Protocols and practices in psilocybin assisted psychotherapy for depression: A systematic review.

BACKGROUND: Psilocybin-assisted psychotherapy (PAP) is a promising treatment option for depression, with randomized controlled trials (RCTs) providing preliminary support for its safety and efficacy. However, there is a lack of consistency across existing treatment protocols and psychotherapeutic approaches. The objective of this review is to summarize and compare current psychotherapy methods of PAP in treating depression and distress in life-threatening illnesses. We sought to comprehensively summarize published psychotherapy protocols from clinical trials to provide insights for future practices. METHODS: A systematic search of four databases (Embase, MEDLINE, PsycINFO, CINAHL) for data relating to psychotherapy protocols was conducted by two independent reviewers. RESULTS: In total, our search identified 1869 articles; after removing duplicates, we screened 1107 articles. We included 70 articles in the full-text review and determined that 28 were eligible for the final review. All protocols include sessions before (preparatory) and after (integration) the psychedelic dosing session with supportive monitoring. However, there was substantial variability and inconsistencies in all other aspects of therapy protocols (e.g., duration and number of sessions, model of therapy). Additionally, significant limitations were identified in the frequent need for more clarity in the description of therapeutic approaches. CONCLUSION: In published clinical trials, PAP has consisted of preparation, supportive dosing, and integration sessions. Beyond this basic framework, significant heterogeneity and lack of clarity were identified in reported psychotherapy protocols, meaning a validated and universally agreed upon protocol for PAP currently does not exist. Future studies should more clearly define and report psychotherapeutic components to identify the safest and most efficacious approaches to PAP.

Clinical evaluation of isotropic MAVRIC-SL for symptomatic hip arthroplasties at 3 T MRI.

BACKGROUND: 3D multi-spectral imaging (MSI) of metal implants necessitates relatively long scan times. OBJECTIVE: We implemented a fast isotropic 3D MSI technique at 3 T and compared its image quality and clinical utility to non-isotropic MSI in the evaluation of hip implants. METHODS: Two musculoskeletal radiologists scored images from coronal proton density-weighted conventional MAVRIC-SL and an isotropic MAVRIC-SL sequence accelerated with robust-component-analysis on a 3-point scale (3: diagnostic, 2: moderately diagnostic, 1: non-diagnostic) for overall image quality, metal artifact, and visualization around femoral and acetabular components. Grades were compared using a signed Wilcoxon test. Images were evaluated for effusion, synovitis, osteolysis, loosening, pseudotumor, fracture, and gluteal tendon abnormalities. Reformatted axial and sagittal images for both sequences were subsequently generated and compared for image quality with the Wilcoxon test. Whether these reformats increased diagnostic confidence or revealed additional pathology, including findings unrelated to arthroplasty that may contribute to hip pain, was also compared using the McNemar test. Inter-rater agreement was measured by Cohen's kappa. RESULTS: 39 symptomatic patients with a total of 59 hip prostheses were imaged (mean age, 70 years ±9, 14 males, 25 females). Comparison scores between coronal images showed no significant difference in image quality, metal artifact, or visualization of the femur and acetabulum. Except for loosening, reviewers identified more positive cases of pathology on the original coronally-acquired isotropic sequence. In comparison of reformatted axial and sagittal images, the isotropic sequence scored significantly (p < 0.01) higher for overall image quality (3.0 vs 2.0) and produced significantly (p < 0.01) more cases of increased diagnostic confidence (42.4% vs 7.6%) or additional diagnoses (50.8% vs 22.9%). Inter-rater agreement was substantial (k = 0.798) for image quality. Mean scan times were 4.2 mins (isotropic) and 7.1 mins (non-isotropic). CONCLUSION: Compared to the non-isotropic sequence, isotropic 3D MSI was acquired in less time while maintaining diagnostically acceptable image quality. It identified more pathology, including postoperative complications and potential pain-generating pathology unrelated to arthroplasty. This fast isotropic 3D MSI sequence demonstrates promise for improving diagnostic evaluation of symptomatic hip prostheses at 3 T while simultaneously reducing scan time.

Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin.

BACKGROUND: Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity. We also evaluated flexible repeated doses over a 6-month period. METHODS: Adults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or a substance use disorder were eligible to participate. Subjects were randomized to immediate treatment or waitlist control, with all eventually receiving PAP. Participants had one, two, or three psilocybin sessions with a fixed dose of 25 mg. Each dose was accompanied by preparation and integration psychotherapy sessions. Acceptability, safety, tolerability, and efficacy were evaluated (this study was registered at ClinicalTrials.gov: NCT05029466). FINDINGS: Participants were randomized to immediate treatment (n = 16) or delayed treatment (n = 14). 29/30 were retained to the week-2 primary endpoint. Adverse events were transient, with no serious adverse events. Greater reductions in depression severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) were observed in the immediate treatment arm compared to the waitlist period arm with a large hedge's g effect size of 1.07 (p < 0.01). Repeated doses were associated with further reductions in MADRS scores compared to baseline. CONCLUSIONS: PAP was feasible in complex patients with preliminary antidepressant efficacy and adequate safety and tolerability. Repeated doses were associated with greater reductions in depression severity. FUNDING: This work was funded by Brain and Cognition Discovery Foundation (BCDF), Usona, and Braxia Scientific.

Real-world effectiveness of repeated intravenous ketamine infusions for treatment-resistant depression in transitional age youth.

BACKGROUND: Ketamine is an emerging treatment for treatment-resistant depression (TRD) associated with rapid and robust improvements in depressive symptoms and suicidality. However, the efficacy and safety of ketamine in transitional age youth (TAY; age 18-25) populations remains understudied. METHODS: In this retrospective analysis, TAY patients (n = 52) receiving ketamine for TRD were matched for sex, primary diagnosis, baseline depression severity, and treatment resistance with a general adult (GA) sample (age 30-60). Patients received four ketamine infusions over 2 weeks (0.5-0.75 mg/kg over 40 min). The primary outcome was the change in Quick Inventory of Depressive Symptomatology Self-Report 16-item (QIDS-SR16) over time. Secondary outcomes were changes in QIDS-SR16 suicidal ideation (SI) item, anxiety (Generalized Anxiety Disorder 7-item (GAD-7)), and adverse effects (ClinicalTrials.gov: NCT04209296). RESULTS: A significant main effect of infusions on reduction of total QIDS-SR16 (p < 0.001), QIDS-SR16 SI (p < 0.001), and GAD-7 (p < 0.001) scores was observed in the TAY group with moderate effect sizes, indicative of clinically significant improvements in depression, anxiety, and suicidality. There were no significant differences between TAY and GA groups on these measures over time, suggesting comparable improvements in both groups. Safety and tolerability outcomes were comparable between groups with only mild, transient adverse effects observed. CONCLUSION: Ketamine was associated with comparable clinical benefits, safety, and tolerability in a TAY sample as compared to a matched GA TRD sample.

Real world effectiveness of repeated ketamine infusions for treatment-resistant depression with comorbid borderline personality disorder.

Borderline personality disorder (BPD) has high rates of comorbidity with mood disorders, including treatment-resistant depression (TRD). Comorbidity of BPD with depression is associated with poorer response to antidepressants. Intravenous ketamine is a novel treatment for TRD that has not been specifically evaluated in patients with comorbid BPD. In this retrospective analysis of data collected from participants who received care at the Canadian Rapid Treatment Centre of Excellence (CRTCE; Braxia Health; ClinicalTrials.gov: NCT04209296), we evaluated the effectiveness of intravenous ketamine in a TRD population with comorbid BPD (N=100; n=50 BPD-positive compared with n=50 BPD-negative). Participants were administered four doses of intravenous ketamine (0.5-0.75mg/kg over 40 minutes) over two weeks. The primary outcome measures were changes in depressive symptom severity (as measured by Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS-SR16)) and borderline symptom severity (as measured by Borderline Symptom List 23-item (BSL-23)). Both BPD-positive and BPD-negative groups improved significantly on the QIDS-SR16, QIDS-SR16 suicide ideation item, anxiety, and functionality scales with large effect sizes. There was no significant difference between groups. The BPD-positive group exhibited significant reduction of 0.64 on BSL-23 scores and a significant reduction of 5.95 on QIDS-SR16 scores. Patients with TRD and comorbid BPD receiving ketamine exhibited a significant reduction in symptoms of depression, borderline personality, suicidality, and anxiety.

A Phase II, Open-Label Clinical Trial of Intranasal Ketamine for Depression in Patients with Cancer Receiving Palliative Care (INKeD-PC Study).

Antidepressants require several weeks for the onset of action, a lag time that may exceed life expectancy in palliative care. Ketamine has demonstrated rapid antidepressant effects, but has been minimally studied in cancer and palliative care populations. Herein, the objective was to determine the feasibility, safety, tolerability and preliminary efficacy of intranasal racemic ketamine for major depressive disorder (MDD) in patients with advanced cancer. We conducted a single-arm, open-label phase II trial at the Princess Margaret Cancer Centre in Toronto, ON, Canada. Participants with advanced cancer with moderate to severe MDD received three flexible doses of intranasal (IN) ketamine (50−150 mg) over a one-week period. The primary efficacy outcome was an antidepressant response and remission rates as determined by the Montgomery−Åsberg Depression Rating Scale (MADRS) from baseline to the Day 8 primary endpoint. Twenty participants were enrolled in the trial, receiving at least one dose of IN ketamine, with fifteen participants receiving all three doses. The Day 8 antidepressant response (MADRS decreased by >50%) and remission (MADRS < 10 on Day 8) rates were high at 70% and 45%, respectively. Mean MADRS scores decreased significantly from baseline (mean MADRS of 31, standard deviation 7.6) to Day 8 (11 +/− 7.4) with an overall decrease of 20 points (p < 0.001). Antidepressant effects were partially sustained in the second week in the absence of additional ketamine doses, with a Day 14 mean MADRS score of 14 +/− 9.9. Common adverse effects included fatigue, dissociation, nausea, dysgeusia and headaches; almost all adverse effects were mild and transient, resolving within 2 h of each ketamine dose with one dropout related to adverse effects (negative dissociative episode). Given these promising findings, larger, controlled trials are merited.

Imaging of Osteoarthritis of the Knee.

Knee osteoarthritis is rising in prevalence, and more imaging studies are being requested to evaluate these patients. Although conventional radiographs of the knee are the most widely requested and available studies, other imaging modalities such as MRI, CT, and ultrasound may also be used. This article reviews commonly used imaging modalities, advantages and limitations of each, and their clinical applicability in diagnosing and monitoring knee osteoarthritis. New and advanced imaging techniques are also discussed as possible methods of early diagnosis and improved understanding of osteoarthritis pathophysiology.

Clinical utility of accelerated MAVRIC-SL with robust-PCA compared to conventional MAVRIC-SL in evaluation of total hip arthroplasties.

OBJECTIVE: To compare the diagnostic performance of a conventional metal artifact suppression sequence MAVRIC-SL (multi-acquisition variable-resonance image combination selective) and a novel 2.6-fold faster sequence employing robust principal component analysis (RPCA), in the MR evaluation of hip implants at 3 T. MATERIALS AND METHODS: Thirty-six total hip implants in 25 patients were scanned at 3 T using a conventional MAVRIC-SL proton density-weighted sequence and an RPCA MAVRIC-SL proton density-weighted sequence. Comparison was made of image quality, geometric distortion, visualization around acetabular and femoral components, and conspicuity of abnormal imaging findings using the Wilcoxon signed-rank test and a non-inferiority test. Abnormal findings were correlated with subsequent clinical management and intraoperative findings if the patient underwent subsequent surgery. RESULTS: Mean scores for conventional MAVRIC-SL were better than RPCA MAVRIC-SL for all qualitative parameters (p < 0.05), although the probability of RPCA MAVRIC-SL being clinically useful was non-inferior to conventional MAVRIC-SL (within our accepted 10% difference, p < 0.05), except for visualization around the acetabular component. Abnormal imaging findings were seen in 25 hips, and either equally visible or visible but less conspicuous on RPCA MAVRIC-SL in 21 out of 25 cases. In 4 cases, a small joint effusion was queried on MAVRIC-SL but not RPCA MAVRIC-SL, but the presence or absence of a small effusion did not affect subsequent clinical management and patient outcome. CONCLUSION: While the overall image quality is reduced, RPCA MAVRIC-SL allows for significantly reduced scan time and maintains almost equal diagnostic performance.

Initial Investigations of the Cranial Size and Shape of Adult Eurasian Otters (Lutra lutra) in Great Britain.

Three-dimensional (3D) surface scans were carried out in order to determine the shapes of the upper sections of (skeletal) crania of adult Eurasian otters (Lutra lutra) from Great Britain. Landmark points were placed on these shapes using a graphical user interface (GUI) and distance measurements (i.e., the length, height, and width of the crania) were found by using the landmark points. Male otters had significantly larger skulls than females (P < 0.001). Differences in size also occurred by geographical area in Great Britain (P < 0.05). Multilevel Principal Components Analysis (mPCA) indicated that sex and geographical area explained 31.1% and 9.6% of shape variation in "unscaled" shape data and that they explained 17.2% and 9.7% of variation in "scaled" data. The first mode of variation at level 1 (sex) correctly reflected size changes between males and females for "unscaled" shape data. Modes at level 2 (geographical area) also showed possible changes in size and shape. Clustering by sex and geographical area was observed in standardized component scores. Such clustering in a cranial shape by geographical area might reflect genetic differences in otter populations in Great Britain, although other potentially confounding factors (e.g., population age-structure, diet, etc.) might also drive regional differences. This work provides a successful first test of the effectiveness of 3D surface scans and multivariate methods, such as mPCA, to study the cranial morphology of otters.

Anomalous Pulmonary Venous Return: Insights Into Prenatal Detection.

OBJECTIVES: To review all cases of total anomalous pulmonary venous return (TAPVR) or partial anomalous pulmonary venous return (PAPVR) identified prenatally or postnatally at a single institution and to identify factors that may lead to a correct or missed diagnosis in both high- and low-risk fetuses on screening examinations. METHODS: Fetal images from 16 cases of prenatally or postnatally diagnosed T/PAPVR were retrospectively reviewed to analyze factors that influenced interpretations and diagnoses. RESULTS: Sixteen diagnoses of T/PAPVR were made, with a final number of 10 confirmed cases, 1 of which was PAPVR. Ten fetuses with a presumptive diagnosis of T/PAPVR before delivery were at an average gestational age of 24.7 weeks, with 5 cases diagnosed postnatally. None of the diagnoses of isolated TAPVR were made during a screening examination. Twelve of the pregnancies were complicated by complex cardiac defects, including 6 with heterotaxy syndromes. Of the 5 abnormal cases identified in the postpartum period, 3 had isolated TAPVR. In the 3 patients with isolated defects, prenatal echocardiography was not performed; the anatomy scan interpretations were confounded by multiple factors. In retrospect, there was no obvious sonographic evidence of TAPVR in these patients; however, color flow Doppler imaging of the pulmonary veins was not performed on any of them. CONCLUSIONS: Although fetal echocardiography has improved the overall detection of TAPVR or PAPVR, this abnormality continues to elude prenatal diagnosis during screening in both low- and high-risk patients. We hypothesize that the use of color flow Doppler imaging in the 4-chamber view may assist in diagnosing TAPVR in screening low-risk patients, especially in those with difficult scans.

Transcranial direct current stimulation of the primary motor cortex affects cortical drive to human musculature as assessed by intermuscular coherence.

Intermuscular coherence analysis can be used to assess the common drive to muscles. Coherence in the beta-frequency band (15-35 Hz) is thought to arise from common cortical sources. Intermuscular coherence analysis is a potentially attractive tool for the investigation of motor cortical excitability changes because it is non-invasive and can be done relatively quickly. We carried out this study to test the hypothesis that intermuscular coherence analysis was able to detect cortical excitability changes in healthy subjects following transcranial direct current stimulation (tDCS). tDCS has been shown to increase (anodal stimulation) or decrease (cathodal stimulation) the size of the muscle potential evoked by TMS. We found that anodal tDCS caused an increase in motor evoked potential (MEP) size that was paralleled by an increase in beta-band intermuscular coherence. Similarly, the reduction in MEP size produced by cathodal tDCS was paralleled by a reduction in beta-band intermuscular coherence, while sham stimulation did not result in any change in either MEP amplitude or beta-band intermuscular coherence. The similar pattern of change observed for MEP and intermuscular coherence may indicate similar mechanisms of action, although this cannot be assumed without further investigation. These changes do suggest that at least some of the action of tDCS is on cortical networks, and that combined tDCS and intermuscular coherence analysis may be useful in the diagnosis of pathologies affecting motor cortical excitability.