Beyond benzodiazepines: a meta-analysis and narrative synthesis of the efficacy and safety of alternative options for alcohol withdrawal syndrome management.

PURPOSE: To compare the efficacy and safety of non-benzodiazepines (non-BZDs) to benzodiazepines (BZDs) in the treatment of alcohol withdrawal syndrome (AWS). METHODS: For relevant literature, Google Scholar, PubMed, Embase, OVID MEDLINE, EBSCO, Cochrane Central Registry of Controlled Trials, Web of Science, and Scopus were searched. Randomized control trials (RCTs) were included, omitted were nonblinded trials, blinded trials that were not randomized, and open-label studies. The Effective Public Health Practice Project Quality Assessment was used to assess the trial's quality. A meta-analysis and a narrative synthesis were carried out. RESULTS: Twenty non-BZDs and five BZDs were investigated in thirty RCTs. Meta-analysis favored gabapentin over chlordiazepoxide and lorazepam (d = 0.563, p < 0.001) and carbamazepine over oxazepam and lorazepam (d = 0.376, p = 0.029), for reducing Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale scores. Eleven non-BZDs fared better than BZDs for reducing CIWA-Ar, Total Severity Assessment, Selective Severity Assessment, Borg and Weinholdt, and Gross Rating Scale for Alcohol Withdrawal scores. Eight non-BZDs outmatched BZDs regarding autonomic, motor, awareness, and psychiatric symptoms. Sedation and fatigue were prevalent in BZDs, while seizures were prevalent in non-BZDs. CONCLUSION: For AWS treatments, non-BZDs are superior to or equally effective as BZDs. Non-BZD adverse events warrant further investigation. Agents that inhibit gated ion channels are promising candidates. PROTOCOL REGISTRATION: PROSPERO CRD42022384875.

A Bayesian meta-analysis of topiramate's effectiveness for individuals with alcohol use disorder.

BACKGROUND: Topiramate (TPM) has the potential to become one of the most prominent treatment options for alcohol use disorder (AUD). We investigated the efficacy of TPM for AUD treatment, considering new randomized controlled trials carried out since the publication of four prior investigations. METHODS: We searched six major databases, comparing TPM to placebo for AUD treatment. We performed a Bayesian meta-analysis. We conducted a meta-regression, analyzing the effect of age, TPM dosage, duration of treatment, gender, and attrition rate on the outcomes measured. The protocol is registered with PROSPERO: CRD42021286266. RESULTS: TPM reduced heavy drinking days (d = 0.401, Bayes factor (BF) = 23.088) and weeks (d = 0.461, BF = 3.784), lowered alcohol craving (d = 0.477, BF = 107.749), prolonged abstinence throughout the duration of trials (d = 0.505, BF = 54.998), and decreased the amount of gamma-glutamyl transferase in the blood (d = 0.345, BF = 39.048). The analysis pointed out that TPM could reduce anxiety (d = 0.517, BF = 5.993). TPM's efficacy in relieving alcohol withdrawal, minimizing relapse, and decreasing depressive symptoms was inconclusive. There was evidence of a meta-regression effect of attrition rate on heavy drinking days and craving and length of treatment on abstinence. CONCLUSION: TPM has the potential to become a key pharmacological agent in the treatment of AUD.

Selective serotonin reuptake inhibitors in the treatment of depression, anxiety, and post-traumatic stress disorder in substance use disorders: a Bayesian meta-analysis.

PURPOSE: Examine SSRIs' efficacy in treating depression, anxiety, PTSD, and substance use in individuals with addiction. METHODS: From their inception until August 6, 2021, we searched Google Scholar, PubMed, Scopus, OVID MEDLINE, and Academic Search Complete. We included randomized controlled trials (RCTs) and omitted open-label studies. Bayesian analysis was performed. Bayes factor (BF) established efficacy and tau (τ) statistical heterogeneity. The RoB2 method assessed potential biases. Subgroup analysis was carried out to determine SSRI performance. Treatment duration, SSRI dosage, and attrition rate were all examined in meta-regression. RESULTS: We investigated 64 RCTs with 6128 participants. SSRIs reduced depressive symptoms in opioid, alcohol, cocaine, cannabis, and nicotine use disorders (d = 0.353, BF > 99); social anxiety symptoms in alcohol use disorder (d = 0.875, BF > 99); and generalized anxiety symptoms in opioid, alcohol, cocaine, marijuana, and nicotine use disorders (d = 0.346, BF = 4.236). Evidence for PTSD was inconclusive. SSRIs facilitated abstinence for opioid, alcohol, cocaine, cannabis, and nicotine use (d = 0.325, BF > 99); reduced craving for alcohol, cocaine, and nicotine use (d = 0.533, BF = 24.129); and reduced alcohol use (d = 0.452, BF > 99) and cocaine use (d = 0.255, BF = 3.87). Fluoxetine showed the highest antidepressant effect. There was no effect of attrition rate, SSRI dosage, or treatment length on SSRI's efficacy. CONCLUSIONS: Results support the use of SSRIs to treat substance use, depression, and anxiety in individuals with addiction. PROTOCOL REGISTRATION: PROSPERO registration number: CRD42020164944.