Propofol-Ketamine Combination: Negative Results From a Small Study

Out on Pubmed, from researchers in France and Canada, is this study:

The Combination of Propofol and Ketamine Does Not Enhance Clinical Responses to Electroconvulsive Therapy in Major Depression-The Results From the KEOpS Study.

Brunelin J, Iceta S, Plaze M, Gaillard R, Simon L, Suaud-Chagny MF, Galvao F, Poulet E.Front Pharmacol. 2020 Sep 15;11:562137. doi: 10.3389/fphar.2020.562137. eCollection 2020.PMID: 33041803
The abstract is copied below:

Objective: We investigated the clinical effects of the combination of ketamine and propofol as anesthetic agents during electroconvulsive therapy (ECT) in patients with uni- or bipolar major depressive episodes. We hypothesized that ketamine may confer short- and long- term advantages in improving depressive symptoms at the early stages of ECT.

Methods: In a randomized placebo-controlled trial, remission rates after 4 and 8 weeks of ECT were compared between patients who were randomly allocated to receive either the combination of ketamine (0.5 mg/kg) + propofol (n= 11) or placebo + propofol (n = 16). Depressive symptoms were assessed weekly using the Montgomery-Åsberg Depression Rating Scale (MADRS); ECT sessions were administered twice per week for a maximum of 8 weeks (16 sessions).

Results: After 4 weeks, we observed significantly fewer remitters (MADRS score < 10) in the ketamine + propofol group (0/11; 0%) than in the placebo + propofol group (5/16; 31%; χ2 = 4.22; p = 0.040). No significant difference was observed between the two groups regarding the number of patients who achieved remission weekly throughout the study period (Chi² = 3.588; p = 0.058). The mean duration of seizures was significantly shorter in the ketamine + propofol group than in the placebo + propofol group.

Conclusions: The results from the current study corroborated results from previously published studies and did not support the use of the combination of ketamine + propofol as an anesthetic agent for ECT in patients with major depressive episodes in clinical settings.

Keywords: bipolar; electroconvulsive therapy; ketamine; major depressive episode; propofol.

The pdf is here.

This is a very small study (total n= 27, 11 in the ketamine group, 16 in the placebo group) with negative and counterintuitive findings (worse outcome and shorter seizures in the ketamine group). There were several potentially confounding variables, including a mix of bilateral and RUL electrode placements.
Thus, we cannot make too much of the results, other than to say that they do not suggest an antidepressant efficacy benefit of adding low-dose ketamine to propofol.
These data, however, do not negate the fact that the combination of ketamine and propofol (often called ketofol) may have significant clinical advantages from an overall anesthetic perspective. 





Comments

  1. Indeed not a helpful study. It is per se not a good idea to use anaesthetics as add-on, which typically just increases side effects.
    I would not expect ketofol to be more effective than propofol. Maybe there is a faster response, but not a better one. In my opinion, it will be crucial to evaluate the stimulation dose: If the amount of charge is the same in both groups, the ketofol group might well show a better response rate. If the charge is adapted, the ketofol group will probably need less charge, which will have a positive effect on cognitive side effects (i.e. less for ketofol).

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