Anticonvulsant May Help Treat Cocaine Addiction

Megan Brooks

October 28, 2013

The anticonvulsant topiramate may help treat cocaine addiction, new research suggests.

In a randomized, placebo-controlled trial, topiramate was far more effective than placebo in improving abstinence. It also reduced cravings and improved global functioning.

"I think topiramate is really promising for cocaine dependence," first author Bankole A. Johnson, MD, of the Department of Psychiatry, University of Maryland in Baltimore, noted in an interview with Medscape Medical News.

"I can't advocate off-label use, but if it were my patient and they had cocaine dependence, I'd give it a try," Dr. Johnson said.

The findings were published online October 16 in JAMA Psychiatry.

Mounting Evidence

There is currently no US Food and Drug Administration–approved medication for cocaine dependence, yet researchers note that millions of Americans adults use the drug.

In an earlier study published in Addiction Biology, Dr. Johnson and colleagues found that topiramate pretreatment reduced cocaine-related craving.

"We actually brought cocaine-dependent adults into the laboratory, gave them topiramate or placebo, and then injected them with cocaine, and topiramate reduced their craving and preference to have another shot of cocaine, which was pretty powerful, in my view," said Dr. Johnson.

The current study was a 12-week, double-blind, randomized trial involving 142 cocaine-dependent adults. Half took placebo and half took topiramate in escalating doses from 50 mg/day to the target maintenance dose of 300 mg/day in weeks 6 to 12. All patients received weekly cognitive-behavioral therapy, which has been shown to help with cocaine abstinence.

The average number of days of self-reported cocaine use during the month prior to informed consent was similar in the topiramate and placebo groups (13.3 and 12.3 days, respectively).

In intent-to-treat analysis, topiramate was more effective than placebo at increasing the number of days per week in which patients did not use cocaine, which was the primary outcome. The reduction from baseline was 13.3% with topiramate vs 5.3% with placebo (P = .02).

Topiramate also increased the likelihood of urinary cocaine–free weeks by 16.6% vs 5.8% with placebo (odds ratio, 3.21; 95% confidence interval, 1.24 - 8.32; P =.02).

Compared with placebo, topiramate also significantly reduced the intensity and frequency of craving in the past 24 hours and improved observer-rated global functioning during the same period.

No serious adverse events were reported in the trial, but decreased weight, fatigue, headache, paresthesia, taste perversion, and diarrhea occurred more often with topiramate than placebo.

Difficulty with concentration was also reported more often with topiramate, but this was "generally transient and did not interfere with normal daily functioning," the researchers say. Slow dose escalation during several weeks appears to reduce the frequency and intensity of these cognitive difficulties, the investigators note.

Curbs Heavy Drinking Too

"Topiramate is really the first compound that has been shown to have an effect that you can replicate and that is robust for treatment of cocaine dependence," said Dr. Johnson. "It is also the first drug that you can demonstrate works in more than 1 addiction."

Dr. Bankole Johnson

In a prior study, Dr. Johnson and colleagues showed that topiramate helps curb heavy drinking among alcohol-dependent adults and has beneficial effect on the physical and psychosocial consequences of alcoholism dependence, as reported by Medscape Medical News.

Frances R. Levin, MD, professor of clinical psychiatry at Columbia University in New York City and director of the addiction psychiatry residency program at New York Presbyterian Hospital, has also seen the benefits of topiramate in cocaine addiction.

In a randomized study of 81 adults with cocaine dependence, her team found that almost twice as many of the participants who received mixed amphetamine salts and topiramate for 3 months achieved 3 consecutive weeks of abstinence as those who received matching placebo, as reported by Medscape Medical News.

This new study, coupled with prior ones, "does suggest that topiramate has some therapeutic utility and worth trying, albeit off-label, and is consistent with other investigators’ findings, albeit off-label," said Dr. Levin.

The study was supported by grants from the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and the Agency for Healthcare Research and Quality. Dr. Johnson reported serving as a consultant for Johnson & Johnson (Ortho-McNeil Janssen Scientific Affairs, LLC) from 2003 to 2008, Transcept Pharmaceuticals, Inc, from 2006 to 2009, Eli Lilly and Company from 2009 to 2010, and Organon from 2007 to 2010; he currently consults for D&A Pharma, ADial Pharmaceuticals, LLC (with which he also serves aschairman), and Psychological Education Publishing Company (PEPCo), LLC. The original article contains a complete list of author disclosures. Dr. Levin reports no relevant financial relationships.

JAMA Psychiatry. Published online October 16, 2013. Abstract

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