A randomised controlled study of an N-Methyl-D-Aspartate antagonist in major depression

A randomised, double blind, active placebo-controlled crossover trial to evaluate the short term efficacy of an N-Methyl-D-Aspartate antagonist for patients with treatment resistant depression

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12615000573550

Enrollment

Registered

2015-06-03

Start date

2016-10-27

Completion date

2018-08-16

Last updated

2021-11-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Depression is the most prevalent mental health disorder in New Zealand. Although many treatments are available for approximately one third of patients these treatments will be ineffective and they will be classified as "treatment-resistant". New research indicates that the approved medicine ketamine given at low doses can be used successfully as antidepressant in approximately two thirds of patients with treatment resistant depression. Moreover ketamine’s rapid antidepressant actions, within several hours, make it remarkable compared to usual therapies. In addition to offering hope to patients, for scientists studying depression ketamine allows new opportunities to study the disease. In this study we will give patients with treatment-resistant depression ketamine to rapidly move them from a state of depression to nondepression. We will use brain imaging technologies and blood biomarkers to attempt to understand what processes occur in these patients that underlie the transition to elevated mood.

Interventions

Ketamine IV. – bolus dose 0.25mg/kg then infusion at 0.25 mg/kg/hr for 45 minutes Washout 3 weeks. Follow-ups at 1,7,14,21 days. Study duration 42 days.

Study design

Allocation

Randomised controlled trial

Intervention model

Crossover

Primary purpose

Treatment

Masking

Blinded (masking used) (Subject, Outcomes Assessor)

Eligibility

Sex/Gender

All

Age

18 Years to 60 Years

Healthy volunteers

Inclusion criteria

* Participant is willing and able to give informed consent for participation in the trial. * Male or female, aged 18 years or above and less than 60. * In the Investigators’ opinion, is able and willing to comply with all trial requirements. * Major depressive disorder for at least three months, as assessed by a Clinical Interview using DSM-IV criteria * MADRS >20 * An inadequate response to at least two antidepressants courses (Antidepressant Treatment History Form) one of which can include the current episode * Stable on antidepressant medication for four weeks prior to Study Day 1

Exclusion criteria

* Female participant who is pregnant, lactating or planning pregnancy during the course of the trial. * Significant renal or hepatic impairment. * Cardiovascular conditions including abnormal heart rate and blood pressure checked at screening. * Participants who have participated in another research trial involving an investigational product in the past 12 weeks. * History of psychosis * Any unstable medical or neurologic condition. * Planned major changes to psychotropic medication. * Imminent risk of suicide as determined by the CSSRS. * Planned or probable use of ECT. * Substance abuse or dependence in previous 6 months. * Any history of abuse of ketamine or phencyclidine. * Contraindication to the use of ketamine according to manufacturer guidelines. * Planned use of ketamine, for example, for pain control. * Unable to fast for four hours prior to each administration of trial drug. * Any other condition judged by the treating clinician as likely to impact on the ability of the participant to complete the trial. * Body-weight <50kg or >120kg. * Current use of NMDA antagonist medications (e.g. memantine / amantadine / rimantadine / lamotrigine / dextromethorphan/procyclidine). * Inability to speak or read English. * Contraindications for MRI scanning

Outcome results