Choosing Between Ketamine and Electroconvulsive Therapy for Outpatients With Treatment-Resistant Depression—Advantage Ketamine?

Mathew, Sanjay J.; Jha, Manish K.; Anand, Amit

doi:10.1001/jamapsychiatry.2023.3979

Cited by 4 publications

(1 citation statement)

References 7 publications

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“…Furthermore, use of precision psychiatry approaches using biomarkers such as those of neural circuit dysfunction 32 may further inform treatment selection of ketamine vs ECT at an individual level. The findings of the ELEKT-D trial may have been limited by low enrollment of patients who were responsive to ECT (such as inpatients, older patients, and patients who are depressed with psychosis) 33 and by the relatively short course length for ECT compared with the common clinical practice. Given the higher dropout rate after randomization to ECT (33 of 203 participants) vs ketamine (5 of 200 participants), generalizability may be limited given that identifying an association with a treatment response would have been unavailable for those who did not complete any posttreatment assessments.…”

Section: Discussionmentioning

confidence: 99%

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression

Jha,

Wilkinson,

Krishnan

et al. 2024

JAMA Netw Open

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ImportanceThe ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD.ObjectiveTo evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT.Design, Setting, and ParticipantsThis secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians.ExposuresEligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks.Main Outcomes and MeasuresAssociation between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses.ResultsAmong the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (−7.7 vs −5.6 points) and those starting treatment as outpatients (−8.4 vs −6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (−8.4 vs −6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (−9.0 vs −9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (−14.0 vs −11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (−16.6 vs −12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (−13.4 vs −9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (−14.3 vs −12.2 points). Other results were not significant after false discovery rate adjustment.Conclusions and RelevanceIn this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

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Section: Discussionmentioning

confidence: 99%

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression

Jha,

Wilkinson,

Krishnan

et al. 2024

JAMA Netw Open

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Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics?

Hashimoto

2024

Eur Arch Psychiatry Clin Neurosci

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The growing interest in the rapid and sustained antidepressant effects of the dissociative anesthetic ketamine and classic psychedelics, such as psilocybin, is remarkable. However, both ketamine and psychedelics are known to induce acute mystical experiences; ketamine can cause dissociative symptoms such as out-of-body experience, while psychedelics typically bring about hallucinogenic experiences, like a profound sense of unity with the universe or nature. The role of these mystical experiences in enhancing the antidepressant outcomes for patients with depression is currently an area of ongoing investigation and debate. Clinical studies have shown that the dissociative symptoms following the administration of ketamine or (S)-ketamine (esketamine) are not directly linked to their antidepressant properties. In contrast, the antidepressant potential of (R)-ketamine (arketamine), thought to lack dissociative side effects, has yet to be conclusively proven in large-scale clinical trials. Moreover, although the activation of the serotonin 5-HT2A receptor is crucial for the hallucinogenic effects of psychedelics in humans, its precise role in their antidepressant action is still under discussion. This article explores the importance of mystical experiences in enhancing the antidepressant efficacy of both ketamine and classic psychedelics.

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Ketamine-Induced Sclerosing Cholangitis Associated With Early Inflammatory Bowel Disease During Chronic Topical Ketamine Use

Lake-Bakaar,

Milgrom,

Kulig

et al. 2024

Gastro Hep Advances

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Choosing Between Ketamine and Electroconvulsive Therapy for Outpatients With Treatment-Resistant Depression—Advantage Ketamine?

Abstract: This Viewpoint examines key issues stemming from several recent reports of electroconvulsive therapy (ECT) vs ketamine for improving depressive symptoms in treatment-resistant depression (TRD).

Cited by 4 publications

References 7 publications

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression

Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics?

Ketamine-Induced Sclerosing Cholangitis Associated With Early Inflammatory Bowel Disease During Chronic Topical Ketamine Use

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