Genetics of Response to ECT, TMS, Ketamine and Esketamine.
Clio E Franklin, Murat Altinay, Kala Bailey, Mahendra T Bhati, Brent R Carr, Susan K Conroy, Khurshid Khurshid, William M. Mcdonald, Brian J Mickey, James W. Murrough, Sean M. Nestor, Thomas Nickl-Jockschat, Irving Reti, Gerard Sanacora, Nicholas T Trapp, Biju Viswanath, Jesse H Wright, Peter P Zandi, James B. Potash
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics June 17, 2025 DOI: 10.1002/ajmg.b.33038 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Electroconvulsive therapy transcranial magnetic stimulation ketamine esketamine |
| Topics | Esketamine Ketamine |
| Keywords | Individualized treatment Tailored therapy Pharmacogenomics Mood disorders Mental healthcare Psychiatric treatment Genetics genetic makeup Genetic profile Genetic markers Personalized care Advanced treatments Ect Tms Neuromodulation Psychopharmacology |
| Citations | 2 |
| Key findings | Genetic predictors of response to intensive psychiatric therapies for treatment-resistant mood disorders remain largely unidentified, with candidate gene studies lacking reproducibility and genome-wide association studies being underpowered. |
Abstract
Treatment-resistant mood disorders are often managed with intensive interventions that include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), ketamine, and esketamine, but the role of genetics in clinical response to those interventions is yet to be clearly determined. Here, we review the current literature on the genetics of response to these treatment modalities. To date, the limited number of studies done to investigate genetic predictors of treatment response have primarily focused on single variants in candidate genes, and none of these have been consistently reproducible. The majority of candidate gene studies examine the effect of variants in the COMT and BDNF genes on treatment response. There are a limited number of genome-wide association studies (GWAS) looking at treatment response, though they are almost all underpowered, with only one study including a sample size > 1000. As a result, there have been few single nucleotide polymorphisms (SNPs) found to be associated with treatment response at a statistically significant level, all in genes other than COMT and BDNF. The challenge is now to generate data from a large group of patients undergoing these therapies in order to more robustly assess the genetic factors affecting treatment response. This will not only help establish genetic predictors of response, but also potentially develop differential predictors of response to available treatments, which could provide clinicians with critical information to aid in deciding which treatment modality to recommend for treatment-resistant depression. We are currently pursuing such a strategy in our 50-site worldwide Gen-ECT-ic consortium.
Comparable studies
Other narrative reviews on esketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Long-term safety of ketamine and esketamine in treatment of depression | 2022 | Review | |
| Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. | 2024 | Review | |
| The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. | 2023 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review |
Citations in the library
Cited by 2
- Pilot study on esketamine response in treatment-resistant depression: impact of pharmacogenetic, clinical, and demographic variables. Frontiers in Pharmacology 2026
- Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders. CNS Spectrums September 28, 2026
Cites 8
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression. New England Journal of Medicine May 24, 2023
- Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials Pharmacological Reports April 16, 2020
- Genome-wide association study and polygenic risk score analysis of esketamine treatment response Scientific Reports July 28, 2020
- Effects of Mu-Opiate Receptor Gene Polymorphism rs1799971 (A118G) on the Antidepressant and Dissociation Responses in Esketamine Nasal Spray Clinical Trials The International Journal of Neuropsychopharmacology May 5, 2020
and 3 more in the library