Ketamine Versus Midazolam for Depression Relapse Prevention Following Successful Electroconvulsive Therapy

Abstract

Objective Depression relapse after electroconvulsive therapy (ECT) is common (40% at 6 months). Ketamine has a robust antidepressant effect, but there are no reported studies of ketamine for depression relapse prevention. This pilot trial (NCT02414932) was designed to assess feasibility of the proposed trial protocol, including examining reasons for nonrecruitment, nonrandomization, and dropout. Methods Patients with unipolar depression referred for ECT were monitored weekly for therapeutic response, using the 24-item Hamilton Rating Scale for Depression (monitoring phase). Those who met standard response criteria were invited to be randomized to a course of 4 once-weekly infusions of ketamine (0.5 mg/kg) or the active comparator, midazolam (0.045 mg/kg), over 40 minutes to examine trial processes (treatment phase). Participants were followed up for 6 months after ECT to assess for relapse. Results One hundred seventy-five referrals were screened over 18 months, and 68% of eligible participants (n = 43) were recruited to the monitoring phase; 60.5% of participants met ECT response criteria (n = 26), but only 26% (6) of these consented to take part in the treatment phase. These were randomized (3 to ketamine and 3 to midazolam), and no participant completed the 4-week treatment protocol. Information was gathered on reasons for nonrecruitment, nonrandomization, and dropout, which included practical aspects of infusions and lack of interest in further treatment after response to ECT. Conclusions The proposed treatment protocol is not suitable for a definitive trial in our center. Information collected on reasons for dropout may inform future clinical trials of intravenous ketamine. Trial registration: www.clinicaltrials.gov NCT02414932.

Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review

“…86 Aside from the use of ketamine as an anaesthetic agent during ECT, one pilot study aimed to examine the effectiveness of ketamine for relapse prevention following response to ECT. 87 However, out of 26 patients who responded to ECT treatment, only six were willing to take part, some because of a lack of interest in further treatment following successful ECT, and none of the participants completed the full 4-week treatment protocol. 87…”

“…87 However, out of 26 patients who responded to ECT treatment, only six were willing to take part, some because of a lack of interest in further treatment following successful ECT, and none of the participants completed the full 4-week treatment protocol. 87…”

“…70 Most studies also reported transient and dose-dependent dissociative and psychotomimetic effects, including unusual thought content, visual hallucinations and conceptual disorganisation that peaked during and immediately following ketamine infusion and rapidly resolved within up to 2 h after infusion. 9,14,34,40,50,52,54,58,60,72,85,87,89,90 Across the whole review, in two separate studies, one out of 41 and 31 patients, respectively, discontinued study participation because of dissociative or hallucinatory effects. 71,93 Dysphoria and treatment-emergent suicidal ideation were reported in one study.…”

PBMC telomerase activity in depression and the response to electroconvulsive therapy

“…All patients with depression were recruited as part of the KEEP-WELL Trial (Ketamine for Depression Relapse Prevention Following ECT; NCT02414932) in St. Patrick’s Mental Health Services, Ireland, between April 2015 and April 2017 [ 27 ]. The Maudsley Staging Method for Treatment Resistance in Depression was used to assess antidepressant treatment resistance, with scores of 3‒6 indicating mild resistance, 7‒10 indicating moderate resistance, and 11‒15 indicating severe resistance [ 29 ].…”

Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial)

“…Interventions Ketamine (0.5 mg/kg) and midazolam (0.045 mg/kg) were made up as 50 ml colourless saline solutions and administered as slow infusions over 40 minutes using an infusion pump, as previously described 38 . Like ketamine at 0.5 mg/kg, midazolam at 0.045 mg/kg has anaesthetic effects and causes some sedation with a similar time course.…”