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Few studies have evaluated the efficacy of ketamine-assisted psychotherapy (KAP) in the treatment of treatment-resistant depression (TRD) and substance use disorders (SUD).A systematic review of clinical trials reporting on the efficacy of KAP and discussing mechanisms of action, identified on PubMed and PsycInfo.Five randomized-controlled trials reported on the efficacy of KAP treatment and discussed active mechanisms. Four of the studies treated adults with SUD and a single study treated adults with TRD. Overall, KAP had a significant positive effect on primary outcome measures compared to controls, however, the data is mixed. The study examining KAP for TRD found no benefit.Lack of large, replicated clinical trials. No studies actively examining mechanisms of action.Evidence suggests that temporary neural changes caused by ketamine such as n-methyl-d-aspartate receptor (NMDAR) inhibition and increase of synaptic neuroplasticity affect treatment outcomes of KAP. Based on reports of preliminary findings, we speculate that adjunct psychotherapy, changes in perspective, and spirituality may also play a role.

Clinical trials have demonstrated rapid antidepressant effects with intravenous (IV) ketamine for major depressive disorder, with relatively less research specifically for bipolar depression. Herein, we describe the real-world effectiveness of repeated ketamine infusions for treatment-resistant bipolar depression.This study was conducted in a community clinic in Mississauga, Ontario (Canadian Rapid Treatment Centre of Excellence; Braxia Health). In this observational study (NCT04209296), patients with treatment-resistant bipolar I/II depression (n=66) received four sub-anesthetic doses of IV ketamine (0.5-0.75mg/kg) over a two-week period. Symptoms of depression, suicidality, anxiety and functioning were assessed with validated self-report measures.Statistically and clinically significant antidepressant effects were observed in the overall sample, as measured by the Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SRReal world effectiveness of IV ketamine for bipolar depression was observed. Repeated doses were associated with greater symptom reduction and adequate tolerability.

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 Conclusion: Ketamine was associated with comparable clinical benefits, safety, and tolerability in a TAY sample as compared to a matched GA TRD sample.