Reduced drug use as an alternative valid outcome in individuals with stimulant use disorders: Findings from 13 multisite randomized clinical trials

Abstract

Background and aims: Total abstinence has historically been the goal of treatment for substance use disorders; however, there is a growing recognition of the health benefits associated with reduced use as a harm reduction measure in stimulant use disorders treatment. We aimed to assess the validity of reduced stimulant use as an outcome measure in randomized controlled trials (RCTs) of pharmacological interventions for stimulant use disorder.

Design: We conducted a secondary analysis of a pooled dataset of 13 RCTs.

Setting and participants: Participants were individuals seeking treatment for cocaine or methamphetamine use disorders (N = 2062) in a wide range of treatment facilities in the United States.

Measurements: We validated reduced stimulant use against a set of clinical indicators drawn from harmonized measurements, including severity of problems caused by drug use, comorbid depression, global severity of substance use and improvement, severity of drug-seeking behavior, craving and high-risk behaviors, all assessed at the end of the trial, as well as follow-up urine toxicology. A series of mixed effect regression models was conducted to validate reduction in frequency of use against no reduction in use and abstinence.

Findings: More participants reduced frequency of primary drug use than achieved abstinence (18.0% vs. 14.2%, respectively). Reduced use was significantly associated with decreases in craving for the primary drug [60.1%, 95% confidence interval (CI) = 54.3%-64.7%], drug seeking behaviors (41.0%, 95% CI = 36.6%-45.7%), depression severity (39.9%, 95% CI = 30.9%-48.3%), as well as multiple measures of global improvement in psychosocial functioning and severity of drug-related problems, albeit less strongly so than abstinence. Moreover, reduced use was associated with sustained clinical benefit at follow-up, as confirmed by negative urine tests (adjusted odds ratio compared with those with no reduction in use: 0.50, 95% CI = 0.35-0.71).

Conclusion: Reduced frequency of stimulant use appears to be associated with meaningful improvement in various clinical indicators of recovery. Assessment of reduced use, in addition to abstinence, could broaden the scope of outcomes measured in randomized controlled trials of stimulant use disorders and facilitate the development of more diverse treatment approaches.

Keywords: Stimulants; cocaine use disorder; harm reduction; methamphetamine use disorder; non‐abstinence outcomes; secondary data analysis.

Figure 1

Percent change in the composite score of Addiction Severity Index (ASI) subscales across three categories of change in the frequency of stimulant use (cocaine or methamphetamine) from baseline to the end of the trial.

Figure 2

Percent change in the other clinical measures across three categories of change in the frequency of stimulant use (cocaine or methamphetamine) from baseline to the end of the trial Abbreviations: GSU-self= Global Severity of Use-self rated, based on Global Clinical Impression Scale (GCIS); GSU-observer= Global Severity of Use-observer rated, based on GCIS; Seek drugs-observer =Global severity of seeking the primary drug- observer rated based on GCIS; HAM-D= Hamilton Depression Scale