JAMA Psychiatry
March 1, 2017
Gerard Sanacora, Mark A Frye, William M. Mcdonald et al.
577 citations
Ketamine can produce rapid and robust antidepressant effects in patients with mood and anxiety disorders that were previously resistant to treatment. However, existing studies have relatively small sample sizes, lack longer-term data on efficacy, and provide limited data on safety. Despite these limitations, ketamine is increasingly used off-label for mood and other psychiatric disorders. This review and consensus statement provides an overview of the data, highlights limitations, and offers suggestions to facilitate evidence-based clinical decision-making and patient safety.
Lancet (London, England)
July 22, 2025
Balwinder Singh, Holly A Swartz, Alfredo B Cuellar-Barboza et al.
66 citations
Bipolar disorder, marked by hypomania or mania and predominantly depression, affects about 40 million people worldwide and carries substantial psychosocial, medical, and financial burdens, along with increased suicide risk. Diagnosis is often delayed due to symptom overlap with ADHD, major depression, psychotic disorders, and personality disorders. Recent research points to multigene risk and possible infectious and mitochondrial causes. Treatment combines pharmacotherapy, psychotherapy, and lifestyle changes, tailored to individual goals. Future priorities include expanding self-management psychosocial interventions, addressing treatment-resistant depression, deepening understanding of pathophysiology, and exploring novel options like ketamine, esketamine, and neuromodulation.
Psychiatry Research
May 1, 2024
Balwinder Singh, Sagar V Parikh, Jennifer L. Vande Voort et al.
18 citations
In a nonrandomized, open-label clinical trial, 74 adults with treatment-resistant depression received three intravenous ketamine infusions, with an additional four infusions for those who remitted. After the acute phase, 53% (39/74) experienced remission of depression symptoms. Higher baseline language domain scores on the RBANS cognitive assessment were associated with greater odds of remission. No significant association was found between remission and baseline immediate or delayed memory, visuospatial, or attention scores. During the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. The findings suggest cognitive improvement, not deterioration, with serial ketamine administration.
Therapeutic Advances in Psychopharmacology
January 1, 2025
Ahmed Elmosalamy, Idil Tarikogullari, Liliana Patarroyo-Rodriguez et al.
7 citations
About one-third of people with depression do not respond to standard treatments, a condition known as treatment-resistant depression (TRD). Intravenous (IV) ketamine and esketamine (given IV or as a nasal spray) are newer options for TRD, but only the nasal spray version of esketamine is FDA-approved. A meta-analysis of eight studies with 978 adults directly comparing IV ketamine with esketamine found that both treatments produced similar rates of response and remission after acute treatment, with a slight but not statistically significant advantage for IV ketamine. IV ketamine may work faster, but the evidence is mostly from observational studies, and large randomized trials are needed to confirm these findings.
Journal of Affective Disorders
September 15, 2025
Brandan K Penaluna, Jennifer L. Vande Voort, William V Bobo et al.
4 citations
In people with treatment-resistant depression, intravenous ketamine improved symptoms across four depression subtypes: Sadness, Negative Thoughts, detachment/Interest and Activity, and Neurovegetative. After three infusions over 11 days, 53% of the 75 participants achieved remission. The Negative Thoughts subtype showed the least improvement, and the Neurovegetative subtype was the least responsive overall. Higher baseline Sadness scores were linked to lower remission rates, and a positive Sadness phenotype reduced the odds of remission (odds ratio 0.32). No meaningful sex differences in response were found by the end of treatment.
The Journal of Clinical Psychiatry
August 25, 2024
Mark A Frye, Balwinder Singh, Scott Breitinger et al.
2 citations
A man with alcohol use disorder (AUD) maintained sobriety while taking an SSRI and naltrexone, but stopped the SSRI to take part in a psilocybin ceremony, after which he relapsed to alcohol use. The case examines factors that likely contributed to the relapse, including the discontinuation of the SSRI, the context of the psilocybin experience, and the absence of structured follow-up care.
The Journal of Clinical Psychiatry
January 21, 2026
Matheus G Marques, Aysegul Özerdem, Simon Kung et al.
1 citation
For treatment-resistant depression (TRD), a panel of 10 psychiatrists reached strong consensus on recommending augmentation with second-generation antipsychotics, transcranial magnetic stimulation, and ketamine/esketamine as next-step treatments after three failed antidepressant trials. Treatment preferences shifted to include nonaugmentative antidepressants and electroconvulsive therapy depending on patient characteristics such as metabolic disease and age. The findings underscore the importance of tailoring TRD treatment strategies to individual patient factors beyond conventional guideline tiers.
The Journal of Clinical Psychiatry
September 17, 2025
Liliana Patarroyo-Rodriguez, Vanessa K. Pazdernik, Jennifer L. Vande Voort et al.
1 citation
Ketamine and esketamine reduced long-term emergency department visits for suicidality among individuals with treatment-resistant depression. Further research with longer follow-up is needed to determine whether these benefits depend on mood state or reflect an independent mechanism.
Biological Psychiatry Global Open Science
July 1, 2025
Stephen A Murata, Zachary B Madaj, Colt D Capan et al.
1 citation
Higher baseline levels of anthranilic acid (AA), a metabolite in the kynurenine pathway, predicted remission in patients with treatment-resistant depression receiving intravenous ketamine. In an open-label trial of 74 patients, 52% achieved remission after three infusions. Composite ratios of AA to intercellular adhesion molecule-1 and AA to tryptophan improved predictive accuracy over AA alone. The findings suggest that immunometabolic biomarkers could guide personalized ketamine treatment.