Z-Drug Use and Benzodiazepine Use and Misuse Among LGB Populations: The Role of Psychological Distress.

BACKGROUND: Z-drugs (hypnotics such as zolpidem, zopiclone, and zaleplon) and benzodiazepines (BZDs) are sedative medications with misuse liability. The goals of this study are to report the (1) prevalence of past-year any Z-drug use, any BZD use, and any BZD misuse by sexual identity category and psychological distress; (2) associations among these 3 categories between sexual identity and past-year psychological distress; (3) associations among these 3 categories with sexual identity by past-year psychological distress status. METHODS: Data were collected from the National Survey on Drug Use and Health (years 2015-2019 [n = 210,392]), a yearly representative national household survey of the American population. We report prevalences of any Z-drug use, any BZD use, and any BZD misuse by sexual identity and past-year psychological distress status. We ran logistic regressions with complex survey design with the 3 dichotomous variables described above as the dependent variables, stratified and not-stratified by psychological distress. RESULTS: Prevalence of any Z-drug an BZD use and any BZD misuse were higher among LGB (lesbian/gay/bisexual) populations, especially gay men and bisexual women. Psychological distress was positively associated with any Z-drug and BZD use and any BZD misuse. Women were at higher risk of Z-drug (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.18-1.37) and BZD use (OR, 1.64; 95% CI, 1.55-1.73), but lower risk of BZD misuse (OR, 0.82; 95% CI, 0.76-0.88). When stratifying by psychological distress, differences between LGB and heterosexuals were more pronounced among those without past-year psychological distress, especially gay men and bisexual women. CONCLUSIONS: The presence of psychological distress attenuates the disparities between LGB and heterosexual individuals in Z-drug use and BZD use and misuse.

Prescription psychostimulants for the treatment of amphetamine-type stimulant use disorder: A systematic review and meta-analysis of randomized placebo-controlled trials.

BACKGROUND AND AIMS: There is currently no standard of care for pharmacological treatment of amphetamine-type stimulant (ATS) use disorder (ATSUD). This systematic review with meta-analysis (PROSPERO CRD42022354492) aimed to pool results from randomized placebo-controlled trials (RCTs) to evaluate efficacy and safety of prescription psychostimulants (PPs) for ATSUD. METHODS: Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random-effect meta-analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random-effect meta-analysis of continuous variables. RESULTS: Ten RCTs (n = 561 participants) were included in the meta-analysis. Trials studied methylphenidate (n = 7), with daily doses of 54-180 mg, and dextroamphetamine (n = 3), with daily doses of 60-110 mg, for 2-24 weeks. PPs significantly decreased end-point craving [SMD  -0.29; 95% confidence interval (CI) = -0.55, -0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85-1.01). No effect was observed for self-reported ATS use, retention in treatment, dropout following adverse events, early-stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79-0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention. CONCLUSIONS: Among individuals with amphetamine-type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications.

Bupropion for treatment of amphetamine-type stimulant use disorder: A systematic review and meta-analysis of placebo-controlled randomized clinical trials.

BACKGROUND: This meta-analysis (PROSPERO-ID: CRD42022362962), pooled effect estimates of outcomes, from placebo-controlled randomized clinical trials (RCTs) examining bupropion efficacy and safety for amphetamine-type stimulant use disorder (ATSUD) treatment. METHOD: Electronic databases were searched for records published to October 31st, 2022, including MEDLINE, CINAHL, PsycINFO, EBM Reviews, EMBASE, PubMed, Web of Science, trial registries. Inclusion criteria were RCTs comparing bupropion to placebo in ATSUD. Cochrane RoB2 tool and GRADE evidence certainty assessment were employed. Outcomes included amphetamine-type stimulant (ATS) use by urinalysis, retention in treatment, treatment adherence, ATS craving, addiction severity, depressive symptom severity, drop-out following adverse events (AEs), and serious AEs. Random-effect meta-analysis was conducted presenting standardized mean difference (SMD), risk ratio (RR), and risk difference (RD). RESULTS: Eight RCTs (total N=1239 participants) were included. Bupropion compared to placebo was associated with reduced ATS use (RR: 0.90; 95% CI: 0.84, 0.96), end-of-treatment ATS craving (SMD: -0.38; 95%CI: -0.63, -0.13), and adherence (RR: 0.91; 95%CI: 0.84, 0.99). Subgroup analysis showed greater reduction in ATS use with longer trial duration (12 weeks) (RR: 0.85; 95%CI: 0.78, 0.93) and greater reduction in end-of-treatment ATS craving in studies with mixed ATS use frequency (SMD: -0.46; 95%CI: -0.70, -0.22) and male-only samples (SMD: -1.26; 95%CI: -1.87, -0.65). CONCLUSION: Bupropion showed a significant modest reduction in ATS use and ATS craving (both rated as very low-quality evidence), larger in males (craving), and with longer treatment (ATS use). These results may inform future studies. More research is warranted on who might benefit from bupropion as ATSUD treatment.

Drug overdose deaths in Brazil between 2000 and 2020: an analysis of sociodemographics and intentionality

Objectives: To examine drug overdose records in Brazil from 2000 to 2020, analyzing trends over time in overdoses and overall sociodemographic characteristics of the deceased. Methods: Using data from the Brazilian Mortality Information System (Sistema de Informações sobre Mortalidade), we identified records from 2000-2020 in which the underlying cause-of-death was one of the following codes: X40-X45 (accidental poisoning), X60-X65 (intentional poisoning), or Y10-Y15 (undetermined intentionality poisoning). The Brazilian dataset included 21,410 deaths. We used joinpoint regression analysis to assess changes in trends over time. Results: People who died of drug overdoses in Brazil between 2000 and 2020 had a mean age of 38.91 years; 38.45% were women, and 44.01% were identified as White. Of the overdose deaths, 44.70% were classified as intentional and 32.12% were classified as unintentional. Among the identified drugs, stimulants were the most common class. However, most records did not report which drug was responsible for death. Conclusion: Sociodemographic trends in overdose deaths in Brazil must guide country-specific policies. Nevertheless, data collection protocols must be improved, particularly regarding the drug used in overdoses.

Drug overdose deaths in Brazil between 2000 and 2020: an analysis of sociodemographics and intentionality.

OBJECTIVES: To examine drug overdose records in Brazil from 2000 to 2020, analyzing trends over time in overdoses and overall sociodemographic characteristics of the deceased. METHODS: Using data from the Brazilian Mortality Information System (Sistema de Informações sobre Mortalidade), we identified records from 2000-2020 in which the underlying cause-of-death was one of the following codes: X40-X45 (accidental poisoning), X60-X65 (intentional poisoning), or Y10-Y15 (undetermined intentionality poisoning). The Brazilian dataset included 21,410 deaths. We used joinpoint regression analysis to assess changes in trends over time. RESULTS: People who died of drug overdoses in Brazil between 2000 and 2020 had a mean age of 38.91 years; 38.45% were women, and 44.01% were identified as White. Of the overdose deaths, 44.70% were classified as intentional and 32.12% were classified as unintentional. Among the identified drugs, stimulants were the most common class. However, most records did not report which drug was responsible for death. CONCLUSION: Sociodemographic trends in overdose deaths in Brazil must guide country-specific policies. Nevertheless, data collection protocols must be improved, particularly regarding the drug used in overdoses.

Gabapentin Use Among Individuals Initiating Buprenorphine Treatment for Opioid Use Disorder.

Importance: Gabapentin prescriptions have drastically increased in the US due to off-label prescribing in settings such as opioid use disorder (OUD) treatment to manage a range of comorbid conditions and withdrawal symptoms, despite a lack of evidence. Objective: To assess the purpose and associated risks of off-label gabapentin use in OUD treatment. Design, Setting, and Participants: This retrospective recurrent-event case-control study with a crossover design used administrative claims data from MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Individuals aged 12 to 64 years with an OUD diagnosis and filling buprenorphine prescriptions were included in the primary analysis conducted from July 1, 2022, through June 1, 2023. Unit of observation was the person-day. Exposures: Days covered by filled gabapentin prescriptions. Main Outcomes and Measures: Primary outcomes were receipt of gabapentin in the 90 days after initiation of buprenorphine treatment and drug-related poisoning. Drug-related poisonings were defined using codes from International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Results: A total of 109 407 patients were included in the analysis (mean [SD] age, 34.0 [11.2] years; 60 112 [54.9%] male). Among the 29 967 patients with Medicaid coverage, 299 (1.0%) were Hispanic, 1330 (4.4%) were non-Hispanic Black, 23 112 (77.1%) were non-Hispanic White, and 3399 (11.3%) were other. Gabapentin was significantly less likely to be prescribed to Black or Hispanic patients, and more likely to be prescribed to female patients, those with co-occurring substance use or mood disorders, and those with comorbid physical conditions such as neuropathic pain. Nearly one-third of persons who received gabapentin (4336 [31.1%]) had at least 1 drug-related poisoning after initiating buprenorphine treatment, compared with 13 856 (14.5%) among persons who did not receive gabapentin. Adjusted analyses showed that days of gabapentin use were not associated with hospitalization for drug-related poisoning (odds ratio, 0.98 [95% CI, 0.85-1.13]). Drug-related poisoning risks did not vary based on dosage. Conclusions and Relevance: Gabapentin is prescribed in the context of a myriad of comorbid conditions. Even though persons receiving gabapentin are more likely to have admissions for drug-related poisoning, these data suggest that gabapentin is not associated with an increased risk of drug-related poisoning alongside buprenorphine in adjusted analyses. More data on the safety profile of gabapentin in OUD settings are needed.

Prescription amphetamines in people with opioid use disorder and co-occurring psychostimulant use disorder initiating buprenorphine: an analysis of treatment retention and overdose risk.

BACKGROUND: Attention-deficit and hyperactivity disorder (ADHD) is frequently diagnosed in patients with substance use disorders (SUDs), including opioids. There remains concern about the safety and efficacy of prescription amphetamines (PAs) and their impact on effectiveness of opioid use disorder (OUD) treatment with buprenorphine. OBJECTIVES: To assess the effect of PAs on OUD buprenorphine treatment retention and/or SUD-related emergency admission or drug-related poisonings. METHODS: We used a retrospective cohort design with a secondary analysis of data from Merative MarketScan Commercial and Multi-State Medicaid Databases from 1 January 2006 to 31 December 2016. Individuals included were aged 12-64 years, had an OUD diagnosis and were prescribed buprenorphine. Our analysis used multivariable Cox regression to evaluate the relationship between PA receipt and time to buprenorphine discontinuation. The second part focused on subsamples of buprenorphine initiators who had either (1) any SUD-related emergency admissions or (2) drug-related poisoning. These outcomes were modelled as a function of PA exposure using conditional logistic regression models as part of a within-person, case-crossover design. FINDINGS: Our sample had 90 269 patients with OUD (mean age 34.2 years (SD=11.3)) who initiated buprenorphine. Being prescribed a PA was associated with improved buprenorphine retention among individuals both with (adjusted HR (aHR) 0.91 (95% CI 0.86 to 0.97)) and without a concurrent psychostimulant use disorder (PSUD) (aHR 0.92 (95% CI 0.90 to 0.93)). CONCLUSIONS: PA use was associated with improved buprenorphine retention in people with OUD with and without co-occurring PSUD. The risks of acute SUD-related events and drug-related poisonings associated with PA use did not differ when comparing PA-using days with days without PA use. CLINICAL IMPLICATIONS: Patients with OUD on buprenorphine should receive treatment with a PA when indicated.

Prescription psychostimulants for cocaine use disorder: A review from molecular basis to clinical approach.

Cocaine use is a public health concern in many countries worldwide, particularly in the Americas and Oceania. Overdose deaths involving stimulants, such as cocaine, have been increasing markedly in North America, especially with concurrent opioid involvement. To date, no pharmacological treatment is available to treat stimulant (including cocaine) use disorders. Prescription psychostimulants (PPs) could be useful to treat cocaine use disorder (CUD) as they share the pharmacological effects with cocaine, as evidenced by a recent meta-analysis that assessed 38 randomized clinical trials (RCTs). PPs were found to promote sustained abstinence and reduce drug use in patients with CUD. The aim of this paper is to provide a narrative review of the clinical pharmacology of PPs and comment on the current stage of evidence supporting PPs to treat CUD. We also propose a model of care that integrates PPs with evidence-based psychosocial interventions (such as cognitive-behavioural therapy [CBT] and contingency management [CM]), a harm reduction approach and case management with social support.

Can Contingency Management Solve the Problem of Adherence to Antiretroviral Therapy in Drug-Dependent Individuals?

Drug misuse among people living with HIV (human immunodeficiency virus) is associated with higher mortality. It is a frequently observed reason for treatment abandonment, with people who misuse drugs showing a 10 to 25 times higher risk of HIV than the general population. The authors conducted a systematic review and meta-analysis to assess the efficacy of contingency management (CM) to improve adherence to antiretroviral therapy in people living with HIV and substance use disorder (SUD). The inclusion criteria consisted of studies written in English, Italian, Spanish, German, and French; studies conducted with humans; and clinical trials that combined SUD treatment with CM for people living with HIV. Two hundred twenty-two articles were identified, five met all inclusion criteria, and three provided enough data to perform the meta-analysis. We considered treatment adherence by measuring the increase in the CD4 count as our primary outcome. We found a significant increase in treatment adherence in the patient group compared with the control groups during the intervention phase. Positive findings did not persist after the cessation of the incentives. The meta-analysis showed that the intervention improved patient adherence by 2.69 (95% confidence interval: [0.08, 0.51]; p = .007) compared with the control group during the intervention period. All short-term CM studies converged on a positive result for adherence to antiretroviral therapy.

The COVID-19 impact and characterization on substance use-related emergency department visits for adolescents and young adults in Canada: Practical implications.

RATIONALE: Coronavirus (COVID-19)-related stressors precipitated the mental health crisis and increased substance use in Canada and worldwide. As the pandemic continues to evolve, monitoring and updating substance use-related ED visit trends is essential to ensure the stability and quality of ED services under the prolonged pandemic timeline. AIMS AND OBJECTIVES: This study examined the trends and characterization of substance use-related ED visits during the pandemic among adolescents and young adults (aged 13-25 years) in Ontario, Canada. METHODS: Descriptive statistics and binary logistic regression analyses were conducted using population-based, repeated cross-sectional data. The volume, patient characteristics (age and sex) and hospital/ED visit features (triage to end time, timing of the visit, triage level and referral source) were compared before (2019) and during COVID-19 (2020 and 2021) by each substance type (alcohol, opioid, cannabis, sedatives, cocaine, stimulants and multiple psychoactive substances). RESULTS: Substance use-related ED visits decreased by 1.5 times during the pandemic compared to the prepandemic level. However, opioid-related ED visits continued to show an increasing trend and did not recover to the prepandemic level in 2021. Moreover, a significant increase in emergent/life-threatening triage levels (Canadian Triage and Acuity Scales 1 and 2) in substance-related ED visits is alarming (2019 = 36.8%, 2020 = 38.7% and 2021 = 38.4%). We also found a general decrease in weekend visits, overnight visits and visits on statutory holidays, and substance use-related ED patients tended to stay longer (over 6 h) in the ED during the pandemic. CONCLUSION: Our findings indicate unmet substance use treatment needs due to the limited accessibility and heightened threshold for ED visits during the pandemic. Providing access to substance treatment/programs outside ED is critical to reducing substance use-related complications presenting in the ED. Also, policies addressing the pandemic-related complexities in the ED and Health Human Resource challenges are warranted.

Marked Increase in Amphetamine-Related Emergency Department Visits and Inpatient Admissions in Toronto, Canada, 2014-2021.

BACKGROUND: We report emergency department and inpatient amphetamine-related trends focusing on co-occurring substance use and psychiatric diagnoses at the Centre for Addiction and Mental Health, the largest mental health teaching hospital in Canada. METHODS: We describe yearly trends in amphetamine-related Centre for Addiction and Mental Health emergency department visits and inpatient admissions out of all emergency department visits and inpatient admissions between 2014 and 2021, along with proportions of concurrent substance-related admissions and mental/psychotic disorders emergency department visits and inpatient admissions among amphetamine-related contacts; joinpoint regression analyses assessed changes in amphetamine-related emergency department visits and inpatient admissions. RESULTS: Amphetamine-related emergency department visits rose from 1.5% in 2014 to 8.3% in 2021, with a peak of 9.9% in 2020. Amphetamine-related inpatient admissions rose from 2.0% to 8.8% in 2021, with a peak of 8.9% in 2020. Significant increasing trends in the percentage of amphetamine-related emergency department visits happened especially between the second and the fourth quarter of 2014 (quarterly percent change = + 71.4, P <0.01). Similarly, the percentage of amphetamine-related inpatient admissions increased mostly between the second quarter of 2014 and the third quarter of 2015 (quarterly percent change = + 32.6, P <0.01). The proportion of concurrent opioid-related contacts among amphetamine-related emergency department visits and inpatient admission increased markedly between 2014 and 2021; psychotic disorders in amphetamine-related inpatient admissions more than doubled from 2015 to 2021. DISCUSSION: Prevalence of amphetamine use, mostly from methamphetamine, has been increasing in Toronto as have co-occurring psychiatric disorders and opioid use. Our findings highlight the need for increases in accessible efficacious treatments for complex populations with polysubstance use and co-occurring disorders.

Patterns of use and adverse events reported among persons who regularly inject buprenorphine: a systematic review.

BACKGROUND AND AIMS: Given the ongoing opioid crisis, novel interventions to treat severe opioid use disorder (OUD) are urgently needed. Injectable opioid agonist therapy (iOAT) with diacetylmorphine or hydromorphone is effective for the treatment of severe, treatment-refractory OUD, however barriers to implementation persist. Intravenous buprenorphine for the treatment of OUD (BUP iOAT) has several possible advantages over traditional iOAT, including a safety profile that might enable take-home dosing. We aimed to characterize injecting practices among real-world populations of persons who regularly inject buprenorphine, as well as associated adverse events reported in order to inform a possible future BUP iOAT intervention. METHODS: We conducted a systematic review. We searched MEDLINE, EMBASE, and PsycINFO from inception through July 2020 and used backwards citation screening to search for publications reporting on dose, frequency among persons who regularly inject the drug, or adverse events associated with intravenous use of buprenorphine. The review was limited to English language publications and there was no limitation on study type. Study quality and risk of bias was assessed using the Mixed Methods Appraisal Tool. Narrative synthesis was used in reporting the results. RESULTS: Eighty-eight studies were included in our review. Regular injection of buprenorphine was identified across diverse settings world-wide. Daily dose of oral buprenorphine injected was < 1-12 mg. Frequency of injection was 0-10 times daily. Adverse events could be characterized as known side effects of opioids/buprenorphine or injection-related complications. Most studies were deemed to be of low quality. CONCLUSIONS: Extramedical, intravenous use of buprenorphine, continues to be documented. BUP iOAT may be feasible and results may inform the development of a study to test the efficacy and safety of such an intervention. Future work should also examine acceptability among people with severe OUD in North America. Our review was limited by the quality of included studies.