Comparative Effectiveness of ECT vs. KETAMINE Over the Lifespan

Official title

Rapid Reversal of Suicidal Depression: Comparative Effectiveness of ECT vs. KETAMINE Over the Lifespan (REaKT-SD)

Overview

This study is a randomized open-label single-blind non-inferiority comparative effectiveness study of ECT vs. KET for the treatment of Acute Suicidal Depression (ASD).

Detailed description

There is a crisis in the treatment of the imminently suicidal patient. Acute Suicidal Depression (ASD) is a life-threatening illness which requires rapid relief. A number of behavioral programs with varying efficacy are available for prevention of suicide. However, once acute suicidal depression has set in, its treatment is woefully inadequate in the current health system despite availability of efficacious treatments. Patients suffering from ASD are usually admitted as inpatients for safety and started on oral antidepressants (which can take 6 - 12 weeks to have an effect) and given nursing care. They are then discharged from the hospital, usually within 4 -5 days, as soon as immediate safety concerns are ameliorated. Essentially, patients do not receive any specific rapidly acting treatment for their suicidal depression. As The immediate post-discharge period has been shown to be of the highest risk for repeat suicide attempts and completed suicides. One important reason for the inadequate treatment of ASD is the lack of large-scale comparative studies of efficacious treatments such as electroconvulsive therapy (ECT) and subanesthetic dose intravenous ketamine (KET). In the absence of data to guide rational treatment choice, neither treatment is being used adequately. Clinicians are less likely to recommend these treatments in the absence of evidence to base their decision regarding which treatment to give first and under what circumstances. Patients are reluctant to choose between these treatments due to uncertainty regarding efficacy and apprehension regarding side effects and social stigma. Finally, in the absence of effectiveness data, hospital administrators and third-party payers are reticent about committing material and financial resources for these services leading to inaccessibility. Hence, there is a critical need for a large-scale comparative effectiveness trial of ECT vs. intravenous ketamine for rapid reversal of ASD to provide rational guidance for all stakeholders.

This study will address this significant clinical dilemma by conducting a large scale (N = 1500) non-inferiority randomized comparative effectiveness trial of ECT vs. KET for rapid treatment of acute suicidal major depression (ASD) across the lifespan.

Interventions

• Drug Subanesthetic dose intravenous ketamine (KET)
  This trial will use standard dose of ketamine (0.5mg/kg infusion over 40 min period) in accordance with research studies that have used ketamine as an antidepressant. Treatments will be given two times a week for a maximum of 8 treatments during the acute arm of the study. The investigators will be able to modify dose and number of treatments as indicated clinically per pragmatic clinical trials procedures. Patients will be clinically assessed prior to each treatment to evaluate response and app
• Device Electroconvulsive therapy (ECT)
  ECT will be given in a standard manner 3 times a week for 4 weeks. The Initial ECT treatment will be Right Unilateral (RUL) ultra-brief pulse at 6x seizure threshold determined during titration at first visit. If there is not satisfactory improvement with RUL the investigator may change to Bilateral (BL) utilizing brief pulse using 0.5 modified half-age method to determine stimulus intensity. The seizure threshold may increase during the course of treatment and the dose of the electric stimulus

Primary outcome measures

• Scale for Suicidal Ideation (SSI) [Time frame: Six weeks]

Secondary outcome measures (12)

• Quick Inventory of Depressive Symptoms Self Report QIDS-SR [Time frame: Six weeks]
• Columbia Suicide Severity Rating Scale (CSSR-S) [Time frame: 6 weeks]
• Montgomery Asberg Depression Rating Scale (MADRS) [Time frame: 6 weeks]
• Working Alliance Inventory (WAI-SR) [Time frame: 6 weeks]
• National Alcohol and Drug Institute (NIDA) Questionnaire [Time frame: 6 weeks]
• Self and clinician rated scales [Time frame: 6 weeks]
• Brief Psychiatric Rating Scale 4 items (BPRS) [Time frame: 6 weeks]
• Clinician Administered Dissociative Symptoms Scale (CADSS) [Time frame: 6 weeks]
• CGI-S [Time frame: 6 weeks]
• CGI-I [Time frame: 6 weeks]
• Young Mania Rating Scale (YMRS) [Time frame: 6 weeks]
• MOCA [Time frame: 6 weeks]

Eligibility criteria

Inclusion criteria

• Considered by a clinician as appropriate for referral to treatment services for rapid reversal of acute suicidal depression.
• Adults 18 - 90 years of age.
• Meet DSM-5 criteria for Major Depressive Episode (MDE) as determined by Mini International Neuropsychiatric Interview (MINI PLUS 5.0.0).
• Acute suicidal ideation or behavior (thinking or behavior suggesting harming or hurting oneself with knowledge that death may result) or attempt (any intentional, non-fatal self-injury regardless of medical lethality, if intent to die was indicated). \*
• Continue to express suicidal ideation since referral as evidenced by Scale for Suicidal Ideation (SSI) ≥6)\*\*
• Meet the following criteria on symptom rating scales at screening:

• Hamilton Depression Scale (HAM-D 17) >15
• Montreal Cognitive Assessment (MoCA) of ≥23(to rule out baseline significant cognitive impairment)

Exclusion criteria

• Meeting DSM-5 criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder.
• Not able to give informed consent to receive ECT or KET treatment.
• Not able to give informed consent to participate in the study.
• Meet exclusion criteria for ECT treatment as described in guidelines.
• Meet exclusion criteria for KET treatment such as:

• Pregnant or breast feeding
• Satisfying DSM-V criteria of current Mood Depressive Disorder Episode with Psychotic Features (i.e. delusions of hallucinations)
• Severe uncontrolled medical illness
• Ketamine allergy
• Intellectual disability and unable to provide consent or follow study procedures.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 9 centers

• UC San Francisco — San Francisco
• Johns Hopkins University — Baltimore
• McLean Hospital — Belmont
• Massachusetts General Hospital — Boston
• Mount Sinai School of Medicine — New York
• Cleveland Clinic — Cleveland
• University of Pittsburgh — Pittsburgh
• UTHealth Houston — Houston
• … and 1 more center

Canada · 1 center

• Center for Addiction and Mental Health (University of Toronto) — Toronto

Identifiers

NCT: NCT06034821 · 2023P001649

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗