NEW YORK (Reuters Health) – In methamphetamine-dependent adults, treatment with the anticonvulsant topiramate (Topamax; Ortho-McNeil Neurologics) does little to promote abstinence, but it seems to help those on the road to abstinence, according to a study accepted for publication in the journal Addiction.
Research has shown that topiramate attenuates downstream midbrain dopamine release, which might help with addiction by lessening the reinforcing and rewarding properties of the abused substance. In prior studies, topiramate has shown efficacy at facilitating abstinence from alcohol and cocaine.
In a 13-week trial, Dr. Bankole A. Johnson from the University of Virginia, Charlottesville, and colleagues tested the efficacy of oral topiramate in achieving abstinence in 140 methamphetamine-dependent adults.
They randomly assigned 71 to placebo and 69 to escalating doses of oral topiramate (50 mg/day to a target maintenance of 200 mg/day in weeks to 6 to 12. Medication was combined with standard brief behavioral compliance enhancement therapy.
The researchers report that topiramate was safe and well tolerated. In the intent-to-treat analysis, topiramate did not increase abstinence from methamphetamine (the primary outcome), but it did decrease methamphetamine use over time.
Topiramate recipients were significantly more likely than placebo recipients to achieve a 50% or 25% reduction in baseline level of methamphetamine use, “suggesting that even when topiramate treatment did not lead to abstinence, it was associated with a significant decrease in risk of harm from methamphetamine use,” the investigators say.
This finding was underscored by a decline in curbed observer-rated severity of methamphetamine dependence in topiramate recipients.
Topiramate reduced methamphetamine use in a small subgroup of adults who were abstinent at the trial’s outset (as determined by weekly median urine methamphetamine levels).
“Subjects with negative urine before randomization (n = 26) had significantly greater abstinence on topiramate versus placebo during study weeks 6-12,” the investigators report.
“With the caveat that these findings were observed in a subset of the total cohort, it is reasonable to propose that topiramate should be considered for relapse prevention rather than simply being targeted to decrease methamphetamine use in current users,” the investigators say.
Limitations of the study include a “relatively high” attrition rate after the first six weeks, similar to previous pharmacotherapy studies with methamphetamine, the authors say.
The fact that few subjects achieved the target topiramate dose of 200 mg/day is another limitation, one that could have reduced the ability to demonstrate a stronger therapeutic effect, the authors say.
Based on their findings, they think topiramate’s utility in preventing relapse in those who have ceased methamphetamine use should be explored further.
Dr. Johnson discloses having served as a consultant to Johnson & Johnson (Ortho-McNeil Janssen Scientific Affairs, LLC). A complete list of investigator disclosures can be found with the article.
SOURCE:
Topiramate for the treatment of methamphetamine addiction: a multi-center placebo-controlled trial
Addiction. 2011.
