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.

Antipsychotics for Amphetamine Psychosis. A Systematic Review.

Background: Among individuals experiencing amphetamine psychosis, it may be difficult to rule out schizophrenia. The use of antipsychotics for the treatment of amphetamine psychosis is sparse due to possible side effects. Some arguments disfavor their use, stating that the psychotic episode is self-limited. Without treatment, some individuals may not fully recover from the psychosis and may develop full-blown psychosis, emotional, and cognitive disturbance. This review aims to investigate the clinical benefits and risks of antipsychotics for the treatment of amphetamine psychosis. Methods: Electronic search on trials on antipsychotic drugs for amphetamine psychosis from their inception to November 2018 was conducted in PubMed, Scopus, Google Scholar, EBSCOhost, ProQuest, Cochrane Review Database, Medline Ovid, and EMBASE following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The Cochrane risk-of-bias tool assessed the risk of bias, the methodological quality of individual trials was assessed by the Oxford Quality Scoring System, and the quality of evidence for recommendations was judged by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). The results were synthesized qualitatively and quantitatively. Results: The investigation of six randomized controlled trials of 314 participants showed that aripiprazole, haloperidol, quetiapine, olanzapine, and risperidone were able to reduce or control the psychotic episode (positive and negative symptoms) induced by amphetamine use with no adverse event. Although the side-effect profile of these agents varied, no drug was clinically superior to others. Conclusions: This review suggests that antipsychotics seem to be efficacious for amphetamine psychosis on both positive and negative symptoms. Practitioners need to tailor their use based on risks for side effects individually.

Integrating DSM/ICD, Research Domain Criteria, and Descriptive Psychopathology in Teaching and Practice of Psychiatry.

Background: Some believe that Psychiatry relies solely on the Diagnostic and Statistical Manual of Mental Disorders (DSM). Some are not aware of the effort initiated by the Research Domain Criteria (RDoC) to propel the field to a new era of Medicine. Others are not acquainted with studies of Descriptive Psychopathology that can dissect symptoms and signs of mental illness and convert them into reliable clinical data for diagnosis and treatment purpose. This document is to bring keenness of the advances in research, translational or clinical, made in Psychiatry, and to encourage students, psychiatric residents, as well as psychiatric practitioners to integrate DSM/ICD, RDoC, and Descriptive Psychopathology into teaching and practice. Methods: A search of the literature originated from 1985 to 2018 on two central databases: Google Scholar and Pubmed by free-texting: "comparison, strengths and weaknesses, Diagnostic and Statistical Manual of Mental Disorders, Research Domain Criteria, and Descriptive Psychopathology." Results: The DSM and ICD possess algorithms for psychiatric diagnosis, but they are limited to determine psychobiological causes of mental illnesses. Descriptive Psychopathology aims to dissect the mind to understand better "signs and symptoms," their psychological, neurological, or neuropsychological origins but has been criticized for being non-reliable to practically explain the meaning of signs and symptoms that it attempts to describe. The RDoC claims to be a data-driven system of biological and psychological research for an evidence-based approach to Psychiatry. It is said that RDoC utilizes translational research that has been very slow to move to human experimentation. Discussion and conclusion: Despite incommensurable translational research and human trials, the integration of translational research (neurosciences, experimental psychology, and genomics) as available human research data into teaching and practice is lacking. The author believes that the integration will enhance scientific and well-founded communication with our peers, advance psychopharmacologic treatments and improve our patient's mental well-being.

Challenges of the pharmacological management of benzodiazepine withdrawal, dependence, and discontinuation.

BACKGROUND: Benzodiazepines (BZDs) are among the most prescribed sedative hypnotics and among the most misused and abused medications by patients, in parallel with opioids. It is estimated that more than 100 million Benzodiazepine (BZD) prescriptions were written in the United States in 2009. While medically useful, BZDs are potentially dangerous. The co-occurring abuse of opioids and BZD, as well as increases in BZD abuse, tolerance, dependence, and short- and long-term side effects, have prompted a worldwide discussion about the challenging aspects of medically managing the discontinuation of BZDs. Abrupt cessation can cause death. This paper addresses the challenges of medications suggested for the management of BZD discontinuation, their efficacy, the risks of abuse and associated medical complications. The focus of this review is on the challenges of several medications suggested for the management of BZD discontinuation, their efficacy, the risks of abuse, and associated medical complications. METHODS: An electronic search was performed of Medline, Worldwide Science, Directory of Open Access Journals, Embase, Cochrane Library, Google Scholar, PubMed Central, and PubMed from 1990 to 2017. The review includes double-blind, placebo-controlled studies for the most part, open-label pilot studies, and animal studies, in addition to observational research. We expand the search to review articles, naturalistic studies, and to a lesser extent, letters to the editor/case reports. We exclude abstract and poster presentations, books, and book chapters. RESULTS: The efficacy of these medications is not robust. While some of these medicines are relatively safe to use, some of them have a narrow therapeutic index, with severe, life-threatening side effects. Randomized studies have been limited. There is a paucity of comparative research. The review has several limitations. The quality of the documents varies according to whether they are randomized studies, nonrandomized studies, naturalistic studies, pilot studies, letters to the editors, or case reports. CONCLUSIONS: The use of medications for the discontinuation of BZDs seems appropriate. It is a challenge that requires further investigation through randomized clinical trials to maximize efficacy and to minimize additional risks and side effects.

Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom.

BACKGROUND: Kratom (Mitragyna speciosa) is a tropical tree with a long history of traditional use in parts of Africa and Southeast Asia. Kratom is also known as Thom, Thang, and Biak. Its leaves and the teas brewed from them have long been used by people in that region to manage pain and opioid withdrawal and to stave off fatigue. Kratom is actually consumed throughout the world for its stimulant effects and as an opioid substitute (in form of tea, chewed, smoked, or ingested in capsules). Some case reports have associated kratom exposure with psychosis, seizures, intrahepatic cholestasis, other medical conditions, and deaths. The clinical manifestations of kratom effects are not well defined and the clinical studies are limited. Data research suggest that both stimulant and sedative dose-dependent effects do exist, in addition to antinociceptive, antidepressant activity, anxiolytic-like effects, and anorectic effects, but a growing concern for the drug's effects and safety of use has resulted in national and international attention primarily due to an increase in hospital visits and deaths in several countries that are believed to have been caused by extracts of the plant. There is a dearth of double blind controlled studies. In this study, we aim to use existing literature to clarify both benefits and risks of kratom as well as its diagnosis evaluation as kratom misuse is an emerging trend in the Western world. METHODS: Literature review using databases such as Embase, Medline, PubMed, Cochrane Library, and Mendeley from 2007 to 2017 were evaluated by all authors to analyze current state on benefits, risks, and diagnosis evaluation of kratom (M. speciosa). RESULTS: Data analysis suggested that kratom possesses some benefits such as stimulant and sedative effects as wells as antinociceptive effects. It seems to inhibit pro-inflammatory mediator release and vascular permeability and can enhance immunity. In addition, it may be an antidepressant and anorectic. However, kratom can cause intrahepatic cholestasis, seizure, arrhythmia, impair memory function, coma, and death. Psychological manifestations described are euphoria and feeling relaxed to severe symptoms such as aggression, hostility, and psychosis. Medical manifestations described are polyuria, dry mouth, vomiting, and jerky movements. Currently, liquid chromatography/mass spectrometry and ion mobility spectrometry (IMS) are suggested as the most promising to rapidly screen kratom products providing a positive success rate. CONCLUSION: Our data analysis has not determined if biochemical benefits of kratom may prove to outweigh its toxicity and risks. On the contrary, it seems that its potential side effects outweigh the benefits, and severe and real health hazards can, insidiously, lead to death. Kratom clinical, psychological, and medical manifestations can be disturbing. Kratom (M. speciosa) use, among multiple compounds of the leaf, appear to be increasing in the Western world. Promising methods to accurately identify kratom compounds are still ongoing.