Modafinil Treatment of Cocaine Dependence: A Systematic Review and Meta-Analysis

ABSTRACT

Background: Currently, there is none FDA-approved medication to treat cocaine dependency. Studies conducted with various medications, including antipsychotics, antidepressants, anticonvulsants, and others, revealed inconsistent results. Objectives: To meta-analytically investigate the efficacy and safety of modafinil in the treatment of cocaine-dependent patients. Methods: Randomized controlled trials with ≥20 subjects comparing the numerical therapeutic outcomes of modafinil with placebo were identified in databases, such as PUBMED, psycINFO, EMBASE, and Clinicaltrials.gov. Relevant data on efficacy and safety were extracted. Relative risk (RR) and standardized mean difference were applied for reporting dichotomous and continuous outcomes respectively. Random effects, subgroup, and meta-regression analyses were conducted to further explore the results and evaluate for any moderators. Results: In total, 11 studies (participants = 896, duration = 6.7 ± 1.9 weeks) comparing modafinil with placebo were systematically analyzed, which indicated that modafinil was not superior to placebo in improving the treatment retention rate (studies = 11, participants = 891, RR = 1.030, 95% CI = 0.918–1.156, p = .613). Similarly, data from 7/11 studies did not evidence superiority of modafinil in achieving cocaine abstinence (participants = 696, RR = 1.259, 95% CI = 0.813–1.949, p = .302). However, subgroup analysis of six studies conducted in the United States demonstrated superiority of modafinil in cocaine abstinence rate (studies = 6, participants = 669, 95% CI = 1.027–2.020, p = 0.035). In addition, no evidence suggested modafinil-related discontinuation or specific adverse events than placebo. Conclusions: Overall, there is no evidence to conclude superiority of modafinil in increasing cocaine abstinence and treatment retention rate. However, promising result in subgroup analysis of cocaine abstinence, secondary outcomes, and good safety profile urged the need of larger studies to derive more conclusive results.

KEYWORDS:

• Modafinil
• crack
• cocaine
• dependence
• addiction
• efficacy

Acknowledgments

We would like to acknowledge and thank Dr. Ann L Anderson, Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on Drug Abuse, National Institute of Health, Bethesda, MD for supporting our work by providing the requested data for our meta-analysis.

Declaration of interest

The authors report no conflicts of interest and are solely responsible for the content and writing of the article.

Notes

¹ Reader is referred to DSM-V manual for reading the revised diagnostic criteria for substance use disorder.

2 Also known as systematic use of reinforcement, contingency management is a type of psychotherapy in which patients' behavior is reinforced by reward or punishment.

3 Benzylecgonine: It is the main metabolite of cocaine formed in the liver and excreted in urine. Urine BE level is used to determine the cocaine use.