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.

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.