In people with treatment-resistant depression who do not have psychosis, intravenous ketamine works as well as electroconvulsive therapy (ECT) overall. Among outpatients with moderately severe or severe depression, ketamine produced greater improvement in depressive symptoms than ECT. In contrast, inpatients with very severe depression improved more with ECT early in treatment, though by the end of the three-week course both treatments were similarly effective. Higher premorbid intelligence and a diagnosis of posttraumatic stress disorder were linked to greater improvement with ECT, but not with ketamine. These findings may help patients and clinicians decide between the two treatments.
For treatment-resistant mood disorders, intensive interventions such as electroconvulsive therapy, transcranial magnetic stimulation, ketamine, and esketamine are commonly used, but how genetics influences response to these therapies remains unclear. A review of the current literature finds that most studies have examined single variants in candidate genes, particularly COMT and BDNF, yet none have been consistently reproducible. Genome-wide association studies are few and mostly underpowered, with only one exceeding 1000 participants, yielding few statistically significant single nucleotide polymorphisms outside COMT and BDNF. Large-scale data collection is needed to establish genetic predictors and differentiate responses among treatments, a goal being pursued by the worldwide Gen-ECT-ic consortium.
Patients with treatment-resistant depression who preferred ketamine over electroconvulsive therapy (ECT) were more likely to respond to treatment, regardless of which treatment they actually received. Matching patients to their preferred treatment improved response rates for ketamine but not for ECT, and reduced adverse events for ECT-treated patients. Ketamine was the more popular choice overall. The findings suggest that aligning treatment with patient preference can influence effectiveness, safety, and possibly adherence, but these effects vary by treatment modality and context.