A Novel Ketamine Dosing Protocol May Decrease the Efficacy-Effectiveness Gap

A novel ketamine infusion protocol can improve clinical outcomes in patients with treatment-resistant depression.

A novel ketamine infusion protocol associated with improved effectiveness and response durability among patients with treatment-resistant depression. These findings were presented at Psych Congress 2022, held September 17 to 20, 2022.

Ketamine is a rapid-acting antidepressant. It remains unclear whether ketamine may be an effective treatment strategy for patients with depression, as there is an efficacy-effectiveness gap, in which efficacy is reported as high (70%-85%) and effectiveness as low (18.3%-45.5%) in community-based studies.

The Rigorous Evaluation and Systemic Therapeutic Optimization for increased Response/Remission Effectiveness (RESTORE) trial sought to address the efficacy-effectiveness gap by using a novel ketamine infusion protocol. Patients (n=87) with treatment-resistant depression received a ketamine infusion dose using pharmacokinetic modeling to achieve optimal blood concentrations. Infusions were given on 3 days and lasted over 30 minutes. Two additional infusions were administered within 3 to 6 months after which time patients entered the maintenance phase of treatment. The study lasted a total of 60 months. Findings from this novel protocol study were compared with the Yale (n=54) and Harvard (n=85) studies which used standard infusions and lasted 30 and 12 months, respectively.

In the RESTORE study, the acute outcomes at 3 days indicated that 88.4% of patients responded to treatment, the dropout rate was 1.2%, and 5.7% experienced an adverse event. For the Yale study, at 2 weeks 45.5% of patients responded to treatment, 11.4% dropped out, and 33.3% had an adverse event, respectively. At 3 weeks in the Harvard study, 18.3% of patients responded, 30.6% dropped out, and 8.2% had an adverse event, respectively.

It remains unclear whether ketamine may be an effective treatment strategy for patients with depression, as there is an efficacy-effectiveness gap, in which efficacy is reported as high (70%-85%) and effectiveness as low (18.3%-45.5%) in community-based studies.

In RESTORE, 90.7% of patients entered maintenance therapy and 9.3% dropped out. The cumulative response rate increased from 88.3% to 100%, with an average durability of efficacy of 245.1 (range, 48-1103) days. No adverse events were reported.

For the Yale and Harvard studies, 31.8% and 49.4% entered the maintenance phase; 68.2% and 28.8% dropped out; and the average durability of response was 22.3 (range, 2-189) and 28 (range, 4.9-51.1) days, respectively. In the Yale cohort, 9 of the original 14 responders maintained their response in the maintenance phase. Response was not reported in the Harvard study.

This analysis may be limited by comparing data from multiple studies with differing patient populations.

The study author wrote, “The novel RESTORE infusion protocol represents a clinically applicable methodological approach to ketamine infusion therapy that results in significantly improved effectiveness by three-fold and response durability by nine-fold compared to the standard ketamine infusion.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

References:

Grass GW. A New Methodological Approach to Improve the “Real Word” Effectiveness of Ketamine Infusion Therapy for Treatment-Resistant Depression. Abstract presented at Psych Congress 2022; September 17-20, 2022; New Orleans, LA. Abstract 51.