Question. How many double blind studies have been done on the use of antiepileptics for rapid cyclers? If anxiety is a factor, what other drugs should be used with them?

Answer. There are now four main anticonvulsant (anti-epileptic) agents that are either established or being actively investigated as mood stabilizers: valproate (Depakote), carbamazepine (Tegretol), gabapentin (Neurontin) and lamotrigine (Lamictal). Another anticonvulsant, Topiramate (Topamax), is being investigated for this purpose.

Your question involves the conjunction of three factors: a double-blind condition, use of an anticonvulsant and rapid-cycling bipolar patients (i.e., those with four or more major mood swings per year). While I can’t give you a definitive answer as to the number of such studies, my review of the literature suggests that there are fewer than five that meet all three of your criteria. I refer you to papers by Denicoff et al (Journal of Clinical Psychiatry, 1997) and Bowden et al (Journal of the American Medical Association, March 23-30, 1994) for details.

In a recent review of lamotrigine and gabapentin, Dr. Nassir Ghaemi of Massachusetts General Hospital found only a small number of double-blind studies with these agents (International Drug Therapy Newsletter, April and May 1999). In many of the recent studies of lamotrigine and gabapentin, these agents have been used as adjuncts for most patients, rather than as the sole treatment, meaning that judgments about their efficacy must be put in this limited context.

For example, in three non-double blind studies, lamotrigine appeared useful in between 50-75% of rapidly cycling patients, but most of these patients were taking other mood stabilizers or medications. Regarding bipolar patients with concomitant “anxiety,” it is, of course, difficult to distinguish anxiety from agitation in manic patients. In either case, benzodiazepines such as lorazepam or clonazepam are frequently used.

Atypical antipsychotics like olanzapine are also finding a role as adjunctive agents in bipolar illness. Gabapentin appears to have anti-anxiety properties even in patients who are not bipolar, and thus would be a reasonable “add-on” for anxious bipolar patients.

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