Bupropion for the treatment of methamphetamine dependence.

Bupropion was tested for efficacy in increasing weeks of abstinence in methamphetamine-dependent patients, compared to placebo. This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 30-day follow-up. Five outpatient substance abuse treatment clinics located west of the Mississippi participated in the study. One hundred and fifty-one treatment-seekers with DSM-IV diagnosis of methamphetamine dependence were consented and enrolled. Seventy-two participants were randomized to placebo and 79 to sustained-release bupropion 150 mg twice daily. Patients were asked to come to the clinic three times per week for assessments, urine drug screens, and 90-min group psychotherapy. The primary outcome was the change in proportion of participants having a methamphetamine-free week. Secondary outcomes included: urine for quantitative methamphetamine, self-report of methamphetamine use, subgroup analyses of balancing factors and comorbid conditions, addiction severity, craving, risk behaviors for HIV, and use of other substances. The generalized estimating equation regression analysis showed that, overall, the difference between bupropion and placebo groups in the probability of a non-use week over the 12-week treatment period was not statistically significant (p=0.09). Mixed model regression was used to allow adjustment for baseline factors in addition to those measured (site, gender, level of baseline use, and level of symptoms of depression). This subgroup analysis showed that bupropion had a significant effect compared to placebo, among male patients who had a lower level of methamphetamine use at baseline (p<0.0001). Comorbid depression and attention-deficit/hyperactivity disorder did not change the outcome. These data suggest that bupropion, in combination with behavioral group therapy, was effective for increasing the number of weeks of abstinence in participants with low-to-moderate methamphetamine dependence, mainly male patients, regardless of their comorbid condition.

Modafinil for the treatment of cocaine dependence.

AIM: Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo. METHODS: This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Six outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, having a diagnosis of cocaine dependence; 72 participants were randomized to placebo, 69 to modafinil 200mg, and 69 to modafinil 400mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy weekly. The primary outcome measure was the weekly percentage of cocaine non-use days. RESULTS: The GEE regression analysis showed that for the total sample, there was no significant difference between either modafinil group and placebo in the change in average weekly percent of cocaine non-use days over the 12-week treatment period (p>0.79). However, two secondary outcomes showed significant effects by modafinil 200mg: the maximum number of consecutive non-use days for cocaine (p=0.02), and a reduction in craving (p=0.04). Also, a post hoc analysis showed a significant effect of modafinil that increased the weekly percentage of non-use days in the subgroup of those cocaine patients who did not have a history of alcohol dependence (p<0.02). CONCLUSIONS: These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing cocaine craving.

A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of methamphetamine dependence.

Methamphetamine dependence is an increasing public health problem in the United States. No efficacious medication for methamphetamine dependence has been developed. As ondansetron, a 5-HT3 receptor antagonist and modulator of cortico-mesolimbic dopamine function, has been shown to reduce some of the rewarding effects of d-amphetamine in animal and human laboratory studies, we decided to test whether it would be superior to placebo at reducing methamphetamine use. In a preliminary, multi-site, randomized, double-blind, 8-wk controlled trial, 150 methamphetamine-dependent men and women received ondansetron (0.25 mg, 1 mg, or 4 mg b.i.d.) or placebo. Participants were assessed on several measures of methamphetamine use including urine methamphetamine level up to three times per week. As a psychosocial adjunct to the medication condition, cognitive behavioural therapy also was administered three times per week. Ondansetron was well tolerated and was less likely than placebo to be associated with serious adverse events. Nevertheless, none of the ondansetron doses was superior to placebo at decreasing any of the measures of methamphetamine use, withdrawal, craving, or clinical severity of methamphetamine dependence. Our preliminary results do not support the utility of ondansetron, at the doses tested, as a treatment for methamphetamine dependence. These findings should be viewed in light of the possibility that a less intensive cognitive behavioural therapy regimen might have yielded more positive results in this initial phase II trial exploring for the efficacy of ondansetron.