Preferences of Young Adults With Psychosis for Cannabis-Focused Harm Reduction Interventions: A Cross-Sectional Study: Préférences des jeunes adultes souffrant de psychose pour les interventions de réduction des méfaits axées sur le cannabis : une étude transversale.

OBJECTIVES: Cannabis use is common in people with early-phase psychosis (EP) and is associated with worse treatment outcomes. Few targeted interventions for cannabis use behaviour in this population exist, most focusing on abstinence, none focusing on harm reduction. Many people with EP will not seek treatment for their cannabis use with current therapeutic options. Understanding preferences for cannabis-focused harm reduction interventions may be key to improving outcomes. This study aimed to determine preferences of young adults with EP who use cannabis for cannabis-focused harm reduction interventions. METHODS: Eighty-nine young adults across Canada with EP interested in reducing cannabis-related harms were recruited. An online questionnaire combining conventional survey methodology and two unique discrete choice experiments (DCEs) was administered. One DCE focused on attributes of core harm reduction interventions (DCE 1) and the second on attributes of boosters (DCE 2). We analysed these using mixed ranked-ordered logistic regression models. Preference questions using conventional survey methodology were analysed using summary statistics. RESULTS: Preferred characteristics for cannabis-focused harm reduction interventions (DCE 1) were: shorter sessions (60 min vs. 10 min, odds ratio (OR): 0.72; P < 0.001); less frequent sessions (daily vs. monthly, OR: 0.68; P < 0.001); shorter interventions (3 months vs. 1 month, OR: 0.80; P < 0.01); technology-based interventions (vs. in-person, OR: 1.17; P < 0.05). Preferences for post-intervention boosters (DCE 2) included opting into boosters (vs. opting out, OR: 3.53; P < 0.001) and having shorter boosters (3 months vs. 1 month, OR: 0.79; P < 0.01). Nearly half of the participants preferred to reduce cannabis use as a principal intervention goal (vs. using in less harmful ways or avoiding risky situations). CONCLUSIONS: Further research is required to see if technology-based harm reduction interventions for cannabis featuring these preferences translate into greater engagement and improved outcomes in EP patients.

Evaluation of a Cannabis Harm Reduction Intervention for People With First-Episode Psychosis: Protocol for a Pilot Multicentric Randomized Trial.

BACKGROUND: Cannabis use is highly prevalent in young people with first-episode psychosis (FEP). Most report cannabis use and are often diagnosed with a cannabis use disorder upon admission to specialized services for psychosis. Cannabis use in this population is associated with worse clinical and psychosocial outcomes, rendering it an important clinical target. Despite this, few cannabis-specific interventions have been developed for FEP and empirically evaluated through randomized controlled trials. Most evaluated interventions have targeted cannabis abstinence, with limited efficacy, but none have centered on harm reduction outcomes for people with FEP who use cannabis. Early intervention services (EIS), the standard of care for FEP, have not successfully addressed problematic cannabis use in people with FEP either. Clinical trials are needed to explore the potential of harm reduction strategies, although these should be preceded by robust pilot studies to establish optimal design and approaches. OBJECTIVE: Recognizing the need for harm reduction strategies for individuals with FEP who use cannabis and based on research on patients' preferences supporting harm reduction interventions, we developed a mobile app-based cannabis harm reduction intervention for this population. This intervention is called Cannabis Harm-reducing Application to Manage Practices Safely (CHAMPS). Here, we describe the protocol for a multicenter, 2-arm, parallel group, randomized pilot trial evaluating the acceptability of CHAMPS for people with FEP who use cannabis and the feasibility of conducting a full-scale trial in this population using CHAMPS. The impact on key clinical outcomes will also be explored. METHODS: This pilot trial aims to recruit 100 young people with FEP using cannabis from 6 Canadian EIS clinics. Participants will be randomized in a 1:1 ratio to CHAMPS+EIS or EIS-only. CHAMPS acceptability will be assessed using completion rates for the intervention arm. Trial feasibility will be assessed using a retention rate for randomized participants. Secondary outcomes will explore tendencies of change in the use of protective behavioral strategies and in motivation to change strategies. Exploratory outcomes include cannabis use-related problems, other substance use, the severity of dependence, psychotic symptoms, and health care service use. RESULTS: Recruitment began in December 2021. Data collection and analysis are expected to be completed in early 2024. Study results describing CHAMPS acceptability and trial feasibility will then be submitted for publication in a peer-reviewed journal. CONCLUSIONS: CHAMPS uniquely combines evidence-based approaches, patient perspectives, and mobile health technology to support harm reduction in people with FEP who use cannabis. Attaining adequate acceptability and feasibility through this trial may justify further exploration of harm reduction tools, particularly within the context of conducting a larger-scale randomized controlled trial. This pilot trial has the potential to advance knowledge for researchers and clinicians regarding a feasible and user-acceptable research design in the cannabis and early psychosis fields. TRIAL REGISTRATION: ClinicalTrials.gov NCT04968275, https://clinicaltrials.gov/ct2/show/NCT04968275. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53094.

Evaluating preferences for online psychological interventions to decrease cannabis use in young adults with psychosis: An observational study.

Innovative technology-based solutions have the potential to improve access to clinically proven interventions for cannabis use disorder (CUD) in individuals with first episode psychosis (FEP). High patient engagement with app-based interventions is critical for achieving optimal outcomes. 104 individuals 18 to 35 years old with FEP and CUD from three Canadian provinces completed an electronic survey to evaluate preferences for online psychological intervention intensity, participation autonomy, feedback related to cannabis use, and technology platforms and app functionalities. The development of the questionnaire was informed by a qualitative study that included patients and clinicians. We used Best-Worst Scaling (BWS) and item ranking methodologies to measure preferences. Conditional logistic regression models for BWS data revealed high preferences for moderate intervention intensity (e.g., modules with a length of 15 min) and treatment autonomy that included preferences for using technology-based interventions and receiving feedback related to cannabis use once a week. Luce regression models for rank items revealed high preferences for smartphone-based apps, video intervention components, and having access to synchronous communications with clinicians and gamification elements. Results informed the development of iCanChange (iCC), a smartphone-based intervention for the treatment of CUD in individuals with FEP that is undergoing clinical testing.

Reducing Cannabis Use in Young Adults With Psychosis Using iCanChange, a Mobile Health App: Protocol for a Pilot Randomized Controlled Trial (ReCAP-iCC).

BACKGROUND: Cannabis use is the most prevalent among adolescents and young adults; frequent consumption is associated with cannabis use disorder (CUD) and psychosis, with a high prevalence (up to 50%) of CUD in individuals with first-episode psychosis (FEP). Early Intervention Services (EIS) for psychosis include face-to-face psychosocial interventions for CUD, because reducing or discontinuing cannabis use improves clinical and health care service use outcomes. However, multiple barriers (eg, staff availability and limited access to treatment) can hinder the implementation of these interventions. Mobile health (mHealth) interventions may help circumvent some of these barriers; however, to date, no study has evaluated the effects of mHealth psychological interventions for CUD in individuals with FEP. OBJECTIVE: This study describes the protocol for a pilot randomized controlled trial using a novel mHealth psychological intervention (iCanChange [iCC]) to address CUD in young adults with FEP. iCC was developed based on clinical evidence showing that in individuals without psychosis, integrating the principles of cognitive behavioral therapy, motivational interviewing, and behavioral self-management approaches are effective in improving cannabis use-related outcomes. METHODS: Consenting individuals (n=100) meeting the inclusion criteria (eg, aged 18-35 years with FEP and CUD) will be randomly allocated in a 1:1 ratio to the intervention (iCC+modified EIS) or control (EIS) group. The iCC is fully automatized and contains 21 modules that are completed over a 12-week period and 3 booster modules available during the 3-month follow-up period. Validated self-report measures will be taken via in-person assessments at baseline and at 6, 12 (end point), and 24 weeks (end of trial); iCC use data will be collected directly from the mobile app. Primary outcomes are intervention completion and trial retention rates, and secondary outcomes are cannabis use quantity, participant satisfaction, app use, and trial recruiting parameters. Exploratory outcomes include severity of psychotic symptoms and CUD severity. For primary outcomes, we will use the chi-square test using data collected at week 12. We will consider participation in iCC acceptable if ≥50% of the participants complete at least 11 out of 21 intervention modules and the trial feasible if attrition does not reach 50%. We will use analysis of covariance and mixed-effects models for secondary outcomes and generalized estimating equation multivariable analyses for exploratory outcomes. RESULTS: Recruitment began in July 2022, and data collection is anticipated to be completed in July 2024. The main results are expected to be submitted for publication in 2024. We will engage patient partners and other stakeholders in creating a multifaceted knowledge translation plan to reach a diverse audience. CONCLUSIONS: If feasible, this study will provide essential data for a larger-scale efficacy trial of iCC on cannabis use outcomes in individuals with FEP and CUD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05310981; https://www.clinicaltrials.gov/ct2/show/NCT05310981. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/40817.

[A Healthy Mind in a Healthy Body: The Value of Physical Activity for Youth With First Episode Psychosis]. / Mens sana in corpore sano : l'intérêt de l'activité physique auprès des jeunes ayant eu un premier épisode psychotique.

Objectives In recent years, issues related to physical health took on a major role in the care of youth who experienced a first episode psychosis (FEP). Compared to the general population, people with a psychotic disorder have a reduced life expectancy of 15 years, with physical health problems accounting for 60 to 70% of that part. With the increased awareness about these issues, physical activity is considered as a new prevention and intervention strategy in the recovery process for youth with a FEP. The objective of the present article is to summarize the different physical health issues in FEP and the impacts of physical activity. Methods Narrative review addressing physical health issues, the role of antipsychotics, the need for metabolic monitoring, and for improvement of lifestyle habits (e.g., smoking, sedentary lifestyle, physical inactivity, poor diet) in youth with a FEP. The impact of physical activity on physical and mental health, on smoking cessation as well as the interest of adventure therapy in the recovery process will be discussed. Finally, we will propose motivational strategies and tools to promote physical activity. In the different sections, we will support our arguments with the highest levels of evidence available (e.g., meta-analyses, systematic reviews, randomized controlled trials, cohort studies, N-of-1) and highlight implications for clinical practice. Results Metabolic health problems progress rapidly after the initiation of antipsychotic treatment, and inadequate lifestyle habits contribute to the development of these problems. In an early intervention context, several types of physical activity have shown benefits on physical health, psychotic symptoms, functioning and more generally in the recovery process. Nevertheless, few patients spontaneously engaged in regular physical activity because of low motivation. Physical activity interventions should be adapted to the FEP population and several factors taken into consideration such as the type of physical activity, its context, intensity, frequency, motivational parameters, and support/supervision from health professionals. Conclusion From a physical and a psychiatric perspective, the years following treatment initiation for FEP are critical. Considering its positive impacts on different dimensions of recovery physical activity interventions should be integrated into the range of services offered in early intervention services.

[First Episode Psychosis and Substance Use Disorder: Narrative Review of Best Practices and Adapted Approaches for Assessment and Monitoring]. / Premier épisode psychotique et trouble de l'usage de substance concomitants : revue narrative des meilleures pratiques et pistes d'approches adaptées pour l'évaluation et le suivi.

Objectives About half of young adults with early psychosis also have substance use disorders (SUD). For young adults with first episode psychosis (FEP), the persistence of SUD negatively impacts the symptomatic and functional outcome as well as the management of the problems. This article aims to identify and synthetize the best therapeutic approaches for the treatment of young adults with concurrent disorders (FEP and SUD) and to present avenues for practical and adapted approaches for the assessment and follow-up of people with concurrent FEP and SUD. Method Narrative literature review on the treatment of young adults with concurrent disorder (FEP and SUD). Results Several studies demonstrate the usefulness of early intervention for psychosis services (EIS) in the management of SUD with approximately 50% decrease in SUD during the first year of follow-up. A variety of therapeutic interventions have been studied, but none have demonstrated substantial long-term superiority over the standard treatment offered in EIS. The studies also have several methodological limitations. To date, clinical guidelines suggest offering an adapted and integrated treatment for psychosis and SUD and recommend the use of various approaches such as case management, comprehensive assessment and feedback on SUD and psychosis as well as their interplay, harm reduction interventions, motivational interviewing, cognitive behavioural therapy, and pharmacotherapy. It is proposed here to proactively adjust the treatment to consider the severity of the disorders, their impact on the various dimensions of psychosis outcomes, the developmental stage of the young person and his or her stage of change with respect to substance use. Conclusion Data on best practice in the treatment of concurrent PEP-SUD disorders are relatively limited. Some approaches appear to have the potential to improve the clinical course of young people living with such conditions, especially if they are adapted to this population. Furthermore, research and innovations in the management of concurrent disorders must continue to offer better adapted care to young adults with early psychosis and SUD.

[Comment les services d'intervention précoce pour la psychose peuvent-ils mieux servir les migrants, les minorités ethniques et les populations autochtones ?] / How could Early Intervention Services for Psychosis better serve migrants, ethnic minorities and Indigenous populations?

Objectives To synthesize the available epidemiological and clinical evidence relevant to the mental health care of migrant, ethnic minority and Indigenous populations in the context of early psychosis. Methods This study provides a narrative review of the literature on psychosis in these populations, including issues related to the provision of early intervention services for psychosis. Results Migrant status has long been reported as a significant risk factor for psychosis in many geographic contexts. This increased risk among migrants seems to persist beyond the first generation and has been found to be higher in all migrant populations, but especially for black ethnic minorities and individuals migrating from economically developing countries to developed ones. Recent evidence suggests that this higher risk is at least in part due to migrants' and minorities' cumulative exposure to social adversities, such as racial discrimination, marginalization and socio-economic disadvantage. Systemic racism affects migrant and minority populations by creating bias in diagnostic practices and aggravating treatment disparities in addition to contributing to causation of psychosis. Furthermore, migrant and ethnic minority groups are known to seek mental healthcare after longer delays, to be more frequently forcibly hospitalized, to disengage from treatment prematurely and to be less satisfied with their treatment. The consideration of social and cultural context and factors is essential to the provision of good healthcare, especially in a culturally diverse society. Furthermore, acknowledging power relationships that stem from the societal context and shape institutions and models of care is a key step towards structural competence and safety in mental healthcare. Several strategies have been proposed to make mental healthcare services and systems more culturally and structurally competent. These include the use of interpreters and cultural brokers, tailored assessments and specialised cultural interventions. However, these strategies have yet to be adopted broadly in early intervention for psychosis. Conclusion Given its emphasis on meaningful engagement and person-centered care, early intervention should integrate inclusive, structurally competent and context-informed interventions as a priority. Efforts must be made to apply knowledge from and adapt the tools of social and cultural psychiatry to the field of early intervention in psychosis. Sociocultural considerations, hitherto inconsistently applied in psychosis research and service design in Quebec, are especially relevant to the province given its distinct linguistic context, its increasing cultural diversity, and its ongoing effort to systematize and expand the delivery of early intervention services.

Preventive interventions targeting cannabis use and related harms in people with psychosis: A systematic review.

AIM: While most users will not experience severe adverse health outcomes from cannabis, it can be associated with negative outcomes in people with psychosis. People with psychosis who use cannabis have more severe psychiatric symptoms, higher rates of hospitalization, and diminished psychosocial functioning compared to those who do not use cannabis. Most studies of people with psychotic disorders have focused on cannabis use treatments and only a few on preventive interventions for cannabis. This systematic review aims to evaluate the effectiveness of preventive interventions focusing on cannabis use for people with psychosis. METHODS: We searched CINAHL Plus, EBM reviews, EMBASE, MEDLINE, PsycInfo and PubMed databases for controlled studies assessing the effects of preventive interventions on cannabis use and related harms in people with psychosis. We conducted the search using a combination of the following concepts: cannabis, psychosis, intervention and prevention. Risk of bias was assessed. RESULTS: The search yielded 11 460 unique studies. Of these, five studies met our eligibility criteria. None of the studies demonstrated clear efficacy of prevention interventions in reducing cannabis use, and none measured cannabis-related harms. All studies had high risk of bias. CONCLUSION: The small number of studies and the considerable risk of bias made it difficult to conclude whether any of the existing interventions were promising. With increased acceptance and accessibility of cannabis due to liberalizing cannabis policies, it is imperative to improve the evidence base for preventive interventions, in particular their effectiveness in decreasing the risk of cannabis-related harms in people with psychosis.

Cannabidiol for the treatment of psychosis among patients with schizophrenia and other primary psychotic disorders: A systematic review with a risk of bias assessment.

Current treatments for primary psychotic disorders include antipsychotics, some of which have significant side effects or suboptimal efficacy. Cannabidiol is a cannabinoid with potential antipsychotic properties. This systematic review examines the use of cannabidiol as an antipsychotic treatment for primary psychotic disorders. CINAHL, EBM, EMBASE, MEDLINE and PubMed databases were searched from 1970 to 2019 for experimental and observational studies evaluating the antipsychotic and cognitive modulation properties of cannabidiol in individuals with psychotic disorders. There were eight eligible studies evaluating the antipsychotic potential of cannabidiol, involving a total of 210 participants. Due to study heterogeneity, we present the extracted data on general psychopathology, positive and negative symptoms, cognition and functioning outcomes as a narrative synthesis. We found limited evidence supporting antipsychotic efficacy for cannabidiol and none supporting its benefits for cognition or functioning. Cannabidiol treatment had an advantageous side effect profile compared to other antipsychotics and was well tolerated across studies. Observational studies had a higher risk of bias than experimental studies. Factors potentially contributing to variability in outcome results included cannabidiol dosage, treatment duration, use as an adjunctive treatment and participant inclusion criteria, which warrant further investigation to determine whether cannabidiol can be effective as a treatment for psychosis.

Specialized assertive community treatment intervention for homeless youth with first episode psychosis and substance use disorder: A 2-year follow-up study.

AIM: No previous study has investigated interventions for homeless youth suffering from first episode psychosis and comorbid substance use disorder (HYPS). An intensive assertive community intervention team (IACIT) offering outreach interventions, housing support as well as integrated care for early psychosis and substance use disorder (SUD) was created in 2012 at the Centre Hospitalier de l'Université de Montréal (CHUM). To explore the impact of the addition of an IACIT to an early intervention for psychosis service (EIS) on housing stability, functional and symptomatic outcomes and mental health service use. METHODS: A two-year longitudinal study comparing the outcome of HYPS receiving combined EIS and IACIT since 2012, to a historical cohort of HYPS receiving EIS only between 2005 and 2011. Socio-demographic data, housing stability, functioning, illness severity, SUD severity, emergency room visits and hospitalizations were assessed at admission, at 1 month, and every 3 months thereafter. RESULTS: HYPS receiving EIS + IACIT achieved housing stability more rapidly and spent less time hospitalized than HYPS getting EIS only (RR 2.38, P = .017). HYPS with cocaine misuse were less likely to attain housing stability (RR 0.25, P = .04). No between-group differences were found for psychiatric symptoms, functioning and SUD outcomes. CONCLUSION: The addition of IACIT-HYPS to EIS was associated with earlier housing stability and reduced total hospitalization days compared to EIS alone.

How to help homeless youth suffering from first episode psychosis and substance use disorders? The creation of a new intensive outreach intervention team.

In Canada, about 6,000 youth are homeless every night, many of whom suffer from addiction and psychotic disorders. To facilitate the exit out of homelessness, access to care and to improve psychosis and addiction outcomes, a new intensive outreach intervention team (EQIIP SOL) was created in Montreal (2012). It offers intensive outreach services dedicated to homeless youth suffering from first episode psychosis and addiction (HYFEPA) in addition to an early psychosis intervention service (EIS) in collaboration with the Addiction Psychiatry Unit. Our aim is to describe the characteristics, clinical, functional and housing outcomes of HYFEPA followed by EQIIP SOL. This two years long prospective longitudinal study with all HYFEPA (n = 42) admitted to EQIIP SOL between 2012-2015 reports at multiple time points, clinical (CGI, GAF), functional (SOFAS, work/study, housing autonomy) and substance use disorder (DUS, AUS) outcomes and acute services use (hospitalizations, emergency room visits). We observed that, at baseline, HYFEPA showed poor prognostic factors (eg. cluster B personality, substance use disorders, legal problems, childhood trauma and lower education level). The majority reached housing stability after 6 months and their functioning and illness severity improved with time. This suggests that HYFEPA improve with an intensive outreach intervention team integrated to an EIS.

A pilot, open-label, 8-week study evaluating desvenlafaxine for treatment of major depression in methadone-maintained individuals with opioid use disorder.

Depression is one of the most prevalent psychiatric disorders among opioid-dependent individuals. Clinical trials testing selective serotonin reuptake inhibitors among depressed patients on methadone maintenance therapy (MMT) failed to show efficacy, whereas those on tricyclic antidepressants produced mixed results with potential for cardiotoxicity. Desvenlafaxine (DESV) is a SNRI with minimal cardiotoxicity and drug interactions. This study sought to assess feasibility and tolerability of using DESV in depressed patients on MMT. A total of 18 depressed individuals on MMT received DESV (50-100 mg/day) for 8 weeks. Participants were assessed for the following: (a) Safety of DESV using Systematic Assessment for Treatment Emergent Events-GI, ECG [corrected Q-T (QTc) interval measurement] and methadone serum levels; (b) depressive symptoms using Montgomery-Äsberg Depression Rating Scale (MADRS); and (c) other outcomes including anxiety, suicidality, craving, substance use, quality of life, and other depression scales. Registration number on ClinicalTrials.gov is NCT02200406. Among participants who completed the study, MADRS scores significantly decreased at week 8 compared with baseline. Responders and remitters on MADRS at week 8 were 61 and 50%, respectively. There was no significant change in [corrected Q-T (QTc) interval measurement] between baseline and week 4. DESV was well tolerated and associated with improvement of depressive symptoms. DESV may be a promising contender to treat depression in individuals on MMT and deserves further exploration in a randomized double-blinded clinical trial.

Immigrants' outcome after a first-episode psychosis.

AIM: Immigration is a risk factor for psychosis emergence, and previous studies show that immigrants are less likely to engage in treatment for psychosis. However, the literature on outcome is scant and heterogeneous. This study was designed to compare first-generation (FGI) and second-generation immigrants (SGI) to non-immigrants' symptomatic and functional outcomes 2 years after a first-episode psychosis (FEP). METHODS: A 2-year prospective longitudinal study of 223 FEP patients between 18 and 30 years took place in two early intervention services (EIS) in Montreal, Canada. RESULTS: Forty-two per cent of the sample were immigrants (FGI (n = 56), SGI (n = 38)). Compared with non-immigrants, immigrants had similar symptomatic and functioning profiles at baseline, 1 and 2 years, except that fewer SGI had a history of homelessness and more were living with their families. FGI were less likely to have a substance use disorder but more likely to pursue their studies and to present depressive symptoms. CONCLUSIONS: Even if immigrants are known to be at greater risk of developing psychosis, probably secondary to stress related to immigration, their symptomatic and functional outcomes, once engaged in EIS treatment, are similar to or sometimes better than non-immigrants' outcomes. Because immigrants tend to be less engaged in their follow-up, understanding why they disengage from treatment is crucial to develop better therapeutic approaches to better engage them as EIS treatment can improve their outcomes effectively.

Symptomatic and functional outcomes of substance use disorder persistence 2 years after admission to a first-episode psychosis program.

Substance use disorders (SUD) in first-episode psychosis (FEP) are highly prevalent and linked with poor outcomes. However, most longitudinal studies investigating their impacts in FEP have not reported proportions of patients who ceased SUD. Our aim was to examine the influence of SUD course on functional and symptomatic outcomes as well as service use in FEP. We performed a 2-year longitudinal study of 212 FEP patients, aged between 18 and 30 years, admitted to 2 early psychosis services in Montréal, Québec, Canada. We observed that cannabis was the first substance abused (42.9% at baseline), followed by alcohol (19.3%). The SUD rate decreased by approximately 30% during the first year. Patients with persistent SUD had worse functional outcomes (Quality of Life Scale, Social and Occupational Functioning Assessment Scale, employment), more symptoms (Positive and Negative Symptoms Scale) and heavier service use (emergency and hospitalization). SUD persistence was associated with illness severity, homelessness and cluster-B personality. Those living with their parents and financially supported by them were more likely to cease SUD. Our results indicate that SUD course was more significant than having SUD at admission; persistent SUD was associated with worse outcomes. SUD decreased during a general early psychosis intervention program (with no specialized SUD treatment). An integrated, specialized approach targeting FEP patients with predictive factors of SUD persistence during the first years of treatment might increase SUD cessation and possibly improve outcomes.

Engaging Immigrants in Early Psychosis Treatment: A Clinical Challenge.

OBJECTIVE: The study compared engagement in treatment and medication adherence of immigrants and nonimmigrants in early intervention services for persons with first-episode psychosis. METHODS: This two-year longitudinal prospective cohort study recruited patients with first-episode psychosis who were entering early intervention services in Montreal, Canada (N=223). Data on sociodemographic characteristics, symptoms, and social functioning were collected annually. RESULTS: At two years, immigrants had more than three times the odds of attrition than nonimmigrants after the analysis controlled for potential confounding factors (first-generation immigrants: odds ratio [OR]=3.11, 95% confidence interval [CI]=1.01-9.57, p=.049); second-generation immigrants: OR=3.65, CI=1.07-12.50, p=.039). Medication adherence was similar among those who remained in the programs. CONCLUSIONS: During the two years after entering a program for first-episode psychosis, immigrants were more likely than nonimmigrants to disengage from treatment. Further research is warranted to understand this phenomenon and to improve the ability of services to engage immigrants with first-episode psychosis.

[Craving as a core symptom in substance use disorders: epidemiology, neurobiological substrates and clinical relevance]. / Le craving comme symptôme central de la toxicomanie : de ses fondements neurobiologiques à sa pertinence clinique.

OBJECTIVE: Observed by physicians and often reported by patients, craving is a core symptom of addiction, although not well defined nor understood completely. In the last several years, functional imaging as well as the measurement of different biological substrates of addiction have greatly evolved, allowing for a better understanding of the underlying neurobiological pathways of craving. Furthermore, with the development of the DSM-V and its inclusion as a diagnostic criterion for substance use disorders, craving has gained a whole new level of interest. Hence, the general objective of this article is to examine findings of studies that have led to a better understanding of craving and its implications. First, we address the definition of craving and its epidemiology in individuals with substance use disorders. We then summarize the results of the research conducted on the neurobiological substrates of craving. Finally, we present the role of craving in the cycle of addiction and its potential as a therapeutic target for pharmacological and non-pharmacological interventions. METHODS: Narrative review of the literature. RESULTS: The definition of craving has greatly evolved throughout the years, and it is commonly described as an abnormal desire or need to take a drug. While its conscious aspect is well known, whereas it is expressed subjectively, it is growingly also defined as an unconscious phenomenon illustrated by a physiologic activation that is not perfectly correlated with subjective measures. Available data on craving have also demonstrated the presence of this symptom in all three phases of the addiction cycle, including early and prolonged abstinence, long after the acute physical withdrawal syndrome. Three factors have been identified as potent craving inducers: the drug itself, drug related cues and stress. PET scan studies and fMRI studies confirmed the implication of dopaminergic pathways in craving, and have more recently shed light on the contribution of other neurotransmission systems, such as GABA, norepinephrine as well as the endocannabinoid and opioid systems, but their roles are not yet fully understood. Furthermore, craving-related activations of specific areas of the brain involved in learned habits and behavior as well as memory have been demonstrated by various studies; in contrast, regions associated with regulation and control of emotion have been demonstrated to be hypoactive during craving episodes. Finally, several studies have demonstrated that craving is a valid predictive indicator of relapse, making it an interesting target for pharmacological and non-pharmacological treatment. Several anti-craving medications have been shown to decrease craving, including varenicline for tobacco and naltrexone for alcohol dependence. Studies examining the efficacy of other anti-craving medications for other substances are growing in numbers. CONCLUSIONS: Available data on craving support its role as a core symptom of addiction and allow for a better understanding of the underlying neurobiological substrates. Studies tend to show that it is a valid indicator of relapse during early and prolonged abstinence. Further research is needed to truly understand the complexity of the neurobiological substrates involved in craving as well as to develop new anti-craving interventions to facilitate long-term abstinence in individuals with substance use disorders.

[Opioid use disorder in patients with chronic non-cancer pain]. / Les troubles liés à l'utilisation des opioïdes prescrits médicalement.

Epidemiology Canada now has the second highest number of opioid prescriptions per capita in the world. The rate of prescriptions has increased over the last decade, most notably in adults over 55 years of age. A recognition of the importance of treating pain has influenced this increase, but higher rates of opioid prescribing have produced undesirable outcomes including the misuse of medication as well as an increased number of deaths and emergency department visits attributable to opioids. Diverse psychiatric disorders, such as major depression, now also occur in 40% of those with an opioid use disorder (OUD). Neuroscience We now understand that addictive behaviors are caused by both environmental and genetic factors. Although OUD has historically been perceived as a weakness of character, it is now clear that it is a chronic disease, which results from a complex interaction between a substance, such as opioid, environmental factors, and an individual's genotype. Unfortunately, this evidence has yet to be successfully translated into clinical practice and most physicians are unable to diagnose and manage OUD patients appropriately.Clinical guidelines Many clinical guidelines for the management of chronic, non-cancer pain are available. All guidelines identify the need to assess the patient appropriately and screen for factors associated with misuse before prescribing opioids. Guidelines generally acknowledge that patients should not be denied appropriate pain management, but that some patients will require close supervision and frequent follow-up to prevent the misuse of prescription opioids.

Neurocognitive endophenotypes in schizophrenia: modulation by nicotinic receptor systems.

Cigarette smoking is the leading preventable cause of death in the Western world, with a considerably higher prevalence observed in schizophrenia compared to the general population. Despite the negative health consequences of smoking heavily, it has been proposed that individuals with schizophrenia may maintain smoking behaviors to remediate symptoms associated with the disorder. Neurocognitive deficits are a core feature of schizophrenia and are present in approximately 80% of patients. Further, these deficits constitute an endophenotype of schizophrenia, as they are stable across disease phases, and are heritable. The neurocognitive deficits that are present in schizophrenia are especially debilitating, since they are associated with poor clinical and functional outcomes and community integration. Interestingly, these deficits may also constitute a vulnerability factor towards the initiation and maintenance of tobacco use. Contributing to the potential shared vulnerability between schizophrenia and tobacco dependence is a dysregulation of the nicotinic acetylcholine receptor (nAChR) system. Pre-clinical evidence has shown that nicotine affects several neurotransmitter systems, including dopamine (DA), glutamate, and γ-aminobutyric acid (GABA), and certain neuropsychological deficits associated with these neurotransmitters (reaction time, spatial working memory, sustained attention, and sensory gating) are improved after nicotine administration in patients with schizophrenia. These positive effects on neurocognition appear to be more pronounced in smokers with schizophrenia, and may be an important mechanism that explains the co-morbidity of schizophrenia and tobacco dependence.

Pharmacotherapy challenges in patients with first-episode psychosis.

The first episode of a psychotic disorder typically occurs in late adolescence or young adulthood, a critical time of development with respect to personality, social role, education, and vocation. The first few years of psychosis appear to be a critical period during which intervention needs to be initiated before the consequences of psychosis become more severe. Early intervention is therefore crucial in maximizing outcomes. Although response rates to antipsychotic medication in first-episode psychosis (FEP) are good, there is a relatively high risk of relapse. The greatest challenges that physicians face in treating FEP and preventing relapse are engaging patients in treatment and preventing non-adherence to therapy. Overall rates of non-adherence to antipsychotic medications for FEP patients are estimated to be at or higher than 50% within the first year of treatment, suggesting that malleable factors linked to non-adherence need to be targeted in interventions provided. Factors influencing adherence can be categorized into four groups: (1) environment-related, (2) patient-related, (3) medication-related, and (4) illness-related. This paper will review the factors associated with adherence and discuss solutions to optimize engagement, adherence to medication, and treatment in order to prevent relapse. Factors like social and family support, therapeutic alliance, attitudes and beliefs toward illness and medication, insight, substance use disorders, medication efficacy, tolerability, and accessibility will be discussed. Solutions, such as early psychosis specialized services integrating psychosocial therapies and careful selection of appropriate antipsychotic medication, will be proposed.