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.

Systematic Review and Meta-Analysis: Treatment of Substance Use Disorder in Attention Deficit Hyperactivity Disorder.

BACKGROUND AND OBJECTIVES: Treating substance use disorder (SUD) in patients with co-occurring attention deficit hyperactivity disorder (ADHD) and SUD may lower medical, psychiatric, and social complications. We conducted a systematic review with meta-analysis to investigate the clinical benefits of pharmacological interventions to treat SUD in patients with ADHD. METHODS: Articles were searched on Cochrane Central Register of Controlled Trials, PubMed, EBSCO, Google Scholar, Embase, Web of Science, and Ovid MEDLINE from 1971 to 2020. Data for SUD treatment as primary study endpoints and ADHD symptoms management as secondary outcomes were synthesized using random-effects model meta-analysis. Studies (N = 17) were included. The principal measure of effect size was the standardized mean difference (SMD). PROSPERO registration: CRD42020171646. RESULTS: The pooled effect of pharmacological interventions compared with placebo was small for the reduction in substance use (SMD = 0.405, 95% confidence interval [CI]: [0.252, 0.557], P < .001), abstinence (SMD = 0.328, 95% CI: [0.149, 0.507], P < .001), craving (SMD = 0.274, 95% CI: [0.103, 0.446], P = .002), and the reduction in the frequency of ADHD symptoms (SMD = 0.420, 95% CI: [0.259, 0.582], P < .001). The pooled effect was moderate for the management of withdrawal symptoms (SMD = 0.577, 95% CI: [0.389, 0.764], P = .001]) and the decrease in the severity of ADHD symptoms (SMD = 0.533, 95% CI: [0.393, 0.672], P < .001). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: The magnitude of benefits for pharmacological interventions varies. Despite some limitations, it was positive. This meta-analysis is the first to appraise the benefits of medications to treat SUD in ADHD. It is the groundwork for treatment and risk mitigation. (Am J Addict 2020;00:00-00).

Clinical benefits and risks of N-methyl-d-aspartate receptor antagonists to treat severe opioid use disorder: A systematic review.

BACKGROUND: Demand for treatments for severe opioid use disorder is increasing worldwide. The current pharmacotherapy is mainly focused on opioid and adrenergic receptors. The N-methyl-d-aspartate receptor (NMDAR) is among other receptors that can also be targeted to treat the disease. Findings from randomized controlled trials (RTCs) on NMDAR antagonists to treat severe opioid use disorder amply varied. This study aimed to evaluate the clinical benefits and assess the potential risks for adverse events or side effects of NMDAR antagonists that were investigated for the treatment of severe opioid use disorder. METHODS: Articles were searched in PubMed, Scopus, Google Scholar, Proquest. Cochrane Review Database, Medline Ovid, and EMBASE from their inception to March 2019. RTCs on NMDAR antagonists for the treatment of severe opioid use disorder were independently screened and assessed by two authors. The results were synthesized qualitatively. RESULTS: Nineteen RTCs of 1459 participants met the inclusion criteria. There is moderate evidence suggesting that ketamine, memantine, amantadine, and dextromethorphan may be able to manage opioid withdrawal symptoms. There is little evidence suggesting that memantine may be able to reduce methadone maintenance dose in participants on methadone, reduce opioid use, and reduce craving. Dropout is noticeable among dextromethorphan's participants. Safety concerns are more likely associated with dextromethorphan and ketamine. CONCLUSIONS: NMDAR antagonists have the potentiality to treat severe opioid use disorder. There is insufficient evidence to recommend them for the treatment of severe opioid use disorder due to several limitations inherent to the RCTs reviewed. Further exploration is needed.