Pharmacodynamic interactions between ketamine and psychiatric medications used in the treatment of depression: a systematic review

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.