Abstract



 



Purpose   The purpose of this study was to test the hypothesis that ketamine anesthesia was associated with antidepressant outcomes following Electroconvulsive Therapy (ECT) that were superior to ECT with propofol anesthesia.



 



Background   Depression is a common psychiatric diagnosis and is often treated with oral antidepressants. When major depression persists despite pharmacologic treatment, psychiatrists may employ Electroconvulsive Therapy (ECT). ECT often produces rapid antidepressant effects. Side effects of ECT include cognitive changes, impaired memory, and relapse. Ketamine has been shown to produce rapid improvement in depression. Studies of a single IV infusion of ketamine have resulted in significant and almost immediate antidepressant effects in patients with both unipolar and bipolar depression. Repeat ketamine administration for two to four weeks has resulted in a marked decrease in depression for weeks after ketamine administration was ended. At least one study has suggested that ketamine without ECT compares favorably to ECT with sodium pentothal anesthesia. Lastly, ketamine may help reduce suicidal thoughts that sometimes occur early in the administration of oral antidepressant medications.



 



Methodology   This was a randomized, double blind comparison of ketamine vs. propofol for ECT anesthesia. The ketamine group received ketamine 0.75 mg/Kg. The propofol group received propofol 1 mg/Kg. Both groups also received remifentanil 1 µg/Kg and succinylcholine 0.75 mg/Kg. The ketamine was mixed with Intralipid to look like propofol and the disguised ketamine and propofol was randomized for use in the study by the pharmacist. The patient, anesthesia provider, psychiatrist, nurses, and research assistant were each blinded to the patients study group.



 



Adult patients scheduled for ECT were eligible for the study. Patients were excluded if they were ASA physical status IV or V, had untreated hypertension or other major comorbidities or were pregnant. Outcomes were assessed in two categories: Remission and Response. Remission was defined as a reduction in the MADRS score (Montgomery–Åsberg Depression Rating Scale) to levels indicating no more than mild depression (≤ 10). Response was a 50% reduction in depression score. As a result, the study examined the number of ECT treatments needed to achieve Response and Remission.



 



Result   The study was ended early following a planned interim analysis; only 27 subjects were studied, 14 ketamine patients and 13 propofol patients. Demographics were similar between groups.



 



The time from induction of anesthesia for ECT to meeting discharge criteria was no different between groups, about 63 minutes. The rates of adverse events were also similar between groups. There was no statistical difference between groups in the rates of hypertension, hypotension, emergence agitation, or PONV. No patient in either group experienced hallucinations.



 



All ketamine patients achieved a Response vs. 83% of propofol patients. Ketamine patients achieved a Response with a median of 2 ECT treatments vs. 4 ECT treatments in the propofol group (P=0.01). All ketamine patients achieved Remission vs. 58% of propofol patients. Ketamine patients achieved Remission with a median of 3 ECT treatments vs. 7 ECT treatments in the propofol group (P=0.01).



 



Conclusion   Compared to a propofol induction for ECT, ketamine was associated with a faster improvement in symptoms of depression, required fewer ECT treatments to achieve improvement, and had an identical 30-day remission rate. Ketamine anesthesia for ECT may reduce the number of ECT treatments needed for remission of treatment resistant depression.



 



Comment



 



Because we don’t know why ECT treatments reduce major depression we have to pay attention when we find something that makes ECT more effective. For years now, the psychiatrists have been studying ketamine’s effect on depression. Now we have some tentative evidence that using ketamine and ECT together may produce added benefit.



 



This study was planned to be “small” and include only 56 patients. For reasons that are unclear the investigators planned an interim external review of the results at 20 patients. Somehow that resulted in the study being ended at 27 patients because the external reviewers believed the results were so lopsided in favor of ketamine that it was unethical to continue the study knowing that some patients were going to be randomized to a less effective treatment. My point is this. It is unusual for a study to show such profound clinical significance, ketamine patients needed half as many ECT treatments, and statistical significance, with such a small sample size. This is one of the rare studies where one should pay less attention to how small it was and more attention to how big the results were.



 



Now we know psychiatrists often express a preference for induction drugs for ECT for fears that the seizure may not be long enough to produce therapeutic results with some induction drugs. So it’s not like anesthesia is going to “help out” and do ECTs with ketamine and keep it to ourselves. But, you may want to share this study with the psychiatrists and make the offer to use ketamine. At the time I’m writing this ketamine is on the FDA shortage list and is not expected to be in normal supply until sometime in 2019, but that, as they say, is another problem.