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Acute intravenous ketamine treatment in treatment-resistant depression: a feasibility study

Feasibility study of ketamine treatment

30

Age 39.5 +- 11.9 years Female 9 participants (30.0%) Asian 30 participants (100.0%) Duration of illness 8.9 +- 7.5 years Total MADRS score 30.6 +- 6.1 points

A total of 30 study participants participated in the following time periods: June-August, 2022: 6 participants September-November, 2022: 5 participants December, 2022-February, 2023: 4 participants March-May, 2023: 7 participants Jun-Aug, 2023 5 participants Sep-Nov, 2023 3 participants

Serious adverse events: Protocol violation due to ketamine administration during the 1-year follow-up (n=2): One case was attributed to a relapse of depression, while the other may have developed a dependence on ketamine. Both deviations were causally related to ketamine. Dissociative symptoms during treatment: 20 participants (66.7%) New symptoms observed after the start of treatment on the UKU Adverse Reaction Rating Scale: Any side effect: 8 participants (26.7%) Drowsiness 4 participants (13.3%) Nausea 3 participants (10.0%) Headache 1 participant (3.3%) Decreased sleeping time 1 participant (3.3%) Abnormal sensation 1 participant (3.3%)

(1) Primary endpoint Infusion completion rate: 100% (2) Secondary endpoints MADRS: 30.6 +- 6.1 (baseline), 20.3 +- 11.5 (after the 4th dose) QIDS-SR: 16.9 +- 3.5 (baseline), 2.3 +- 5.0 (after the first dose), 11.2 +- 5.1 (after the second dose), 11.4 +- 5.0 (after the third dose), 10.3 +- 5.2 (after the fourth dose) C-SSRS: 1.1 +- 1.3 (baseline), 0.8 +- 1.2 (after completion of 4th administration) Apathy scale: 27.7 +- 6.5 (baseline), 25.0 +- 7.6 (after the first dose), 24.5 +- 8.9 (after the second dose), 23.1 +- 9.6 (after the third dose), 22.6 +- 10.0 (after the fourth dose) CGI-S 5.0 +- 0.9 (baseline), 4.5 +- 1.2 (after completion of 1st dose), 4.1 +- 1.5 (after completion of 2nd dose), 3.9 +- 1.6 (after completion of 3rd dose), 3.5 +- 1.7 (after completion of 4th dose) Remission rate (percentage of patients with total MADRS score of 10 or less) 26.7% Response rate (percentage of patients whose MADRS total score improved by 50% or more) 40.0% Percentage of patients whose total MADRS score improved by 25% or more 53.3% MADRS: 18.5 +- 11.6 (after 3 months), 19.8 +- 11.8 (after 6 months), 17.1 +- 11.8 (after 9 months), 17.1 +- 10.0 (after 12 months) QIDS-SR: 11.6 +- 5.1 (after 1 month), 11.5 +- 5.3 (after 2 months), 10.5 +- 5.3 (after 3 months), 10.8 +- 5.0 (after 4 months), 10.4 +- 5.4 (after 5 months), 11.5 +- 5.2 (after 6 months), 10.9 +- 6.2 (after 7 months), 11.2 +- 5.6 (after 8 months), 10. 4 +- 5.3 (after 9 months), 11.3 +- 6.6 (after 10 months), 10.6 +- 6.2 (after 11 months), 10.8 +- 5.3 (after 12 months) C-SSRS: 0.5 +- 0.9 (after 3 months), 0.5 +- 0.8 (after 6 months), 0.5 +- 0.8 (after 9 months), 0.3 +- 0.6 (after 12 months) Apathy scale: 23.3 +- 9.8 (after 1 month), 22.7 +- 11.5 (after 2 months), 21.5 +- 12.2 (after 3 months), 21.0 +- 11.5 (after 4 months), 21.3 +- 11.4 (after 5 months), 21.2 +- 9.8 (after 6 months), 21.1 +- 11.7 (after 7 months), 20.7 +- 11.8 (after 8 months) ), 20.8 +- 11.6 (after 9 months), 22.8 +- 10.8 (after 10 months), 20.9 +- 10.7 (after 11 months), 21.9 +- 11.5 (after 12 months) CGI-S: 3.4 +- 1.6 (after 3 months), 3.5 +- 1.6 (after 6 months), 3.2 +- 1.5 (after 9 months), 3.4 +- 1.7 (after 12 months)

All study participants completed the four infusions. The mean total MADRS score decreased from 30.6 +- 6.1 at baseline to 20.3 +- 11.5 after the fourth dose, with 26.7% in remission. Adverse events such as dissociative symptoms were observed. However, all were temporary and there were no serious adverse events during the infusions. During the 12-month follow-up of all participants, the total MADRS score remained between 17 and 19 points.

Nov. 24, 2025

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs031210648

Sakurai Hitoshi

Kyorin University Hospital

6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan

hitoshi-sakurai@ks.kyorin-u.ac.jp

Sakurai Hitoshi

Kyorin University Faculty of Medicine

6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan

+81-422-47-5511

hitoshi-sakurai@ks.kyorin-u.ac.jp

Complete

Mar. 07, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

other

1.Outpatients who meet the criteria for depression according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
2. Men and women aged 18 or more at the time of registration
3. Inadequate response to 2 or more antidepressants at approved doses for 6 weeks or more
4. A Montgomery-Asberg Depression Rating Scale (MADRS) total score of 20 or higher at the time of screening
5. Being capable of providing informed consent confirmed with scores above 70% in the following four items: understanding, appreciation, reasoning, and the ability to express a choice in the MacArthur Competence Assessment Tool (MacCAT)
6. Written consent being provided by study participant

1. Depression with psychotic features according to the diagnostic criteria of the DSM-5
2. Dose change of taken antidepressants, antipsychotics, lithium carbonate, or mood stabilizers within 1 week prior to enrollment
3. Receiving electroconvulsive therapy within 3 months prior to enrollment
4. Substance-related disorders (excluding nicotine and caffeine) within 6 months
5. Positive urine screening for dependent substances (except for those who are positive for drugs taken for treatment)
6. Being pregnant, breastfeeding, or hoping to become pregnant
7. A history of ketamine hypersensitivity
8. A history of epilepsy or seizures
9. High blood pressure (systolic pressure 160 mmHg or more, diastolic pressure 100 mmHg or more)
10. A history of acute cerebrovascular disorder within 3 months
11. A history of cerebral hypertension within 3 months
12. A history of severe cardiac compensatory failure within 3 months
13. At the time of registration, any of the following abnormal laboratory values
Serum creatinine 1.5 mg/dl or more
AST 150 IU/L or more
ALT 150 IU/L or more
14. Participated in another clinical trial within 3 months prior to enrollment (limited to those with invasion/intervention)
15. Imminent suicide risk at the time of registration
16. Those deemed unsuitable as research subjects by the principal investigator

Both

Treatment-resistant depression

Twice a week, four administrations in total, intravenous administration of ketamine hydrochloride (0.5 mg/kg) plus saline solution (total amount 50 mL) will be performed over 40 minutes

Completion rate of acute intravenous ketamine treatment (twice a week, four administrations in total)

- Severity of mood symptoms assessed with MADRS
- Severity of mood symptoms assessed with QIDS-SR
- Severity assessed with CGI
- Degree of suicidal ideation assessed with C-SSRS
- Degree of declined motivation assessed with Apathy scale
- Adverse events assessed with UKU side effect rating scale

+81-42-341-2712-7828

Feb. 04, 2022

none