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

  • Brian ChanEmail author
  • Karli Kondo
  • Michele Freeman
  • Chelsea Ayers
  • Jessica Montgomery
  • Devan Kansagara



Currently, there are no accepted FDA-approved pharmacotherapies for cocaine use disorder, though numerous medications have been tested in clinical trials. We conducted a systematic review and meta-analysis to better understand the effectiveness of pharmacotherapy for cocaine use disorder.


We searched multiple data sources (MEDLINE, PsycINFO, and Cochrane Library) through November 2017 for systematic reviews and randomized controlled trials (RCTs) of pharmacological interventions in adults with cocaine use disorder. When possible, we combined the findings of trials with comparable interventions and outcome measures in random-effects meta-analyses. We assessed the risk of bias of individual trials and the strength of evidence for each outcome using standardized criteria. Outcomes included continuous abstinence (3+ consecutive weeks); cocaine use; harms; and study retention. For relapse prevention studies (participants abstinent at baseline), we examined lapse (first cocaine positive or missing UDS) and relapse (two consecutive cocaine positive or missed UDS′).


Sixty-six different drugs or drug combinations were studied in seven systematic reviews and 48 RCTs that met inclusion criteria. Antidepressants were the most widely studied drug class (38 RCTs) but appear to have no effect on cocaine use or treatment retention. Increased abstinence was found with bupropion (2 RCTs: RR 1.63, 95% CI 1.02 to 2.59), topiramate (2 RCTs: RR 2.56, 95% CI 1.39 to 4.73), and psychostimulants (14 RCTs: RR 1.36, 95% CI 1.05 to 1.77), though the strength of evidence for these findings was low. We found moderate strength of evidence that antipsychotics improved treatment retention (8 RCTs: RR 1.33, 95% CI 1.03 to 1.75).


Most of the pharmacotherapies studied were not effective for treating cocaine use disorder. Bupropion, psychostimulants, and topiramate may improve abstinence, and antipsychotics may improve retention. Contingency management and behavioral interventions along with pharmacotherapy should continue to be explored.

SR Registration

Prospero CRD42018085667


substance use pharmacotherapy systematic review cocaine 



The authors wish to thank Robin Paynter for developing the search strategy and running electronic searches.


This research was funded by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. Dr. Chan’s time was supported by grant number K12HS022981 from the Agency for Healthcare Research and Quality.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they do not have a conflict of interest.


The findings and conclusions in this document are those of the authors who are responsible for its contents; the findings and conclusions do not necessarily represent the views of the Department of Veterans Affairs or the US government.

Supplementary material

11606_2019_5074_MOESM1_ESM.docx (757 kb)
ESM 1 (DOCX 756 kb)


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Copyright information

© Society of General Internal Medicine (This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply) 2019

Authors and Affiliations

  • Brian Chan
    • 1
    • 2
    Email author
  • Karli Kondo
    • 3
    • 4
  • Michele Freeman
    • 3
  • Chelsea Ayers
    • 3
  • Jessica Montgomery
    • 3
  • Devan Kansagara
    • 1
    • 3
    • 5
  1. 1.Division of General Internal Medicine and GeriatricsOregon Health & Science UniversityPortlandUSA
  2. 2.Central City ConcernPortlandUSA
  3. 3.Evidence Synthesis Program CenterVA Portland Health Care SystemPortlandUSA
  4. 4.Research Integrity OfficeOregon Health & Science UniversityPortlandUSA
  5. 5.Department of MedicineVA Portland Health Care SystemPortlandUSA

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