Trial Outcomes & Findings for Ketamine as an Adjunctive Therapy for Major Depression (NCT NCT03256162)

Last Updated: 2020-01-18

Results Overview

The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms. Response to antidepressant treatment is defined as achieving ≥60% decrease from baseline HRSD-24 and score ≤16. Remission criteria are ≥60% decrease in HRSD from baseline and score ≤10. Criteria for relapse are ≥10 point increase in HRSD-24 compared to responder baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later. Participants will have a baseline (T0) HRSD-24 score. This will be repeated 1 week after each of 4 once-weekly infusions (T1-4) and follow-up measures after another 5 (T9) and 11 (T15) weeks, week 15 is reported.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

25 participants

Primary outcome timeframe

15 weeks

Results posted on

2020-01-18

Participant Flow

Potential participants were those who were admitted to St Patrick's University Hospital, Dublin, for treatment of a major depressive episode (either unipolar or bipolar depression) between 06.09.17 and 12.06.18.

Treatment-as-usual, by the participants' treating teams, continued throughout the entire trial.

Participant milestones

Participant milestones
Measure	Ketamine Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.	Midazolam Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
Overall Study STARTED	13	12
Overall Study COMPLETED	8	8
Overall Study NOT COMPLETED	5	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ketamine as an Adjunctive Therapy for Major Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ketamine n=13 Participants Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.	Midazolam n=12 Participants Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.	Total n=25 Participants Total of all reporting groups
Age, Continuous	48.9 years STANDARD_DEVIATION 13.1 • n=5 Participants	52.3 years STANDARD_DEVIATION 12.5 • n=7 Participants	50.5 years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)	28.4 units on a scale STANDARD_DEVIATION 4.3 • n=5 Participants	27.4 units on a scale STANDARD_DEVIATION 4.3 • n=7 Participants	27.7 units on a scale STANDARD_DEVIATION 3.9 • n=5 Participants

PRIMARY outcome

Timeframe: 15 weeks

Outcome measures

Outcome measures
Measure	Ketamine n=8 Participants Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.	Midazolam n=8 Participants Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)	11.2 score on a scale Interval 6.2 to 16.2	16.6 score on a scale Interval 7.8 to 25.3

SECONDARY outcome

Timeframe: 15 weeks

The QIDS-SR16 is a validated self-report measure of depressive symptoms. This consists of 16 questions rated 0-3. Its score range is 0-48, with higher scores reflecting greater burden of depressive symptoms. Participants will have a baseline (T0) QIDS-SR16 score. This will be repeated one week after each of four once-weekly infusions (T1-4) and follow-up measures after another five (T9) and 11 (T15) weeks. Week 15 scores are reported.

Outcome measures

Outcome measures
Measure	Ketamine n=8 Participants Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.	Midazolam n=8 Participants Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
The Quick Inventory of Depressive Symptoms, Self-report Version (QIDS-SR16)	9.1 score on a scale Interval 5.6 to 12.6	11.4 score on a scale Interval 4.9 to 18.0

SECONDARY outcome

Timeframe: 4 weeks

The CADSS measures dissociative symptoms. It will be administered before, during and after infusions in order to capture the range of possible subjective side effects of either agent. This consists of 23 questions and scores for each question range from 0-4. The maximum score is 92 with higher scores indicating more dissociative symptoms. Participants will have the CADSS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.

Outcome measures

Outcome measures
Measure	Ketamine n=8 Participants Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.	Midazolam n=8 Participants Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
The Clinician-Administered Dissociative States Scale (CADSS)	5.3 score on a scale Standard Deviation 7.2	2.5 score on a scale Standard Deviation 3.5

SECONDARY outcome

Timeframe: 4 weeks

The BPRS measures psychotomimetic effects. The investigators will use the positive symptoms subscale of the Brief Psychiatric Rating Scale. The 4-item positive symptoms subscale measures suspiciousness, hallucinations, unusual thought content, and conceptual disorganisation. Each question is scored between 0-7. The maximum score in this 4-item questionnaire is 28. Higher scores indicate more severe psychotic symptoms. Participants will have the BPRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.

Outcome measures

Outcome measures
Measure	Ketamine n=8 Participants Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.	Midazolam n=8 Participants Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
The Brief Psychiatric Rating Scale (BPRS)	4.1 score on a scale Standard Deviation 0.4	4.0 score on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: 4 weeks

Investigators will use the mood item of them YMRS to assess for psychotomimetic effects. This item is rated 0-4. The higher scores reflect elevated mood. Participants will have the YMRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.

Outcome measures

Outcome measures
Measure	Ketamine n=8 Participants Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.	Midazolam n=8 Participants Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
Young Mania Rating Scale (YMRS; Mood Item)	0.1 score on a scale Standard Deviation 0.4	0.1 score on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: 4 weeks

The PRISE will be used to document other general adverse events by patients before, during and after infusions. This is a patient self-report used to qualify side effects by identifying and evaluating the tolerability of each symptom. It is a 9 item assessment of the side effects in the following symptom domains; Gastrointestinal, Heart, Skin, Nervous System, Eyes/Ears, Genital/Urinary, Sleep, Sexual Functioning, and Other. Each domain has multiple symptoms which can be endorsed. For each domain the patient rates whether or not the symptoms are tolerable or distressing. Data below represent the number of participants from which there was an endorsement of each listed event. Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.

Outcome measures

Outcome measures
Measure	Ketamine n=8 Participants Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.	Midazolam n=8 Participants Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
The Patient-Rated Inventory of Side Effects (PRISE) dry mouth	1 participants	1 participants
The Patient-Rated Inventory of Side Effects (PRISE) diarrhoea	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Constipation	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Nausea / vomiting	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Palpitation	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Chest pain	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Rash	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Headache	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Tremors	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Poor coordination	1 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Dizziness	2 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Blurred vision	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Difficulty urinating	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Difficulty sleeping	0 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Sleeping too much	0 participants	1 participants
The Patient-Rated Inventory of Side Effects (PRISE) Anxiety	2 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Poor concentration	0 participants	1 participants
The Patient-Rated Inventory of Side Effects (PRISE) Restlessness	2 participants	0 participants
The Patient-Rated Inventory of Side Effects (PRISE) Fatigue	3 participants	1 participants

SECONDARY outcome

Timeframe: 15 weeks

The MOCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, conceptual thinking, calculations, and orientation. It is scored out of a maximum of 30. The higher scores indicate better cognition. The MOCA will be performed at baseline, one day after infusions 1 and 4 and 12 weeks after the final infusion.

Outcome measures

Outcome measures
Measure	Ketamine n=8 Participants Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.	Midazolam n=8 Participants Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
The Montreal Cognitive Assessment (MoCA)	26.4 score on a scale Standard Deviation 3.1	28.5 score on a scale Standard Deviation 1.4

Adverse Events

Ketamine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Midazolam

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr Bronagh Gallagher

Trinity College Dublin

Phone: 01 249

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place