What is the role of Anticonvulsant Mood Stabilizers in the treatment of bipolar disorder?
Valproate (Depakote®) was approved in the United States in 1995 for the treatment of manic episodes associated with bipolar disorder. It is believed that valproate exerts its effect through the inhibition of sodium and/or calcium channels, thereby boosting GABA function and reducing glutamate function. This medication may increase GABA levels and decrease glutamate levels. It has been found to be effective in patients who are unresponsive to lithium. Valproate appears to be more effective than lithium in the treatment of people with mixed or dysphoric mania, rapid-cycling bipolar disorder, or mania with mild depression.
Valproate is associated with significant side effects, although its side-effect profile is more favorable than that of lithium. It may cause mild liver inflammation and may affect the production of platelets; as a result, periodic blood monitoring is required. Rare but potentially serious side effects include hepatic failure and life-threatening pancreatitis.
Other Anticonvulsants:
Carbamazepine (Tegretol®, Carbatrol®) appears to have a profile similar to valproate. It is not approved for use in bipolar disorder, but is used as a mood stabilizer. This medication may act by enhancing GABA function through actions on sodium and/or potassium channels. Carbamazepine is effective in both euphoric and mixed manic states. Carbamazepine is associated with aplastic anemia and agranulocytosis (black box warnings). As with valproate, treatment with carbamazepine is associated with sedation and gastrointestinal side effects and requires periodic blood testing. When utilized with other medications, the potential for significant drug interactions exists due to carbamazepine’s induction of liver enzymes.
At this time, lamotrigine (e.g., Lamictal®, Glaxo Wellcome) is not indicated for bipolar disorder, but it has been used as a mood stabilizer. It is believed that lamotrigine inhibits glutamate release through the inhibition of sodium channels. Lamotrigine has the most data to support its possible use in abating the depressive phase of bipolar disorder. Lamotrigine is associated with a rare but serious rash as side effect (a black box warning). Other side effects include dizziness, headaches, and difficulties with vision.
Gabapentin (e.g., Neurontin®, Parke-Davis) is being evaluated for use in bipolar disorder. This medication may increase GABA levels and decrease glutamate levels. Gabapentin appears to be very well tolerated, and it does not appear to interact with other psychotropic medications. Gabapentin may be effective as an adjunctive agent; however, studies to date have failed to show efficacy in bipolar disorder. Side effects include somnolence, dizziness, and fatigue.
Topiramate (Topamax®) is another anticonvulsant that has been investigated for the treatment of bipolar disorder, especially acute mania. Its mechanism of action appears to be to increase GABA levels and decrease glutamate levels. Topiramate is gaining more use in bipolar patients due to its potential to cause weight loss. It is increasingly used as an adjunct to improve efficacy and to reduce weight gain induced by other agents used to treat bipolar disorder.
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