Ketamine and chronic treatment-resistant depression: real-world practice and after relapse

Chronic treatment-resistant depression (TRD) poses a major challenge for clinicians. Ketamine has shown a rapid but short-lived antidepressant effect in several studies involving TRD patients with different demographic and clinical profiles. Our study aimed to assess the antidepressant effect of serial infusion sessions of ketamine in patients with chronic TRD and evaluate the severity of symptoms after relapse and the general psychiatric health of the responding patients.

In this single arm open-label study, six infusions of ketamine at 0.5 mg/kg were administered to chronic TRD patients for approximately two weeks. Response and remission rates, side effects, adverse events and after-relapse symptoms were evaluated, and patients were followed for three months.

23 patients underwent at least one infusion session, and 18 patients completed the six sessions. Twelve (66.67%) patients responded to the treatment at some point, and 11 (61.11%) patients maintained response after the end of the treatment protocol. One infusion was not sufficient to achieve a response (P > 0.9999, z = 1.81), and more than half of the responders met the response criteria after the third infusion. Only one patient (5.56%) achieved remission at the end of the infusion phase. All but one ketamine responders relapsed within one month after the end of the treatment. There was no statistical difference between baseline and after-relapse MADRS scores (P = 0.7886, 95% CI=-5.512-4.312, R² = 0,008411). However, a high incidence of serious adverse events related to suicidality was evident; one of the non-responding patients attempted suicide and several attempts to sedate this patient with benzodiazepines failed. Two responding patients ended up with a suicidal attempt or severe suicidal thoughts.

Introducing rapid-acting antidepressant to manage TRD patients in clinical practice demands further investigation, and the benefit-to-harm ratio should be assessed in the light of the increased risk of suicidality.