A Clinical Trial of Add-on Oral Slow-release Ketamine Treatment in Major Depression

NCT07396272 | Recruiting Phase 2

• 1 other identifier: 2025-524841-28-00
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

• The goal of this clinical trial is to explore if the treatment with ketamine tablets in addition to standard antidepressant therapy can reduce depressive symptoms in adults with Major Depressive Disorder. The main question it aims to answer is: Does adjunctive ketamine therapy reduce depressive symptoms after one week of treatment compared to baseline, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS)?
• Participants will start ketamine treatment together with a new standard antidepressant. During the treatment week, patients will receive four doses of Ketamine Hydrochloride Prolonged-Release Tablets (240 mg) at the clinic. They will fill in different questionnaires and rating scales during screening, treatment and follow-up, and will leave blood samples at five of the visits to monitor side effects and identify possible biomarkers. After a week, the ketamine treatment is finished while the standard antidepressant therapy continues. The participation in this trial is completed after three aditional weeks of follow-up.

Conditions

Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) after one week of treatment compared to baseline visit

  * In MADRS, 10 items are rated with a score of 0 to 6 (total score: 0 to 60). A higher MADRS score indicates more severe depression. * Cut-off points: 0 to 6: normal/symptom-free, 7 to 19: mild depression, 20 to 34: moderate depression 35 to 60: severe depression.

  Between day 1 (baseline visit) and day 8 (day of last dosing)

Secondary Outcomes (23)

• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at other timepoints than the primary endpoint

  Between day 1 (baseline visit) and visits on day 3, 5, 15 and 29

• Change in Clinical Global Impression - Severity (CGI-S) rating scale from baseline to every post-baseline measurement (day 3, 5, 8, 15, 29)

  Between day 1 (baseline visit) and visits on day 3, 5, 15 and 29

• Total score of Clinical Global Impression - Efficacy Index (CGI-E) rating scale at every post-baseline measurement (day 3, 5, 8, 15, 29)

  Between first evaluation after treatment start (day 3) and last follow-up visit (day 29)

• Change in Patient Health Questionnaire-9 (PHQ-9) and the composite inflammatory depressive symptom score (InfDep score) consisting of PHQ-9 items # 3, 4 and 5 between baseline (day 1) and the two follow-up visits (day 15 and 29)

  Between baseline visit (day 1) and last follow-up visit (day 29)

• Change in generalized anxiety disorder-7 (GAD-7) between baseline (day 1) and two follow-up visits (day 15 and 29)

  Between baseline visit (day 1) and last follow-up visit (day 29)

Study Arms (1)

Ketamine-treated

EXPERIMENTAL

Only arm of this pilot study, all 12 patients enrolled will be included in this arm. Treated with Ketamine Hydrochloride Prolonged-Release Tablets (KET01, 240 mg) for one week (8 days) with four doses.

Drug: Treatment with Ketamine Hydrochloride Prolonged-Release Tablets

Interventions

Treatment with Ketamine Hydrochloride Prolonged-Release Tablets DRUG

Only intervention of this pilot study, administered to all 12 patients enrolled. Treatment with Ketamine Hydrochloride Prolonged-Release Tablets (KET01, 240 mg) for one week (8 days) with four doses.

Ketamine-treated

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has given their written consent to participate in the trial.
• BMI ≥ 18 and ≤ 35 kg/m2.
• Primary diagnosis of MDD meeting DSM-5-TR criteria and one of the following episode characteristics: (a)MDD, single episode, moderate (ICD-10-CM: F32.1); (b) MDD, single episode, severe, without psychotic features (ICD-10-CM: F32.2); (c) MDD, recurrent, moderate (ICD-10-CM: F33.1); (d) MDD, recurrent, severe, without psychotic features (ICD-10-CM: F33.2)
• Duration of current depressive episode no longer than 12 months prior to screening.
• MADRS score ≥ 22 at screening
• Willingness to start a new, conventional antidepressant treatment which is chosen by the treating physician with regards to side effect profile and previous treatments, together with KET01, dosed according to the prescribed schedule.
• Willingness to terminate any ongoing antidepressant treatment if deemed ineffective by study physician in accordance with clinical practice (tapering or immediate stop), followed by a wash-out phase of at least 7 days without medication before treatment with the new antidepressant is initiated together with KET01.
• For females of childbearing potential: Must be willing to undergo pregnancy tests and will be required to use highly effective contraceptive measures from the time of informed consent until 28 days after last IMP intake. Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral or injectable); implantable intrauterine device (IUD); intrauterine hormone-releasing system (IUS), bilateral tubal occlusion or practicing sexual abstinence (if this is in line with the preferred and usual lifestyle of the participant).
• For male participants with a partner of childbearing potential: Must be willing to use adequate contraceptive measures (barrier method) or practice sexual abstinence (if this is in line with the preferred and usual lifestyle of the participant) from the time of informed consent until 28 days after last IMP intake. Note: These requirements also apply for male participants who have had a vasectomy.

You may not qualify if:

• Known hypersensitivity or intolerance to ketamine or any of the excipients.
• Pregnancy, breastfeeding or planned pregnancy (if female).
• High suicide risk according to the overall assessment of the research physician.
• Known psychiatric and neurological concomitant condition of:
• MDD, single episode, severe, with psychotic features (ICD-10-CM: F32.3), MDD, recurrent, severe, with psychotic features (ICD-10-CM: F33.3), Schizophrenia spectrum and other psychotic disorders (ICD-10-CM: F21, F22, F23, F20.81, F20.9, F25.0, F25.1, F06.0, F06.1, F06.2, F28 and F29) or bipolar disorder (ICD-10-CM: F31), other mental disorder due to known physiological condition (ICD-10-CM: F06). Participants with first-degree relatives (parents, brothers, sisters or children) with psychotic or bipolar disorders are also not considered eligible. Paranoid or schizoid personality disorder (ICD-10-CM: F60.0, F60.1). Antisocial, borderline, histrionic or narcissistic personality disorder (ICD-10-CM: F60.2, F60.3, F60.4, F60.81). Neurodevelopmental disorders, e.g. moderate to profound intellectual developmental disorders (ICD-10-CM: F71, F72, F73), or autism spectrum disorders (ICD-10-CM: F84).
• Known or suspected lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder, epilepsy (excluding uncomplicated childhood febrile seizures with no sequelae) or any other disease/procedure/accident/intervention which, according to the investigator is deemed associated with significant injury to or malfunction of the CNS.
• History of significant head trauma within the past 2 years prior to Visit 1.
• History of cerebrovascular event (e.g. stroke, prolonged ischaemic neurologic deficit \[PRIND\], transient ischaemic attack).
• Known or suspected ongoing cardiac disease (e.g. unstable angina, congestive heart failure, tachyarrhythmia or myocardial infarction).
• Clinically significant abnormal electrocardiogram findings at Visit 1 which may jeopardize participant's safety according to the investigator.
• Untreated or uncontrolled hypertension (after 5 minutes of rest, systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 120 mmHg confirmed by three sequential measurements with at least 5 minutes between the single measurements).
• Laboratory findings suggesting impaired hepatic function or liver cirrhosis i.e. gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values \> 2x times the upper limit of normal (ULN) or total bilirubin \> 1.5 times the ULN at Visit 1. Participants with an isolated increase of indirect bilirubin not previously documented as a diagnosis of Gilbert's syndrome must be discussed with the medical monitor.
• Known hepatitis B or C.
• eGFR \< 60 mL/min/1.73 m2 or creatinine \> 200 μmol/L at Visit 1 or ongoing dialysis or kidney transplants.
• Diabetes mellitus with a haemoglobin A1c (HbA1c) value \> 64 mmol/mol at the screening visit.

Sponsors & Collaborators

• Daniel Lindqvist: lead
• Ketabon: collaborator
• Lund University: collaborator

Study Sites (1)

Adult Psychiatry

Lund, Skåne County, 22240, Sweden

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Daniel Lindqvist, PhD, MD

  Region Skane

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mirjam Wolfschlag, PhD

CONTACT

+46724596431; mirjam_katharina.wolfschlag@med.lu.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Psychiatry Division and research, Principal Investigator, Senior Consultant

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: February 9, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)