This multicenter, randomized, placebo-controlled, clinical trial was designed to investigate the efficacy and safety of esketamine (ESK) for smoking cessation. The study enrolled a sample of 236 patients diagnosed with lung cancer and major depression disorder (MDD). Treatment included intranasal delivery of ESK or placebo once a week for 8 sessions. The primary outcomes were self-reported and...
Chronic stress is a risk factor for depression and may contribute to treatment resistance. This historical cohort study examined the association between baseline perceived stress, measured with the Perceived Stress Scale (PSS), and response to (es) ketamine in treatment-resistant depression (TRD). Adult TRD patients who received intravenous racemic ketamine or intranasal esketamine were...
OBJECTIVE To evaluate the safety of esketamine in bipolar depression, focusing on suicide-related outcomes and manic switch across timeframe and demographic subgroups. METHODS This retrospective cohort study was conducted in May 2025 using data from the TriNetX global collaborative network. Adults with bipolar depression treated with esketamine plus a mood stabilizer were propensity...
Frontiers in PsychiatryAugust 4, 2025Fernando Mora, J. Ramos-Quiroga, Enrique Baca-García et al.5 citations
Introduction Depression is a highly prevalent disease that severely impacts the life of patients. Inadequate response to at least two antidepressants despite adequacy of treatment and adherence is known as treatment-resistant depression (TRD), which entails a higher social and economic burden than non-resistant major depression. The lack of consensus on the definition of TRD and other aspects...
Ketamine has emerged as a promising treatment for major depression, though its efficacy and safety remain incompletely characterized in older adults. This systematic review synthesizes current evidence for ketamine in geriatric depression. A search of PubMed, EMBASE, and PsycINFO was conducted. Prospective clinical trials were included, with age restriction to participants ≥60 years applied at...
Background & Aims Esketamine, a promising treatment for treatment-resistant depression, has shown potential advantages over traditional antidepressants. However, its mechanisms remain unclear. This study explores how esketamine alleviates depressive behaviors through activation of the BDNF/TrkB/PI3K/AKT signaling pathway. Methods Using a Chronic Unpredictable Mild Stress (CUMS) rat model,...
The rapid and clinically meaningful antidepressant effects of ketamine and esketamine are well-established in major depressive disorder (MDD) and treatment-resistant depression (TRD) as evidenced by improvement in clinician- and patient-reported depression measures. However, there remains a need to determine how these agents affect patient-reported quality of life (QoL). Herein, we aimed to...
Pharmacological ResearchJuly 31, 2025C. Pisanu, R. Carvalho Silva, Mattia Meattini et al.6 citations
Treatment-resistant depression (TRD) remains a challenge in psychiatry, necessitating novel therapeutic strategies beyond traditional monoaminergic antidepressants. Ketamine and its S-enantiomer esketamine have demonstrated rapid and robust antidepressant effects in TRD, probably through mechanisms involving glutamatergic modulation, neuroplasticity, and anti-inflammatory properties. However,...
Objective: This study examines the durability (defined as time between treatments) of intravenous ketamine (IV-KET) and intranasal esketamine (IN-ESKET) for treatment-resistant depression (TRD), in a real-world clinical setting with repeated ketamine/esketamine maintenance therapy. Methods: This was a single-center, observational study of adults with TRD who completed acute-phase treatment...
JAMA Network OpenJuly 30, 2025Fredrik Hieronymus, Evana López, Helena Werin Sjögren et al.21 citations
Importance Psilocybin has demonstrated rapid and sustained antidepressant efficacy, with acute-phase effect sizes often more than double those for conventional antidepressants. However, concerns have been raised that high rates of functional unblinding in combination with trial participants with positive expectations of psychedelic use might bias treatment outcomes. Objective To compare...