Carvedilol does not reduce cocaine use in methadone-maintained cocaine users

Abstract

Introduction The goal of this study was too test the efficacy of carvedilol (CAR), an adrenergic blocker, for reducing cocaine use in individuals with cocaine use disorder (CUD). We conducted a 17-week, double-blind, randomized controlled trial with 3 treatment arms: 25 mg CAR, 50 mg CAR, and placebo. Methods One hundred and six treatment-seeking opioid and cocaine-dependent participants, who were also maintained on methadone during study participation, were randomized to placebo (n=34), 25 mg/day CAR (n=37) or 50 mg/day CAR (n=35). The main outcome measures were cocaine and opioid use as assessed by urine drug screening and self-reported drug use. Results No significant group differences were found for treatment retention with 56 % of the placebo, 76 % of the 25 mg and 66 % of the 50 mg CAR groups (p>0.05) completing treatment. The percentage (SD) of cocaine positive urines during the trial showed an overall treatment effect: 59.2 (38.9) for the placebo, 50.8 (33.8) for the 25mg and 75.1 (33.2) for the 50 mg CAR group. In post hoc comparisons, neither the 25 nor 50 mg CAR condition differed significantly from the placebo; however, the 25 mg CAR group had a significantly lower proportion of cocaine-positive urines than the 50 mg group. No significant group differences were found for the percentage of self-reported days of cocaine abstinence during the trial: 72.9 (25.3) for placebo, 72.9 (29) for CAR 25 mg, and 59.3 (31.7) for CAR 50 mg. Significant groups differences in the proportion of opioid positive urines submitted were not observed (p>0.05). Baseline cocaine withdrawal severity did not predict treatment response (p>0.05). Conclusions These findings did not support the efficacy of CAR for the treatment of cocaine use in cocaine and opioid dependent participants maintained on methadone. Further, CAR doses greater than 25 mg should not be used to avoid possible increases in cocaine and opioid use.

Pharmacotherapy for Cocaine Use Disorder—a Systematic Review and Meta-analysis

“…Other Pharmacotherapies. Nineteen trials [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71] examined the effects of other drugs or drug combinations for cocaine use disorder ( Table 2). Although there is insufficient evidence to form conclusions due to limited power, positive findings on abstinence and use reduction were reported in studies of doxazosin, 59 ondansetron, 66 propranolol, 70 and topiramate combined with mixed amphetamine salts.…”

Comparison of Treatments for Cocaine Use Disorder Among Adults

“…After exclusions, 157 studies (18.9%) with 402 treatment groups and 15 842 participants were included in the meta-analysis. 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , ...…”

“…In total, 1580 records were identified, and 831 records were screened; of those, 305 full-text articles were assessed for eligibility. After exclusions, 157 studies (18.9%) with 402 treatment groups and 15 842 participants were included in the meta-analysis . The PRISMA diagram shows detailed information on the number of ineligible studies and the reasons for exclusion (Figure).…”

A systematic review and meta-analysis of medications for stimulant use disorders in patients with co-occurring opioid use disorders

“…A study of carvedilol (25 mg, 50 mg, placebo) in 106 methadone-maintained participants did not assess abstinence but found differences in cocaine use based on dosing; the lower (25 mg) dosage arm had lower rates of positive UDS compared to placebo, while the higher (50 mg) dosage arm had higher rates of positive UDS (25 mg 51% versus 50 mg 75% versus placebo 59%, P=0.03). There were no statistically significant differences in retention (76% versus 66% versus 56%, P=0.21) (Sofuoglu et al, 2017). A study of magnesium L-aspartate versus placebo found no differences in cocaine use (74.5% versus 75.5%, P=NS) or treatment retention (10.9 versus 8.9 weeks in treatment, P>0.5) (Margolin et al, 2003).…”