The Association Between Self-Reported Anxiety and Retention in Opioid Agonist Therapy: Findings From a Canadian Pragmatic Trial.

BACKGROUND: Prescription-type opioid use disorder (POUD) is often accompanied by comorbid anxiety, yet the impact of anxiety on retention in opioid agonist therapy (OAT) is unclear. Therefore, this study investigated whether baseline anxiety severity affects retention in OAT and whether this effect differs by OAT type (methadone maintenance therapy (MMT) vs. buprenorphine/naloxone (BNX)). METHODS: This secondary analysis used data from a pan-Canadian randomized trial comparing flexible take-home dosing BNX and standard supervised MMT for 24 weeks. The study included 268 adults with POUD. Baseline anxiety was assessed using the Beck Anxiety Inventory (BAI), with BAI ≥ 16 indicating moderate-to-severe anxiety. The primary outcomes were retention in assigned and any OAT at week 24. In addition, the impact of anxiety severity on retention was examined, and assigned OAT was considered an effect modifier. RESULTS: Of the participants, 176 (65%) reported moderate-to-severe baseline anxiety. In adjusted analyses, there was no significant difference in retention between those with BAI ≥ 16 and those with BAI < 16 assigned (29% vs. 28%; odds ratio (OR) = 2.03, 95% confidence interval (CI) = 0.94-4.40; P = 0.07) or any OAT (35% vs. 34%; OR = 1.57, 95% CI = 0.77-3.21; P = 0.21). In addition, there was no significant effect modification by OAT type for retention in assigned (P = 0.41) or any OAT (P = 0.71). In adjusted analyses, greater retention in treatment was associated with BNX (vs. MMT), male gender identity (vs. female, transgender, or other), enrolment in the Quebec study site (vs. other sites), and absence of a positive urine drug screen for stimulants at baseline. CONCLUSIONS: Baseline anxiety severity did not significantly impact retention in OAT for adults with POUD, and there was no significant effect modification by OAT type. However, the overall retention rates were low, highlighting the need to develop new strategies to minimize the risk of attrition from treatment. CLINICAL TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (NCT03033732).

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes.

BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults. METHODS: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process. RESULTS: The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted. CONCLUSIONS: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.

Impact of Depressive Symptom Severity on Buprenorphine/Naloxone and Methadone Outcomes in People With Prescription-Type Opioid Use Disorder: Results From a Pragmatic Randomized Controlled Trial.

OBJECTIVE: To evaluate the impact of depressive symptom severity on opioid use and treatment retention in individuals with prescription-type opioid use disorder (POUD). METHOD: We analyzed data from a multi-centric, pragmatic, open-label, randomized controlled trial comparing buprenorphine/naloxone to methadone models of care in 272 individuals with POUD. Opioid use was self-reported every two weeks for 24 weeks using the Timeline Followback. Depressive symptom severity was self-reported with the Beck Depression Inventory at baseline, week 12 and week 24. RESULTS: Baseline depressive symptom severity was not associated with opioid use nor treatment retention. At week 12, moderate depressive symptoms were associated with greater opioid use while mild to severe depressive symptoms were associated with lowered treatment retention. At week 24, moderate depressive symptoms were associated with greater opioid use. CONCLUSIONS: Ongoing depressive symptoms lead to poorer outcomes in POUD. Clinicians are encouraged to use integrative approaches to optimize treatment outcomes. This study was registered in ClinicalTrials.gov (NCT03033732) on January 27th, 2017, prior to participants enrollment.

Factors Associated with Bothersome Symptoms in Individuals With and Without HIV Who Report Alcohol Use.

Bothersome symptoms potentially related to drinking are commonly reported by people with and without HIV (PWH/PWoH). However, the relationship between bothersome symptoms and level of alcohol use is often not appreciated by patients or providers. Therefore, among persons reporting prior-year alcohol use, we assessed whether alcohol use level (AUDIT-C score), HIV status, and demographic covariates influenced the likelihood of the patient reporting a bothersome symptom. We used the Veterans Aging Cohort Study (VACS) surveys (2002-2018), including a validated symptoms index. Among 3679 PWH and 3830 PWoH currently drinking alcohol, the most commonly reported symptoms were muscle/joint pain (52%), sleep disturbance (51%), and fatigue (50%). Level of alcohol use was independently associated with 18 of 20 bothersome symptoms, including seven symptoms more common among PWH. Results can help inform PWH/PWoH who drink alcohol about the strong relationship between level of alcohol use and bothersome symptoms, potentially motivating reduced use.

Comparative Efficacy and Tolerability of Antipsychotics for Juvenile Psychotic Disorders: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Psychotic disorders produce important morbidity and disability in children and adolescents. There have been few relevant treatment trials, encouraging assessment of research aimed at testing efficacy and safety of antipsychotics for juveniles. We aimed to compare the short- and long-term efficacy and safety of antipsychotics to treat psychotic disorders among children and adolescents. METHODS: Four major bibliographic databases (PubMed, MEDLINE, PsycINFO, and EMBASE) were searched for clinical trials of antipsychotics in children or adolescents, from database inception to May 2021. We searched for clinical trials comparing antipsychotics with control conditions for juvenile psychosis based on blinded review by 2 independent investigators (C.S.Y. and M.L.). We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and applied the Cochrane risk-of-bias tool to appraise study quality. One reviewer (A.B.) performed data abstraction which was confirmed by 2 independent, blinded reviewers (C.S.Y. and M.L.). Primary outcomes were scores rating psychosis symptoms and dichotomized retention in treatment protocols versus dropouts because of adverse events. Effect sizes were pooled using frequentist random-effects network meta-analysis modeling to generate summary rate ratios (RRs) and Cohen d standardized mean differences. RESULTS: Systematic searching generated 1330 unique records. Of these, short-term (n = 15, for 6 [3-12] weeks) and long-term (n = 10, for 12 [6-60] months) treatment trials involved 2208 (39.2% females; median age, 15.3 years), and 1366 subjects (35.0% females; median age, 15.6 years), respectively. Short-term reduction of psychosis scores ranked clozapine (d = -1.35; 95% confidence interval [CI], -1.97 to -0.73]), molindone (-1.22; 95% CI, -1.68 to -0.75), olanzapine (-1.12; 95% CI, -1.44 to -0.81), and risperidone (-0.93; 95% CI, -1.22 to -0.63) as the most effective agents. In longer-term treatment, only lurasidone was effective. Clozapine (RR, 12.8) and haloperidol (RR, 5.15) led to more all-cause and adverse event-related dropouts. There were few trials/drug (1 each for aripiprazole, asenapine, lurasidone, molindone, paliperidone, and ziprasidone, short term; aripiprazole, clozapine, haloperidol, lurasidone, and molindone, long-term). Heterogeneity and inconsistency were high, especially in long-term trials, without evidence of publication bias. CONCLUSIONS: Some antipsychotics were effective and tolerated short term, but longer-term evidence was very limited. The overall paucity of trials and of adequate controls indicates that more well-designed randomized controlled trials are required for adequate assessment of antipsychotic drug treatment for juveniles. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021232937.

Making a case for the inclusion of refractory and severe mental illness as a sole criterion for Canadians requesting medical assistance in dying (MAiD): a review.

BACKGROUND: Following several landmark rulings and increasing public support for physician-assisted death, in 2016, Canada became one of a handful of countries legalising medical assistance in dying (MAiD) with Bill C-14. However, the revised Bill C-7 proposes the specific exclusion of MAiD where a mental disorder is the sole underlying medical condition (MAiD MD-SUMC). AIM: This review explores how some persons with serious and persistent mental illness (SPMI) could meet sensible and just criteria for MAiD under the Canadian legislative framework. METHODS: We review the proposed Bill C-7 criteria (capacity, voluntariness, irremediability and suffering) as well as the nuances involved in separating a well-reasoned request for assisted suicide from what might be solely a manifestation of a SPMI. FINDINGS: In this paper, we argue against the absolute exclusion of patients with SPMIs from accessing MAiD. Instead, we propose that in some circumstances, MAiD MD-SUMC may be justifiable while remaining the last resort. Conducting MAiD eligibility assessments removes the need to introduce diagnosis-specific language into MAiD legislation. Competent psychiatric patients who request MAiD should not be treated any differently from other eligible candidates. Many individuals with psychiatric disorders will be incapable of consenting to MAiD. The only ethical option is to assess eligibility for MAiD on an individual basis and include as legitimate candidates those who suffer solely from psychiatric illness who have the decisional capacity to consent to MAiD.

Prevalence and factors associated with polypharmacy: a systematic review and Meta-analysis.

INTRODUCTION: Polypharmacy is commonly associated with adverse health outcomes. There are currently no meta-analyses of the prevalence of polypharmacy or factors associated with polypharmacy. We aimed to estimate the pooled prevalence of polypharmacy and factors associated with polypharmacy in a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for studies with no restrictions on date. We included observational studies that reported on the prevalence of polypharmacy among individuals over age 19. Two reviewers extracted study characteristics including polypharmacy definitions, study design, setting, geography, and participant demographics. The risk of bias was assessed using the Newcastle-Ottawa Scales. The main outcome was the prevalence of polypharmacy and factors associated with polypharmacy prevalence. The pooled prevalence estimates of polypharmacy with 95% confidence intervals were determined using random effects meta-analysis. Subgroup analyses were undertaken to evaluate factors associated with polypharmacy such as polypharmacy definitions, study setting, study design and geography. Meta-regression was conducted to assess the associations between polypharmacy prevalence and study year. RESULTS: 106 full-text articles were identified. The pooled estimated prevalence of polypharmacy in the 54 studies reporting on polypharmacy in all medication classes was 37% (95% CI: 31-43%). Differences in polypharmacy prevalence were reported for studies using different numerical thresholds, study setting, and publication year. Sex, study geography, study design and geographical location were not associated with differences in polypharmacy prevalence. DISCUSSION: Our review highlights that polypharmacy is common particularly among older adults and those in inpatient settings. Clinicians should be aware of populations who have an increased likelihood of experiencing polypharmacy and efforts should be made to review the appropriateness of prescribed medications and occurrence of adverse effects potentially associated with polypharmacy. CONCLUSIONS AND IMPLICATIONS: Clinicians should be aware of the common occurrence of polypharmacy and undertake efforts to minimize inappropriate polypharmacy whenever possible.

Ketamine for Bipolar Depression: A Systematic Review.

BACKGROUND: Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, its efficacy in bipolar depression is less clear. This study aimed to assess the efficacy and tolerability of ketamine for bipolar depression. METHODS: We conducted a systematic review of experimental studies using ketamine for the treatment of bipolar depression. We searched PubMed, MEDLINE, Embase, PsycINFO, and the Cochrane Central Register for relevant studies published since each database's inception. We synthesized evidence regarding efficacy (improvement in depression rating scores) and tolerability (adverse events, dissociation, dropouts) across studies. RESULTS: We identified 6 studies, with 135 participants (53% female; 44.7 years; standard deviation, 11.7 years). All studies used 0.5 mg/kg of add-on intravenous racemic ketamine, with the number of doses ranging from 1 to 6; all participants continued a mood-stabilizing agent. The overall proportion achieving a response (defined as those having a reduction in their baseline depression severity of at least 50%) was 61% for those receiving ketamine and 5% for those receiving a placebo. The overall response rates varied from 52% to 80% across studies. Ketamine was reasonably well tolerated; however, 2 participants (1 receiving ketamine and 1 receiving placebo) developed manic symptoms. Some participants developed significant dissociative symptoms at the 40-minute mark following ketamine infusion in 2 trials. CONCLUSIONS: There is some preliminary evidence supporting use of intravenous racemic ketamine to treat adults with bipolar depression. There is a need for additional studies exploring longer-term outcomes and alterative formulations of ketamine.

Comparative Efficacy and Tolerability of Adjunctive Pharmacotherapies for Acute Bipolar Depression: A Systematic Review and Network Meta-analysis.

OBJECTIVE: We investigated the comparative efficacy and tolerability of augmentation strategies for bipolar depression. DATA SOURCES: We conducted a systematic review and network meta-analysis of 8 electronic databases for double-blind, randomized controlled trials of adjunctive pharmacotherapies for acute bipolar depression. DATA EXTRACTION AND SYNTHESIS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and applied the Cochrane risk of bias tool for study quality appraisal. Two reviewers independently abstracted data. We resolved all discrepancies by consensus. MAIN OUTCOMES AND MEASURES: Primary outcomes were response and completion of treatment. We estimated summary rate ratios (RRs) and standardized mean differences (SMDs) relative to placebo controls using frequentist random-effects network meta-analysis. RESULTS: We identified 69 trials meeting eligibility criteria (8,007 participants, 42.8 years, 58.0% female). Adjunctive racemic intravenous ketamine, coenzyme Q10, pramipexole, fluoxetine, and lamotrigine were more effective than placebo. Summary RRs for response ranged between 1.51 (95% confidence interval [CI], 1.11 to 2.06) for fluoxetine and 12.49 (95% CI, 3.06 to 50.93) for racemic intravenous ketamine. For completion of treatment, risperidone appeared less tolerable than placebo (RR = 0.59; 95% CI, 0.38 to 0.94), while fluoxetine seemed more tolerable than placebo (RR = 1.13; 95% CI, 1.02 to 1.24). None of the investigated agents were associated with increased treatment-emergent mood switches. CONCLUSIONS AND RELEVANCE: The evidence for augmentation strategies in bipolar depression is limited to a handful of agents. Fluoxetine appeared to have the most consistent evidence base for both efficacy and tolerability. There remains a need for additional research exploring novel treatment strategies for bipolar depression, particularly head-to-head studies.

Psychotherapies for Adolescents with Subclinical and Borderline Personality Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND: Evidence regarding the efficacy of psychotherapy in adolescents with borderline personality disorder (BPD) symptomatology has not been previously synthesized. OBJECTIVE: To conduct a systematic review and meta-analysis of the randomized controlled trials (RCTs) in order to assess the efficacy of psychotherapies in adolescents with BPD symptomatology. METHODS: Seven electronic databases were systematically searched using the search terms BPD, adolescent, and psychotherapy from database inception to July 2019. Titles/abstracts and full-texts were screened by one reviewer; discrepancies were resolved via consensus. We extracted data on BPD symptomatology, including BPD symptoms, suicide attempts, nonsuicidal self-injury, general psychopathology, functional recovery, and treatment retention. Data were pooled using random-effects models. RESULTS: Of 536 papers, seven trials (643 participants) were eligible. Psychotherapy led to significant short-term improvements in BPD symptomatology posttreatment (g = -0.89 [-1.75, -0.02]) but not in follow-up (g = 0.06 [-0.26, 0.39]). There was no significant difference in treatment retention between the experimental and control groups overall (odds ratio [OR] 1.02, 95% confidence interval [CI], 0.92 to 1.12, I2 = 52%). Psychotherapy reduced the frequency of nonsuicidal self-injury (OR = 0.34, 95% CI, 0.16 to 0.74) but not suicide attempts (OR = 1.03, 95% CI, 0.46 to 2.30). CONCLUSIONS: There is a growing variety of psychotherapeutic interventions for adolescents with BPD symptomatology that appears feasible and effective in the short term, but efficacy is not retained in follow-up-particularly for frequency of suicide attempts.

Cannabinoids for the Neuropsychiatric Symptoms of Dementia: A Systematic Review and Meta-Analysis.

BACKGROUND: In 2016, the global number of individuals living with dementia was 43.8 million, representing a 117% increase from 1990-mainly due to increases in aging and population growth. Up to 90% of individuals with dementia experience neuropsychiatric symptoms (NPS). However, the limitations of current treatments for NPS have drivent he search for safer pharmacotherapies-including cannabinoids. AIM: To assess the efficacy and acceptability of cannabinoids for the treatment of NPS in individuals with dementia. DESIGN: Systematic review and meta-analysis of clinical trials. SETTING AND PARTICIPANTS: Of 6,902 papers, 9 were eligible (n = 205, 44% female, 78 ± 7 years, 85% Alzheimer disease). Trials were in North America and Europe and explored tetrahydrocannabinol (n = 3), dronabinol (n = 5), or nabilone (n = 1). MEASUREMENT: Titles/abstracts were independently screened by one reviewer and reviewed by a second. Full-text screening was by two reviewers with discrepancies resolved via a third reviewer. We extracted data on the standardized mean difference (SMD) for several NPS instruments, trial completion, and adverse events. Data were pooled using random-effects models. FINDINGS: Cannabinoids led to significant improvements across NPS instruments, including the Cohen Mansfield Agitation Inventory (SMD = -0.80; 95% confidence interval [CI], -1.45 to -0.16), the Neuropsychiatric Inventory (SMD = -0.61; CI, -1.07 to -0.15), and nocturnal actigraphy (SMD = -1.05; CI, -1.56 to -0.54h). Cannabinoids were well-tolerated, with an overall trial completion rate of 93% (193/205) and no serious treatment-related adverse events. Treatment efficacy was associated with baseline dementia severity and dose, but not dementia subtype, age, or sex. The overall study quality was rated as low. CONCLUSIONS: There is preliminary evidence for the efficacy and tolerability of cannabinoids as treatments for NPS. Population-based studies are needed to characterize their real-world effectiveness and acceptability.

Characterizing inpatient care for adults with schizophrenia using the Health Quality Ontario indices: A single-centre retrospective cohort study.

PURPOSE: This single-center retrospective cohort study is one of the first reports to evaluate the inpatient care provided to persons diagnosed with schizophrenia in Canada. METHODS: This study examined all admissions for adults diagnosed with schizophrenia over a 6-month period in 2017 to an inpatient psychiatric unit situated in a nonprofit general hospital in Kingston, Ontario, Canada. The Health Quality Ontario standards for the inpatient care of adults with schizophrenia were used to assess the quality of care provided in hospital. Standards were determined to have been met by doing a thorough chart review for each patient, reviewing all documentation in progress notes, admission notes, discharge notes and emergency room notes for quality standard completion. RESULTS: The average length of stay per patient was 18.64 days. The treatment at this facility largely focused on medication management of schizophrenia; however, it was found that several areas of care did not meet the standard of care as set by the Health Quality Ontario Quality Standards for Schizophrenia Care for Adults in Hospitals, which was set in 2016. Problematic areas were promoting physical activity and healthy eating (4.9% compliance), treatment with clozapine (13.1% compliance) and cognitive behavioural therapy (9.8% compliance). The study site is fully accredited and attending physicians were all psychiatrists. How pervasive these deficiencies are in other settings is not known.

Endocarditis in the setting of IDU: multidisciplinary management.

PURPOSE OF REVIEW: The purpose of this article is to provide a brief overview of the medical and surgical management of infective endocarditis secondary to IDU, with a focus on the underlying substance use disorder. RECENT FINDINGS: Patients with infective endocarditis secondary to IDU are often young with unique comorbidities including mental illness, chronic hepatitis C, HIV infection, which are often compounded by limited social and familial supports. The focus of management has been treatment of endocarditis using IV antibiotics alongside surgery. Surgical outcomes compare favorably with those of infective endocarditis in the general population but long-term outcomes of IDUs are significantly worse. This is primarily due to the high rate of recidivism of drug use and the risk of prosthetic valve infective endocarditis. Contemporary management of addiction utilizes an integrative approach, combining both pharmacologic and nonpharmacologic strategies while remaining patient-centered. Given the complexity of care required, we advocate for a multidisciplinary team-based approach including psychiatry, infectious disease, cardiology, cardiac surgery and social services. SUMMARY: Infective endocarditis secondary to IDU remains a medical and surgical challenge with dismal outcomes. Here we offer practical suggestions on the multidisciplinary management of this challenging and high-risk patient cohort.