Clinical Predictors of Intravenous Ketamine Response in Treatment-Resistant Depression

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

For patients with treatment-resistant depression (TRD), a single low dose of intravenous (IV) ketamine can help relieve symptoms as quickly as 24 hours later.

The main problem with IV ketamine for TRD is that the effect is short-lived, lasting only days to 1 or 2 weeks. Furthermore, IV ketamine is a resource-intensive treatment, and the safety of long-term, repeated use for depression is unknown. To provide this treatment in a safe and cost-effective way, we must allocate it efficiently to those patients who have the greatest need and probability of benefit. Therefore, our project aims to find clinical features (signs, symptoms, and parts of a patient's history) that will help predict which patients are most likely to respond to a single dose of IV ketamine for TRD. This will help guide patient selection and triaging.

We will recruit 40 patients with TRD over one year, and randomize them to one of two conditions (ketamine followed by an active placebo 3-weeks later, or vice versa). With clinical data collected through detailed interviews and questionnaires, this study design will let us evaluate how well such factors predict (A) rapid response at 24-hours, and (B) sustained response at 7 and 14 days.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Abraham Nunes
• Collaborator: Nova Scotia Health Authority
• Treatments: Ketamine; Midazolam

Criteria

Inclusion Criteria:

• Able to fluently read in English with or without optical correction

• Native English speaker (to ensure appropriateness for neurocognitive paradigms)

• Ability to understand and comply with the study requirements

• This is determined by the investigators

• Provision of written informed consent

• Documented diagnosis of MDD meeting DSM-5 criteria (as confirmed by the Diagnostic Assessment Research Tool), currently in a single or recurrent episode without psychotic features

• Failure of at least two antidepressant medications from different pharmacological classes, as well as at least one augmentation agent, each of which must have been given at adequate doses for at least 6 weeks during the present episode (recorded using the Antidepressant Treatment History Form - Short Form).

• Augmentation strategies include those listed in the 2016 Canadian Network for Mood and Anxiety Treatments (CANMAT) depression guidelines, including a 12-week course of cognitive behavioural therapy or interpersonal therapy.

• MADRS score of ≥25 at initial assessment and randomization, and no more than 20% improvement between those visits.

• For premenopausal females who are currently sexually active with male partners:

• Negative urine pregnancy test at enrolment

• AND commitment to using an appropriate birth control method of their choice throughout the duration of the study, including

• intrauterine device

• oral contraceptive

• long-term injectable contraceptive

• double-barrier method

• implant

• dermal contraception

• tubal ligation

• Abstinence from grapefruit juice consumption on the day of infusion

• Abstinence from benzodiazepine use within 24 hours of infusion

• Adherence to maintaining current antidepressant management

Exclusion Criteria:

• Substance related exclusion criteria:

• Concomitant use of naltrexone or narcotics

• Positive urine drug screen or history of DSM-5 substance use disorder (except caffeine or nicotine)

• Psychiatric exclusion criteria:

• Previous ketamine use (therapeutic or recreational)

• Concurrent use of naltrexone

• History of electroconvulsive therapy

• Comorbid DSM-5 personality disorder with a major impact on mental status

• Secondary depressive disorders

• E.g. secondary to stroke, cancer, or other somatic pathology

• Subjects who will be starting psychotherapy during the trial period, or have only recently started psychotherapy within 2 months of the trial

• Medical comorbidity related exclusion criteria:

• Evidence on history or chart review of any of the following:

• Epilepsy

• Renal or hepatic impairment

• Myocardial infarct within a year prior to initial randomization

• Cerebrovascular disease,

• Viral hepatitis B or C

• Acquired immunodeficiency syndrome.

• Abnormal liver function tests.

• Liver enzymes three times the upper normal limit at screening

• Current uncorrected thyroid pathology or recent correction within 30 days (correction of thyroid function for longer than 1 month is admissible).

• Any unstable somatic pathology or clinically significant investigational abnormality (biochemical, ECG) that investigators believe would be negatively impacted by study procedures or that would negatively impact study procedures