Potential of Levetiracetam in
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Levetiracetam is a newer antiepileptic agent that was first approved by the US FDA in 1999 as an adjunctive therapy for the treatment of refractory partial epilepsy in adults. Since then, it has been approved for a wider patient population, i.e. as adjunctive therapy for partial seizures in patients >4 years of age (worldwide) and as first-line monotherapy for partial seizures in patients >16 years of age (in Europe); and as adjunctive therapy for juvenile myoclonic seizures (in Europe and the US). It has a favourable pharmacokinetic profile and appears to act at a specific site in the CNS. Pharmacodynamic evidence indicates that levetiracetam indirectly facilitates GABAergic function, and an increasing body of evidence suggests an important role for GABA in the pathophysiology of mood disorders. Preclinical studies using animal models of depression, anxiety and mania provide evidence for levetiracetam as a mood stabiliser. Preliminary clinical evidence from case reports and open-label pilot studies indicates that the drug, both as add-on therapy and as monotherapy, has efficacy in a wide range of bipolar spectrum disorders. Most recently, a 31% remission rate was reported in patients with bipolar disorder who were in the depressed phase at baseline and who received levetiracetam as add-on therapy for 8 weeks in an open-label trial. While these results are encouraging, placebo-controlled data are needed to further clarify the role of levetiracetam in the treatment of mood disorders.
KeywordsBipolar Disorder Olanzapine Mood Disorder Levetiracetam Partial Seizure
The authors would like to thank the Stanley Foundation for funding the first placebo-controlled clinical trial of levetiracetam in bipolar depression, which is being conducted at the Department of Psychiatry, Yale School of Medicine through the Clinical Neuroscience Research Unit at the Connecticut Mental Health Center, New Haven, Connecticut, USA.
Dr Bhagwagar is the primary investigator on a double-blind, placebo-controlled trial of levetiracetam as an adjunctive therapy in bipolar depression, funded by the Stanley Medical Research Institute (SMRI 05T-681). This study has been running since October 2005.
Dr Bhagwagar is on the speakers panel for AstraZeneca and Bristol Myers Squibb and has served on advisory boards for Janssen Cilag in the US, as well as Eli Lilly, GlaxoSmithKline and Bristol Myers Squibb in the UK. Dr Muralidharan has no conflicts of interest that are directly relevant to the contents of this review.
No sources of funding were used to assist in the preparation of this manuscript.
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