Severity of TRD Predicts Ketamine vs ECT Response


BOSTON — The severity of treatment-resistant depression (TRD) appears to predict response to intravenous (IV) ketamine vs electroconvulsive therapy (ECT), new research suggested. However, experts said more study is needed before drawing any definitive conclusions.

Investigators found patients with moderate TRD had greater symptom improvement following ketamine treatment, while those with more severe TRD had better outcomes with ECT.

Outpatients at the start of the trial were also likely to benefit more from ketamine, while inpatients had better results with ECT.

The secondary analysis of a randomized noninferiority trial could help identify factors that can be used to personalize treatment selection.

photo of Manish Jha
Manish Jha, MD

“More studies need to test whether personalizing based on these factors” improves outcomes, lead author Manish Jha, MD, associate professor of psychiatry at University of Texas Southwestern Medical Center in Dallas, told Medscape Medical News.

The findings were presented on April 11 at the Anxiety and Depression Association of America (ADAA) 2024 annual conference.

A Population in Need

Patients with TRD represent about one third of those seeking treatment for depression. ECT is considered the gold standard for resistant treatment, but it can cause memory loss. This has led some to look for other treatment options for this population.

Investigators conducted a secondary analysis of data from ELEKT-D trial, a multicenter, open-label randomized trial of ECT and IV ketamine for TRD.

In the trial, 365 participants (52% women; 87% White) received ECT (n = 170) or IV ketamine (n = 195) for 3 weeks.

As previously reported by Medscape Medical News, the results showed ketamine was not inferior to ECT, with a 55% response rate for ketamine and 40% for ECT.

Patients’ depression severity was assessed at seven visits using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS) and the Montgomery and Asberg Depression Rating Scale.

The new analysis was designed to identify factors that could be used to flag which patients would benefit most from ECT and which ones might have better outcomes with ketamine.

Depression severity and outpatient status at baseline were significantly associated with a more favorable response to ketamine (P = .004 and .0006, respectively).

Participants with moderate depression (QIDS score ≤ 20) had better outcomes with ketamine, a difference that was evident after only a few treatments, said Jha. Those with more severe TRD (QIDS score ≥ 20) experienced greater improvement with ECT.

Those who were outpatients at the beginning of the study were also more likely to have greater improvement with ketamine, while the 10% who were inpatients experienced greater improvement with ECT. The study did not track whether participants remained inpatient for the duration of treatment.

Larger Studies Needed

“This is just one study and needs to be replicated before we go about making practice changes” Jha said. He also cautioned that the study did not include intranasal esketamine, so the study results may not extend to that treatment.

In addition, the study was underpowered to assess whether ECT or IV ketamine offers the best outcomes for inpatients, Jha noted.

Research to answer this question is currently underway, led by study coauthor Amit Anand at Harvard Medical School in Boston. In that trial, the participant mix is 90% inpatients and 10% outpatients.

Commenting on the findings for Medscape Medical News, Maurizio Fava, MD, psychiatrist-in-chief at Massachusetts General Hospital in Boston, called the findings interesting but noted that the trial only included 3 weeks of treatment.

“ECT efficacy increases over time and is not as rapid as ketamine,” he said. “The shorter duration of the trial tends to favor ketamine over ECT and might explain why ketamine actually did slightly better than ECT.”

A longer trial comparing 12 weeks of ECT and ketamine is needed, Fava said.

The study was funded by the Patient-Centered Outcomes Research Institute. Jha reported grants from Acadia Pharmaceuticals, Neurocrine Biosciences, Navitor/Supernus, and Janssen Research & Development; honorarium to serve as Section Editor of the Psychiatry & Behavioral Health Learning Network and as Guest Editor for Psychiatric Clinics of North America from Elsevier; consultant fees from Eleusis Therapeutics US, Inc, Janssen Global Services, Janssen Scientific Affairs, Boehringer Ingelheim, and Guidepoint Global; fees to serve on Data Safety and Monitoring Board for Worldwide Clinical Trials (Eliem and Inversargo), Vicore Pharma, and IQVIA (Click); and honoraria for educational presentations from North American Center for Continuing Medical Education, Medscape Medical News/WebMD, Clinical Care Options, H.C. Wainwright & Co., and Global Medical Education. Fava reported his lifetime disclosures here:

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