Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report
Boney Joseph, Nicolas A. Nunez, Simon Kung, Jennifer L. Vande Voort, Vanessa K. Pazdernik, Kathryn M Schak, Stacey M. Boehm, Brooke Carpenter, Emily K. Johnson, G. Malyshev, N.a.c. Smits, Daniel O. Adewunmi, Sarah K. Brown, Balwinder Singh
Pharmaceuticals August 1, 2023 DOI: 10.3390/ph16081164 (opens in new tab)
The journal has published a correction to this paper. Read the correction (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Historical cohort study Randomized Peer reviewed |
|---|---|
| Population | Adult patients with treatment-resistant depression receiving serial IV ketamine or IN esketamine |
| Interventions | Ketamine Esketamine Lamotrigine |
| Dose | IV ketamine 0.5 mg/kg over 40-100 min; IN esketamine 56/84 mg |
| Measures | QIDS-SR, CADSS |
| Topics | Depression Esketamine Ketamine |
| Citations | 14 |
| Key findings | No significant differences in antidepressant response or remission were found between patients on or not on lamotrigine during ketamine or esketamine treatment; a trend toward lower dissociation was observed among lamotrigine users receiving IV ketamine. |
Abstract
Intravenous (IV) ketamine and FDA-approved intranasal (IN) esketamine are increasingly used for treatment-resistant depression (TRD). Preliminary studies have suggested a synergistic effect of ketamine and lamotrigine, although the data are inconclusive. Herein, we report the response to serial ketamine/esketamine treatment among patients with TRD with or without lamotrigine therapy. In this historical cohort study, we included adult patients with TRD who received serial IV racemic ketamine (0.5 mg/kg over 40−100 min) or IN esketamine (56/84 mg) treatments. A change in depressive symptoms was assessed using the 16-item Quick Inventory of Depressive Symptomatology self-report (QIDS-SR) scale. There were no significant differences in response or remission rates among the patients on or not on lamotrigine during the ketamine/esketamine treatments. For a percent change in the QIDS-SR from baseline, no interaction was found between the lamotrigine groups and treatment number (p = 0.70), nor the overall effect of the group (p = 0.38). There was a trend towards lower dissociation (based on the CADSS score) among current lamotrigine users, especially in patients who received IV ketamine. A major limitation is the limited number of patients taking lamotrigine (n = 13). This preliminary study provides insufficient evidence that continuing lamotrigine therapy attenuates the antidepressant effect of repeated ketamine/esketamine; however, there seems to be a signal toward attenuating dissociation with lamotrigine in patients receiving serial ketamine treatments. Further observational studies or randomized controlled trials are needed to replicate these findings.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |
Citations in the library
Cited by 6
- Demographic and clinical predictors of response and remission in the treatment of major depressive disorder with ketamine and esketamine: A systematic review. Psychiatry Research March 1, 2025
- Hypersomnia as a predictor of response to intravenous ketamine/intranasal esketamine in treatment resistant depression. Journal of Affective Disorders 2024
- Low-Dose Buprenorphine Following Ketamine Treatment for Suicidal Ideation in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial. American Journal of Psychiatry June 1, 2026
- Baseline perceived stress as a predictor of ketamine/esketamine treatment response in treatment-resistant depression. Journal of Affective Disorders August 15, 2025
- An Update on Somatic Treatments for Suicide Risk. American Journal of Psychiatry June 1, 2026
and 1 more in the library
Cites 20
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
and 15 more in the library