In eight patients with treatment-resistant depression, repeated oral esketamine was tested as a replacement for maintenance electroconvulsive therapy (M-ECT). Over six weeks, esketamine doses were gradually increased up to 3.0 mg/kg twice weekly. Depression severity remained stable or improved in five patients, while three worsened and resumed M-ECT. Among five patients with available scores, all showed improvement on the Outcome Questionnaire 45. Four patients continue to receive oral esketamine. Oral esketamine may offer a suitable, patient-friendly alternative to M-ECT, though controlled trials are needed to confirm long-term safety and efficacy.
A genetic variation in the CYP2B6 enzyme, known as 516 G > T, is linked to higher blood levels of oral esketamine four hours after dosing in people with treatment-resistant depression. In a small sample of 18 participants from a placebo-controlled trial, carriers of the variant had median esketamine levels of 5.1 µg/L, compared to 2.1 µg/L in non-carriers. No significant associations were found for two other genetic variants, CYP3A4*22 and CYP3A5*3, but the numbers of carriers were very small. Larger studies are needed to clarify their effects.