Deirdre Santos

Aripiprazole for the treatment of methamphetamine dependence: a randomized, double-blind, placebo-controlled trial.

AIMS To test aripiprazole for efficacy in decreasing use in methamphetamine-dependent adults, compared to placebo. DESIGN Participants were randomized to receive 12 weeks of aripiprazole or placebo, with a 3-month follow-up and a platform of weekly 30-minute substance abuse counseling. SETTING The trial was conducted from January 2009 to March 2012 at the San Francisco Department of Public Health. PARTICIPANTS Ninety actively using, methamphetamine-dependent, sexually active adults were recruited from community venues. MEASUREMENTS The primary outcome was regression estimated reductions in weekly methamphetamine-positive urines. Secondary outcomes were study medication adherence [by self-report and medication event monitoring systems (MEMS)], sexual risk behavior and abstinence from methamphetamine. FINDINGS Participant mean age was 38.7 years, 87.8% were male, 50.0% white, 18.9% African American, and 16.7% Latino. Eighty-three per cent of follow-up visits and final visits were completed. By intent-to-treat, participants assigned to aripiprazole had similar reductions in methamphetamine-positive urines as participants assigned to placebo [risk ratio (RR) 0.88, 95% confidence interval (CI): 0.66-1.19, P = 0.41]. Urine positivity declined from 73% (33 of 45 participants) to 45% (18 of 40) in the placebo arm and from 77% (34 of 44) to 44% (20 of 35) in the aripiprazole arm. Adherence by MEMS and self-report was 42 and 74%, respectively, with no significant difference between arms (MEMS P = 0.31; self-report P = 0.17). Most sexual risk behaviors declined similarly among participants in both arms (all P > 0.05). There were no serious adverse events related to study drug, although participants randomized to aripiprazole reported more akathisia, fatigue and drowsiness (P < 0.05). CONCLUSION Compared with placebo, aripiprazole did not reduce methamphetamine use significantly among actively using, dependent adults.

Feasibility and acceptability of a phase II randomized pharmacologic intervention for methamphetamine dependence in high-risk men who have sex with men.

Objective:To determine whether actively using, methamphetamine (meth)-dependent men who have sex with men (MSM) could be enrolled and retained in a pharmacologic intervention trial, and the degree to which participants would adhere to study procedures, including medication adherence. Study design:Phase II randomized, double-blind trial of bupropion vs. placebo. Methods:Thirty meth-dependent, sexually active MSM were randomized to receive daily bupropion XL 300 mg or placebo for 12 weeks. Participants received weekly substance use counseling, provided weekly urine specimens, and completed monthly audio-computer assisted self-interview (ACASI) behavioral risk assessments. Adherence was measured by medication event monitoring systems (MEMS) caps (the number of distinct MEMS cap openings divided by the number of expected doses) and self-report. Results:Ninety percent completed the trial: 89% of monthly ACASIs were completed, 81% of study visits were attended, and 81% of urine samples were collected. Adherence by MEMS cap was 60% and by self-report was 81% and did not differ significantly by treatment assignment. The median number of positive urine samples was 5.5 out of a possible 11 (50%). Participants in both arms reported similar declines in the median number of sex partners (P = 0.52). No serious adverse events occurred and there were no significant differences in adverse events by treatment assignment (P = 0.11). Conclusions:It is feasible to enroll and retain actively using, meth-dependent MSM in a pharmacologic intervention. Bupropion was well tolerated. Study participation and retention rates were high, however, study drug medication adherence was only moderate. Findings support a larger trial with improved adherence support to evaluate the efficacy of bupropion and other pharmacologic interventions for meth dependence in this population.

Feasibility, Acceptability, and Tolerability of Targeted Naltrexone for Nondependent Methamphetamine-Using and Binge-Drinking Men Who Have Sex with Men.

Background:There are no effective pharmacologic strategies for nondependent methamphetamine (meth)-using and binge-drinking men who have sex with men (MSM) at high-risk for HIV. We sought to determine the feasibility of enrolling and retaining this population in a pharmacologic trial; the acceptability of pharmacotherapy study procedures; and the tolerability of targeted naltrexone versus placebo. Methods:Thirty meth-using and binge-drinking MSM were randomly assigned 1:1 to 50 mg naltrexone or placebo for 8 weeks for targeted administration (ie, during craving or in anticipation of meth or alcohol use). Substance use counseling and behavioral assessments were conducted every 2 weeks. Medication use was measured using WisePill dispensers. Results:Trial completion was 93%; visit completion rate was 95%. Mean weekly number of medication pills taken was 2.1 and was similar between arms. Participant satisfaction rate was 96%. There were neither serious adverse events nor differences in adverse event rates between arms. In exploratory intention-to-treat analyses, there were no differences in meth use and drinking. Naltrexone participants had greater reductions in serodiscordant receptive anal intercourse [incident rate ratio (IRR) = 0.15; 95% CI = 0.05 to 0.42] and serodiscordant condomless receptive anal intercourse (IRR = 0.11; 95% CI = 0.03 to 0.37), compared with placebo. In subgroup analyses among frequent meth users, naltrexone participants had greater reductions in meth-using days (IRR = 0.78; 95% CI = 0.62 to 0.99). In as-treated analyses, frequent study medication users in the naltrexone arm had greater reductions in binge drinking days (IRR = 0.72; 95% CI = 0.54 to 0.97). Conclusions:Targeted naltrexone is a feasible, acceptable, and tolerable intervention strategy for nondependent meth-using and binge-drinking MSM. Naltrexone was associated with significant sexual risk reductions; and for some individuals, naltrexone was associated with meth and binge-drinking reductions.

Event-level relationship between methamphetamine use significantly associated with non-adherence to pharmacologic trial medications in event-level analyses

BACKGROUND Methamphetamine use has been previously associated with poor medication adherence, but, to date, there have been no studies that have conducted event-level analyses on correlates of medication adherence in studies of pharmacologic agents for methamphetamine dependence. METHODS We pooled data from two previous, randomized controlled trials (using bupropion and mirtazapine, respectively) for methamphetamine dependence and used a mixed effects logistic model to examine correlates of daily opening of the medication event monitoring system (MEMS) cap as a repeated measure. We explored whether periods of observed methamphetamine use via urine testing were associated with study medication adherence based on MEMS cap openings. RESULTS We found a significant negative association between methamphetamine-urine positivity and event-level study medication adherence as measured by MEMS cap openings (AOR: 0.69; 95% CI: 0.49-0.98). In addition, age (AOR: 1.07; 95% CI: 1.02-1.11) and depressive symptoms (AOR: 0.78; 95% CI: 0.64-0.90) were significantly associated with adherence. Finally, participants were more likely to open their study medication bottles on days when they presented for in-person urine testing. CONCLUSIONS Our event-level analysis shows that methamphetamine use can be associated with reduced medication adherence as measured by MEMS cap openings in pharmacologic trials, which corroborates prior research. These findings may suggest that medication adherence support in pharmacologic trials among methamphetamine users may be needed to improve study compliance and could be targeted towards periods of time when there are more likely to not open their study medication pill bottles.

Race/ethnicity, education, and age are associated with engagement in ecological momentary assessment text messaging among substance-using MSM in San Francisco.

BACKGROUND Ecological momentary assessments (EMA) are data collection approaches that characterize behaviors in real-time. However, EMA is underutilized in alcohol and substance use research among men who have sex with men (MSM). The aim of this analysis is to explore the correlates of engagement in EMA text messages among substance-using MSM in San Francisco. METHODS The present analysis uses data collected from the Project iN pilot study (n=30). Over a two-month period, participants received and responded to EMA daily text messages inquiring about their study medication, alcohol, and methamphetamine use. Baseline characteristics including demographics, alcohol use, and substance use were examined as potential correlates of engagement in EMA text messages in logistic regression and proportional hazards models. RESULTS Participants had a 74% response rate to EMA text messages over the study period. MSM of color had significantly lower adjusted odds of responding to EMA texts 80% of the time or more, compared to white MSM (adjusted odds ratio=0.05, 95%CI=0.01-0.38). College-educated MSM had a lower adjusted hazard of week-long discontinuation in EMA texts (adjusted hazard ratio=0.12, 95%CI=0.02-0.63). Older MSM had a higher adjusted hazard of week-long discontinuation in EMA texts (adjusted hazard ratio=1.15, 95%CI=1.01-1.31). CONCLUSION Differences in engagement in EMA text prompts were discovered for MSM with different racial/ethnic backgrounds, ages, and education levels. Substance use variables were not correlated with engagement in text messages, suggesting that EMA may be a useful research tool among actively substance-using MSM in San Francisco.