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.
Oral esketamine is a promising treatment for depression that does not respond to other therapies, but how much of the drug reaches the bloodstream varies from person to person. This study tested whether common genetic variations in two drug-transport proteins, ABCB1 and ABCG2, affect esketamine levels in the blood. In 18 participants from a placebo-controlled trial, esketamine concentrations four hours after dosing did not differ significantly among people with different ABCB1 or ABCG2 genotypes. Metabolite levels also showed no association with these genetic variants. The findings suggest that these transporter polymorphisms do not influence oral esketamine pharmacokinetics, though the small sample size means the results are preliminary and need confirmation in larger studies.