Ketamine And ECT Compared For Nonpsychotic Treatment-Resistant Depression

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Major depressive disorder (MDD) is a global issue causing significant disability, with an estimated 21 million adults affected in the United States alone. While antidepressants are widely available, they are ineffective for more than a third of patients. In treatment-resistant major depression, defined as a lack of satisfactory response to two or more adequate antidepressant trials, alternative options are necessary.  

Electroconvulsive therapy (ECT) has a long-standing history of being an effective and rapid treatment for treatment-resistant major depression. Recent advancements, such as administering ECT while the patient is under brief general anesthesia, using unilateral electrode placement, and employing refined seizure elicitation techniques, have made it more feasible to perform as an outpatient procedure. However, ECT remains underutilized due to limited availability, social stigma, and concerns regarding cognitive impairment as a potential adverse effect.  

As per a report published in the New Journal England of Medicine, Ketamine, an N-methyl-d-aspartate receptor antagonist, has gained attention for its rapid antidepressant effects in major depressive disorder and treatment-resistant major depression. The Food and Drug Administration has approved it for sedation, analgesia, and general anesthesia.

Ketamine is increasingly used as an alternative treatment for patients with treatment-resistant major depression, as it does not require general anesthesia and is not associated with significant memory impairment. However, ketamine is classified as a Schedule III medication due to its potential for abuse.  

The ELEKT-D trial, a pragmatic comparative-effectiveness trial, aimed to address the current gap in evidence by comparing the efficacy of ketamine and ECT in treating nonpsychotic treatment-resistant major depression. The trial sought to determine whether ketamine is non-inferior to ECT in terms of effectiveness. Concerns over the transient changes in perception and thinking caused by ketamine and its relative efficacy compared to ECT were also examined. 

Results from a randomized trial comparing the effectiveness of ketamine and electroconvulsive therapy (ECT) in patients with treatment-resistant depression without psychosis have revealed that ketamine is non-inferior to ECT regarding treatment response.

Based on the QIDS-SR-16, the primary outcome measure showed comparable response rates between the two treatments. However, there were some differences in memory performance, with ECT showing a more significant decline than ketamine immediately after treatment, although the effects were similar at the 1-month follow-up.  

Both ketamine and ECT were associated with improved quality of life following the initial treatment phase. However, it is worth noting that a higher percentage of patients withdrew from the trial before treatment in the ECT group, reflecting patient preferences and logistical issues. Sensitivity analyses performed using multiple imputations in the intention-to-treat population supported the noninferiority of ketamine to ECT.  

The efficacy of ECT has been shown to vary based on factors such as patient age, the presence of psychosis, and treatment settings. The results of this pragmatic trial align more closely with reports of lower remission rates observed in community and outpatient settings rather than higher rates in inpatient and research settings. Notably, the trend in the United States is shifting towards outpatient administration of ECT for treatment-resistant major depression.  

The trial has limitations, including using the proper unilateral placement of ECT that may have influenced response rates. The study did not assess maintenance treatment or include a placebo group. The flexibility of treatment methods and the open-label design of the trial could have influenced outcomes. Future studies are needed to investigate the comparative effectiveness of ketamine and ECT in older patients, those with bipolar depression, and emergency inpatient settings. 



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