The safety and efficacy of varenicline in cocaine using smokers maintained on methadone: a pilot study

Abstract

In this double-blind, placebo-controlled trial, we compared varenicline (2 mg) to placebo for treatment for cocaine and tobacco dependence in 31 methadone-maintained subjects. Subjects received weekly counseling during the 12-week study participation. Our results indicate that varenicline is safe to give to this subject population, as there were no adverse events related to medication during this study. Varenicline was no more effective than placebo for abstinence from cocaine. Treatment with varenicline was associated with a reduced number of cigarettes smoked per day, even though subjects received only a brief education for smoking cessation. The self-report reduction in smoking was corroborated by CO levels and the Fagerström Test of Nicotine Dependence. However, self-ratings of positive mood on the Positive Affect Negative Affect Schedule did significantly decrease in the varenicline group as compared to the placebo group, although this appears to be due to randomization differences related to lifetime depression diagnosis. These preliminary findings may point to potential therapeutic value of varenicline for smoking cessation in cocaine users maintained on methadone.

Trial registration: ClinicalTrials.gov NCT00567320.

Conflict of interest statement

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Figures

FIGURE 1

Subject retention across 12 weeks by medication condition. The two treatment groups did not differ in retention (log rank χ2 = 1.3, p < 0.26).

FIGURE 2

Proportion of cocaine positive urine results by medication condition and week. There are no significant changes in slope for either group and these slopes do not differ from each other (Z = 0.20, p < 0.84).

FIGURE 3

Proportion of opioid positive urine results by medication condition and week. Both the placebo and varenicline groups reduced their opioid use across 12-weeks, but there was no differential effect of treatment condition (Z = −1.29, p < 0.20).

FIGURE 4

Mean self-reported number of cigarettes smoked per day by medication condition. Includes only subjects who smoked while in treatment (one subject excluded). An autoregressive 1 (AR1) covariance structure provided the best fit to the model. Both treatment groups reduced the mean number of cigarettes smoked per week, but the varenicline group’s reductions were significantly greater when compared to placebo (F = 16.5, p < 0.0001).

FIGURE 5

Fagerström mean weekly total score by medication condition. The results show that the placebo group did not change over 12 weeks. The varenicline group showed significant reductions across 12 weeks (Z = −7.38, p < 0.000001) with a highly significant difference in slopes between the two groups (Z = 3.35, p < 0.0008).

FIGURE 6

Brief Questionnaire of Smoking Urges Total Score across 12 weeks by medication group. Heterogeneous Toeplitz covariance structure provided the best model fit. Both groups significantly reduced their smoking urges while in treatment but did not differ from each other (F = 0.35, p < 0.56). BQSU scores can range from 10 to 70.

FIGURE 7

Minnesota Nicotine Withdrawal Scale (MNWS) Total Score across 12 weeks by medication group (Heterogeneous AR1 covariance structure). Both groups significantly reduced their nicotine withdrawal scores while in treatment and these reductions did not differ from each other in slope (F = 0.001, p < 0.97). MNWS scores can range from 0 to 32.

FIGURE 8

PANAS positive scale total by med code and week: Heterogeneous AR1 covariance structure used. The placebo group showed no difference on the positive scale of the PANAS, while the varenicline group showed a reduction over time (F = 13.05, p < 0.0001). This difference in slopes for the placebo vs. varenicline groups is significant (F = 2.43, p < 0.12). PANAS negative scale total by Medication Condition and Week: Heterogeneous AR1 covariance structure used. Both treatment groups showed significant reductions in the PANAS negative scale over time, but this rate of reduction did not differ between the two groups (F = 2.43, p < 0.12). The PANAS subscale scores range from 10 to 50.