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Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
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Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression.

Amit Anand1, Sanjay J Mathew1, Gerard Sanacora1

  • 1From the Department of Psychiatry, Mass General Brigham, and Harvard Medical School - both in Boston (A.A.); Baylor College of Medicine (S.J.M., A.A.A.-A., S.I., L.C.C.) and Michael E. DeBakey Veterans Affairs Medical Center, Houston (S.J.M., A.A.A.-A., S.I.), and the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas (M.K.J.) - all in Texas; the Department of Psychiatry, Yale University School of Medicine, New Haven, CT (G.S., S.N., R.B.O., S.T.W.); the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (J.W.M., A.S.A.), and the Division of Clinical Research, Nathan Kline Institute for Psychiatric Research, Orangeburg (K.A.C.) - both in New York; the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore (F.S.G., I.M.R.); the Department of Psychiatry and Psychology, Center for Behavioral Health, Neurological Institute (M.A., B.S.B., D.A.M.), Lou Ruvo Center for Brain Health (K.K.), Cleveland Clinic Center for Clinical Research (C5Research), Heart, Vascular, and Thoracic Institute (S.E.N., K.W.), and the Department of Quantitative Health Sciences (B.H.), Cleveland Clinic, Cleveland; and the Psychopharmacology Laboratory, Department of Psychiatry, University of Oxford, Oxford, United Kingdom (S.C.).

The New England Journal of Medicine
|May 24, 2023
PubMed
Summary

Subanesthetic intravenous ketamine is noninferior to electroconvulsive therapy (ECT) for treatment-resistant major depression. Ketamine showed a higher response rate with fewer memory side effects than ECT.

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Clinical Trials

Background:

  • Major depression resistant to conventional treatments poses a significant clinical challenge.
  • Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are established treatments, but their comparative effectiveness is not well-defined.

Purpose of the Study:

  • To compare the effectiveness of ketamine and ECT in patients with treatment-resistant major depression without psychosis.
  • To determine if ketamine is noninferior to ECT based on treatment response rates.

Main Methods:

  • An open-label, randomized, noninferiority trial comparing ketamine (0.5 mg/kg IV twice weekly) with ECT (three times weekly) for 3 weeks.
  • Primary outcome: ≥50% decrease in Quick Inventory of Depressive Symptomatology-Self-Report scores.
  • Secondary outcomes: memory function tests and quality of life assessments over 6 months.

Main Results:

  • Ketamine demonstrated noninferiority to ECT, with a 55.4% response rate versus 41.2% for ECT (difference 14.2 percentage points, P<0.001).
  • ECT was associated with significant short-term memory recall decline, while ketamine showed minimal impact.
  • Quality of life improvements were similar; adverse effects included dissociation with ketamine and musculoskeletal issues with ECT.

Conclusions:

  • Subanesthetic intravenous ketamine is a viable and effective alternative to ECT for treatment-resistant major depression without psychosis.
  • The findings support ketamine's use, offering a potentially better side-effect profile regarding memory compared to ECT.