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Abstract Background Primary health care systems are designed to provide comprehensive patient care. However, the ICD 9 coding system used for billing purposes in Canada neither characterizes nor captures the scope of clinical practice or complexity of physician-patient interactions. This study aims to describe the content of primary care clinical encounters and examine the limitations of using administrative data to capture the content of these visits. Although a number of U.S studies have described the content of primary care encounters, this is the first Canadian study to do so. Methods Study-specific data collection forms were completed by 16 primary care physicians in community health and family practice clinics in Winnipeg, Manitoba, Canada. The data collection forms were completed immediately following the patient encounter and included patient and visit characteristics, such as primary reason for visit, topics discussed, actions taken, degree of complexity as well as diagnosis and ICD-9 codes. Results Data was collected for 760 patient encounters. The diagnostic codes often did not reflect the dominant topic of the visit or the topic requiring the most amount of time. Physicians often address multiple problems and provide numerous services thus increasing the complexity of care. Conclusion This is one of the first Canadian studies to critically analyze the content of primary care clinical encounters. The data allowed a greater understanding of primary care clinical encounters and attests to the deficiencies of singular ICD-9 coding which fails to capture the comprehensiveness and complexity of the primary care encounter. As primary care reform initiatives in the U.S and Canada attempt to transform the way family physicians deliver care, it becomes increasingly important that other tools for structuring primary care data are considered in order to help physicians, researchers and policy makers understand the breadth and complexity of primary care.

Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic effects. However, no psychedelic trials to date have substantiated this finding in a clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) (n = 15) 4 weeks later. Dosing sessions were embedded within a manualized psychotherapy that incorporated principles of Acceptance and Commitment Therapy. Depression severity, psychological flexibility, mindfulness, and values-congruent living were measured over a 16-weeks study period. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved following psilocybin and were maintained through week 16. Additionally, improvements in psychological flexibility and experiential acceptance were strongly associated with reductions in depression severity following psilocybin. These findings support the theoretical premise of integrating psilocybin treatment with psychotherapeutic platforms that target psychological flexibility and add to emerging evidence that increasing psychological flexibility may be an important putative mechanism of change in psilocybin-assisted therapy for MDD and potentially, other mental health conditions., (© 2024. The Author(s).)

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD)., Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD., Design, Setting, and Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing., Interventions: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support., Main Outcomes and Measures: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment., Results: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs., Conclusions and Relevance: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD., Trial Registration: ClinicalTrials.gov Identifier: NCT03866174.

Background: Several early phase studies have demonstrated that psilocybin-assisted therapy has rapid-acting and persisting antidepressant effects from just one or two doses. However, methodological limitations (e.g., placebo-control, blinding) limit interpretability of the existing literature., Methods: In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe major depressive disorder were administered placebo ( n = 19) followed by psilocybin (0.3 mg/kg) ( n = 15) 4 weeks later. Dosing sessions were embedded within an manualized course of psychotherapy. Enhanced blinding procedures were used. Depression, anxiety, and quality of life were measured over a 16-week study period., Results: Depression and anxiety significantly improved following both placebo and psilocybin with no significant difference in the degree of change between the two conditions. However, antidepressant effect sizes were larger after psilocybin ( d ' = 1.02-2.27) than after placebo ( d ' = 0.65-0.99) and there were high rates of response (66.7%) and remission (46.7%) following psilocybin administration. Antidepressant effects following psilocybin persisted, on average, for 2 months and there were persisting improvements in mood-related quality of life domains. The strength of mystical-type experience during psilocybin dosing was not correlated with subsequent antidepressant effects., Conclusions: The results of this exploratory study highlight the complex interplay between expectancy, therapy effects, and drug/placebo effects in psychedelic-assisted psychotherapy studies. Nonetheless, the acute and persisting clinical improvements observed following psilocybin support further study of its potential in the treatment of major depression. Future studies should more explicitly mitigate and measure expectancy effects and assess the impact of repeated dosing and different forms of psychotherapeutic support.

Background: Evidence suggests that serotonergic psychedelics (e.g. psilocybin), have rapid-acting and long-lasting antidepressant effects after a single dose. However, the mechanism underlying these effects remain unclear. One proposed mechanism is that these drugs promote neuroplasticity. However, this has not been conclusively demonstrated in humans., Aims: We hypothesized that relative to placebo, psilocybin would: (1) increase electroencephalographic (EEG) correlates of neuroplasticity, (2) reduce depression symptoms, and (3) changes in EEG would correlate with improvements in depression., Methods: In this double-blind, placebo-controlled, within-subject study, individuals with major depressive disorder (MDD; n  = 19) were administered placebo followed by psilocybin (0.3 mg/kg) in a fixed order (placebo, followed by psilocybin 4 weeks later). EEG indices of neuroplasticity (tetanus-induced long-term potentiation) as assessed via auditory evoked theta (4-8 Hz) power and measures of depression (GRID Hamilton Rating Scale for Depression-17 (GRID-HAM-D-17)) were measured at several time-points after placebo and psilocybin (24 h and 2 weeks after each session)., Results: EEG theta power doubled in amplitude 2 weeks after a single psychedelic dose of psilocybin but not after placebo. Further, improvements in depression symptoms 2 weeks after psilocybin were correlated with increases in theta power., Conclusions: The increased theta power observed represents evidence of sustained changes in the brain following psilocybin. Given the correlation with enhancement in depressive symptoms, changes in theta may represent an EEG biomarker of the sustained effects of psilocybin, and may shed light on potential mechanisms of psilocybin's antidepressant effect. Taken together, these results complement the emerging notion that psilocybin, and perhaps other psychedelics, can produce long-term alterations in neuroplasticity.

There is a growing resurgence in the study of psychedelic medicines for the treatment of mental health and substance use disorders. However, certain early investigations are marred by questionable research methods, abuses against research participants, and covert Central Intelligence Agency financial involvement. The purpose of this study was to understand how and to what extent people of colour and other vulnerable populations, specifically, individuals who were incarcerated or incapacitated due to mental health issues (inpatients with psychotic disorders), were exploited during the first wave of psychedelic research in the USA (1950-1980). To do so, we reviewed available empirical publications according to current ethical standards. Variables of interest included race and ethnicity of participants, population vulnerability, drug administration conditions, informed consent and undue influence. Our findings draw attention to the history of research abuses against people of colour in Western psychedelic research. In light of these findings, we urge a call-to-action to current psychedelic researchers to prioritise culturally inclusive and socially responsible research methods in current and future studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

: Tianeptine is a tricyclic antidepressant that stimulates mu-opioid receptors at high doses. It is marketed and used across Europe and Latin America as an antidepressant, but is not approved by the Food and Drug Administration for use in the United States. In the United States, tianeptine is sold through online health stores as a cognition enhancer, dietary supplement, or as research chemical. We report the case of a 36-year-old man with a history of major depressive disorder, responsive to sertraline, who turned to the unmonitored use of tianeptine purchased online to treat residual feelings of apathy and boredom. His use of tianeptine was marked by rapidly escalating doses and a significant withdrawal syndrome that made discontinuation of this substance difficult. This case serves as a reminder that unscheduled pharmaceutical agents are available for misuse by the general population and have the potential to cause significant harm. Therefore, medical providers must be aware of and screen for the use of such products amongst their patients.