Ketamine for Headache Disorders (Cluster & Migraine)

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD A Randomized Clinical Trial

In a multicentre, double‑blind, placebo‑controlled phase 2 trial of 65 adults with chronic PTSD, once‑weekly oral TSND‑201 produced significantly greater reductions in clinician‑rated PTSD severity (CAPS‑5; LS mean difference 9.64, P = .01) and improvements in self‑reported symptoms, functioning and depression versus placebo. TSND‑201 was generally well tolerated — common adverse events included headache, decreased appetite, nausea, dizziness and transient blood‑pressure increases — supporting its potential as a rapid‑acting, durable treatment for PTSD.

Published: February 18, 2026
Journal: JAMA Psychiatry
Authors: Jones, A., Warner-Schmidt, J., Kwak, H., Stogniew, M., Mandell, B., Ching, T. H., Stein, M. B., Kelmendi, B.

Open Accessindividual

Effect of Esketamine on Depressive Symptoms in Adolescents with Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study

This double-blind Phase IIb trial (n=147) evaluated the efficacy, safety, and tolerability of esketamine nasal spray versus midazolam in reducing depressive (MDD) symptoms in adolescents at imminent risk for suicide (SI). The study finds that pooled doses of esketamine (56 and 84 mg) significantly reduce depressive symptoms at 24 hours, with common side effects including dizziness, nausea, and dissociation.

Published: January 1, 2026
Journal: Journal of the American Academy of Child & Adolescent Psychiatry
Authors: Kosik-Gonzalez, C., Chen, L. N., Lane, R., Bloch, M. H., DelBello, M., Moreno, C., Drevets, W. C., Canuso, C. M., Fu, D. J.

Open Accessindividual

Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial

In a phase 4, multicentre, double-blind randomised trial in adults with treatment‑resistant depression, intranasal esketamine monotherapy (56 mg and 84 mg) produced significant reductions in MADRS score versus placebo at day 28 (LS mean differences −5.1 and −6.8; effect sizes 0.48 and 0.63) and demonstrated rapid benefit at 24 hours. The tolerability profile was consistent with prior reports, most commonly nausea, dissociation, dizziness and headache.

Published: September 1, 2025
Journal: JAMA Psychiatry
Authors: Janik, A., Qiu, X., Lane, R., Popova, V., Drevets, W. C., Canuso, C. M., Macaluso, M., Mattingly, G. W., Shelton, R. C., Zajecka, J. M., Fu, D. J.

Open Accessindividual

Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis

This pharmacovigilance analysis (n=751) examines suspected adverse reactions (SARs) to esketamine nasal spray (Spravato) reported in the EudraVigilance database across European countries. The study identifies increased blood pressure (15.4%) and dissociation (15%) as the most common SARs, with data suggesting a potentially higher risk of suicidality with esketamine compared to fluoxetine and venlafaxine, prompting recommendations for careful monitoring of patients with a history of suicidal ideation.

Published: May 9, 2025
Journal: Pharmaceuticals
Authors: Ammendolia, I., Mannucci, C., Esposito, E., Calapai, G., Currò, M., Midiri, P., Mondello, C., Cardia, L., Calapai, F.

Open Accessindividual

Safety and Efficacy with Esketamine in Treatment-Resistant Depression: Long-Term Extension Study

In the phase 3 SUSTAIN-3 long-term extension (1,148 patients, 3,777 patient‑years), intermittent intranasal esketamine plus an oral antidepressant showed no new safety signals and an adverse event profile consistent with earlier studies. Depression severity improved during induction and was generally maintained during optimisation/maintenance, with remission in 35.6% at induction and about 48–50% at week 112/maintenance endpoint.

Published: May 4, 2025
Journal: International Journal of Neuropsychopharmacology
Authors: Zaki, N., Chen, N. )., Lane, R., Doherty, T., Drevets, W. C., Morrison, R. L., Sanacora, G., Wilkinson, S. T., Young, A. H., Chb, M. B., Lacerda, A. L. T., Paik, J. W., Popova, V., Fu, D. J.

Open Accessindividual

Randomized Placebo-Controlled Phase 2 Study of Extended-Release Ketamine Tablets (R-107) for Treatment-Resistant Depression - the BEDROC Study

In this phase 2 randomised, placebo‑controlled enrichment study, extended‑release oral ketamine tablets (R‑107) given twice weekly maintained antidepressant response in treatment‑resistant depression, with the 180 mg dose producing a significant 13‑week MADRS improvement versus placebo (least‑square mean difference −6.1, P = 0.019). R‑107 was generally well tolerated with minimal blood‑pressure, sedation or dissociation effects, showed a dose–response reduction in relapse rates, and most dosing was performed at home.

Published: June 24, 2024
Journal: Nature Medicine
Authors: Glue, P., Loo, C., Fam, J., Lane, H. Y., Young, A., Surnam, P.

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Headache Disorders (Cluster & Migraine)

Academic Research

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD A Randomized Clinical Trial

Effect of Esketamine on Depressive Symptoms in Adolescents with Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study

Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial

Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis

Safety and Efficacy with Esketamine in Treatment-Resistant Depression: Long-Term Extension Study

Randomized Placebo-Controlled Phase 2 Study of Extended-Release Ketamine Tablets (R-107) for Treatment-Resistant Depression - the BEDROC Study

Clinical Trials

Ketamine, SGB and Combination Treatment for TBI

Multi-center RCT of IV Ketamine Efficacy and Safety in Chronic Daily Headaches

Ketamine + Magnesium for Chronic Cluster Headache (KETALGIA)

An Efficacy and Safety of Proprietary Formulations of Oral Ketamine + Aspirin in Treatment of Acute Headache

Proof of concept study for evaluation of the effect of ketamine intranasal spray in treatment of chronic Cluster Headache (CCH)

The CHECK Trial: A Comparison of Headache Treatment in the Emergency Department: Compazine Versus Ketamine (Check)

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