Anticonvulsant Zonisamide (Zonegran) May Treat Alcohol Abuse

April 29, 2010 · Posted in Potential Treatments 

Albert Arias and collaborators from the University of Connecticut Health Center presented a study of zonisamide in which the drug provided significant benefits over placebo in patients with primary alcoholism (i.e., not with comorbid bipolar illness).  Treatments began at 100 mg/day and increased to a maximum of 500 mg/day.

EDITOR’S NOTE:  If replicated, this study would place zonisamide in a category with topiramate (Topamax), which has also been shown to decrease alcohol intake and craving. Both drugs also share the ability to cause minor weight loss as a potentially positive side effect, and both drugs have also proven effective in double-blind studies in the treatment of bulimia.

However, four double-blind, placebo-controlled studies found that topiramate did not have acute antimanic efficacy. Zonisamide has not been studied in a systematic fashion, but open studies suggest its potential utility in mania and, to a lesser degree, in depression.

Since zonisamide may have positive effects on mood in patients with bipolar disorder, and there is now placebo-controlled documentation of its efficacy in primary alcohol abuse disorders, its ultimate potential utility in patients with bipolar disorder and comorbid alcoholism deserves consideration.

A variety of approaches are now available to those with alcohol-related problems. These include several that are FDA-approved for those with primary alcoholism, including the opiate antagonist naltrexone, the glutamate-active agent acamprosate, and disulfuram (Antabuse) which makes patients sick if they revert to alcohol use.   Zonisamide and topiramate are two drugs with anticonvulsant properties that now may also be of assistance in alcohol avoidance.

Researchers Litten and Falk have examined the time course of the emergence of anti-alcohol effects from naltrexone and topiramate seen in previous studies.  They found that the drugs took one and two months, respectively, to achieve their maximum effects in decreasing the number of days of heavy drinking. The researchers suggest that this long delay be taken into consideration in the design of subsequent clinical trials, but the delayed onset of effect also has implications for clinical therapeutics. Those who are attempting to reduce days of heavy drinking with either agent should be persistent while waiting for positive effects to appear.

There are also other options for treating comorbid bipolar disorder and alcoholism.  The anticonvulsant valproate, which, in contrast to topiramate and zonisamide, is effective and FDA-approved for the treatment of mania, has also been reported to have positive effects for alcohol avoidance in bipolar patients with comorbid problems with alcoholism. The anticonvulsant carbamazepine is widely used in Scandinavian countries instead of benzodiazepines for the acute management of alcohol withdrawal and for longer-term treatment of alcohol-related dysphoria and associated mood disturbances. Carbamazepine and valproate may have important roles to play in patients who have comorbid anxiety disorders, which are known to be highly associated with increased risk for alcohol abuse. These agents can be utilized readily to treat anxiety syndromes and related alcohol withdrawal symptomatology without the risks of using benzodiazepines with their potential for abuse.

Because all of these potential approaches to alcohol-related problems in patients with bipolar disorder are considered off-label, and even those that are FDA-approved for primary alcoholism have not been systematically studied in patients with bipolar illness, careful discussion and consultation between patient and physician is absolutely necessary before any of these types of approaches to alcohol abuse in the context of bipolar disorder are considered.


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