Cocaine Addicts Benefit From Treatment Combination

Combining bupropion with behavioral therapy that reinforces a drug-free lifestyle may significantly reduce cocaine use in those in a methadone-maintenance program, according to Yale University researchers.

The combination of treatments worked better than either alone, according to findings published in the February Archives of General Psychiatry.

Researchers recruited 106 people who met DSM criteria for opiate and cocaine dependence through ads in a New Haven, Conn., community paper and assessed them from September 2001 to November 2003.

The article noted that combined opioid and cocaine use is not uncommon and that some studies have even shown that cocaine use increases in some people who begin receiving methadone for the treatment of opiate addiction.

Study subjects were randomized to receive one of four treatments for 25 weeks. A nurse administered methadone to each of the participants for the duration of the study. An initial dose of 30 mg was increased to a target dose of 60 mg by the end of the first week of the study.

The first group received “contingency management” and bupropion, and the second received contingency management and placebo.

Those randomized to contingency management received vouchers for submitting cocaine- and opiate-free urine samples three times a week. For example, the vouchers could be exchanged for a gift card to Wal-Mart and clothes or be used toward a down payment on a car or a rent payment.

Each time subjects submitted a clean urine sample, they received a $3 voucher. This amount increased by $1 for each subsequent clean urine sample to a maximum of $15 per sample. Neither of the latter two groups received the contingency management.

In addition, those in the contingency management groups also received vouchers for completing steps that were meant to help them remain drug free, such as attending meetings of 12-step programs or working toward the completion of a General Educational Development equivalency exam.

The other subjects were randomized to either the third or fourth group. The former received vouchers with an increasing dollar amount for each urine sample submitted, no matter what the results, plus a placebo pill, while those in the latter group received vouchers under the same conditions, along with bupropion.

The two groups assigned to receive bupropion took an initial dose of 75 mg a day, with the dose increased to the target dose of 300 mg a day by the end of the second week.

James Poling, Ph.D., the study's lead investigator, found that in the group assigned to contingency management plus bupropion, the proportion of cocaine-positive urine samples decreased significantly between the third and 15th week of the study (p<.001) and remained low for the remainder of the 25-week study.

In contrast, the groups that received vouchers and bupropion or vouchers and placebo showed no significant reduction in cocaine use.

Poling, an assistant professor of psychiatry at Yale, told Psychiatric News that because “there is currently no effective medication for the treatment of cocaine abuse,” it is excellent news that when combined with contingency management, bupropion helps to reduce cocaine use.

Thomas Kosten, M.D., who obtained a grant from the National Institute on Drug Abuse to conduct the study, explained why bupropion and contingency management may work so well together.

Kosten is a professor of psychiatry and medicine at Yale and deputy chief of psychiatry at the VA Connecticut Healthcare System.

Chronic cocaine use disrupts a person's ability to experience the pleasure he or she would normally experience upon redeeming the reward vouchers, he explained, because repeated cocaine use leads to a marked reduction in dopamine receptors. “The neurobiology of this reduction in pleasure... occurs through an abnormally low level of stimulation of the dopamine reinforcement pathways.”

Bupropion combined with this behavioral therapy “were synergistic due to the ability of bupropion to help subjects experience the pleasure of successful and rewarded drug abstinence,” he said.

In acknowledging that drug-treatment programs in many community settings don't have the money to implement contingency management rewards on the scale of this study, Poling mentioned research by Nancy Petry, Ph.D., of the University of Connecticut Health Center, who has found that low-cost contingency management can also be effective in reducing drug addiction.

Poling said that future research should explore the issue of whether bupropion and contingency management can successfully reduce cocaine use beyond the 25-week study period and whether contingency management can be paired with another behavioral intervention, such as cognitive-behavioral therapy, for lasting effects.

An abstract of “Six-Month Trial of Bupropion With Contingency Management With Cocaine Dependence in a Methadone-Maintained Population” is posted at<http://archpsyc.ama-assn.org/cgi/content/abstract/63/2/219>.▪

Arch Gen Psychiatry 2005 63 219