Treatment-resistant depression is a poorly defined label that may harm patients' hope. Survey data show many individuals seeking ketamine treatment have long-standing depressive symptoms and dissatisfaction with standard therapies. Fixed low doses of oral esketamine were not effective in a randomized controlled trial, but higher, individualized dosing led to meaningful improvement in a subgroup. Ketamine was often effective and well tolerated in complex cases, including patients with psychotic symptoms, PTSD, or those on maintenance ECT, especially with supportive monitoring. Combining ketamine with psychotherapy appears promising but needs more research. A key pharmacological finding is that repeated oral use may speed up ketamine's own metabolism (auto-induction), potentially reducing long-term effectiveness.
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.