Michel Silvio Duailibi1, Quirino Cordeiro2, Elisa Brietzke2, Marcelo Ribeiro2,3, Steve LaRowe4, Michael Berk5,6, Alisson Paulino Trevizol3. 1. Santa Casa School of Medical Sciences, São Paulo, São Paulo, Brazil. 2. Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil. 3. Reference Center for Alcohol, Tobacco and Other Drugs (CRATOD), São Paulo State Secretariat of Health, São Paulo, São Paulo, Brazil. 4. Department of Psychiatry, Center for Drug and Alcohol Programs, Medical University of South Carolina, Charleston, South Carolina. 5. School of Medicine, IMPACT Strategic Research Centre, Deakin University, Geelong, Victoria, Australia. 6. Department of Psychiatry, The Florey Institute of Neuroscience and Mental Health, and Orygen Youth Health Research Centre, University of Melbourne, Parkville, Victoria, Australia.
Abstract
BACKGROUND AND OBJECTIVES: Recent neurobiological evidences along with clinical observations justify the use of N-acetylcysteine (NAC) as a medication for craving. The objective of our study was to assess the evidence of efficacy of NAC for craving in substance use disorders in randomized clinical trials (RCTs). METHODS: Systematic review of the RCTs literature (PROSPERO number 56698) until February, 2017, using MEDLINE, Cochrane Library and clinicaltrials.gov. We included seven RCTs (n = 245); most with small-to-moderate sample sizes. The main outcome was the Hedges' g for continuous scores in a random-effects model. Heterogeneity was evaluated with the I2 and the χ2 test. Publication bias was evaluated using the Begg's funnel plot and the Egger's test. Meta-regression was performed using the random-effects model. RESULTS: Comparing NAC versus placebo, NAC was significantly superior for craving symptoms (Hedges' g = 0.94; 95%CI 0.55-1.33). The funnel plot showed the risk of publication bias was low and between-study heterogeneity was not significant (I2 = 44.4%, p = 0.07 for the χ2 test). A subgroup analysis performed using meta-regression showed no particular influence. DISCUSSION AND CONCLUSIONS: NAC was superior to placebo for craving reduction in SUDs. The relatively small number of trials and their heterogeneous methodology were possible limitations; however, these positive thrilling results stimulate further studies for clarifying the potential impact of NAC for craving symptoms in SUDs. SCIENTIFIC SIGNIFICANCE: The safety profile of NAC and favorable tolerability, in addition to being an over-the-counter medication, presents with an interesting potential clinical use for craving in SUDs. SCIENTIFIC SIGNIFICANCE: The safety profile of NAC and its favorable tolerability, in addition to being anover-the-counter medication, presents with an interesting potential clinical use for craving in SUDs. (Am J Addict 2017;26:660-666).
BACKGROUND AND OBJECTIVES: Recent neurobiological evidences along with clinical observations justify the use of N-acetylcysteine (NAC) as a medication for craving. The objective of our study was to assess the evidence of efficacy of NAC for craving in substance use disorders in randomized clinical trials (RCTs). METHODS: Systematic review of the RCTs literature (PROSPERO number 56698) until February, 2017, using MEDLINE, Cochrane Library and clinicaltrials.gov. We included seven RCTs (n = 245); most with small-to-moderate sample sizes. The main outcome was the Hedges' g for continuous scores in a random-effects model. Heterogeneity was evaluated with the I2 and the χ2 test. Publication bias was evaluated using the Begg's funnel plot and the Egger's test. Meta-regression was performed using the random-effects model. RESULTS: Comparing NAC versus placebo, NAC was significantly superior for craving symptoms (Hedges' g = 0.94; 95%CI 0.55-1.33). The funnel plot showed the risk of publication bias was low and between-study heterogeneity was not significant (I2 = 44.4%, p = 0.07 for the χ2 test). A subgroup analysis performed using meta-regression showed no particular influence. DISCUSSION AND CONCLUSIONS:NAC was superior to placebo for craving reduction in SUDs. The relatively small number of trials and their heterogeneous methodology were possible limitations; however, these positive thrilling results stimulate further studies for clarifying the potential impact of NAC for craving symptoms in SUDs. SCIENTIFIC SIGNIFICANCE: The safety profile of NAC and favorable tolerability, in addition to being an over-the-counter medication, presents with an interesting potential clinical use for craving in SUDs. SCIENTIFIC SIGNIFICANCE: The safety profile of NAC and its favorable tolerability, in addition to being anover-the-counter medication, presents with an interesting potential clinical use for craving in SUDs. (Am J Addict 2017;26:660-666).
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