Pharmacodynamic interactions between ketamine and psychiatric medications used in the treatment of depression: a systematic review
This systematic review (2021) examines the pharmacodynamic interactions between ketamine and generally prescribed psychiatric drugs based on published evidence and found that lamotrigine and benzodiazepines attenuate and shorten ketamine’s antidepressant effects. There are also indications for interactions between ketamine and antipsychotic drugs, such as haloperidol, risperidone and clozapine (but not olanzapine), although further research is necessary to understand their side effects.
Authors
- Robert Schoevers
- Jeanine Kamphuis
- Jolien Veraart
Published
Abstract
Background
The use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine oxidase-inhibitors (MAOIs), antipsychotics and psychostimulants.
Methods
MEDLINE and Web of Science were searched.
Results
Twenty-four studies were included. For lithium, no significant interactions with ketamine were reported. Two out of five studies on lamotrigine indicated that the effects of ketamine were attenuated. Benzodiazepines were repeatedly shown to reduce the duration of ketamine's antidepressant effect. For the MAO-inhibitor tranylcypromine, case reports showed no relevant changes in vital signs during concurrent S-ketamine use. One paper indicated an interaction between ketamine and haloperidol, two other studies did not. Four papers investigated risperidone, including three neuroimaging studies showing an attenuating effect of risperidone on ketamine-induced brain perfusion changes. Clozapine significantly blunted ketamine-induced positive symptoms in patients with schizophrenia, but not in healthy subjects. One paper reported no effect of olanzapine on ketamine's acute psychotomimetic effects.
Conclusion
Current literature shows that benzodiazepines and probably lamotrigine reduce ketamine's treatment outcome, which should be taken into account when considering ketamine treatment. There is evidence for an interaction between ketamine and clozapine, haloperidol and risperidone. Due to small sample sizes, different subject groups and various outcome parameters, the evidence is of low quality. More studies are needed to provide insight into pharmacodynamic interactions with ketamine.
Research Summary of 'Pharmacodynamic interactions between ketamine and psychiatric medications used in the treatment of depression: a systematic review'
Introduction
Since 2000, repeatedly reported rapid antidepressant effects of ketamine have led to increasing off-label use for depression and to regulatory approval of intranasal S-ketamine for treatment-resistant depression (TRD) in conjunction with an oral antidepressant. Many patients considered for ketamine are already taking other psychiatric medications, yet clinical guidance about pharmacodynamic interactions is limited. Ketamine’s principal action is as a non-competitive NMDA (N-methyl-d-aspartate) glutamate receptor antagonist, but it has affinity at multiple other targets (including monoamine transporters and several receptor classes), and its putative antidepressant mechanism involves disinhibition of prefrontal glutamate release, AMPA receptor stimulation and downstream synaptic plasticity changes in regions such as the anterior cingulate, prefrontal cortex and hippocampus. Veraart and colleagues set out to systematically review human studies reporting pharmacodynamic interactions between ketamine and commonly co-prescribed psychiatric drugs relevant to depression treatment. The review focused on mood stabilizers, benzodiazepines, monoamine oxidase inhibitors (MAOIs), antipsychotics and psychostimulants, with the aim of summarising available clinical, neuroimaging and electrophysiological evidence that might indicate potentiation or attenuation of ketamine’s effects and highlight safety signals or gaps in knowledge important for clinical practice and research planning.
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Study Details
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- APA Citation
Veraart, J. K. E., Smith-Apeldoorn, S. Y., Bakker, I. M., Visser, B. A. E., Kamphuis, J., Schoevers, R. A., & Touw, D. J. (2021). Pharmacodynamic interactions between ketamine and psychiatric medications used in the treatment of depression: a systematic review. International Journal of Neuropsychopharmacology, 24(10), 808-831. https://doi.org/10.1093/ijnp/pyab039
References (7)
Papers cited by this study that are also in Blossom
Abdallah, C. G., Averill, C. L., Salas, R. et al. · Biological Psychiatry (2017)
William Deakin, J. F., Lees, J., McKie, S. et al. · JAMA Psychiatry (2008)
Han, Y., Chen, J., Zou, D. et al. · Neuropsychiatric Disease And Treatment (2016)
Ionescu, D. F., Felicione, J. M., Gosai, A. et al. · Harvard Review of Psychiatry (2018)
Joules, R., Doyle, &. O. M., Schwarz, A. J. et al. · Psychopharmacology (2015)
Kishimoto, T., Chawla, J. M., Hagi, K. et al. · Psychological Medicine (2016)
López-Díaz, A., Fernández-González, J. L., Luján-Jiménez, J. E. et al. · Therapeutic Advances in Psychopharmacology (2017)
Cited By (3)
Papers in Blossom that reference this study
Pepe, M., Bartolucci, G., Marcelli, I. et al. · Brain Sciences (2023)
Martinotti, G., Vita, A., Fagiolini, A. et al. · Journal of Affective Disorders (2022)
Alnefeesi, Y., Chen-Li, D., Jawad, M. Y. et al. · Journal of Psychiatric Research (2022)
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