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Is ketamine and lamotrigine interactions responsible for the sub-therapeutic effect of ketamine?

Published online by Cambridge University Press:  13 August 2021

M. Adnan ,
F. Motiwala ,
Z. Mansuri ,
C. Trivedi  and
A. Reddy
M. Adnan*
Affiliation:
Psychiatry, Mercy Hospital and Medical Center, Lincolnwood, United States of America
F. Motiwala
Affiliation:
Psychiatry, Texas Tech University Health Sciences Center at the Permian Basin, Midland, United States of America
Z. Mansuri
Affiliation:
Department Of Psychiatry, Boston Children’s Hospital/Harvard Medical School, Boston, United States of America
C. Trivedi
Affiliation:
Psychiatry, Psychiatry Austin, Austin, United States of America
A. Reddy
Affiliation:
Psychiatry, Virginia Tech Carilion School of Medicine, Roanoke, United States of America
*
*Corresponding author.

Abstract

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Introduction

The immediate antidepressant effect of Ketamine has become a breakthrough in the treatment of depression. Cytochrome CYP3A4 and 2B6 primarily metabolize Ketamine.

Objectives

The present study explores potential pharmacokinetic and pharmacodynamic interactions of Lamotrigine and Ketamine.

Methods

A literature search was conducted using (“ketamine” OR “Lamotrigine” AND Interactions in PubMed, Embase, and PsycINFO. Our literature search resulted in 72 hits and result in qualified five studies.

Results

We found five studies: one RCT study, a RCT, a crossover design, Two case reports, and one murine model study. In the first RCT conducted on 16 healthy normal volunteer subjects. lamotrigine significantly decreased ketamine-induced perceptual abnormalities (P < 0.001), positive (P < 0.001) and negative symptoms (P < 0.05), and learning and memory impairment (P < 0.05) which shows the counter effect of ketamine. Another study revealed Ketamine evoked increases in all the BPRS subscale scores, and all scores were lower after lamotrigine pretreatment. A case report from 2014 reports the failure of ketamine anesthesia in a patient with lamotrigine overdose. Another case report mentions that Lamotrigine reduced the craving in a patient with ketamine use disorder. A murine model study with lamotrigine showed improved PPI (Prepulse inhibition) ketamine-induced disruption. These results suggest that Lamotrigine may exert this effect via a glutamatergic system.

Conclusions

The literature review suggests that Lamotrigine interferes with glutamatergic neurotransmission reducing the effect of Ketamine. It is not clear how this may impact Ketamine’s antidepressant action. Future large scale and well-designed RCTs are required to confirm these findings.

Conflict of interest

No significant relationships.

Type
Abstract
Information
European Psychiatry , Volume 64 , Special Issue S1: Abstracts of the 29th European Congress of Psychiatry , April 2021 , pp. S395 - S396
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of the European Psychiatric Association
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