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.

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.

Ketamine use in pediatric depression: A systematic review.

Pediatric depression is a common psychiatric disorder that is associated with significant morbidity and mortality. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist with demonstrated antidepressant effects in the adult population, however, the efficacy and safety of ketamine for the treatment of pediatric depression remains poorly understood. Electronic databases were searched from inception to June 2022 to identify relevant articles. Six articles involving 46 participants with a mean age of 15.7 years were included in this systematic review. Out of six articles, three were case reports, one was a randomized clinical trial (RCT) and two were open-label trials. All studies used 0.5 mg/kg intravenous ketamine except for one, which used 2-7 micrograms/kg. Ketamine was significantly associated with reduced depressive symptoms without severe adverse events. Taken together, the results of these studies demonstrated the potential role of ketamine for treating pediatric depression. Several important limitations were identified, most notably the small sample sizes of the component studies, and that all studies administered intravenous ketamine. Further studies with larger sample sizes and different administration modalities are needed to better determine the efficacy and safety of ketamine in pediatric depression.