Evaluation of Intravenous Ketamine Hydrochloride Maintenance Therapy in Treatment-Resistant Major Depressive Disorder: A Multicenter Open-Label Randomized Controlled Trial

The primary objective is to evaluate the long-term efficacy of maintenance therapy using intravenous ketamine hydrochloride following induction treatment for treatment-resistant depression. Secondary objectives include:

• Examination of the durability of the antidepressant effect following the maintenance phase.
• Assessment of the safety of intravenous ketamine administration.
• Evaluation of the dose-response relationship regarding acute therapy duration and dosage.

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female adults diagnosed with Major Depressive Disorder or bipolar-2 disorder. Participants must exhibit a current major depressive episode of at least moderate severity, as indicated by a Montgomery-Åsberg Depression Rating Scale score of ≥ 20. The cohort is specifically composed of individuals meeting the criteria for treatment-resistant depression, defined by an inadequate response to a minimum of two evidence-based interventions according to CANMAT guidelines. Inclusion requires fluency in Norwegian and the ability to provide informed consent. Women of childbearing potential are required to maintain a negative pregnancy test and utilize highly effective contraception throughout the maintenance phase.

This phase II, multicenter, open-label, randomized controlled trial evaluates the long-term efficacy of ketamine hydrochloride maintenance therapy following induction treatment for major depressive disorder. The study design involves comparing three treatment arms to assess the time-to-relapse after the induction phase and following the final infusion, utilizing the Montgomery-Åsberg Depression Rating Scale. The research methodology includes a screening visit to verify eligibility based on DSM-5 criteria, treatment-resistant depression status, and moderate severity of a major depressive episode. Participants will undergo intravenous infusion of 150 mg of the test substance. The protocol includes follow-up monitoring to evaluate the frequency, severity, and duration of adverse events through clinical interviews, observation, and patient chart reviews. Participant involvement concludes at the end-of-study visit. Early termination may occur based on clinical assessment or protocol non-compliance.

The experimental treatment consists of ketamine hydrochloride administered via intravenous infusion. The dosage is established at 150 mg per administration to evaluate long-term efficacy in patients with treatment-resistant depression.

The efficacy of maintenance therapy with intravenous ketamine hydrochloride in patients with major depressive disorder is evaluated through specific primary and secondary endpoints. The primary assessment focuses on the time-to-relapse following the induction phase and after the final infusion, as measured by the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS).

Secondary assessments include the evaluation of the frequency, severity, and duration of adverse reactions. These are monitored through clinical interviews, direct observation, patient chart reviews, and spontaneously reported events. Specific instruments utilized for these assessments include the Symptom Checklist-16 (SCI-2 SF), the Delusional Checklist (DLCQ), and the PreKET symptom checklist.