Prevalence of comorbid substance use disorders among people with opioid use disorder: A systematic review & meta-analysis.

BACKGROUND: Comorbid substance use disorders (SUDs) among people with opioid use disorder (OUD) contribute to poor clinical outcomes, including overdose and mortality. We present the first systematic review and meta-analysis to estimate the prevalence of specific non-opioid SUDs among people with OUD. METHODS: We searched Embase, PsycINFO, and MEDLINE from 1990 to 2022 for studies that used Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) criteria to assess the prevalence of non-opioid SUDs among individuals with OUD. We used random-effects meta-analyses with 95% Confidence Intervals (CIs) to pool current and lifetime prevalence estimates separately. Meta-regressions and stratified meta-analyses were used to examine differences in prevalence estimates by sample characteristics and methodological factors. RESULTS: Of the 36,971 publications identified, we included data from 194 studies and 77,212 participants with OUD. The prevalence of any comorbid SUD among people with OUD was 59.5% (95%CI 49.1-69.5%) for current non-opioid SUDs, with 72.0% (95%CI 52.5-87.9%) experiencing a comorbid SUD in their lifetime. Of the studies that examined current comorbid SUDs, cocaine use disorder (30.5%, 95%CI 23.0-38.7%) was most common, followed by alcohol (27.1%, 95%CI 24.4- 30.0%), cannabis (22.7%, 95%CI 19.0-26.6%), sedative (16.1%, 95%CI 13.1-19.3%), and methamphetamine (11.4%, 95%CI 6.8-17.1%) use disorders. Substantial heterogeneity (I2>90%) across estimates was observed. Substantial heterogeneity (I2>90%) was observed across estimates, with significant variations in prevalence identified across geographic locations, recruitment settings, and other study-level factors. CONCLUSION: Findings from this study emphasize the importance of comorbid SUD treatment access for people with OUD. Our estimates can inform the provision of treatment and harm reduction strategies for people with OUD and specific subpopulations.

Agreement between self-reported illicit drug use and biological samples: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies often rely upon self-report and biological testing methods for measuring illicit drug use, although evidence for their agreement is limited to specific populations and self-report instruments. We aimed to examine comprehensively the evidence for agreement between self-reported and biologically measured illicit drug use among all major illicit drug classes, biological indicators, populations and settings. METHODS: We systematically searched peer-reviewed databases (Medline, Embase and PsycINFO) and grey literature. Included studies reported 2 × 2 table counts or agreement estimates comparing self-reported and biologically measured use published up to March 2022. With biological results considered to be the reference standard and use of random-effect regression models, we evaluated pooled estimates for overall agreement (primary outcome), sensitivity, specificity, false omission rates (proportion reporting no use that test positive) and false discovery rates (proportion reporting use that test negative) by drug class, potential consequences attached to self-report (i.e. work, legal or treatment impacts) and time-frame of use. Heterogeneity was assessed by inspecting forest plots. RESULTS: From 7924 studies, we extracted data from 207 eligible studies. Overall agreement ranged from good to excellent (> 0.79). False omission rates were generally low, while false discovery rates varied by setting. Specificity was generally high but sensitivity varied by drug, sample type and setting. Self-report in clinical trials and situations of no consequences was generally reliable. For urine, recent (i.e. past 1-4 days) self-report produced lower sensitivity and false discovery rates than past month. Agreement was higher in studies that informed participants biological testing would occur (diagnostic odds ratio = 2.91, 95% confidence interval = 1.25-6.78). The main source of bias was biological assessments (51% studies). CONCLUSIONS: While there are limitations associated with self-report and biological testing to measure illicit drug use, overall agreement between the two methods is high, suggesting both provide good measures of illicit drug use. Recommended methods of biological testing are more likely to provide reliable measures of recent use if there are problems with self-disclosure.

Prevalence of mental disorders among people with opioid use disorder: A systematic review and meta-analysis.

BACKGROUND: Opioid use disorder (OUD) and mental disorders are major public health issues and comorbidity is common. Among people with OUD, comorbid mental disorders are associated with poorer health outcomes. To our knowledge, this is the first systematic review and meta-analysis to estimate prevalence of specific mental disorders among people with OUD. METHODS: We searched Embase, MEDLINE, and PsycInfo from 1990 to 2021 for observational studies of depression, anxiety, post-traumatic stress disorder (PTSD), bipolar, personality, and other pre-specified mental disorders among people with OUD. We pooled current and lifetime estimates of each disorder using random-effects meta-analyses with 95% Confidence Intervals (CIs). Meta-regressions and stratified analyses were used to assess heterogeneity of prevalence estimates by methodological factors and sample characteristics. FINDINGS: Of the 36,971 publications identified, we included data from 345 studies and 104,135 people with OUD in at least one pooled estimate. Among people with OUD, the prevalence of current depression was 36.1% (95%CI 32.4-39.7%), anxiety was 29.1% (95%CI 24.0-33.3%), attention-deficit/hyperactivity disorder was 20.9% (95%CI 15.7-26.2%), PTSD was 18.1% (95%CI 15.4-20.9%), and bipolar disorder was 8.7% (95%CI 6.7-10.7%). Lifetime prevalence of anti-social personality disorder was 33.6% (95%CI 29.1-38.0%) and borderline personality disorder was 18.2% (95% CI 13.4-23.1%). Sample characteristics and methodological factors, including sex, were associated with variance of multiple prevalence estimates. INTERPRETATION: Our findings emphasise the need for access to mental disorder treatment among people with OUD. Specific mental disorder estimates may inform clinical guidelines, treatment services, and future research for people with OUD, including subpopulations with distinct treatment needs.

Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis.

Importance: Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality. Objective: To estimate the association of time receiving OAT with mortality. Data Sources: The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews. Study Selection: All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included. Data Extraction and Synthesis: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses. Main Outcomes and Measures: Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. Results: Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56). Conclusions and Relevance: This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains low. Work to improve access globally may have important population-level benefits.

Prevalence of childhood maltreatment among people with opioid use disorder: A systematic review and meta-analysis.

BACKGROUND: Experience of childhood maltreatment (CM) is a risk factor for opioid use disorder (OUD). CM is also associated with comorbid mental disorders and poor treatment outcomes among people with OUD. To our knowledge, this is the first systematic review and meta-analysis to estimate the prevalence of CM among people with OUD. METHODS: We searched MEDLINE, EMBASE, and PsycINFO to identify observational studies that evaluated CM among people with OUD from January 1990 to June 2020. Prevalence of each CM type, sample characteristics, and methodological factors were extracted from each eligible study. Random-effects meta-analyses were used to pool prevalence estimates. Stratified meta-analyses were used to assess heterogeneity. RESULTS: Of the 6,438 publications identified, 113 studies reported quantitative CM data among people with OUD and 62 studies (k = 62; N = 21,871) were included in primary analyses. Among people with OUD, the estimated prevalence of sexual abuse was 41% (95% CI 36-47%; k = 38) among women and 16% (95% CI 12-20%; k = 25) among men. Among all people with OUD, prevalence estimates were 38% (95% CI 33-44%; k = 48) for physical abuse, 43% (95% CI 38-49%; k = 31) for emotional abuse, 38% (95% CI 30-46%; k = 17) for physical neglect, and 42% (95% CI 32-51%; k = 17) for emotional neglect. Sex, history of injecting drug use, recruitment methods, and method of assessing CM were associated with substantial heterogeneity. CONCLUSIONS: People with OUD frequently report the experience of CM, supporting the need for trauma-informed interventions among this population. Future research should consider the impact of CM on OUD presentations and when assessment is appropriate, use of validated instruments.

All-cause and cause-specific mortality among people with regular or problematic cocaine use: a systematic review and meta-analysis.

AIMS: To estimate pooled all-cause and cause-specific mortality risk for people with regular or problematic cocaine use. METHODS: Systematic review and meta-analysis of prospective or retrospective cohort studies or clinical trials (n ≥30) of people with regular or problematic cocaine use with data on all-cause or cause-specific mortality. Of 2808 papers, 28 were eligible and reported on 21 cohorts, with a total 170 019 individuals. Cohorts identified based on acute care for drug poisoning or other severe health presentation were excluded. Title/abstract screening was conducted by one reviewer; a second reviewer independently checked 10% of excluded studies. Two reviewers conducted full-text screening. Data were extracted by one reviewer and checked by a second. A customized review-specific study reporting quality/risk of bias tool was used. Data on crude mortality rates (CMR) and standardized mortality ratios were extracted for both all-cause and cause-specific mortality. Standardized mortality ratios were imputed where not provided by the author using extracted data and information from the Global Burden of Disease Study 2017. Data were pooled using a random-effects model. RESULTS: The pooled all-cause crude mortality rate was 1.24 per 100 person-years [95% confidence interval (CI) = 0.86, 1.78; n = 16 cohorts], but with considerable heterogeneity (I2  = 98.8%). The pooled all-cause standardized mortality ratio (SMR) was 6.13 (95% CI = 4.15, 9.05; n = 16 cohorts). Suicide (SMR = 6.26, 95% CI = 2.84, 13.80), accidental injury (SMR = 6.36, 95% CI = 4.18, 9.68), homicide (SMR = 9.38, 95% CI 3.45-25.48) and AIDS-related mortality (SMR = 23.12, 95% CI = 11.30, 47.31) were all elevated compared with age and sex peers in the general population. CONCLUSIONS: There are elevated rates of mortality among people with regular or problematic cocaine use for traumatic deaths and deaths attributable to infectious disease.

Injecting risk behaviours amongst people who inject drugs: A global multi-stage systematic review and meta-analysis.

BACKGROUND: Injecting risk behaviour, such as receptive sharing of injecting equipment and/or re-using one's equipment, is associated with bloodborne virus transmission and infections in people who inject drugs (PWID). We aimed to estimate prevalence and correlates of injecting risk behaviours amongst PWID. METHODS: We conducted a systematic review and meta-analyses to estimate country, regional, and global prevalences of injecting risk behaviours (including sharing or re-using needle/syringe and sharing other injecting equipment). Using meta-regression analyses, we determined associations between study- and country-level characteristics and receptive needle/syringe sharing. RESULTS: From 61,077 identified papers and reports and 61 studies from expert consutation, evidence on injecting risk behaviours was available for 464 studies from 88 countries. Globally, it is estimated that 17.9% (95%CI: 16.2-19.6%) of PWID engaged in receptive needle/syringe sharing at last injection, 23.9% (95%CI: 21.2-26.5%) in the past month, and 32.8% (95%CI: 28.6-37.0%) in the past 6-12 months. Receptive sharing of other injecting equipment was common. Higher prevalence of receptive needle/syringe sharing in the previous month was associated with samples of PWID with a lower proportion of females, shorter average injecting duration, a higher proportion with ≥daily injecting, and older studies. Countries with lower development index, higher gender inequality and lower NSP coverage had higher proportions reporting receptive needle/syringe sharing. CONCLUSIONS: High levels of injecting risk behaviours were observed amongst PWID globally, although estimates were only available for half of the countries with evidence of injecting drug use. There is a need for better capturing of injecting risk behaviours in these countries to inform implementation of harm reduction services and evaluate potential impacts of interventions to reduce risk.

All-Cause and Cause-Specific Mortality Among People Using Extramedical Opioids: A Systematic Review and Meta-analysis.

Importance: Extramedical opioid use has escalated in recent years. A better understanding of cause-specific mortality in this population is needed to inform comprehensive responses. Objective: To estimate all-cause and cause-specific crude mortality rates (CMRs) and standardized mortality ratios (SMRs) among people using extramedical opioids, including age- and sex-specific estimates when possible. Data Sources: For this systematic review and meta-analysis, MEDLINE, PsycINFO, and Embase were searched for studies published from January 1, 2009, to October 3, 2019, and an earlier systematic review on this topic published in 2011. Study Selection: Cohort studies of people using extramedical opioids and reporting mortality outcomes were screened for inclusion independently by 2 team members. Data Extraction and Synthesis: Data were extracted by a team member and checked by another team member. Study quality was assessed using a custom set of items that examined risk of bias and quality of reporting. Data were pooled using random-effects meta-analysis models. Heterogeneity was assessed using stratified meta-analyses and meta-regression. Main Outcomes and Measures: Outcome measures were all-cause and cause-specific CMRs and SMRs among people using extramedical opioids compared with the general population of the same age and sex. Results: Of 8683 identified studies, 124 were included in this analysis (100 primary studies and 24 studies providing additional data for primary studies). The pooled all-cause CMR, based on 99 cohorts of 1 262 592 people, was 1.6 per 100 person-years (95% CI, 1.4-1.8 per 100 person-years), with substantial heterogeneity (I2 = 99.7%). Heterogeneity was associated with the proportion of the study sample that injected opioids or was living with HIV infection or hepatitis C. The pooled all-cause SMR, based on 43 cohorts, was 10.0 (95% CI, 7.6-13.2). Excess mortality was observed across a range of causes, including overdose, injuries, and infectious and noncommunicable diseases. Conclusions and Relevance: The findings suggest that people using extramedical opioids experience significant excess mortality, much of which is preventable. The range of causes for which excess mortality was observed highlights the multiplicity of risk exposures experienced by this population and the need for comprehensive responses to address these. Better data on cause-specific mortality in this population in several world regions appear to be needed.

Responding to global stimulant use: challenges and opportunities.

We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.

Mortality among people with regular or problematic use of amphetamines: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Amphetamines are the second most commonly used class of illicit drugs. We aimed to produce pooled estimates of mortality risks among people with regular or dependent use of amphetamines, with a focus upon all-cause mortality as well as specific causes of death. DESIGN: Systematic review and meta-analysis of cohorts of people with problematic use or dependence on amphetamines with data on all-cause or cause-specific mortality. SETTING AND PARTICIPANTS: Of 4240 papers, 30 were eligible, reporting on 25 cohorts that measured all-cause mortality, drug poisoning, suicide, accidental injuries, homicide and cardiovascular mortality. Cohorts (n = 35-74 139) were in North America, several Nordic countries and Asia Pacific. MEASUREMENT: Titles/abstracts were independently screened by one reviewer and excluded those reviewed by a second reviewer. Full-text screening was by two reviewers with discrepancies resolved via a third reviewer. We extracted data on crude mortality rates (CMR) per 100 person-years (py), standardized mortality ratios (SMRs). We imputed SMRs where possible if not reported by study authors. We also calculated mortality relative risks. Data were pooled using random-effects models; potential reasons for heterogeneity were explored using subgroup analyses and meta-regressions. FINDINGS: Twenty-three cohorts contributed data for the pooled all-cause CMR: 1.14 per 100 py [95% confidence interval (CI) = 0.92-1.42]. Pooled cause-specific mortality rates were: drug poisoning, 0.14 per 100 py (95% CI = 0.06-0.34); cardiovascular disease, 0.13 per 100 py (95% CI = 0.06-0.29); suicide, 0.20 per 100 py (95% CI = 0.07-0.55); accidental injury, 0.20 per 100 py (95% CI = 0.08-0.47) and homicide, 0.03 per 100 py (95% CI = 0.02-0.06). There was substantial heterogeneity for all pooled CMR estimates except homicide. The pooled all-cause SMR was 6.83 (95% CI = 5.27-8.84). Pooled cause-specific SMRS were: poisoning, 24.70 (95% CI = 16.67, 36.58); homicide, 11.90 (95% CI = 7.82-18.12); suicide, 12.20 (95% CI = 4.89-30.47); cardiovascular disease, 5.12 (95% CI = 3.74-7.00) and accidental injury, 5.12 (95% CI = 2.88-9.08). CONCLUSIONS: People with regular or dependent amphetamine use are at elevated risk of a range of causes of mortality compared with people without regular or dependent amphetamine use.