Comparison of Treatments for Cocaine Use Disorder Among Adults: A Systematic Review and Meta-analysis | Psychiatry and Behavioral Health | JAMA Network Open | JAMA Network
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    Original Investigation
    Substance Use and Addiction
    May 7, 2021

    Comparison of Treatments for Cocaine Use Disorder Among Adults: A Systematic Review and Meta-analysis

    Author Affiliations
    • 1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California
    • 2Department of Neurosurgery, Stanford University, Stanford, California
    • 3Veterans Affairs Palo Alto Health Care System, Palo Alto, California
    • 4Department of Psychiatry, University of Pennsylvania, Philadelphia
    JAMA Netw Open. 2021;4(5):e218049. doi:10.1001/jamanetworkopen.2021.8049
    Key Points

    Question  What treatments for cocaine use disorder are associated with objective reductions in cocaine use among adults?

    Findings  In this meta-analysis of 157 clinical trials comprising 402 treatment groups and 15 842 participants, only contingency management programs were significantly associated with an increased likelihood of having a negative test result for the presence of cocaine, and this association remained significant in all sensitivity analyses.

    Meaning  The findings suggest that contingency management programs may be beneficial for the treatment of cocaine use disorder among adults who actively use cocaine.


    Importance  In the US and the United Kingdom, cocaine use is the second leading cause of illicit drug overdose death. Psychosocial treatments for cocaine use disorder are limited, and no pharmacotherapy is approved for use in the US or Europe.

    Objective  To compare treatments for active cocaine use among adults.

    Data Sources  PubMed and the Cochrane Database of Systematic Reviews were searched for clinical trials published between December 31, 1995, and December 31, 2017.

    Study Selection  This meta-analysis was registered on (study 8731) on December 31, 2015. Clinical trials were included if they (1) had the term cocaine in the article title; (2) were published between December 31, 1995, and December 31, 2017; (3) were written in English; (4) enrolled outpatients 18 years or older with active cocaine use at baseline; and (5) reported treatment group size, treatment duration, retention rates, and urinalysis results for the presence of cocaine metabolites. A study was excluded if (1) more than 25% of participants were not active cocaine users or more than 80% of participants had negative test results for the presence of cocaine metabolites at baseline and (2) it reported only pooled urinalysis results indicating the presence of multiple substances and did not report the specific proportion of positive test results for cocaine metabolites. Multiple reviewers reached criteria consensus. Of 831 records screened, 157 studies (18.9%) met selection criteria and were included in the analysis.

    Data Extraction and Synthesis  This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Search results were imported from PubMed XML into then Microsoft Excel. Data extraction was completed in 2 iterations to ensure fidelity. Analyses included a multilevel random-effects model, a multilevel mixed-effects meta-regression model, and sensitivity analyses. Treatments were clustered into 11 categories (psychotherapy, contingency management programs, placebo, opioids, psychostimulants, anticonvulsants, dopamine agonists, antidepressants, antipsychotics, miscellaneous medications, and other therapies). Missing data were imputed using multiple imputation by chained equations. The significance threshold for all analyses was P = .05. Data were analyzed using the metafor and mice packages in R software, version 3.3.2 (R Foundation for Statistical Computing). Data were analyzed from January 1, 2018, to February 28, 2021.

    Main Outcomes and Measures  The primary outcome was the intention-to-treat logarithm of the odds ratio (OR) of having a negative urinalysis result for the presence of cocaine metabolites at the end of each treatment period compared with baseline. The hypothesis, which was formulated after data collection, was that no treatment category would have a significant association with objective reductions in cocaine use.

    Results  A total of 157 studies comprising 402 treatment groups and 15 842 participants were included. Excluding other therapies, the largest treatment groups across all studies were psychotherapy (mean [SD] number of participants, 40.04 [36.88]) and contingency management programs (mean [SD] number of participants, 37.51 [25.51]). Only contingency management programs were significantly associated with an increased likelihood of having a negative test result for the presence of cocaine (OR, 2.13; 95% CI, 1.62-2.80), and this association remained significant in all sensitivity analyses.

    Conclusions and Relevance  In this meta-analysis, contingency management programs were associated with reductions in cocaine use among adults. Research efforts and policies that align with this treatment modality may benefit those who actively use cocaine and attenuate societal burdens.