Pharmaceuticals (Aug 2023)

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,
  • Grigoriy Malyshev,
  • Nathan Smits,
  • Daniel O. Adewunmi,
  • Sarah K. Brown,
  • Balwinder Singh

DOI
https://doi.org/10.3390/ph16081164
Journal volume & issue
Vol. 16, no. 8
p. 1164

Abstract

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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.

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