N-acetylcysteine in the treatment of craving in substance use disorders: Systematic review and meta-analysis.

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).

Laboratory-induced stress and craving among individuals with prescription opioid dependence.

BACKGROUND: Stress and conditioned drug cues have been implicated in the initiation, maintenance and relapse to substances of abuse. Although stress and drug cues are often encountered together, little research exists on whether stress potentiates the response to drug cues. METHOD: Participants (N=75) were 39 community recruited individuals with current prescription opioid (PO) dependence and 36 healthy controls. Participants stayed overnight in the hospital for one night and then completed laboratory testing the following morning. During laboratory testing, participants were randomly assigned to a stress task (Trier Social Stress Task; TSST) or a no-stress condition. Following the stress manipulation, all participants completed a PO cue paradigm. Immediately before and after the stress and cue tasks, the following were assessed: subjective (stress, craving, anger, sadness, happiness), physiological (heart rate, blood pressure, galvanic skin response), and neuroendocrine responses (cortisol and dehydroepiandrosterone). RESULTS: Internal validity of the stress task was demonstrated, as evidenced by significantly higher subjective stress, as well as cortisol, heart rate and blood pressure in the TSST compared to the no-stress group. Individuals with PO dependence evidenced significantly greater reactivity to the stress task than controls. Craving increased significantly in response to the drug cue task among PO participants. No stress×cue interaction was observed. CONCLUSIONS: In this study, heightened stress reactivity was observed among individuals with PO dependence. Exposure to acute stress, however, did not potentiate craving in response to conditioned drug cues.

A retrospective chart review comparing tiagabine and benzodiazepines for the treatment of alcohol withdrawal.

Although benzodiazepines are the standard of care in the treatment of alcohol withdrawal, several studies have suggested that anticonvulsants may be equally effective at alleviating alcohol withdrawal symptoms and may pose less of a risk of causing rebound of symptoms which could contribute to relapse. This report compares treatment outcomes for patients (N=13) treated for alcohol withdrawal with either the anticonvulsant tiagabine or the benzodiazepines oxazepam and lorazepam. The Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) was utilized to gauge alcohol withdrawal symptoms over the course of the study. When possible, follow-up data was obtained on alcohol use post-treatment. Both benzodiazepines and tiagabine appeared to reduce CIWA-Ar scores at about the same magnitude. There was a trend for tiagabine patients to have less post-detoxification drinking (Fisher exact test, p = 0.12). The reduction in alcohol withdrawal symptoms and decreased tendency to relapse observed in patients treated with the anticonvulsant tiagabine suggests that a double-blind, placebo controlled trial may be warranted.