of Depakine Chrono, its results are limited.

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Source: Ladea M., Sinca M., Barbu C., Bran, M. Clinical and therapeutic aspects of bipolar disorder: the switch to Depakine Chrono^® from other valproate treatments – retrospective data collection. Farmacia 2015; 6: 446–452.