Citation

Cigognini MA, Guirado AG, Meene DVD, Schneider MA, Salomon MS, Alexandria VSD, Adriano JP, Thaler AM, Fernandes FDS, Carneiro A, Moreno RA. Front. Psychiatry 2022; 13.

Copyright

(Copyright © 2022, Frontiers Media)

DOI

10.3389/fpsyt.2022.830301

PMID

unavailable

Abstract

OBJECTIVE: Ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, can promote rapid action in the management of individuals with treatment-resistant depression (TRD) at sub-anesthetic doses. However, few studies have investigated the long-term use of ketamine administered intravenously (IV) and intranasally (IN). We report the design and rationale of a therapeutic trial for assessing the efficacy, safety, and tolerability of repeated-dose intramuscular (IM) ketamine vs. active treatment (escitalopram and aripiprazole) in TRD patients.

METHODS: A comparative, parallel-group, randomized double-blind trial assessing the efficacy, safety, and tolerability of acute (4 weeks) and maintenance (24 weeks) use of IM ketamine (0.75 mg/kg) vs. active control (escitalopram 15 mg and aripiprazole 5 mg) in individuals with moderate-severe intensity TRD (no psychotic symptoms) with or without suicide risk will be conducted. Patients with TRD (18-40 years) will be randomized and blinded to receive ketamine IM or active treatment at a 1:1 ratio for 4 weeks (active treatment) and 24 weeks (maintenance treatment). Subjects will be assessed using clinical scales, monitored for vital signs (VS) after application of injectable medication, and undergo neuropsychological tests. The primary outcome will be changed on the Montgomery-Åsberg Depression Rating Scale (MADRS) during the course of the trial. The study is in running.

RESULTS: This study can potentially yield evidence on the use of IM ketamine in the treatment of depressive disorders as an ultra-rapid low-cost therapy associated with less patient discomfort and reduced use of medical resources, and can elucidate long-term effects on different outcomes, such as neuropsychological aspects.

CONCLUSIONS: The trial can help promote the introduction of a novel accessible approach for the treatment of complex disease (TRD) and also allow refinement of its long-term use. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04234776, identifier: NCT04234776. Copyright © 2022 Cigognini, Guirado, Meene, Schneider, Salomon, Alexandria, Adriano, Thaler, Fernandes, Carneiro and Moreno.

Language: en

Keywords

adult; human; homicide; female; quality of life; psychotherapy; ketamine; suicidal ideation; depression; psychosis; randomized controlled trial; major depression; risk assessment; Brief Psychiatric Rating Scale; disease severity; vomiting; controlled study; fluoxetine; sedation; tachycardia; double blind procedure; emergency ward; placebo; follow up; borderline state; drug tolerability; drug withdrawal; hypertension; escitalopram; maintenance therapy; heart rate; allergy; glaucoma; heart arrhythmia; clonazepam; insulin; neuropsychological test; nausea and vomiting; electrocardiography; physical abuse; aripiprazole; oxygen saturation; neurologic examination; Article; working memory; outcome assessment; vital sign; Positive and Negative Syndrome Scale; parallel design; Young Mania Rating Scale; breathing rate; n methyl dextro aspartic acid receptor blocking agent; Wisconsin Card Sorting Test; birth control; comparative effectiveness; medication compliance; sleep quality; treatment resistant depression; Hamilton Depression Rating Scale; treatment-resistant depression; intramuscular (IM); N-methyl-D-aspartate receptor antagonist; randomized clinical trial