Medical assistance in dying for mental illness: a complex intervention requiring a correspondingly complex evaluation approach.

Medical assistance in dying for mental illness as a sole underlying medical condition (MAiD MI-SUMC) is a controversial and complex policy in terms of psychosocial and ethical medical practice implications. We discuss the status of MAiD MI-SUMC in Canada and argue for the use of the UK Medical Research Council's framework on complex interventions in programme evaluations of MAiD MI-SUMC. It is imperative to carefully and rigorously evaluate the implementation of MAiD MI-SUMC to ensure an understanding of the multiple facets of implementation in contexts permeated by unique social, economic, cultural and historical influences, with a correspondingly diverse array of outcomes. This requires a complexity-informed programme evaluation focused on context-dependent mechanisms and stakeholder experiences, including patients, service providers and other people affected by the policy. It is also important to consider the economic impact on health and social welfare systems. Such evaluations can provide the data needed to guide evidence-informed decision-making that can contribute to safer implementation and refinement of MAiD MI-SUMC.

Care considerations in medical assistance in dying for persons with mental illness as the sole underlying medical condition: a qualitative study of patient and family perspectives.

BACKGROUND: Persons with mental illness as their sole underlying medical condition are eligible to access medical assistance in dying (MAiD) in a small number of countries, including Belgium, the Netherlands, Luxemburg and Switzerland. In Canada, it is anticipated that people experiencing mental illness as their sole underlying medical condition (MI-SUMC) will be eligible to request MAiD as of March 17th 2024. To date, few studies have addressed patient and family perspectives on MAiD MI-SUMC care processes. This study aimed to address this gap and qualitatively explore the perspectives of persons with lived experience of mental illness and family members on care considerations during MI-SUMC implementation. METHODS: Thirty adults with lived experience of mental illness and 25 adult family members residing in Ontario participated in this study. To facilitate participant engagement, the semi-structured interview used a persona-scenario exercise to discuss perspectives on MAiD MI-SUMC acceptability and care considerations. Framework analysis was used to inductively analyze data using NVivo 12 Pro. Steps, processes, or other care considerations suggested by the participants were charted in a framework matrix after familiarization with the narratives. Key themes were further identified. A lived-experience advisory group participated in every aspect of this study. RESULTS: Six themes were developed from the patient and family narratives: (1) Raising MAiD MI-SUMC awareness; (2) Sensitive Introduction of MAiD MI-SUMC in goals of care discussions; (3) Asking for MAiD MI-SUMC: a person-focused response; (4) A comprehensive circle of MAiD MI-SUMC care; (5) A holistic, person-centered assessment process; and (6) Need for support in the aftermath of the decision. These themes highlighted a congruence of views between patient and family members and described key desired process ingredients, including a person-centred non-judgmental stance by care providers, inter-professional holistic care, shared decision making, and the primacy of patient autonomy in healthcare decision making. CONCLUSIONS: Family and patient perspectives on the implementation of MAiD MI-SUMC offer important considerations for service planning that could complement existing and emerging professional practice standards. These stakeholders' perspectives will continue to be essential in MAiD MI-SUMC implementation efforts, to better address the needs of diverse communities and inform improvement efforts.

Medical Assistance in Dying for Mental Illness as a Sole Underlying Medical Condition and Its Relationship to Suicide: A Qualitative Lived Experience-Engaged Study: Aide Médicale à Mourir Pour Maladie Mentale Comme Seule Condition Médicale Sous-Jacente et Son Lien Avec le Suicide: Une Etude Qualitative Engagée Dans l'Expérience Vécue.

OBJECTIVE: This lived experience-engaged study aims to understand patient and family perspectives on the relationship between suicidality and medical assistance in dying when the sole underlying medical condition is mental illness (MAiD MI-SUMC). METHOD: Thirty individuals with mental illness (age M = 41.8 years, SD = 14.2) and 25 family members (age M = 47.5 years, SD = 16.0) participated in qualitative interviews examining perspectives on MAiD MI-SUMC and its relationship with suicide. Audio recordings were transcribed and analysed using reflexive thematic analysis. People with lived experience were engaged in the research process as team members. RESULTS: Four main themes were developed, which were consistent across individuals with mental illness and family members: (a) deciding to die is an individual choice to end the ongoing intolerable suffering of people with mental illness; (b) MAiD MI-SUMC is the same as suicide because the end result is death, although suicide can be more impulsive; (c) MAiD MI-SUMC is a humane, dignified, safe, nonstigmatized alternative to suicide; and (4) suicidality should be considered when MAiD MI-SUMC is requested, but suicidality's role is multifaceted given its diverse manifestations. CONCLUSION: For patient-oriented mental health policy and treatment, it is critical that the voices of people with lived experience be heard on the issue of MAiD MI-SUMC. Given the important intersections between MAiD MI-SUMC and suicidality and the context of suicide prevention, the role that suicidality should play in MAiD MI-SUMC is multifaceted. Future research and policy development are required to ensure that patient and family perspectives guide the development and implementation of MAiD MI-SUMC policy and practice.

Seven decades of antipsychotic drugs: Why is the life of Australians with schizophrenia still so suboptimal?

The advent of dopamine (D2) receptor-blocking medications over 70 years ago, ushered in a new era of biological treatment for schizophrenia. However, we argue that little subsequent progress has been made in translating this into fulfilled and fulfilling lives for people with schizophrenia. This Viewpoint asks why this is the case, and suggests ways forward for capitalising on extant and emerging new treatments for psychotic disorders, to the betterment of the lives of people living with schizophrenia.

Risk prevalence, readiness and confidence to change lifestyle risk factors among clients of community mental health services.

OBJECTIVE: People with mental health conditions have high rates of chronic physical diseases, partially attributable to lifestyle risks factors. This study examined risk prevalence among community mental health service clients, their readiness and confidence to change, and associations with participant characteristics. METHODS: Cross-sectional survey of adult clients from 12 community mental health services across 3 local health districts in New South Wales, Australia, collected from 2021 to 2022. Participants (n = 486) completed a telephone interview determining five risk factors, and readiness and confidence to change these. Multiple binary logistic regression models determined associations between readiness and confidence (for each risk), and participant characteristics (demographics and diagnosis). RESULTS: Participants most commonly reported a diagnosis of schizophrenia (36.7%) or depression (21.1%). Risk factors were prevalent: ranging from 26% (harmful alcohol use) to 97% (poor nutrition). High readiness was greatest for smoking (68%), weight (66%) and physical inactivity (63%), while confidence was highest for changing alcohol use (67%). Two significant associations were identified; females were more likely than males to have high readiness to change nutrition (odds ratio = 1.14, confidence interval = [1.13, 2.34], p = 0.0092), with males more likely to have high confidence to change physical activity (odds ratio = 0.91, confidence interval = [0.45, 0.99], p = 0.0109). CONCLUSIONS: Many participants were ready and confident to change risk factors. Gender influenced readiness to change nutrition and physical activity confidence. Training to upskill mental health clinicians in provision of preventive care that builds confidence and readiness levels may aid in supporting positive behaviour change.

'Quitlink': Outcomes of a randomised controlled trial of peer researcher facilitated referral to a tailored quitline tobacco treatment for people receiving mental health services.

OBJECTIVE: The aim of this study was to test the effectiveness of a tailored quitline tobacco treatment ('Quitlink') among people receiving support for mental health conditions. METHODS: We employed a prospective, cluster-randomised, open, blinded endpoint design to compare a control condition to our 'Quitlink' intervention. Both conditions received a brief intervention delivered by a peer researcher. Control participants received no further intervention. Quitlink participants were referred to a tailored 8-week quitline intervention delivered by dedicated Quitline counsellors plus combination nicotine replacement therapy. The primary outcome was self-reported 6 months continuous abstinence from end of treatment (8 months from baseline). Secondary outcomes included additional smoking outcomes, mental health symptoms, substance use and quality of life. A within-trial economic evaluation was conducted. RESULTS: In total, 110 participants were recruited over 26 months and 91 had confirmed outcomes at 8 months post baseline. There was a difference in self-reported prolonged abstinence at 8-month follow-up between Quitlink (16%, n = 6) and control (2%, n = 1) conditions, which was not statistically significant (OR = 8.33 [0.52, 132.09] p = 0.131 available case). There was a significant difference in favour of the Quitlink condition on 7-day point prevalence at 2 months (OR = 8.06 [1.27, 51.00] p = 0.027 available case). Quitlink costs AU$9231 per additional quit achieved. CONCLUSION: The Quitlink intervention did not result in significantly higher rates of prolonged abstinence at 8 months post baseline. However, engagement rates and satisfaction with the 'Quitlink' intervention were high. While underpowered, the Quitlink intervention shows promise. A powered trial to determine its effectiveness for improving long-term cessation is warranted.

A new network analysis model in anorexia nervosa patients based on self-reported eating disorder symptoms, psychological distress, and cognitive flexibility.

OBJECTIVES: Cognitive flexibility and psychological distress, such as depression and anxiety, have been implicated in the aetiology of Anorexia Nervosa (AN). Despite the known associations between eating disorder (ED) symptoms, depression, anxiety, and cognitive flexibility, the specific pathways that connect these constructs are unclear. We therefore used network analysis to examine the relationship between these symptoms in an AN sample. METHODS: One hundred and ninety-three treatment-seeking individuals diagnosed with AN (95.6% female, M = 26.89 [SD = 9.45] years old) completed self-report measures assessing depression, anxiety, cognitive flexibility, and ED symptoms. To determine each symptom's influence in the network, we calculated the expected influence. RESULTS: The two relationships with the greatest edges were those between (1) weight/shape concerns and eating/dietary restraint and (2) weight/shape concerns and psychological distress (a measure that combined depression and anxiety). Cognitive flexibility was not connected to weight/shape concerns but had negative partial associations with eating concerns/dietary restraint and psychological distress. There was also a slight, non-zero connection between eating concerns/dietary restraint and psychological distress. CONCLUSIONS: The findings underscore the importance of weight/shape, eating/dietary concerns, and psychological distress in the AN network and suggest that addressing cognitive flexibility may be a useful target for eating concerns/dietary restraint and psychological distress. Future studies assessing the longitudinal course of psychopathology within the AN network structure may help in identifying whether specific symptoms function as risk factors or maintaining factors for this co-occurrence.

A hierarchy of visual processing deficits in body dysmorphic disorder: a conceptual review and empirical investigation.

OBJECTIVE: Abnormal visual processing has been proposed as a mechanism underlying excessive focus on minor appearance flaws in body dysmorphic disorder (BDD). Existing BDD research has not differentiated the various stages of face processing (featural, first-order configural, holistic and second-order configural) that are required for higher-order processes such as emotion recognition. This study investigated a hierarchical visual processing model to examine the nature of abnormalities in face processing in BDD. METHOD: Thirty BDD participants and 27 healthy controls completed the Navon task, a featural and configural face processing task and a facial emotion labelling task. RESULTS: BDD participants performed similarly to controls when processing global and local non-face stimuli on the Navon task, when detecting subtle changes in the features and spacing of a target face, and when labelling emotional faces. However, BDD participants displayed poorer performance when viewing inverted faces, indicating difficulties in configural processing. CONCLUSIONS: The findings only partially support prior work. However, synthesis of results with previous findings indicates that heterogenous task methodologies may contribute to inconsistent findings. Recommendations are provided regarding the task parameters that appear most sensitive to abnormalities in BDD.

Clinical outcomes of deep brain stimulation for obsessive-compulsive disorder: Insight as a predictor of symptom changes.

AIM: Deep brain stimulation (DBS) is a safe and effective treatment option for people with refractory obsessive-compulsive disorder (OCD). Yet our understanding of predictors of response and prognostic factors remains rudimentary, and long-term comprehensive follow-ups are lacking. We aim to investigate the efficacy of DBS therapy for OCD patients, and predictors of clinical response. METHODS: Eight OCD participants underwent DBS stimulation of the nucleus accumbens (NAc) in an open-label longitudinal trial, duration of follow-up varied between 9 months and 7 years. Post-operative care involved comprehensive fine tuning of stimulation parameters and adjunct multidisciplinary therapy. RESULTS: Six participants achieved clinical response (35% improvement in obsessions and compulsions on the Yale Brown Obsessive Compulsive Scale (YBOCS)) within 6-9 weeks, response was maintained at last follow up. On average, the YBOCS improved by 45% at last follow up. Mixed linear modeling elucidated directionality of symptom changes: insight into symptoms strongly predicted (P = 0.008) changes in symptom severity during DBS therapy, likely driven by initial changes in depression and anxiety. Precise localization of DBS leads demonstrated that responders most often had their leads (and active contacts) placed dorsal compared to non-responders, relative to the Nac. CONCLUSION: The clinical efficacy of DBS for OCD is demonstrated, and mediators of changes in symptoms are proposed. The symptom improvements within this cohort should be seen within the context of the adjunct psychological and biopsychosocial care that implemented a shared decision-making approach, with flexible iterative DBS programming. Further research should explore the utility of insight as a clinical correlate of response. The trial was prospectively registered with the ANZCTR (ACTRN12612001142820).

Association Between Pharmacologic Treatment of Depression and Patient-Reported Outcomes Following Total Hip and Knee Arthroplasty.

BACKGROUND: Depression is associated with inferior outcomes following hip or knee arthroplasty, though it remains unclear if this relationship is modifiable. This study examined the association between pharmacologic treatment of depression and patient-reported outcomes. METHODS: This retrospective cohort study of 1,651 total hip arthroplasty (THA) and 1,792 total knee arthroplasty (TKA) procedures between October 2012 and June 2019 used institutional registry data linked to nationwide pharmaceutical claims. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, with pain and function subscales assessed as secondary outcomes. The TKA and THA patients were analyzed separately via mixed-effect linear regression to compare patients who had depression treated with antidepressants (TKA, n = 210; THA, n = 150) to those who had untreated depression (TKA, n = 43; THA; n = 50), and those who did not have depression (TKA, n = 1,539; THA, n = 1,451). RESULTS: Among patients who had depression, not receiving preoperative antidepressant therapy was associated with smaller improvements in WOMAC global scores (TKA, adjusted mean difference [MD]: -13.1 points, 95% CI [confidence interval]: -21.4 to -4.8; THA, MD: -8.5 points, 95% CI: -15.7 to -1.2) at 2 years after surgery, but not at 1 year (TKA, MD: -5.4 points, 95% CI: -12.9 to 2.1; THA, MD: -6.3 points, 95% CI: -12.9 to 0.3). Those who did not have depression had similar improvements in WOMAC global scores to those who had treated depression at both one (TKA, MD: 0.8 points, 95% CI: -2.7 to 4.4; THA, MD: 1.8 points, 95% CI: -1.8 to 5.4) and 2 years (TKA, MD: -1.1 points, 95% CI: -4.9 to 2.7; THA, MD: -1.6 points, 95% CI: -5.6 to 2.3). The findings were consistent with secondary outcomes. CONCLUSIONS: Among patients who have depression, antidepressant therapy before TKA or THA is associated with improved outcomes. Additional studies are needed to establish the impact of interventions to address untreated depression before surgery.

Aggressive behaviours associated with MDMA and psychedelics: a narrative review.

OBJECTIVE: Monoamine neurotransmitters play a role in aggression, especially when altered by illicit substances. However, some literature suggests that not all illicit substances may lead to aggression, notably psychedelics. This narrative review investigates the associations between serotonergic psychedelics and MDMA on aggressive behaviour. METHODS: PubMed and PsycINFO were searched for original, peer-reviewed articles evaluating the effects of serotonergic psychedelics and 3,4-methyl enedioxy methamphetamine (MDMA) on violent and aggressive behaviour using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: After removing duplicates, a total of 555 articles were screened, with 16 meeting the inclusion criteria. One additional article was obtained through reference screening bringing the total to 17 articles. Of these 17 articles, 14 studies focused on MDMA and three on serotonergic psychedelics. Findings were mixed, with some results demonstrating increased aggression following psychedelics and others suggesting protective effects. Limitations in the current literature include varied definitions of psychedelics, lack of standardised objective outcome measures and failure to control for confounding. CONCLUSION: As psychedelic research continues to expand, further assessment on the effects of serotonergic psychedelics and MDMA on aggressive behaviour is required.

Characterising the nature of psychiatric disorders and patterns of antipsychotic medications prescribed in a psychiatric ward in a public hospital in Tasmania.

OBJECTIVE: We present an evaluation of antipsychotic prescribing in an inpatient psychiatry ward in Hobart, Tasmania, to establish pattern of use, alignment with other psychiatric wards or centres and the recommendations in the Royal Australian and New Zealand College of Psychiatry Clinical Practice Guidelines, and to determine predictors of polypharmacy. METHODS: A descriptive cross-sectional survey design was used. Data from 118 patients discharged from the Royal Hobart Hospital (RHH) Mental Health Inpatient Unit between 01/02/2021 to 01/08/2021 were evaluated. RESULTS: Antipsychotic polypharmacy (APP) was observed in 40% of patients. When low doses of adjunctive ('PRN') use of olanzapine and quetiapine were excluded, the APP proportion was 35%. APP was predicted by age and by a schizophrenia diagnosis. Long-acting injections (LAIs) were used in 46% of the patients. The most common LAI was risperidone (52%). Average daily dose of antipsychotic at the time of discharge was 529 mg chlorpromazine (CPZ) equivalents. High dose antipsychotics (more than 1000 mg CPZ equivalents per day) was observed in 13% of the patients. CONCLUSIONS: The observed prescribing practice is consistent with other clinical settings. Antipsychotic prescribing practice should, however, continue to be monitored to ensure adherence to best practice guidelines.

Psychiatric comorbidity and severity in anorexia nervosa: a comparative study of the DSM-5, the ICD-11, and overvaluation of Weight/Shape severity ratings.

This study assessed the rate of a.) the total and b.) specific psychiatric comorbidities among the three severity ratings for Anorexia Nervosa (AN): DSM-5, ICD-11 and overvaluation of weight and shape (OWS). The sample comprised 312 treatment-seeking patients with AN (mean age = 26.9). Weight and height were taken at intake to calculate BMI, the foundation for the DSM-5 and ICD-11 severity indices. The EDE-Q was used to assess OWS, and the Mini International Neuropsychiatric Interview was conducted to assess psychiatric comorbidities. For the DSM-5, the mild severity group showed a higher total number of psychiatric comorbidities, especially for panic, social anxiety, generalised anxiety, and post-traumatic stress disorders compared to the severe and extremely severe groups. ICD-11 and OWS severity groups did not significantly differ in total comorbidities, except for major depressive disorder and obsessive-compulsive disorders being more prevalent in the "significantly low BMI" ICD-11 group. The high OWS group displayed a notably higher rate of major depressive disorder than the low OWS group. The study underscores inconsistent patterns across the three severity systems, emphasising the need to recognise the current limitations of the assessed severity classification systems in AN assessment and guiding treatment.

Default Mode Network Modulation by Psychedelics: A Systematic Review.

Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering, and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents-lysergic acid diethylamide, psilocybin, and ayahuasca-modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics, and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research in such a way as to elucidate the neurocognitive mechanisms of psychedelics.

Comparing analytical strategies for balancing site-level characteristics in stepped-wedge cluster randomized trials: a simulation study.

BACKGROUND: Stepped-wedge cluster randomized trials (SWCRTs) are a type of cluster-randomized trial in which clusters are randomized to cross-over to the active intervention sequentially at regular intervals during the study period. For SWCRTs, sequential imbalances of cluster-level characteristics across the random sequence of clusters may lead to biased estimation. Our study aims to examine the effects of balancing cluster-level characteristics in SWCRTs. METHODS: To quantify the level of cluster-level imbalance, a novel imbalance index was developed based on the Spearman correlation and rank regression of the cluster-level characteristic with the cross-over timepoints. A simulation study was conducted to assess the impact of sequential cluster-level imbalances across different scenarios varying the: number of sites (clusters), sample size, number of cross-over timepoints, site-level intra-cluster correlation coefficient (ICC), and effect sizes. SWCRTs assumed either an immediate "constant" treatment effect, or a gradual "learning" treatment effect which increases over time after crossing over to the active intervention. Key performance metrics included the relative root mean square error (RRMSE) and relative mean bias. RESULTS: Fully-balanced designs almost always had the highest efficiency, as measured by the RRMSE, regardless of the number of sites, ICC, effect size, or sample sizes at each time for SWCRTs with learning effect. A consistent decreasing trend of efficiency was observed by increasing RRMSE as imbalance increased. For example, for a 12-site study with 20 participants per site/timepoint and ICC of 0.10, between the most balanced and least balanced designs, the RRMSE efficiency loss ranged from 52.5% to 191.9%. In addition, the RRMSE was decreased for larger sample sizes, larger number of sites, smaller ICC, and larger effect sizes. The impact of pre-balancing diminished when there was no learning effect. CONCLUSION: The impact of pre-balancing on preventing efficiency loss was easily observed when there was a learning effect. This suggests benefit of pre-balancing with respect to impacting factors of treatment effects.

Psychotherapies and digital interventions for OCD in adults: What do we know, what do we need still to explore?

BACKGROUND: Despite significant advances in the understanding and treatment of obsessive compulsive disorder (OCD), current treatment options are limited in terms of efficacy for symptom remission. Thus, assessing the potential role of iterative or alternate psychotherapies is important. Also, the potential role of digital technologies to enhance the accessibility of these therapies, should not be underestimated. We also need to embrace the idea of a more personalized treatment choice, being cognisant of clinical, genetic and neuroimaging predictors of treatment response. PROCEDURES: Non-systematic review of current literature on emerging psychological and digital therapies for OCD, as well as of potential biomarkers of treatment response. FINDINGS: A number of 'third wave' therapies (e.g., Acceptance and Commitment Therapy, Mindfulness-Based Cognitive Therapy) have an emerging and encouraging evidence base in OCD. Other approaches entail employment of elements of other psychotherapies such as Dialectical Behaviour Therapy; or trauma-focussed therapies such as Eye Movement Desensitisation and Reprocessing, and Imagery Rescripting and Narrative Therapy. Further strategies include Danger Ideation Reduction Therapy and Habit Reversal. For these latter approaches, large-scale randomised controlled trials are largely lacking, and the precise role of these therapies in treating people with OCD, remains to be clarified. A concentrated 4-day program (the Bergen program) has shown promising short- and long-term results. Exercise, music, and art therapy have not been adequately tested in people with OCD, but may have an adjunctive role. Digital technologies are being actively investigated for enhancing reach and efficacy of psychological therapies for OCD. Biomarkers, including genetic and neuroimaging, are starting to point to a future with more 'personalised medicine informed' treatment strategizing for OCD. CONCLUSIONS: There are a number of potential psychological options for the treatment of people with OCD who do not respond adequately to exposure/response prevention or cognitive behaviour therapy. Adjunctive exercise, music, and art therapy might be useful, albeit the evidence base for these is very small. Consideration should be given to different ways of delivering such interventions, including group-based, concentrated, inpatient, or with outreach, where appropriate. Digital technologies are an emerging field with a number of potential applications for aiding the treatment of OCD. Biomarkers for treatment response determination have much potential capacity and deserve further empirical testing.

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

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

Feasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial.

OBJECTIVES: Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD. METHODS: The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial (n = 15) of enema-delivered FMT (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. RESULTS: Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD. CONCLUSIONS: All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder.

OBJECTIVE: Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder. METHODS: A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria. RESULTS: Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient. CONCLUSIONS: There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.

Gonadal hormones in borderline personality disorder: implications for understanding symptoms and supporting treatment.

OBJECTIVE: To review the literature on the impact of gonadal hormones on features of borderline personality disorder. BACKGROUND: Oestrogen flux and absolute sex hormone levels are known to be associated with various mood states in women. We investigated whether this was particularly relevant for borderline symptoms in women with or without borderline personality disorder (BPD). METHODS: Systematic literature review. DISCUSSION: There is some evidence that borderline symptoms are more severe during certain phases on the menstrual cycle in non-clinical samples of women. There is also a small evidence base that suggests that women with BPD show symptom exacerbation during the late luteal phase of their menstrual cycle. CONCLUSION: More work is required to establish the nature and mechanisms of interactions between gonadal hormones and symptom expression in BPD patients, and therapeutic endeavours need stringent empirical testing.