Ketamine vs. ECT- The Straw Man?

Out on PubMed, from investigators in The Netherlands, is this study:

Is ketamine an appropriate alternative to ECT for patients with treatment resistant depression? A systematic review.

Veraart JKE, Smith-Apeldoorn SY, Spaans HP, Kamphuis J, Schoevers RA.J Affect Disord. 2020 Nov 30;281:82-89. doi: 10.1016/j.jad.2020.11.123. Online ahead of print.PMID: 33307338 

The abstract is copied below:

Objective: Ketamine has repeatedly shown to have rapid and robust antidepressant effects in patients with treatment resistant depression (TRD). An important question is whether ketamine is as effective and safe as the current gold standard electroconvulsive therapy (ECT).

Methods: The literature was searched for trials comparing ketamine treatment with ECT for depression in the Pubmed/MEDLINE database and Cochrane Trials Library.

Results: A total of 137 manuscripts were identified, 6 articles were included in this review. Overall quality of the included studies was diverse with relevant risk of bias for some of the studies. Results suggest that ketamine treatment might give faster but perhaps less durable antidepressant effects. Side effects differed from ECT, in particular less cognitive impairment was apparent in ketamine treatment.

Limitations: The included studies have limited sample sizes, use different treatment protocols and in most trials, longer term follow up is lacking. Furthermore, allocation bias appears likely in the non-randomized trials.

Conclusions: Current available literature does not yet provide convincing evidence to consider ketamine as an equally effective treatment alternative to ECT in patients with TRD. There are indications for a more favourable short term cognitive side effect profile after ketamine treatment. Methodologically well-designed studies with larger sample sizes and longer follow up duration are warranted.

Keywords: Cognition; Depression; Electroconvulsive therapy; Ketamine; Treatment resistance.

And from the text:

Limited data is available on whether ketamine treatment may serve as a proper alternative to ECT in TRD treatment. Based on the few studies, no definite conclusions can be drawn. Results of the included studies do not point unanimously to one outcome. One of the three RCTs found significantly more improvement after ECT, whereas two RCTs found no significant differences between ECT and ketamine treatment. But, risk of bias evaluation raises concerns about the validity of the latter two studies.

...In conclusion, the results of trials comparing ketamine treatment with ECT should be interpreted with caution considering the discussed methodological limitations of the studies. Conclusions regarding the antidepressant efficacy, its durability and time to response are pending larger RCTs. Additional information on antidepressant efficacy and predictors of response is necessary, but the potentially more favorable cognitive side effect profile might be a future reason to consider ketamine as a treatment alternative to ECT for patients with depression.

This systematic review is a scholarly effort to provide an up-to-date snapshot of the literature comparing ECT and ketamine. The most obvious conclusion is that the evidence base for this comparison remains very small: 6 studies, with a combined "n" of 205 patients. Furthermore, it's apples and oranges, or more like McDonald's vs. Beyond Beef (millions and millions of ECT patients treated over 80 years vs. not so much (yet) for ketamine).
Another problem is the patient population with "TRD." TRD is variously diagnosed (as pointed out by these authors) and can cover a multitude of sins, not always clear-cut, severe, episodic mood disorder (the ECT population, which importantly also includes psychotic depression). But in a systematic review or meta-analysis, the sausage is fully cooked, nicely and neatly presented on the plate.
It is now evident that ketamine is more than a parlor trick, but it is by no means clear yet that it is a definitive treatment for an episode of severe depression in the context of a mood disorder. These authors list the larger-scale ECT vs. ketamine trials (with better methodologies) that are now being conducted; hopefully, results from those trials will clarify this issue.
And let us not forget that this review is limited to depression; ECT also treats mania, catatonia, schizophrenia, NMS, Parkinson's Disease, SIB in autism, etc...

Thanks to our Dutch colleagues for this academically rigorous contribution to the depression treatment literature.