Key Message

A preponderance of evidence identified in this review indicates a relative benefit in the clinical effectiveness of heroin-assisted treatment, injectable hydromorphone, or diacetylmorphine compared to methadone in patients with opioid use disorder. Most of the evidence in this review describing sustained-release oral morphine versus methadone shows no significant difference in measures of clinical effectiveness for patients with opioid use disorder. There is a lack of evidence reported in systematic reviews and randomized controlled trials describing the clinical effectiveness of oral hydromorphone, fentanyl patches, and fentanyl buccal tablets. Most of the evidence in this review, describing various forms of opioid substitution treatments, has been characterized as low quality and draws from the same several trials.

Key Message

Overdose deaths have been occurring at high rates in many parts of Canada. From January 2016 (when national surveillance began) to March 2019, an estimated 12,800 Canadians died of an opioid overdose.1 In addition to opioid-related harms, stimulants such as methamphetamine have re-emerged in some regions and are also contributing to the current rise in overdose deaths.

COVID-19 has resulted in a more compromised illicit drug supply, and those who use drugs have had limited access to formal and informal supports because of public health measures regarding physical distancing. As a result, overdose deaths have increased during the pandemic.

Harm reduction approaches provide a mechanism to prevent overdose deaths and have additional health and public safety benefits. The current crisis has been exacerbated by COVID-19; therefore, it is an appropriate time to consider the entire continuum of harm reduction approaches available to reduce preventable overdose deaths.

People with lived experience of drug use should be meaningfully included in policy discussions about harm reduction and overdose prevention interventions. This would enhance the person-centredness of programs and ensure they are reflective of the lived realities of those who use drugs.

Although societal attitudes about drug use are changing, harm reduction interventions remain politically contentious. Countering stigma, being prepared to engage with community concerns, and clearly articulating that harm reduction services are intended to complement and not replace drug treatment are all important in enhancing public understanding of harm reduction.

Key Message

Thirty-four studies were identified that were relevant for this report. Eight studies were systematic reviews (SRs), three were randomized controlled trials (RCTs), and 23 were non-randomized studies. No relevant evidence-based guidelines were identified. The studies included a variety of populations, including individuals with bipolar disorder, schizophrenia, MDD, postpartum depression, post-traumatic stress disorder, and individuals who have suicidal ideation or have attempted suicide. No specific information on subgroups (such as immigrant, refugee, ethnocultural, or racialized individuals; or First Nations, Métis, Inuit; or lesbian, gay, bisexual, transgender, queer or questioning, and two-spirited [LGBTQ2+]) were found. Two studies focused on young children (ages three to seven), and one study used the National Health and Nutrition Examination Survey (NHANES), which includes children and adults. No effectiveness or accuracy information was found on adolescents or older adults with mental health conditions, as the majority of studies focused on adults over the age of 18 and under the age of 65. Intended users of these AI technologies were primarily clinicians (for diagnosis), but three studies examined models that were intended for use by patients. The primary purpose of the AI or ML models was to differentiate patients who have or do not have mental health conditions or to assist in treatment. Diagnostic accuracy of AI or ML models was generally moderate to high when compared with physician assessment, and AI-based applications for the treatment of patients significantly reduced depression symptoms and increased the use of crisis resources in studies that compared various versions of electronic applications for mental health.

This literature review was commissioned by The Mental Health Commission of Canada to address the role of AI in mental health services. This report is a companion to an Environmental Scan, which provides more information on the types and trends of AI either emerging or currently in use for the prevention, diagnosis, or treatment of mental health problems and illnesses, research and development initiatives, and the professional groups and organizations involved in the development or use of these technologies in Canada and internationally [Artificial Intelligence and Machine Learning in Mental Health Services: An Environmental Scan. Ottawa: Canadian Agency for Drugs and Technology in Health (CADTH), Mental Health Commission of Canada (MHCC); 2021 June.]

Key Message

​• Two systematic reviews, 3 randomized controlled trials, and 2 single-arm safety trials were identified that evaluated several combinations of psychedelic-assisted psychotherapy. Psilocybin was the psychedelic most tested. Other psychedelics identified in the systematic reviews and primary studies were 3,4-methylenedioxymethamphetamine (or MDMA), lysergic acid diethylamide (or LSD), ayahuasca (also named N,N-dimethyltryptamine [or DMT]), ibogaine, ketamine, and nitrous oxide. • Manualized therapy (not defined) and non-directive support (not defined) were the psychotherapies most studied in the relevant primary studies in the 2 systematic reviews. Other psychotherapies identified included integrative psychotherapy, cognitive behavioural therapy (CBT), CBT and motivational enhancement therapy, psychosocial interventions, non-directive support, group talk therapy, and guided support. • Clinical effectiveness lasting weeks to months was observed in 1 systematic review that reviewed primary studies examining various combinations of psychedelics and psychotherapy in patients with various mental health conditions. Significant improvement in symptom scores related to mental illnesses and no serious and long-term adverse events were reported in the other systematic review. • Various combinations of psychedelics and psychotherapies were evaluated in 3 randomized controlled trials (RCTs) and 2 safety studies. Ketamine-assisted psychotherapies were associated with improvements in the symptoms related to substance use disorder in 2 RCTs. Psilocybin-assisted psychotherapy was reported to be efficacious in treating MDD in 1 RCT. No serious adverse effects were reported in the RCTs or in 2 safety trials using MDMA-assisted psychotherapy. • There were several limitations to the included studies, including small sample sizes (less than 20 in the majority of primary studies), relatively short follow-ups (1 week to 3 years; less than or equal to 1 year in 27 out of 31 relevant publications), differences in psychotherapy classification between systematic reviews, considerable heterogeneity between studies, and unclear generalizability and availability of the interventions in Canadian contexts. Therefore, findings should be interpreted with caution. No relevant guidelines were identified.

Key Message

Moderate to weak evidence suggests that patients with substance use disorders who received residential treatment were more likely than outpatients to complete treatment and be considered abstinent. Comparisons between residential treatment and outpatient programs for other outcomes were unclear. Strong- to weak-quality evidence showed that residential treatment services for patients with substance use disorders was effective in improving various outcomes including substance use, social, criminal activity, and mental health outcomes. However, residential treatment was likely associated with poorest survival outcomes after discharge compared to other treatments.Managed alcohol programs in hospital settings appeared to be effective and safe in preventing and treating alcohol withdrawal syndrome in surgical patients, trauma patients, or hospitalized patients. The level of evidence was not assessed.There was evidence that managed alcohol programs in community settings improved drinking patterns, alcohol-related harm, criminal activity, mental health, and social and physical well-being. The level of evidence was not assessed.The American Society of Addiction Medicine clinical practice guideline provides recommendations for the identification and management of alcohol withdrawal in inpatient and ambulatory settings. Patients’ current signs and symptoms, levels of risk for developing severe or complicated withdrawal or complications of withdrawal, and other dimensions should be taken into consideration in the assessment process to determine the appropriate level of care. Strength of recommendations was not assessed.The Canadian Coalition for Seniors’ Mental Health recommends that patients with cannabis use disorder should be considered for residential treatment if they are unable to effectively reduce or cease their cannabis use (level of evidence: Low; strength of recommendation: Strong).

Key Message

Five relevant reports were identified. These comprised one systematic review, two randomized controlled trials (RCT), and two economic evaluations.

One systematic review found that compared to patients treated with other treatments (i.e., methadone, or any other treatment program) those treated with injectable diacetylmorphine (DAM) (with or without the addition of methadone) had statistically significantly greater retention in treatment, reduction in illicit drug use, reduction in criminal activities, and fewer convictions and imprisonments, but no statistically significant difference in mortality and greater occurrence of adverse events.

One RCT showed that injectable hydromorphone (HDM) was not inferior to injectable DAM with respect to days of street opioid use, and proportions of urinalysis positives for street heroin metabolites in urine samples. There were no statistically significant between-group differences with respect to retention to treatment, criminal activity, and physical health and psychological health, however there was statistically significantly higher risk of adverse events related to the intervention in the DAM group compared to the HDM group.

One crossover RCT with 28 patients showed that there was statistically significant improvement after injectable DAM treatment compared to before treatment with respect to anxiety, anger, emotional excitement and well-being, and statistically significantly less heroin craving with injectable DAM compared to injectable placebo.

The results of the economic evaluations, considering a lifetime time horizon and societal perspective, indicated that DAM and HDM treatments each provided more benefits than methadone treatment, and at lower cost for individuals who had previously used other treatment options. Based on incremental cost-effectiveness ratios, it was found that both DAM and HDM dominated methadone. One evaluation reported that the probability of DAM being cost-effective was 76% at a willingness-to-pay (WTP) threshold of $0 per QALY gained, and 95% at a WTP threshold of $100,000 per QALY gained. The second evaluation did not report the WTP threshold.

Findings need to be interpreted with caution, considering the overall limited quantity of evidence, and that the economic evaluations were based on several assumptions.

Key Message

Three systematic reviews, nine randomized controlled trials, and two guidelines were identified that addressed the research questions, and the results were mixed.

One randomized controlled trial was identified and provided results regarding the clinical effectiveness of pharmacological and non-pharmacological smoking interventions for youth. Evidence from this randomized controlled trial suggested that there were no significant differences in smoking cessation or smoking frequency outcomes between brief advice, nicotine patch therapy and a 6-week text messaging intervention (intervention) and brief advice and nicotine patch therapy (control).

Three systematic reviews and eight randomized controlled trials were identified and examined the clinical effectiveness a variety of different non-pharmacological smoking interventions for youth. Evidence from the systematic reviews did not reveal improved smoking cessation outcomes for most comparisons; two comparisons via meta-analyses did find improved smoking cessation outcomes in favour of the intervention. Of the seven randomized controlled trials that examined smoking cessation outcomes, three studies found reductions in favour of the smoking cessation intervention, three did not find differences between groups, and one study found improvements at 3-months in favour of the intervention but not at 6-month follow-up. Mixed findings were found for other key clinical outcomes, such as smoking behaviour and quitting outcomes.

Two evidence-based guidelines regarding smoking cessation interventions for youth were identified; one guideline was commissioned by National Institute for Health and Care Excellence and the other by the Canadian Task Force on Preventive Health Care. The National Institute for Health and Care Excellence guideline recommends the consideration of nicotine replacement therapy for young people who are dependent on nicotine (strength of recommendation: weak); if nicotine replacement therapy is prescribed, the guideline recommends offering it with behavioural support (strength of recommendation: strong). The Canadian Task Force on Preventive Health Care guidelines recommend asking children and youth smokers or their parents about tobacco use by the child or youth and offering brief information and advice during primary care visits (strength of recommendation: weak). Both guidelines used rigorous methodology to inform their recommendations, but the studies included to inform the recommendations were of varying quality, ranging from low to moderate quality.

It may be premature to draw conclusions about pharmacological and non-pharmacological smoking cessation interventions for youth given the mixed findings identified in this report.

Key Message

Two relevant systematic reviews, three randomized controlled trials (in four publications), six non-randomized studies, and two economic evaluations were identified regarding the clinical effectiveness, safety, and cost-effectiveness of various buprenorphine formulations for the treatment of OUD.Though there were some instances where specific formulations of buprenorphine demonstrated statistically significant improvements in outcomes of interest compared to other formulations, no clear patterns emerged regarding the comparative clinical effectiveness of buprenorphine for the treatment of OUD. The economic evaluation concluded that buprenorphine implant did not provide cost-effective benefit over generic sublingual buprenorphine-naloxone (BUP-NAL). The second economic evaluation reported that implantable buprenorphine was cost-effective compared to sublingual buprenorphine. It remains uncertain whether the findings of the reviewed literature are generalizable to the Canadian population as all of the included studies were conducted outside of Canada.Two evidence-based guidelines were identified regarding the use of various buprenorphine formulations for the treatment of OUD. One guideline recommends BUP-NAL as a first-line therapy for individuals who require opioid agonist treatment (strong recommendation based on high quality evidence). The second guideline recommends offering either BUP-NAL or methadone, while considering patient preferences, for individuals with OUD (strong recommendation). The limitations of the included studies, such as several with lack of blinding to treatment or few studies from Canadian settings, and of this report should be considered when interpreting the results.