Psychological stress worsens cancer outcomes by activating adrenergic signaling between nerves and tumors, a process called tumor-neuron crosstalk. Preclinical models show stress triggers sympathetic pathways that promote cancer progression and treatment resistance. Conventional antidepressants are often less effective for cancer patients, but psilocybin has achieved 60-80% long-term remission of cancer-related depression and anxiety in limited samples, while ketamine provides rapid but short-lived symptom control. These agents may normalize HPA axis function and upregulate neurotrophic factors, reducing sustained adrenergic tone and interrupting stress-driven tumor-neuron signaling. Integrating these drugs into oncology could improve survival, and hospital-based psychiatrists are positioned to lead interdisciplinary research with biomarker-rich trials.
Fatigue, a multidimensional condition that often overlaps with depression, responds only modestly to standard antidepressants and mood stabilizers but has shown positive response to intravenous ketamine, which is limited by cost and access. This study evaluated a single 50 mg dose of intranasal ketamine in 28 individuals with major depressive disorder or bipolar depression, about 60% of whom also had alcohol use disorder. The group by time interaction for the NIH-Brief Fatigue Inventory score was significant, favoring intranasal ketamine over placebo at 4, 24, and 48 hours post-treatment. Intranasal ketamine was well-tolerated with minimal adverse effects. The findings suggest intranasal ketamine induces rapid anti-fatigue effects and may serve as an alternative rapid-acting option for fatigue across different medical conditions.
Treatment-resistant depression (TRD) lacks a consensus definition, with studies requiring between 1 and 4 failed antidepressant therapies. An imbalance between the neurotransmitters L-glutamate and GABA is emerging as key in TRD. Among glutamatergic targets, NMDA receptor antagonism, particularly with ketamine and esketamine (Spravato), has shown robust responses. NMDA-glycine site modulators D-cycloserine and apimostinel show promising safety and efficacy. Dextromethorphan-bupropion (Auvelity) demonstrates positive results, especially in subpopulations with cognitive dysfunction. The most promising GABA modulators are synthetic neurosteroid analogs like brexanolone. Three compounds are FDA-approved: esketamine for TRD, Auvelity for MDD, and brexanolone for postpartum depression, though concerns exist with esketamine and brexanolone.