Evidence-based Interventions for Youth With Concurrent Mental Health and Substance Use Disorders: A Scoping Review: Interventions fondées sur des données probantes pour les jeunes atteints de troubles concomitants de santé mentale et liés à l’usage de substances psychoactives : une étude de la portée
Department of Psychiatry, 12357Faculty of Medicine & Dentistry, 3158University of Alberta, Edmonton, Alberta, Canada
School of Public Health, 3158University of Alberta, Edmonton, Alberta, Canada
Department of Health Sciences, 4257Queen's University, Kingston, Ontario, Canada
Department of Medicine, 70401Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Department of Political Science, Faculty of Arts, University of Alberta, Edmonton, Alberta, Canada
Department of Philosophy, 170234Faculty of Arts, 3158University of Alberta, Edmonton, Alberta, Canada
Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada
Geoffrey & Robyn Sperber Health Sciences Library, 3158University of Alberta, Edmonton, Alberta, Canada
Tyler Marshall, Department of Psychiatry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada. Email: tyler.marshall@ualberta.caAbstract
Background
Mental health and substance use disorders typically onset during youth and commonly co-occur. Integrated treatment of two or more co-existing mental health and substance use disorders (i.e., concurrent disorders) is increasingly prevalent in real-world clinical settings. However, the depth of the evidence base on best practices remains unclear.
Objectives
This scoping review aimed to identify, map and summarize peer-reviewed studies of interventions for concurrent disorders in youth.
Methods
Six electronic health databases were systematically searched, in addition to a hand search of the reference lists of relevant systematic reviews. Only peer-reviewed studies of interventions treating concurrent disorders (i.e., simultaneous treatment of two or more disorders) in youth (10–29 years old) were eligible. Two independent reviewers conducted screening and data extraction. Results were charted according to studies employing pharmacological and non-pharmacological interventions.
Results
Thirty peer-reviewed studies were included, 19 (63.3%) were randomized controlled trials (RCTs). Most studies enrolled participants with an unspecified substance use disorder (n=17, 56.7%), while alcohol use was the primary substance use disorder in seven (23.3%) studies, followed by cannabis use disorder in six (20.0%) studies. Mood disorders (e.g., depression, dysthymia) were the most common concurrent mental health disorders comprising 15 (50%) studies, followed by nine (30.0%) studies of behavioural disorders (e.g., ADHD) and five (16.7%) studies of unspecified psychiatric disorders. Eighteen (60.0%) studies (n=1,699 participants) investigated the effectiveness of various non-pharmacological interventions, while 12 (40.0%) studies examined pharmacotherapies (n=765 participants).
Conclusion
Although several RCTs were identified, substantial clinical and methodological heterogeneity was evident among the studies (e.g., patients with multiple disorders, and multi-faceted interventions). Smaller systematic reviews focused on specific interventions (e.g., behavioural therapies) and concurrent disorders (e.g., depression and substance use) may be warranted. Due to considerable heterogeneity, more RCTs are needed before conducting larger systematic reviews or meta-analyses.
Plain Language Summary Title
Evidence-based interventions for youth with concurrent mental health and substance use disorders: A scoping review
Plain Language Summary
Why was the study done?
This study aimed to explore the treatment of concurrent mental health and substance use disorders in youth, as these conditions often occur together and are difficult for clinicians to treat. Best practices remain unclear.
What did the researchers do?
The researchers conducted a scoping review, systematically searching six electronic health databases for peer-reviewed studies focused on interventions for youth (ages 10-29) dealing with both mental health and substance use disorders. They screened and extracted data independently from eligible studies.
What did the researchers find?
The review included 30 studies, and 63.3% were randomized controlled trials (RCTs). A majority (56.7%) of the studies included participants with unspecified substance use disorders. The most common specified substance use disorders were alcohol (23.3%), and cannabis (20.0%). Mood disorders were prevalent in 50.0% of the studies, followed by behavioural disorders (30.0%) and unspecified psychiatric issues (16.7%). Non-pharmacological interventions were investigated in 60.0% of the studies, and pharmacological interventions were examined in 40.0%.
What do the findings mean?
The review found several studies, but they varied significantly in participant population and study design, highlighting a need for more RCTs for youth with concurrent disorders. Additional research will help establish clearer clinical practice guidelines and inform future systematic reviews and meta-analyses.
Abrégé
Contexte
Les troubles de santé mentale et les troubles liés à l'usage de substances psychoactives apparaissent généralement pendant la jeunesse et sont souvent concomitants. Le traitement intégré de deux ou plusieurs troubles coexistants de santé mentale et liés à l'usage de substances psychoactives (c.-à-d. troubles concomitants) est de plus en plus prévalent dans le milieu clinique réel. Toutefois, la profondeur de la base de connaissances sur les meilleures pratiques reste peu claire.
Objectifs
Cette étude de la portée visait à recenser, cartographier et résumer les études évaluées par des pairs portant sur les interventions relatives aux troubles concomitants chez les jeunes.
Méthodologie
Six bases de données électroniques sur la santé ont fait l'objet d'une recherche systématique, en plus d'une recherche manuelle des listes de référence des revues systématiques pertinentes. Seules les études évaluées par des pairs et portant sur des interventions destinées à traiter des troubles concomitants (c.-à-d. le traitement simultané de deux troubles ou plus) chez les jeunes (10 à 29 ans) étaient retenues. Deux examinateurs indépendants ont procédé à la sélection et à l'extraction des données. Les résultats ont été classés en fonction des études utilisant des interventions pharmacologiques et non pharmacologiques.
Résultats
Trente études évaluées par des pairs ont été incluses, dont 19 (63,3 %) étaient des essais cliniques randomisés (ECR). La plupart des études ont recruté des participants souffrant d'un trouble lié à l'usage de substances psychoactives non spécifié (n = 17, 56,7 %), tandis que la consommation d'alcool était le principal trouble lié à l'usage de substances psychoactives dans sept études (23,3 %) suivi par le trouble lié à l'usage du cannabis dans six études (20,0 %). Les troubles de l'humeur (p. ex., dépression, dysthymie) étaient les troubles mentaux concomitants les plus fréquents, avec 15 études (50 %), suivies de neuf études (30 %) consacrées aux troubles du comportement (p. ex., TDAH) et de cinq études (16,7 %) portant sur des troubles psychiatriques non spécifiés. Dix-huit études (60 %) (n = 1 699 participants) ont examiné l'efficacité de diverses interventions non pharmacologiques, tandis que 12 études (40 %) s'intéressaient aux pharmacothérapies (n = 765 participants).
Conclusion
Bien que plusieurs ECR aient été recensés, une grande hétérogénéité clinique et méthodologique a été constatée entre les études (p. ex., patients souffrant de troubles multiples et interventions à volets multiples). Des revues systématiques plus restreintes, axées sur des interventions particulières (p. ex., thérapies comportementales) et sur des troubles concomitants (p. ex., dépression et toxicomanie), pourraient être justifiées. En raison de l'hétérogénéité considérable, davantage d'ECR sont nécessaires avant de procéder à des revues systématiques ou à des méta-analyses de plus grande envergure.
Introduction
Addressing the rising prevalence of mental health disorders and substance use disorders (SUDs) in youth is an urgent global health priority.1,2 Since the onset of the COVID-19 pandemic, the prevalence rates of these conditions have increased, impacting youth disproportionately, globally. 3 As a result, there is a need for research and policy focus to better support mental health in this age group. Mental health disorders and SUDs often co-exist and function in tandem, complicating both research and intervention strategies. 4 Herein known as “concurrent disorders,” having a diagnosis of a mental health disorder and SUD simultaneously is associated with a myriad of poorer health outcomes compared to having either condition alone. These may include increased mental health or substance use symptom severity (e.g., depression symptoms, more frequent substance use), elevated risk of substance-related overdose or poisoning, and increased risk of chronic physical health conditions such as diabetes or HIV. The presence of one or more concurrent disorders may compound deficits in executive function, which can impair decision-making processes that serve to regulate engagement in high-risk behaviours such as solitary or poly-substance use, unhealthy dietary habits, and unsafe sexual practices. 5
The onset of mental health symptoms typically begin in childhood or adolescence, while substance use and SUDs more commonly initiates later in adolescence or emerging adulthood. 6 Authors of a previous review suggested that over half of adults with SUDs are diagnosed with three or more comorbid mental health disorders. 7 Similarly, authors of a study found that 63% of 1167 adolescents enrolled in a community-based addiction treatment program in the United States met the diagnostic criteria for an additional mental health disorder. 8 Evidence also suggests disruptive behavioural/impulse-control disorders, mood and anxiety disorders, eating disorders, and personality disorders are the most commonly comorbid psychiatric disorders among youth and young adults with SUDs. 9
The period of rapid brain development during adolescence and young adulthood represents a particularly vulnerable developmental stage for the onset of mental health disorders and SUDs. 10 For instance, multiple childhood-onset mental health disorders, including depression, anxiety, and disruptive behaviour disorders have been shown to increase the risk of adolescent-onset SUD. 11 Early onset mental health disorders in youth are associated with earlier onset of substance use, increased risk of future opioid use disorders in young people, 12 increased utilization of SUD treatment resources and generally poorer SUD treatment response. 13 Conversely, problematic substance use during adolescence may worsen preexisting mental disorders or increase the risk of developing new mental health disorders. For example, regular cannabis use during adolescence has been shown to dramatically increase the risk of developing psychotic symptoms, depressive symptoms, anxiety symptoms and functional impairment in a dose-dependent manner. 14 The high prevalence of concurrent disorders may be further explained by shared genetic and environmental risk factors and common brain regions and neural circuits implicated in both disorders. 15
Clinical experts suggest that standard care for youth with SUD is often insufficient and may not adequately address underlying comorbidities and psychosocial issues, which may limit recovery potential and increase the risk of relapse. 15 However, treatment for concurrent disorders in youth is notoriously challenging due to the complicated interplay between multiple disorders, causing a further burden on individual patients, families and healthcare systems. 16 Moreover, the treatments that exist for these conditions in youth are poorly accessible due to costs, geographic location (e.g., urban/rural disparities) or are developmentally inappropriate (e.g., adult psychiatry services for young adults 18–25 years). 17 Insufficient or untimely intervention consequently increases the risk of poor outcomes such as academic underachievement, incarceration, unemployment, homelessness and long-term health complications such as cardiovascular disease, substance-related overdose and early death. 13
Treatment of concurrent disorders has traditionally involved treating the mental health and substance use conditions separately, which often results mixed outcomes. 17 As evidenced by previous systematic reviews and guidelines, integrated treatment (i.e., simultaneous) of concurrent disorders may promote enhanced health outcomes for adults with these conditions.18,19 Although there is growing empirical support for integrated treatments for concurrent disorders in adults, the evidence base for youth is still emerging. Youth may benefit the most from early intervention and treatment, and evidence-based interventions are urgently needed. 19 As a result, we believe that a scoping review is necessary to map the available evidence and guide the development of future studies required to inform clinical practice and health policy, which aligns with recommendations from the World Health Organization (WHO) for the early identification and treatment of mental health disorders. 20 The objective of this scoping review was to identify, map and summarize peer-reviewed studies of interventions for concurrent disorders in youth aged 10–29 years. Additionally, this study aimed to provide an overview of the existing knowledge on this topic, and identify gaps and limitations in the literature.
Methods
Study Design
A scoping review was conducted. For this study, we used an iterative team-based approach to guide the methodological framework based on steps suggested by Arksey & O’Malley, 21 Levac et al. 22 and Daudt et al. 23 The reporting of the results was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklists. 24 The protocol for this scoping review was registered a priori on Open Science Framework (https://osf.io/ck8eu/).
Data Sources
Prior to conducting the review, PubMed and The International Prospective Register of Systematic Reviews (PROSPERO) were searched for systematic reviews related to concurrent disorders in youth to avoid duplicating any pre-existing work. The following six health databases were systematically searched from 1980 until 8 February 2024: (i) MEDLINE, (ii) PsycINFO, (iii) EMBASE, (iv) Cochrane Database of Systematic Reviews, (v) Cochrane Central Register of Controlled Trials (CENTRAL) and (vi) Scopus.
Search Strategy
A librarian (MK) experienced with systematic searching for scoping reviews conducted searches in the following bibliographic databases from inception to 25 October 2021: Medline, EMBASE, PsycINFO via OVID; Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCOhost; Scopus; and Cochrane Library via Wiley. The search comprised natural language keywords and subject headings, such as MeSH. The comprehensive search strategy was derived from four main concepts: (1) SUDs including both drugs and alcohol; (2) mental health disorders; (3) concurrent or dual diagnosis; (4) adolescents or youth. Non-peer-reviewed publication types, such as editorials and letters, were removed from the results. No language limits were used during the search to increase sensitivity despite “published in English” being a requirement in the eligibility criteria below. See Appendix 1 for the complete search strategies.
Two search updates were completed in December 2022 and February 2024. The search strategy used for each update did not deviate from the original. Results were exported in complete batches and the synthesis review management software, Covidence was used to remove duplicate records (Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. Available at www.covidence.org). After the database searches were complete, the reference lists of relevant systematic reviews25,26 were searched to ensure the accuracy of the database searches and reduce the risk of missing potentially relevant articles.
Study Selection Process
The Population Intervention Comparator Outcomes Study-type (PICOS) model 27 was used to guide the development of the eligibility criteria.
Eligibility Criteria
Population
Studies of participants with a mean age between 15 and 24 were included based on the United Nations definition of youth. 28 If the participant age was reported as a range rather than a mean, studies with participants beyond 10 to 29 were excluded.
To be included, a study was required to report that all study participants had symptoms of at least one mental health disorder and one substance use disorder. This could be determined by diagnosis via established diagnostic criteria such as Diagnostic and Statistical Manual third edition (DSM-III), newer editions, the International Classification of Disease (ICD-7), or newer editions, a positive screen for a mental health and substance use disorder using a validated instrument (e.g., PHQ-9) or enrolment into an inpatient psychiatric hospital (equates to a mental health diagnosis) or residential addiction treatment facility (equates to a substance use disorder diagnosis).
Intervention
Any intervention targeting concurrent disorders in youth (as defined above) was eligible for inclusion, such as pharmacotherapy, psychotherapy, family-based interventions or combined approaches. All clinical settings (e.g., inpatient, outpatient, virtual) were eligible for inclusion.
Control
Studies with or without a control group were eligible for inclusion. For controlled studies, all types of control groups were eligible.
Outcomes
For eligibility, studies must have reported at least one clinically relevant patient health outcome (e.g., substance use, mental health, quality of life, education attainment, functional status). Studies of interventions that only aimed to promote healthcare provider outcomes (e.g., physician knowledge) were excluded.
Study Type
Only peer-reviewed primary research studies were eligible for inclusion. Conference proceedings/abstracts, posters, theses/dissertations, grey literature, systematic reviews, dissertations, protocols and studies without a full-text PDF were excluded.
Screening
Each article was initially screened by title and abstract; those abstracts deemed relevant were then reviewed by full-text pdf. Two independent reviewers were given the same a priori eligibility criteria to screen articles. A third reviewer (TM), who has previous experience with systematic reviews, resolved disagreements by discussion when necessary. Covidence software was utilized to facilitate the screening and extraction (Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. Available at www.covidence.org). To pilot the screening process, 10% of the identified studies were initially reviewed to ensure accuracy. For abstract screening, studies with “yes” and “maybe” votes were sent to full text for assessment, while studies with “yes” and “no” votes were reviewed by a third reviewer (TM). A similar process was used for full-text screening, with the added requirement of listing a reason for exclusion if the text garnered a “no” vote (see list of exclusions in the PRISMA diagram).
Data Extraction
Two reviewers developed the extraction sheet by randomly selecting two included studies to extract independently; then, a consensus meeting was held to confirm the extraction sheet before extracting the remaining articles. The reviewers extracted on two separate extraction sheets and then met and collated their responses on a third extraction sheet. A third reviewer (AEL) reviewed the final extraction sheet. Author (TM) was designated as the arbitrator for any disagreements that could not be resolved by discussion between the reviewers.
Collating, Summarizing, and Reporting the Results
Upon completion of data extraction, data most relevant to the objectives of our review were reported narratively. The data obtained from the included studies was charted in summary tables derived from our data extraction sheet. The data synthesis was reported narratively/qualitatively according to (i) study type, (ii) intervention type, (iii) patient population and (iv) clinically relevant outcomes. Studies were categorized into two groups based on whether the objective was to evaluate a pharmacological or non-pharmacological intervention. A meta-analysis was not conducted as this approach was outside the scope of our review. Our narrative reporting approach was adopted in anticipation of substantial heterogeneity among the included studies. Due to inconsistent reporting of participants’ age groups, a subgroup analysis comparing adolescents (10–17 years) and emerging adults (18–29 years) was not conducted.
Risk of Bias Assessment
The included studies were not critically appraised because the objective of our scoping review was to map the literature, not draw firm conclusions about safety or effectiveness, aligning with the latest scoping review reporting guidelines. 24
Stakeholder Engagement
Throughout the study, including during the research question setting process, study design and interpretation of results, clinicians with expertise in treating youth with complex mental health and substance use conditions were engaged to identify real-world challenges in treating this population. Prior, qualitative interviews were conducted (TM, AAA) as part of a study with emerging adults 18–25 with anxiety, depression and substance use in mental health settings in Alberta. Clinicians and clients suggested individuals may have complex and unique needs, and a variety of services and interventions may be available, which often leads to difficulty navigating the mental health system such as finding timely and age appropriate services. The results will be shared with youth mental health practitioners, and policymakers to inform youth mental and addiction service delivery. The results and manuscript will be presented at relevant academic conferences, presented to policymakers, and will inform future research (e.g., clinical trials and systematic reviews).
Deviations From Registered Protocol
One protocol deviation occurred as the authors decided to only include studies where all study participants of a potential eligible study were reported to have at least one mental health disorder and at least one substance use disorder. The original protocol included studies of participants with a mental health disorder, and at least 50% of the study population had substance use disorders, this however posed feasibility concerns.
Results
After identifying an initial n = 3,557 unique records, 30 studies were included, comprising 2,464 youth participants (Figure 1).
Characteristics of Included Studies
Table 1 displays the characteristics of the included studies. Most studies (n = 24, 80%) were conducted in the United States, while three (10%) were conducted in Australia, and one study (3.33%) was conducted in New Zealand and Italy, respectively. The most common study designs employed were randomized controlled trials (RCTs) (n = 19%), and the remaining 12 studies (40%) were observational designs, three (10%) of which were case studies. All studies identified were published in English. Males comprised 62.1% of the study sample (n = 1,530). Eighteen (60%) studies were sampled from outpatient addiction or mental health clinics, while seven (23.3%) were conducted in a psychiatric hospital, three (10%) in residential addiction treatment centers, one (3.33%) from acute care, one (3.33%) from social services, and one study (3.33%) recruited partcipants from both inpatient and outpatient settings. Affective disorders (anxiety, depression, dysthymia) were included as concurrent mental health diagnoses in 11 (36.7%) studies. Five (16.7%) studies reported participants having non-psychotic mental health disorders, while four (13.3%) reported various mental health disorders (e.g., psychiatric inpatients). Most studies (n = 17, 56.7%) enrolled participants with an unspecified SUD (i.e., participants may use a variety of substances), while alcohol was the primary drug of research in seven studies (23.3%), cannabis in six studies (20%), tobacco smoking in two studies (6.67%). Fourteen (46.7%) studies used interventions that targeted mental health disorders primarily, eight (26.6%) studies employed interventions focused on addressing SUD, and nine (30%) targeted both mental health and substance use simultaneously. Finally, reported participants’ ages ranged from 12 to 25 years; however, (n = 8) studies did not report an age range, only a mean age.
| Author, year (country) | Study design | Mental health disorder(s) | Substance use disorder(s) | N sample size | Age range, years | Mean (SD) age | N (%) Male | Primary outcome measures |
|---|---|---|---|---|---|---|---|---|
| Basedow et al., 2023 29 | Cluster-RCT | Depression, ADHD, CD, PTSD, psychoticism | Nicotine, Alcohol, Cannabis, Methylenedioxymethamphetamine, Amphetamine, Methamphetamine, Hallucinogens, Opiates, Inhalants, Illicit psychoactive substances | 146 | 12.7–18.8 | 16.1 (1.2) | 90 (61.6) | Drug Use Disorder Identification Test (DUDIT)); Youth Self Report (YSR). |
| Boger et al., 2014 30 | Open label trial | Psychiatric disorders (unspecified) | Alcohol, Cannabis, Sedatives/Sleeping pills, Prescription opioids, Prescribed amphetamine-based stimulants, Cocaine, Hallucinogens, Non-prescription cough medicine | 40 | 15–19 | 17.07 (0.98) | 24 (60) | Center for Epidemiologic Studies Depression Scale; Snaith-Hamilton Pleasure Scale; Multidimensional Anxiety Scale for Children; The Stages of Change Readiness and Treatment Eagerness Personal Drug Use and Personal Drinking Questionnaires |
| Brown et al., 2003 (USA) 31 | RCT | Psychiatric disorders (unspecified) | Alcohol and Tobacco/Nicotine | 191 | 13–17 | 15.4 (1.27) | 72 (37.7) | Point prevalence abstinence, quit attempts, changes in smoking rate and longest quit attempt. Proximal outcomes included intent to change smoking behaviour (upon hospital discharge), and self-efficacy for smoking cessation. |
| Brown et al., 2009 (USA) 32 | RCT | Psychiatric disorders (unspecified) | Tobacco/Nicotine use | 191 | 13–17 | 15.4 (1.27) | 72 (37.7) | Timeline follow-back was used to assess the number of cigarettes smoked, the number of standard alcoholic drinks consumed, and classes of illicit substances used for each of the 90 days preceding hospitalization and at each follow-up going back to the point of the last study interview AND Columbia—Diagnostic Interview Schedule for Children (C-DISC) was used to determine the diagnostic status of study participants. |
| Cornelius et al., 2001 (USA) 33 | Open label trial | MDD | Alcohol use disorder | 13 | 15–20 | NR | 3 (23.1) | BDI, HAM-D 27, DSM IV |
| Cornelius et al., 2006 (USA) 34 | RCT | MDD | Alcohol use disorder | 50 | 15–20 | NR | 22 (44) | Alcohol use disorder (DSM). Drinks per day. Drinks per occasion. Days of alcohol use per week. Heavy drinking days per week. BDI total. Current major depression symptom count (DSM). HAM-D 27. |
| Cornelius et al., 2010 (USA) 35 | RCT | MDD | Cannabis use disorder | 70 | 14–25 | 21.1 (2.4) | 43 (61.4) | Days of alcohol use in the past month. Total drinks in the past month. Average drinks per drinking occasion in the past month. Days used cannabis in the past month. Days smoked cigarettes in the past month. Days of binge drinking (≥5) in the past month. DSM AUD total count. DSM cannabis abuse count. DSM cannabis dependence count. DSM CUD total count, BDI total. HAM-D 27. DSM current MDD symptom count. |
| Cornelius et al., 2011 (USA) 36 | RCT | MDD | Alcohol | 50 | NR | 19.5 (1.6) | 22 (44) | Observer-rated depressive symptoms were assessed with the Hamilton Rating Scale for Depression (HAM-D-27). Drinking behaviour was evaluated using the timeline follow-back method (TLFB). Participant-rated depressive symptoms were assessed with the Beck Depression Inventory (BDI) |
| Curtis et al., 2015 (USA) 37 | Longitudinal cohort | Psychiatric disorders (unspecified) | Substance use disorder (unspecified) | 107 | 12–24 | NR | 83 (77.5) | Nights in jail, unprotected sex, substance usage, ratings of social connectedness, using the For evaluation of the program, the Substance Abuse and Mental Health Services Administration (SAMHSA) Center for Substance Abuse and Prevention Government Performance and Results Act (GPRA) and the Global Appraisal of Individual Needs (GAIN) instruments were used. |
| Danielson et al., 2020 (USA) 38 | RCT | PTSD | Substance use(unspecified) | 124 | 13–18 | 15.4 (1.3) | 16 (12.9) | The primary outcome was the number of substance-using days, measured at baseline and 3, 6, 12, and 18 months after baseline using the timeline follow-back method. Participants reported the specific daily amounts of non-tobacco drugs and alcohol consumed during the previous 90 days. |
| Deas et al., 2000 (USA) 39 | RCT | MDD | Alcohol dependence | 10 | NR | 16.6 (0.52) | 8 (80) | Percent days drinking. Drinks per day. KSADS, HAM-D, SCID, and the TimeLine Follow Back |
| Deas et al., 2005 (USA) 40 | Open-label trial | CD, ODD | Alcohol dependence | 5 | NR | 16.8 (3.11) | 4(80) | Timeline Follow Back; Adolescent Obsessive Compulsive Drinking Scale; Craving analog scale |
| Donohue et al., 1998 (USA) 41 | RCT | CD | Substance use (unspecified) | 39 | NR | 15.4 (1.1) | 27 (69.0) | (a) Number of youths who kept their first appointment (intake), (b) Percentage of appointments that were kept (c) Average time (minutes) late to sessions. |
| Esposito-Smythers et al., (2011) (USA) 42 | RCT | Psychiatric disorders (unspecified) | Alcohol and cannabis | 40 | 13–17 | 15.7 (1.9) | 12 (32) | The Kaufman Brief Intelligence Test (K-BIT); The Child and Adolescent Services Assessment (CASA); Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version (K-SADS-PL); Timeline Followback (TLFB); K-SADS-PL depression module for suicide. |
| Findling et al., 2009 (USA) 43 | RCT | MDD | Alcohol and cannabis | 34 | 12–17 | 16.5 (1.1) | 29(85.3) | Urine toxicology screens, Serum ethanol levels, The Children's Depression Rating Scale-Revised (CDRS-R). Clinical Global Impressions Scale- Severity and Improvement (CGI). The Beck Depression Inventory (BDI). Beck Hopelessness Scale (BHS). The Children's Global Assessment Scale (CGAS). |
| Gentile et al., 2011 (NED) 44 | Case report | Psychosis | Cannabis | 1 | 23 | 23 (0) | 1(100) | Positive and Negative Syndrome Scale (PANSS); The Visual Analog Scale for Cannabis Craving (VASc) |
| Greenfield et al., 2011 (USA) 45 | Secondary analysis of a longitudinal cohort study | MDD | Substance use (unspecified) | 302 | 18–24 | 20.35 (1.58) | 223 (73) | ASE was measured with the Alcohol and Drug Use Self-Efficacy (ADUSE) scale; depressive symptoms were assessed with the Brief Symptom Inventory 18 (BSI 18) Depression scale; and current MDD diagnoses were deduced from the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM–IV). R |
| Hides et al., 2010 (AUS) 46 | Open label trial | Mood, anxiety, or psychotic disorders | Substance use (unspecified) | 60 | NR | 20.7 (2.7) | 56.7 (34) | Treatment response was determined at weeks 10, 20 and 44 using absolute mean change in the primary (depression, substance use) and secondary (anxiety, coping, cognition) outcome variables. Mixed effects models repeated measures analysis of variance was employed to determine whether there was a significant change in symptoms |
| Hirschtritt et al., 2012 (USA) 47 | RCT | MDD | Cannabis, alcohol | 34 | 12–17 | 16.46 (1.08) | 29 (85) | Depression symptom severity. The CDRS-R is a 17-item scale that assesses the severity and presence of depressive symptoms in children and adolescents. Total scores range from 17 to 113, with a score of 40 or higher indicative of clinical depression |
| Kemp et al., 2007 (AUS) 48 | RCT | Psychotic illness (substance-induced psychotic disorder, schizophreniform disorder, schizophrenia or psychotic mood disorder | Substance use (unspecified) | 16 | 17–25 | SUS group: 20.6 (2.1);TAU group 20.8 (1.7) | 13 (81.3) SUS = 7, TAU = 6 | Positive and Negative Syndrome Scale (PANSS), Drug Abuse Screening Test (DAST-10), The Alcohol Use Disorders, Identification Test (AUDIT), Depression Anxiety Subscale (DASS), The Self Efficacy Scale (SES), The World Health Organization Quality of Life Scale (Brief Version) |
| Liddle et al., 2018 (USA) 49 | RCT | MDD, ADHD, CD | Cannabis, alcohol, stimulants, opioids | 113 | 13–18 | 15.36 (1.07) | 84 (75) | The Personal Experience Inventory (PEI), Timeline Follow-Back Method, Externalizing and Internalizing subscales of the Youth Self-Report (YSR), Externalizing and Internalizing subscales of the Youth Self-Report (YSR) |
| Pagey et al., 2010 (NZ) 50 | Retrospective file audit | CD, ADHD, depression, other | Cannabis, nicotine, alcohol | 64 | 13–18 | 15.3 (1.0) | 42 (65.6) | Retention to the Youth Special Service alcohol and drug group |
| Riggs et al., 2007 (USA) 51 | RCT | MDD, CD | Substance use (unspecified) | 126 | 13–19 | 17.16 (1.66) | 85 (67.4) | Self-reported non-tobacco substance use, and urine substance use screen results in the past 30 days, Childhood Depression Rating Scale–Revised, Clinical Global Impression Improvement |
| Riggs et al., 2011 (USA) 52 | RCT | ADHD, CD, MDD | Substance use (unspecified) | 303 | 13–18 | 16.5 (1.3) | 239 (78.9) | The Schedule for Affective Disorders and Schizophrenia for School-Age Children- Epidemiologic Version (K-SADS-E); Clinical Global Impression—Improvement; ADHD-RS (parent informant) |
| Rohde et al., 2014 (USA) 53 | RCT | Depressive disorders | Non-nicotine SUD | 170 | 13–18 | FFT/CWD group: 16.24 (1.40); CWD/FFT group: 16.10 (1.40); CT group: 16.83 (1.13) | FFT/CWD: 46 (75.4%); CWD/FFT: 43 (76.8%); CT 43 (81.1%) | Schedule for Affective Disorders and Schizophrenia for School-Age Children-present and Life version (K-SADS-PL); Children's Depression Rating Scale-Revised (CDRS-R); Timeline Followback Interview (TLFB) |
| Santisteban et al., 2015 (USA) 54 | RCT | BPD | Substance use (unspecified) | 40 | 14–17 | I-BAFT group: 16 (0.8); IDC group: 15.6 (0.8) | I-BAFT: 12 (60%); IDC 13 (65%) | Borderline Personality scale from the Millon Adolescent Clinical Inventory (MACI); Diagnostic Interview Schedule for Children—Predictive Scales (DPS); Timeline Followback (TLFB) |
| Scholar-Root et al., 2022 (Australia) 55 | Case study | PTSD | Alcohol and cannabis | 2 | 14–17 | 15.5 (2.12) | n = 0 | CAPS-CA-5; CRAFFT |
| Sevy et al., 2011 (USA) 56 | RCT | Schizophrenia, schizoaffective disorder | Cannabis | 49 | NR | 21.7 (2.6) | 40 (81.6) | Lifetime and current (the last 3 months) substance use was assessed at study entry using the alcohol and substance abuse/dependence sections of the SCID interview. |
| Thurstone et al., 2010 (USA) 57 | RCT | ADHD | Substance use (unspecified) | 70 | NR | Atomoxetine + MI/CBT 16.06 (1.35); Placebo + MI/CBT 16.11 (1.78) | Atomoxetine + MI/CBT 25 (71.4); Placebo + MI/CBT 30 (85.7) | the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime version (KSADS-PL); Timeline Followback (TLFB); Clinician Global Impression- Improvement (CGI-I) |
| Tonarely et al., 2021 (USA) 58 | Case study | ADHD | Cannabis | 1 | NR | 17 (0) | 0 (0) | Top Problems Assessment, Revised Child Anxiety and Depression Scale (RCADS), The Distress Tolerance Scale (DTS); Borderline Personality, Features Scale for Children, Child Emotional Management Scale |
Summary of Main Findings
Non-Pharmacological Therapies
Table 2 displays the summary of findings from the non-pharmacological studies. Eighteen (60%) studies (n = 1,699 participants) employed various non-pharmacological interventions targeting concurrent disorders. The included articles investigated interventions such as cognitive-behavioural therapy, motivational interviewing, motivational enhancement therapy (MET) and family therapy. Hides et al. 46 reported integrated cognitive-behavioural therapy to be an effective treatment for comorbid depression and SUDs in youth; however, no control group was implemented. Cornelius et al. 36 investigated the combination of MET and CBT in adolescents with comorbid alcohol use disorder and major depressive disorder compared to no MET and CBT. They reported significant improvement in depression and alcohol-related outcomes. Motivational interviewing compared to brief advice for psychiatric inpatients with tobacco addiction was assessed in the studies conducted by Brown et al.31,32 While the impact on smoking outcomes was inconclusive, patients showed improved smoking cessation-related self-efficacy after six months.
| Study | Concurrent disorders | Sample size | Intervention(s) | Control(s) | Main findings |
|---|---|---|---|---|---|
| Basedow et al., 2023 (Swiss) 29 | Admitted to outpatient addiction and mental health services, substance use disorder (ICD-10) | 146 | DELTA- manualized group intervention for adolescents with SUD. Involved 16 weekly sessions with 1–2 trained and, experienced psychologists leading a group of 3–8 adolescents, lasting 60min. Additionally, each patient receives up to 8 individual sessions every 2 weeks. | Waitlist controls - TAU | DELTA intervention for adolescents with SUD is viable, and preliminary results show that DELTA had a small but statistically insignificant effect on reducing SUD severity, as well as psychopathologies related to depression and conduct disorder. |
| Boger et al., 2014 (USA) 30 | Admitted to residential addiction treatment center, mental health disorder diagnosis (DSM-IV). | 40 | Residential treatment program provided short-term treatment consisting of motivational interviewing (MI), 12-step facilitation, cognitive– behavioral (CBT), and dialectical behavioral (DBT) therapies. | None | Patients showed statistically significant improvements in depressive symptoms, hedonic capacity, and motivation for change in relation to drug use over the course of acute residential treatment with a relatively brief length of stay. |
| Brown et al., 2003 31 | Admitted to psychiatric hospital and tobacco use disorder | 191 | Motivational interviewing (MI) | Brief advice | MI had a moderate impact on self-efficacy of quitting and intent to change but little to no impact on smoking cessation. |
| Brown et al., 2009 32 | Admitted to psychiatric hospital and tobacco use disorder | 191 | Motivational interviewing (MI) consisted of 45-min individualized sessions followed by providing self-help material as well as 6 brief telephone sessions after discharge from the hospital. This also involved parent intervention component which included 4 brief telephone counseling sessions | Brief advice | MI was superior to brief advice in reducing the number of substance use days and improving substance abuse outcomes. |
| Cornelius et al., 2011 36 | Major Depressive Disorder (DSM-IV) and alcohol Use Disorder (DSM-IV) | 50 | CBT & MET was provided during each protocol visit during the acute phase treatment trial, so persons who participated in the acute phase treatment trial received psychotherapy on nine occasions from week 1–week 12. | No CBT & MET | CBT/MET group had better depression and alcohol use disorder outcomes as compared to the non-CBT/MET group. SSRI (Fluoxetine) vs. placebo showed no significant difference. |
| Curtis et al., 2015 37 | Substance abuse or substance dependence and a mental health disorder (DSM-IV-TR) | 107 | Assertive Community Reinforcement Approach coupled with Assertive Continuing Care is designed to address the epidemic of substance abuse and co-occurring mental health disorders among adolescents (age 12–17) and transition-age youth (age 18 –24). | None | The Assertive Adolescent Family Treatment Program led to a decrease in drug use, alcohol consumption, criminal activity, and violent behaviours, as well as improvements in cognition. No comparison group, however. |
| Danielson et al., 2020 38 | PTSD (Clinical interview, UCLA-PTSD-RI) and non-tobacco SUD | 140 | Risk Reduction Family Therapy (RRFT) is an adaptation and integration of evidence-based, cognitive-behavioral interventions that address PTSD symptoms (TF-CBT18), SUP (multisystemic therapy17), and sexual health. RRFT was administered weekly for 40–90 min | Treatment as usual (TAU) | RRFT led to greater reduction in substance use and PTSD outcomes vs. treatment as usual (TAU) group. |
| Donohue et al., 1998 41 | Conduct disorder (DSM-IV) and substance abuse (DSM-IV) | 39 | Intensive intervention with parents and youth which was used to measure (a) the number of youths who kept their first appointment (intake), (b) the percentage of appointments that were kept, and (c) the average number of minutes late to sessions that were attended. | Less intensive intervention | Intensive intervention involving youth led to greater attendance to initial and follow-up appointments as compared to less intensive intervention with no youth involvement. |
| Esposito-Smythers et al., 2011 42 | Suicide attempt or clinically significant suicidal ideations, and alcohol or cannabis use disorder | 40 | Cognitive–behavioral intervention for co-occurring AOD and suicidality (I-CBT). Integrated CBT protocol (I-CBT) was used to assess for co-occurring AOD and suicidality in comparison to an enhanced treatment as usual (E-TAU) | Enhanced treatment as usual (E-TAU) | I-CBT was associated with significantly fewer heavy drinking days and days of marijuana use relative to E-TAU but not with fewer drinking days. Those randomized to I-CBT in comparison to E-TAU also reported significantly less global impairment as well as fewer suicide attempts, inpatient psychiatric hospitalizations, emergency department visits, and arrests. Adolescents across groups showed equivalent reductions in suicidal ideation. |
| Greenfield et al., 2011 45 | Major depressive disorder (DSM-IV) and SUD (alcohol, cannabis, opioid, cocaine, polysubstance) (DSM-IV) | 302 | 12-Step program + CBT + MI + Group/Individual therapy | None | Residential treatment led to higher abstinence self-efficacy regardless of baseline depression. Those with higher baseline depression scores tended to have lower abstinence self-efficacy at baseline. |
| Hides et al., 2010 46 | Axis I/Axis II disorders and Substance abuse or dependence (DSM-IV) | 60 | Integrated CBT was used to assess for co-occurring depression and substance misuse in young people presenting to a youth mental health service | None | Integrated CBT was associated with significant improvements in depression, anxiety, substance use, coping skills, depressive and substance use cognitions and functioning. |
| Kemp et al. 2007 48 | SUD and psychotic illness (substance-induced psychotic disorder, schizophreniform disorder, schizophrenia or psychotic mood disorder) | 19 | SUS is a manualized intervention using motivational interviewing and cognitive behavior practices for substance abuse | Treatment as usual | Brief CBT was effective at improving and reducing the frequency of alcohol and cannabis use in young people with psychosis. |
| Liddle et al., 2018 49 | SUD and at least one psychiatric disorder | 70 | Multidimensional Family Therapy in-home/community was used to assess for substance use disorders | Residential treatment | During the early phase of treatment, youth in both treatments showed significant reductions in substance use problems, frequency of use, delinquent behaviours, and externalizing symptoms; youth receiving Multidimensional Family Therapy (MDFT) reported significantly greater reductions in internalizing symptoms than youth receiving Residential Treatment (RT) (d = 0.42). Long-term, youth in MDFT maintained their early treatment decreases in substance use problems and delinquent behaviours more effectively than youth in RT. |
| Pagey et al., 2010 50 | Conduct, depression ADHD, Other (DSM-IV)/Substance dependence (DSM-IV) | 64 | Individual, Family, Group Therapies was used as a measure to determine ways to improve retention in the therapy program. The parameters that were analyzed are: attendance, weekly group focus, sex mix of attendees, and facilitator sex | None | Five characteristics were shown to have a significant impact on enhancing participant group retention: (1) Maori and Pacific Island ethnicity, (2) past or current legal charges, (3) youth drug court (YDC) involvement, (4) having a diagnosis of cannabis dependence, (5) a diagnosis of conduct disorder. Logistic regression found that YDC involvement on its own significantly predicted treatment retention. |
| Rohde et al., 2014 53 | MDD, Dysthymia, Adjustment Disorder with Depressed Mood, Depression Not Otherwise Specified (D-NOS) | 170 | Coping With Depression (CWD) course (for depression), functional family therapy (FFT) for SUDs | None | FFT/CWD (substance use treatment before depression treatment) had the most efficacy in reducing substance use. However, individuals with depression at baseline benefited from the CWD/FFT program, suggesting that reduction in depression early in treatment could improve substance use outcomes. |
| Santisteban et al., 2015 54 | Depression and SUD | 40 | Integrative Borderline Personality Disorder–oriented Adolescent Family Therapy (I-BAFT) or individual drug counseling | None | Primary analyses showed that both interventions had a clinically significant impact on borderline personality disorder behaviours 12 months after baseline but with no differential treatment effect. The impact on substance abuse was more complex. |
| Schollar-Root et al., 2022 55 | PTSD (DSM-5) and history of problematic drug or alcohol use | 2 | CORE-A: 16 individual sessions combining CBT and PE | None | Both participants showed a noticeable reduction in reported PTSD throughout treatment. Cannabis use for one participant decreased, while alcohol use in the other was sporadic. |
| Tonarely et al., 2021 58 | ADHD(DSM-V)/CUD (DSM-V) | 1 | Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) | None | Treatment led to clinically significant reductions in symptoms of anxiety and depression and improvements in borderline features. |
Family therapy may decrease substance use and mental health symptoms. Danielson et al. 38 compared risk reduction family therapy (RRFT) to treatment-as-usual in youth with comorbid PTSD and non-tobacco substance use; they reported greater reductions in both PTSD and substance use in the RRFT group. Liddle et al. 49 investigated multidimensional family therapy as an alternative to residential treatment for youth with concurrent substance use and mental health disorders. Participants reported reduced depression and anxiety symptoms after treatment. Furthermore, Boger et al. 30 and Greenfield et al. 45 demonstrated that a 12-step program consisting of motivational interviewing and CBT resulted in improvements in scores associated with substance use disorder; however, no control groups were used (Table 2).30,45 Studies looking at the effectiveness of integrated CBT concluded that it was effective in improving depression, anxiety and substance use compared to no CBT as well as reducing the number of heavy drinking days, days of marijuana use, suicide ideation and suicide attempts compared to enhanced treatment as usual.42,46 Finally, other treatments that utilized Individual, Family, Group Therapies, 50 Intensive intervention with parents and youth 41 and Assertive Community Reinforcement Approach coupled with Assertive Continuing Care 37 all reported positive outcomes for youth in relation to SUD; however, among these, only Donohue et al. 41 implemented a control group comparing Intensive intervention with parents and youth to a less intensive intervention.
Pharmacotherapies
Table 3 displays the summary of findings from the pharmacological studies. Twelve (40%) studies (n = 765 participants) were included. The two RCTs43,47 investigated the impact of the antidepressant fluoxetine on depression symptoms in adolescents with SUD and major depressive disorder. The study conducted by Findling et al. 43 reported no significant difference between the fluoxetine and the placebo groups, while the study conducted by Hirschtritt et al. 47 reported greater improvements in depression symptoms in the fluoxetine group compared to placebo.
| Study | Concurrent disorders | Sample size | Intervention(s) | Control(s) | Main findings |
|---|---|---|---|---|---|
| Cornelius et al., 2001 33 | Major depressive disorder (DSM-IV); Alcohol use disorder (DSM-IV) | 13 | Fluoxetine and psychotherapy | None | A significant within-group decrease (improvement) was found for both depressive symptoms and drinking during the study. Flluoxetine was well tolerated during the study. |
| Cornelius et al., 2006 34 | Alcohol use disorder (DSM-IV); major depressive disorder (DSM-IV) | 50 | Fluoxetine; CBT; MET | Placebo; CBT; MET | Subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in both depressive symptoms and level of alcohol consumption. End-of-study levels of depression and drinking were low in both treatment groups. No significant difference between groups. |
| Cornelius et al., 2010 35 | Cannabis use disorder (DSM-IV); major depressive disorder (DSM-IV) | 70 | Fluoxetine; CBT; MET | Placebo; CBT; MET | Fluoxetine did not demonstrate greater efficacy than a placebo for treating either the depressive symptoms or the cannabis-related symptoms of our study sample of comorbid adolescents and young adults. Subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in depressive symptoms and the number of DSM diagnostic criteria for a CUD. |
| Deas et al., 2000 39 | Primary depressive disorder and alcohol use disorder. | 5 | Sertraline (25 mg/day increased weekly by 25 mg to a maximum dose of 100mg); cognitive behaviour group therapy | Placebo; cognitive behaviour group therapy | Sertraline was safe and well tolerated to treat adolescents with depression and alcohol dependence. Participants showed a significant reduction in depression scores; however, larger sample sizes are required. |
| Deas et al., 2005 40 | Alcohol dependence in adolescents (DSM-IV) and opposition defiant disorder and conduct disorder | 5 | Naltrexone (50 mg) and a 100-mg riboflavin capsule | None | Naltrexone was safe and well-tolerated in adolescent alcoholics and may lead to a significant reduction in alcohol consumption in adolescent alcoholics; larger, randomized, controlled trials are needed. |
| Findling et al., 2009 43 | SUD and Major depressive disorder | 34 | Fluoxetine | Placebo | Fluoxetine was not superior to placebo in alleviating depressive symptoms or in decreasing rates of positive drug screens in the acute treatment of adolescents with depression and a concurrent substance use disorder. |
| Gentile et al., 2022 44 | Major Depressive Disorder (DSM-IV)/SUD (alcohol, cannabis, opioid, cocaine, poly) (DSM-IV) | 1 | Cariprazine at 1,5 mg/daily, reaching 3mg/daily in 3 weeks. | None | In this clinical case, Cariprazine was safely employed with a high level of tolerability. The patient showed improvement and both positive and negative symptoms, as well as abstinence from cannabis use. |
| Hirschtritt et al., 2012 47 | current major depressive disorder or a depressive disorder, comorbid substance use disorder, and a Revised Children's Depression Rating Scale score of 40 or higher | 34 | Fluoxetine | Placebo | The fluoxetine group showed greater improvement compared to placebo in adolescents with comorbid depression, substance abuse disorders, and moderate alcohol consumption during therapy. |
| Riggs et al., 2007 51 | Non-tobacco SUD; major depressive disorder; lifetime conduct disorder | 480 | Fluoxetine; CBT | Placebo; CBT | Fluoxetine and CBT had greater efficacy compared to placebo; CBT on one but not both depression measures and was not associated with a greater decline in self-reported substance use or CD symptoms. |
| Riggs et al., 2011 59 | ADHD, SUD, CD, MDD (DSM-IV) | 303 | Osmotic-Release Methylphenidate (OROS-MPH) and CBT | Placebo | OROS-MPH did not demonstrate greater efficacy in reduction in substance use in adolescents as compared to placebo. OROS-MPH was associated with moderately greater improvement in some substance outcome measures. |
| Sevy et al., 2022 56 | Schizophrenia, schizophreniform, schizoaffective disorder (DSM-IV), Cannabis use disorder (DSM-IV) | 49 | Risperidone vs. Olanzapine | Comparison between the two drugs | Olanzapine and risperidone have a similar initial efficacy on psychotic symptoms and substance use outcomes in first-episode patients with a lifetime diagnosis of cannabis use disorders |
| Thurstone et al., 2010 57 | ADHD (DSM-IV)/non-nicotine SUD (DSM-IV) | 70 | Atomoxetine + MI; CBT | Placebo + MI/CBT | No difference was observed across groups in self-reported ADHD symptoms. There was no difference between groups in non-nicotine substance use in the past 30 days. Decrease of self-reported symptoms of ADHD from baseline to week 12. |
Deas et al. 40 investigated the effect of naltrexone and riboflavin for treatment-seeking adolescents with alcohol use disorder and a comorbid mental health condition. The findings supported the safety and efficacy of this intervention for reducing alcohol consumption, but no control group was utilized and the authors emphasized the need for larger studies. Finally, Sevy et al. 56 compared the effectiveness of the antipsychotic drugs risperidone and olanzapine for adolescents with alcohol use disorder and a concurrent psychotic disorder. The study outcomes revealed no significant difference between the two interventions but noted positive symptom improvements in both groups.
Seven studies utilized a combined intervention approach utilizing various pharmacotherapies combined with non-pharmacotherapy interventions.33,34,35,39,51,52,57 Six administered fluoxetine as part of their intervention,33bibr34-07067437241300957–35,43,47 one administered atomoxetine (selective norepinephrine reuptake inhibitor), 57 and one administered methylphenidate (psychostimulant). 51 In addition to the pharmacotherapies, five used cognitive behavioural therapy,34,35,51,52,57 two used MET,34,35 and one used “psychotherapy.” 35 One study used a single-arm open-label design. 34 The studies investigated varying concurrent disorders. For substance use disorders, non-tobacco SUD was explored in three studies,51,52,57 alcohol use disorder in two studies33,34 and cannabis use disorder in one study. 35 Concurrent mental health disorders included major depressive disorder in six studies,33,34,43,51,52 ADHD in two studies52,57 and conduct disorder in two studies.51,52
Fluoxetine was well tolerated in each study; however, it did not show greater efficacy on primary outcomes compared to placebo for SUD or major depressive disorder. Initial results from Cornelius et al. 34 reported that fluoxetine plus psychotherapy was beneficial among youth with comorbid major depressive disorder and alcohol use disorder; however, these results were not replicated in a larger RCT. 35 Additionally, cognitive behavioural therapy and MET were performed in the control group, resulting in a treatment effect which would preclude observing an additive effect from both treatments compared placebo alone. Cornelius et al. 35 replicated this trial in a larger cohort of youth with comorbid cannabis use disorder and major depressive disorder and reported similar results—no significant difference compared to the control group; however, beneficial within-group treatment effects were reported in both groups.
Riggs et al. 51 reported that fluoxetine and cognitive behavioural therapy significantly improved scores on the Childhood Depression Rating Scale-Revised compared to placebo, but not on the Clinical Global Impression Improvement questionnaire. CBT may have contributed to the higher-than-expected treatment response and mixed efficacy outcomes. Riggs et al. 52 concluded that methylphenidate did not indicate superior efficacy in reducing substance use when compared to a placebo in adolescents concurrently undergoing individual CBT for substance use and ADHD. However, methylphenidate was associated with clinical improvement in secondary substance-related and ADHD outcomes. Thurstone et al. 57 reported no difference across groups in both self-reported ADHD symptoms and the use of non-nicotine substances in patients receiving atomoxetine combined with motivational interviewing compared to placebo; however, there was a decrease in the number of symptoms of ADHD reported by the patient between baseline and week 12.
Discussion
To our knowledge, this was the first scoping review to identify and summarize peer-reviewed studies of interventions for youth with concurrent disorders. To date, few studies have evaluated treatment approaches that aim to treat concurrent disorders simultaneously. Our findings revealed that a modest but limited number of studies have been conducted in this field, but significant heterogeneity was observed among the interventions, populations, and study types examined. However, some key themes and patterns were identified across the body of literature. For example, we found that depression was the most prominent concurrent mental health disorder studied, while alcohol and cannabis use disorders were the most commonly investigated concurrent substance use disorders. Non-pharmacological interventions, specifically CBT, were the most common interventions employed in youth with concurrent disorders. Motivational interviewing, CBT, family-based interventions and other integrated approaches were also employed. The results of the included studies appeared to suggest each of these interventions may help allieviate mental health symptoms, substance use outcomes and patient-reported outcomes such as self-efficacy and functional status. However, the specific outcomes and effectiveness may vary depending on the target population and the nature of the mental health condition or substance use disorder being addressed.
The included research studies investigating pharmacological interventions for youth with concurrent disorders found mainly positive outcomes. Three of the four pharmacological studies investigated therapies in adolescents with SUD and concurrent depression; thus, more research should be conducted to investigate the effect of these pharmacotherapies on other mental health conditions. It should be noted that the number of studies was small, and only two were RCTs. Of the RCTs, only one study reported a beneficial effect of the treatment. Furthermore, there are numerous ethical and logistical challenges when conducting RCTs on vulnerable populations such as youth with concurrent disorders. For instance, upholding patient autonomy during the informed consent process is an ethical concern when researching treatments for adolescents with SUDs. 60 SUDs are associated with intoxication and withdrawal phases that can adversely affect cognitive processes, including decision-making, attention, and perception. 61 The additive effect of mental health disorders (e.g., depression, ADHD) further increases questions about whether adolescents have the cognitive capacity to participate in research without parental consent 60 ; however, requiring parental consent for intervention inclusion may also lead to systemic biases that exclude individuals who may not be able to obtain parental consent or have a conflicting view of the interventional risks than their caregivers. 62 Finally, the period of adolescence is broadly defined and can range anywhere from 12 to 25 years old, which further complicates treatment approaches and the use of pharmacological interventions.
Several studies highlighted the importance of personalized treatment and the implementation of combination therapies to improve treatment outcomes.31,45,48,54 Greenfield et al. 45 concluded that a combination of a 12-step program, CBT, MI and individual/group therapy was effective in improving self-efficacy and sustaining recovery in emering adults with SUD and concurrent major depressive disorder. Similarly, Kemp et al. 48 highlighted the success of a manualized intervention using motivational interviewing and CBT for SUDs in young people with psychotic disorders. These studies suggested potential benefits of non-pharmacological interventions for concurrent disorders. Utilizing only one type of behavioural therapy may benefit people with SUD; however, outcomes were mixed and dependent on treatment modality. For instance, Brown et al. 31 suggested that motivational interviewing displayed modest effects on smoking cessation outcomes; thus, enhancement of this treatment approach would be required for adolescents with psychiatric comorbidities. Conversely, Santisteban et al. 54 reported that individual substance use counseling (i.e., monotherapy) did not reduce substance use in adolescents with depression; however, reductions in substance use were observed with integrative borderline personality disorder-oriented adolescent family therapy (I-BAFT), which utilized an approach comprising weekly family therapy, individual therapy and skills-building interventions.
Our findings were largely consistent with previous reviews.25,26 A meta-analysis analyzing the impacts of outpatient treatment on adolescents with SUDs found any intervention to be superior to no intervention. 63 Another systematic review and meta-analysis reported that brief alcohol interventions were moderately effective for youth aged 11–18. 64 However, neither of these meta-analyses specifically investigated concurrent disorders in youth. Therefore, this scoping review adds to the current literature by highlighting the sparsity in concrete intervention strategies for youth with concurrent disorders. 59 The significant heterogeneity in approaches demands that more research be conducted to investigate effective treatment protocols for this vulnerable population. Previous studies have outlined a pressing need to identify mental health concerns early to improve both substance use concerns and health outcomes. 65 For instance, mood disorders have been associated with developing SUDs within 10 years following an initial diagnosis. 66 Thus, establishing more uniform non-pharmacological, pharmacological and combined therapy protocols is required to inform clinicians on the best treatment approaches for specific conditions and prevent the development of more chronic difficulties into adulthood. 66 Finally, a significant body of literature has reported strong associations between adverse childhood experiences and the development of mental health and SUDs into youth and adulthood. 67 Therefore, research investigating the history of adverse childhood experiences and trauma in youth with concurrent disorders may provide insight into the developmental timeline of both mental health disorders and SUDs to better inform intervention strategies.
Strengths and Limitations of the Review
This scoping review provided a comprehensive overview of the literature on treatments for concurrent disorders in youth and highlighted their complexities. We conducted a broad search of the peer-reviewed literature and used robust eligibility criteria, which reduced the risk of selection bias and promoted replicability.
A few unavoidable methodological limitations of this scoping review should also be considered when interpreting the results. First, the search strategy may not be exhaustive as grey literature was excluded. Second, studies published in languages other than English were excluded for feasibility reasons. To explore the impact of these decisions, we searched the reference lists of previous systematic reviews25,26 and found no evidence of any citations of relevant non-peer-reviewed studies or inclusion of studies published in languages other than English. We also did not conduct backward reference searching of included studies; however, this is a small limitation because we examined the previous systematic reviews.
The decision to only include studies of youth with a confirmed mental health disorder diagnosis may have excluded some potentially relevant studies of youth with mental health symptoms who did not meet diagnostic criteria or were not assessed for the disorder. To inform this decision, we consulted with clinical pediatric psychiatric experts, who suggested that children are not as likely to be diagnosed with a SUD at early ages; therefore, confirming the mental health diagnosis would be imperative for identifying studies with the correct target population. Including only studies with a diagnosis of a mental health disorder promotes replicability as it is an objective measure that is easy to identify during screening.
Conclusions and Clinical Implications
In light of our limitations, our scoping review provides an overview of the preliminary evidence for pharmacological and non-pharmacological interventions for treating youth with concurrent disorders. Historically, treatment guidelines for concurrent disorders recommended treatment of the predominant condition first rather than both disorders simultaneously. More recently, recommendations from the WHO have encouraged the integration of primary care and mental health services, acknowledging the common overlap of mental health, substance use and physical conditions. 28 Clinically, there are many nuances to the treatment of concurrent disorders. For example, people with a SUD and major depressive disorder may demonstrate a blunted treatment response to antidepressant therapy compared to those without a concurrent SUD. 68 Conversely, people in treatment for SUD with anxiety or depression tend to experience greater symptom severity, higher levels of disability and lower treatment retention rates than those without anxiety or depression. 7 Also, people with concurrent disorders risk acquiring serious long-term physical complications such as HIV, hepatitis C, cardiovascular disease and psychosocial issues such as unstable housing, unemployment, physical abuse or trauma and poor quality of life. 69 Without adequate training in concurrent disorder assessment and differential diagnosis, arriving at accurate case formulations and treatment plans can be difficult. 70 Further, treatment plans must be informed by the best available evidence. Unfortunately, based on our findings, there is limited clinical evidence from peer-reviewed studies to strongly inform the treatment approach for youth with concurrent disorders. Evidence-based medicine is predicated on balancing clinical judgment, patient preferences and the existing literature. The results from our review suggest a broad but heterogeneous evidence base to provide additional support for clinicians treating youth with concurrent disorders.
Future Directions
Further research and exploration of these interventions and their long-term effects are necessary to refine treatment approaches, identify optimal strategies for different populations and enhance overall patient outcomes in non-pharmacological treatments. Additional peer-reviewed studies and systematic reviews are needed to inform evidence-based clinical practice guidelines. Smaller systematic reviews focused on specific interventions (e.g., behavioural therapies) and concurrent disorders (e.g., depression and substance use) may be warranted, but due to considerable heterogeneity, more research is needed prior to conducting larger systematic reviews or meta-analyses. Since critical appraisal was outside of the scope of this review, any future systematic reviews should consider critically appraising the included studies. As the most common studies were of youth with depression who had either general SUD—more specifically, cannabis use disorder or alcohol use disorder (which are the most common SUDs in youth), it will be useful to see future systematic reviews on targeted areas, for example focusing on behavioural therapies (e.g., CBT specifically) versus treatment as usual or no treatment.
Continued research is necessary to identify the most appropriate medications and non-pharmacological interventions for specific populations whilst considering the mental health condition and SUD being addressed. Early screening, as well as the collaboration and coordination of services across sectors, continues to be essential for enhancing health outcomes in youth with concurrent disorders, as there is a significant degree of overlap in mental health and substance use concerns in youth. 65
Supplemental Material
Acknowledgments
Thank you to Dr. Johnathan Stea and Dr. Bina Nair for their contributions to the expert panel during the early stages of this study.