Depression

Argues that ketamine's neuroplasticity and psychological openness could complement psychotherapy, but the adjunctive potential remains largely unexplored.

review

Microbiota-derived short-chain fatty acids mediate the synergistic antidepressant effects of DJZT and ketamine by activating FFAR2 and suppressing NLRP3-IL-1β signaling in the medial prefrontal cortex.

animal study with fecal microbiota transplantation, metabolomic profiling, pharmacological interventions, and behavioral approaches

A mindfulness yoga program significantly reduced depression scores (K6 from 11.2 to 9.1) and increased self-compassion, but did not significantly change resilience or happiness.

pre-post intervention study Sample size: 11

Differences in how NMDA antagonists modulate negative affective biases in male rats may serve as a predictor of clinical efficacy in major depressive disorder.

preclinical study

Ketamine provides rapid relief from depressive symptoms in adult cancer patients, often within hours to days, with additional benefits in anxiety, pain, and quality of life.

systematic review Sample size: 14

Argues that peripheral 5-HT2B receptor agonism is linked to valvular heart disease, while centrally selective antagonism represents a tractable augmentation target for treatment-resistant depression provided peripheral activation is avoided.

narrative review

One or two 25 mg doses of psilocybin with adjunct psychotherapy produced a stable and clinically meaningful antidepressant effect lasting up to twelve months in treatment-resistant depression.

naturalistic follow-up of a phase 2b, randomized, active placebo-controlled trial Sample size: 126

Serial intravenous ketamine was not significantly more effective than midazolam in reducing depressive symptoms or improving quality of life, with blinding failures potentially influencing results.

randomized controlled trial Sample size: 63

Argues that lack of public access to novel treatments for treatment-resistant depression in Australia could be addressed by establishing specialist clinics in the public sector.

review

Argues that a two-step therapeutic approach using initial IV ketamine followed by D-cycloserine and lurasidone may provide rapid and sustained anti-suicidal effects, but uncertainties remain about efficacy and optimal use.

review

VR-based mindfulness interventions were associated with significant reductions in depressive and anxiety symptoms, with larger effects among older adults and in Eastern regions.

meta-analysis Sample size: 864

Argues that ketamine has the fastest and most pronounced antidepressant effect with low risk of phase change, while celecoxib significantly increased response and remission rates compared to escitalopram alone.

review

Early reduction in suicidal ideation after ketamine or esketamine treatment is associated with lower rates of emergency department visits for suicidality.

observational cohort

Subanesthetic-dose ketamine infusion reduces the global and regional path length of brain functional connectivity in patients with treatment-resistant depression and suicidal ideation.

preprint

Argues that depression involves dysregulated neurotransmitter systems, neuroinflammation, and disrupted neural connectivity, with emerging treatments including neurosteroid therapies and psychedelic-assisted psychotherapy for treatment-resistant cases.

review

Ketamine induced region-specific changes in hemodynamic response function parameters in brain regions linked to sensory-cognitive integration, mood regulation, and cognitive control, with changes in the thalamus and superior frontal gyrus associated with improvements in suicidal ideation.

randomized controlled trial Sample size: 45

Psychiatric adverse events were reported by patients during ketamine treatment for major depressive disorder.

retrospective analysis

Activation of the prelimbic cortex to zona incerta circuit restored exploratory deficits and alleviated other depression-like behaviors in depressed mice.

experimental study

Corrigendum to a 5-year observational study on intranasal esketamine dosing patterns and clinical outcomes; no new findings.

corrigendum

The guidelines establish expert consensus on the use of intravenous ketamine infusions for depressive disorders, covering patient selection, dosing, safety, and treatment protocols.

consensus guidelines

Oral ketamine produces short-term antidepressant effects compared to placebo or control conditions.

systematic review and meta-analysis

A single dose of psilocybin (25 mg) produced significantly greater reduction in depressive symptoms compared to placebo by day 8, with effects lasting through day 42 but not at one year.

randomized controlled trial Sample size: 35

Argues that the strongest evidence for ketamine in PTSD comes from three randomized trials of intravenous ketamine, while data on intranasal esketamine and psychotherapy combinations are mainly from pilot studies, retrospective analyses, or case reports, and the evidence base remains small, heterogeneous, and largely uncontrolled.

narrative review

Pre-treatment symptom network density was significantly higher in non-responders than in responders, and changes in network density after treatment differed between groups.

observational cohort Sample size: 447

Argues that functional unblinding due to esketamine's side effects and general limitations of psychotherapy studies make it difficult to scientifically investigate causal relationships between ketamine administration and improved psychotherapeutic efficacy.

review