November 15, 2004
UPTON, NY - A second, small-scale clinical trial of a proposed addiction treatment originally investigated at the U.S. Department of Energy's Brookhaven National Laboratory has produced favorable results in the treatment of long-term addiction to methamphetamine and/or cocaine, with no visual side effects in any of the 30 patients enrolled. This research on vigabatrin (a.k.a. gamma vinyl GABA, or GVG) was conducted in collaboration with doctors from the New York University (NYU) School of Medicine and the Nathan Kline Institute for Psychiatric Research at a national addiction treatment center in Mexicali, Mexico. The results are published in the February 2005 issue of Synapse, now available online.
"We now have additional clinical data to back up our belief that GVG can be used safely and effectively to treat people suffering from drug addiction," said Brookhaven neuroanatomist Stephen Dewey. Dewey and Jonathan Brodie, a professor of psychiatry at NYU School of Medicine and this study's lead author, have conducted extensive brain-imaging and behavioral studies on animals at Brookhaven Lab showing that GVG attenuates and in some cases blocks neurological and behavioral changes associated with drug addiction. Last fall, they published results from the first small-scale human clinical trial of GVG for this indication, showing it to be effective in treating cocaine addiction.
"The fact that this drug appears to be effective in treating addiction to both cocaine and methamphetamine is particularly promising, given that methamphetamine abuse is one of the fastest growing drug problems in this country," Brodie said.
These results, especially given the absence of visual side effects in all patients, bring the scientists closer to seeing GVG tested in a larger, placebo-controlled clinical trial in this country.
GVG is approved for the treatment of epilepsy in many countries, including Mexico, but it is not approved for any indication in the U.S., in part because some epilepsy patients who have taken cumulative doses in excess of 1500 grams have experienced a reduction in their field of vision. The current study was designed to look for such visual side effects while testing the efficacy of a relatively low GVG dose.
In response to word-of-mouth and newspaper-ad recruitment, 30 patients enrolled in the study. All had abused methamphetamine and/or cocaine daily for a mean duration of 12 years. The experimental design was "open-label," that is, the subjects knew they were getting GVG, an experimental treatment for drug addiction. During the first two weeks, they were given increasing doses to a maximum of three grams per day, and then maintained on that dose for 28 days before tapering back to zero over the final three weeks.
They were treated as outpatients, returning each day to their normal home environments, subject to all the environmental "triggers" for their addictive behavior. Twice weekly they gave urine samples, which were tested for cocaine, methamphetamine, marijuana, heroin, and alcohol. Visual tests were performed on all 30 subjects prior to, during, and after completion of the trial.
Of the 30 volunteers, 11 dropped out in the first four weeks. One subject completed eight weeks and 18 stayed in the study for the nine-week duration. Of those 18, 16 were methamphetamine- and cocaine-free for more than four consecutive weeks while two continued using but in reduced amounts. 12 of the 16 remained free of methamphetamine and cocaine through the end of the study. No subject, whether they completed the trial or not, developed defects in visual fields or acuity.
"Due to the open-label nature of this study and the lack of a control group, we cannot conclude that these subjects' ability to abstain from drug use was a direct result of being given GVG. However, in a group of heavy users where none had stayed 'clean' for more than several consecutive days in the past year, it is remarkable that 16 of 30 avoided using these highly addictive drugs for approximately four consecutive weeks while on GVG," Dewey said.
"Of course, the conclusive demonstration of treatment efficacy can only be provided by an appropriately blinded randomized study, where some patients are given GVG and others a placebo, and neither the researchers nor the subjects know which is which until after the results are analyzed," said Brodie.
With the lack of visual side effects observed for the doses used in this study - a factor that has been viewed as an impediment to getting GVG approved in the U.S. - the scientists hope to see such a large-scale study conducted soon.
"We are unaware of any pharmacologic strategy that has been useful in treating methamphetamine dependence, making these findings with GVG unique both in terms of safety and efficacy," Brodie said.
This research was funded by the Biochemical Psychiatry Fund at the NYU School of Medicine; Catalyst Pharmaceutical Partners (CPP*) of Coral Gables, Florida; the National Institute on Drug Abuse; and the Office of Biological and Environmental Research within the U.S. Department of Energy's Office of Science.
*In October 2002, CPP received an exclusive worldwide license from Brookhaven Science Associates, operator of Brookhaven Lab, for the use of GVG for its application in treating drug addiction.
2004-244 | Media & Communications Office