Treatment Resistant Depression
Conditions
Interventions
Intervention (active): Racemic ketamine (ketamine).
This is an open-label, single-arm, uncontrolled pilot study. No control intervention (no placebo/active comparator/standard-therapy control) is pla
responders only):
Eligibility for maintenance: Participants meeting response criteria after acute phase (?50% reduction in MADRS)
Drug: Racemic ketamine (ketamine)
Route: Intranasal adm
Sponsors
Professor Shehan Williams
Eligibility
Inclusion criteria
Inclusion criteria: Adults aged 18 to 64 years, inclusive. Both males and females are eligible to participate. Ability and willingness to provide written informed consent and comply with study procedures. Meet DSM-5 diagnostic criteria for a depressive disorder (major depressive disorder or persistent depressive disorder), confirmed using the Mini International Neuropsychiatric Interview (MINI). Presence of treatment-resistant depression, defined as non-response to at least two adequate trials of first-line antidepressant medications, with greater than 25% clinical improvement. Moderate to severe depression, indicated by a Montgomery–Åsberg Depression Rating Scale (MADRS) score greater than 28 at screening. Medically stable based on physical examination, vital signs, ECG, and laboratory investigations. No other mental illness as the primary diagnosis, such as psychotic disorders, primary obsessive-compulsive disorder, or primary anxiety disorders. Women of childbearing potential must use highly effective contraception throughout participation in the study. Willing and able to comply with study procedures and treatment restrictions.
Exclusion criteria
Exclusion criteria: Previous non-response to treatment with ketamine or esketamine. Presence of neurodegenerative disorders, significant cognitive impairment, or intellectual disability. Clinically significant or uncontrolled hypertension. Significant cardiovascular, gastrointestinal, pulmonary, neuroendocrine, or other medical conditions that may increase risk during ketamine treatment, as judged by the investigator. Known allergy, hypersensitivity, or contraindication to ketamine or related compounds. Current or past diagnosis of substance use disorder, or significant substance misuse including alcohol within the last two years. Presence of significant Cluster B personality disorder or traits that may interfere with participation. Pregnant or breastfeeding women, or those planning pregnancy during participation or within six weeks after the last ketamine dose. Any psychosocial or clinical circumstance that, in the investigator’s judgment, makes participation not in the best interest of the participant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in depressive symptom severity measured by the Montgomery–Åsberg Depression Rating Scale (MADRS) from baseline to the specified assessment time points. The principal efficacy analysis will evaluate the mean change in MADRS score from baseline, with additional reporting of: Response rate (participants achieving a greater than 50% reduction in MADRS score from baseline), and Remission rate (participants achieving a MADRS score less than 10). [MADRS assessments will be conducted at screening (baseline), during the acute treatment phase (week 1), at completion of the acute phase (week 4), and during the maintenance phase at week 16 and at completion of treatment at week 28.] | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in depressive symptom severity measured using the Patient Health Questionnaire-9 (PHQ-9). [Assessed at screening (baseline), during the acute treatment phase at week 1, at completion of acute treatment at week 4, and during maintenance treatment at week 16 and week 28.] Change in suicidality measured using the Columbia Suicide Severity Rating Scale (C-SSRS). [Assessed at screening (baseline), during the acute treatment phase at week 1, at completion of acute treatment at week 4, and during maintenance treatment at week 16 and week 28.] Change in functional impairment measured using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). [Assessed at screening (baseline), during the acute treatment phase at week 1, at completion of acute treatment at week 4, and during maintenance treatment at week 16 and week 28.] | — |
Countries
Sri Lanka
Contacts
Public ContactProfessor Shehan Williams
Professor in Psychiatry
Outcome results
None listed