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June 25, 2016

Epilim approved for treatment and prevention of mania

Epilim prolonged release approved for the treatment and prevention of mania associated with bipolar disorders

Epilim Chrono Prolonged Release Tablets and Epilim Chronosphere prolonged-release granules (valproate) has recently been approved for the treatment and prevention of mania associated with bipolar disorders.
The approval follows a number of short term randomised controlled trials showing the efficacy of valproate in the treatment of acute mania. It is also supported by a recent longer term trial showing that Epilim’s antimanic efficacy can be maintained over time (1).
The efficacy of valproate in the treatment of acute mania has been evaluated in 3-week randomised controlled trials, both in monotherapy and in combination with antipsychotics. On the basis of the positive results of these 3-week studies, valproate is recommended for first-line treatment of acute mania, where it has similar efficacy to lithium. It was, however, also important to demonstrate that antimanic efficacy can be maintained.
The following study has been designed to compare the efficacy and tolerability of valproate and lithium over 12 weeks in the treatment of acute mania in patients with type I bipolar disorder.
Study Design
A total of 300 patients (18-75 years) with bipolar I disorder presenting with acute mania were enrolled in the study. Patients were required to have experienced at least one hypomanic/manic or one major depressive episode within the 5 years preceding the current acute episode. Enrollment criteria included:
• Acute mania according to the DSM IV TR criteria
• Total score on the Young Mania Rating Scale (YMRS; Young et al., 1978) of at least 18.
• Score of at least 3 for the YMRS items concerning elevated mood, increased motor activity energy, sleep and content (grandiosity).
• Score on the Clinical Global Impression for Bipolar Illness Severity Scale for bipolar disorder of at least 3.
Participants were randomised to open treatment with lithium (starting dose: 400mg/day) or valproate (starting dose: 20mg/kg/day) for 12 weeks. Valproate was provided as a sustained-release microsphere formulation.
The primary efficacy criterion was remission, defined by:
• YMRS score ≤12 at study end and
• Reduction of ≥2 on the CGI-BP severity scale.
Secondary efficacy criteria included the proportion of responders at 3 weeks and at
study end. Response was defined as a reduction of at least 50% of the YMRS score.
Similar remission and responder rates for Epilim vs. lithium
The remission rate at the end of the 3-month study in patients receiving lithium was 65.5% compared to 72.3% for patients receiving valproate (Fig. 1). The difference between the two groups was 6.78% and the non-inferiority of valproate with respect to lithium was demonstrated. The difference in remission rate between the two treatment groups was not statistically significant (p=0.081).
Responder rates at 3 weeks and at the end of the study were also similar between lithium and valproate treated patients (Fig. 1).
Adverse events were reported in 44% of patients in both groups. The most frequently reported treatment-related adverse events were nausea, tremor and weight gain. Tremor was more frequently reported (p=0.0001) in lithium-treated patients while fatigue was more frequent (p<0.035) in valproate-treated patients.
This study revealed that Epilim and lithium have comparable efficacy and tolerability in the treatment of acute mania over 12 weeks, thus supporting the new indication. Treatment with both lithium and valproate was associated with a high rate of remission of mania over a 12-week study, with treatment effects that were robust and consistent across all efficacy outcome measures.
Epilim Chrono Prolonged Release Tablets is available in Ireland in strengths 200mg, 300mg and 500 mg and Epilim Chronosphere prolonged-release granules is available in Ireland in strengths 100mg, 250mg, 500mg and 1000mg. Prescribing information for bipolar disorder are available section 3.4.
1- Charles Bowden et al. International Clinical Psychopharmacology 2008, 23:254–262
Full prescribing information and references available from sanofi-aventis Ireland Ltd. Telephone: (01) 4035600. MIMS Ireland Copyright®