Treatment Resistant DepressionGDKetNCT04226963
A Naturalistic Study of Ketamine for Treatment Resistant Mood Disorders
An observational study of Treatment Resistant Depression and Bipolar Depression, run by Medical University of Gdansk at 1 site in Poland.
Trial summary
This study aims to openly test the long-term safety, tolerability and effectiveness of repeated administration of IV, nasal spray and oral ketamine for treatment-resistant mood disorders. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Treatment Resistant Depression, Bipolar Depression, Ketamine
- What is being tested?
- Ketamine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 80 participants
- Where
- 1 sitePoland
- Study dates
- 4 Dec 2019to 4 Jul 2022
- How long will I take part?
- 1 Week
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Inpatients with TRD referred to the tertiary-reference unit for mood disorders
Who may be able to join
- Major depressive disorder (MDD) or bipolar disorder (BD) diagnosis as provided by DSM-5 criteria
- TRD defined as the patient does not reach remission within the 8 week trial of an antidepressant or combination at a therapeutic dose of at least two trials of first-line evidence-based treatments and/or electroconvulsive therapy (ECT)
Who cannot join
- Pregnancy and lactation
- Hypersensitivity to ketamine
- Uncontrolled hypertension
- Other uncontrolled somatic diseases that may impact safety per investigators judgement
Trial locations and contacts
1 site in 1 country.
Poland1 site
Department of Psychiatry, Medical University of Gdańsk
Gdansk, 80-952
About this study
Official title: A Naturalistic Study of Ketamine for Treatment Resistant Mood Disorders: Gdansk Depression Ketamine Project
This study aims to openly test the long-term safety, tolerability and effectiveness of repeated administration of IV, nasal spray and oral ketamine for treatment-resistant mood disorders.
Read the detailed description
Current pharmacological treatments for depression prove unsatisfactory efficacy with a proportion of subjects demonstrating treatment-resistant depression (TRD). The observation applies both to major depressive disorder (MDD) as well as bipolar I depression. There is growing evidence that the glutamatergic system plays a role in the pathophysiology and treatment of depression. Discovery of rapid, although transient antidepressant effect of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist used in a single sub-anaesthetic intravenous dose in unipolar, bipolar and treatment-resistant patients provides evidence for a glutamatergic antidepressant. Subsequent studies confirmed this effect in repeated doses. Further research demonstrated that repeated ketamine infusions result in sustainable antidepressant effect with both, twice-weekly and thrice-weekly administration schedules. However, the worsening of depression may occur after infusions are completed. Given the risk of relapses, there is a definite need for the development of new strategies to maintain the beneficial effects of ketamine treatment. In the present study, the investigators aim to openly assess the safety, tolerability, and effectiveness of repeated, individually tailored IV, nasal spray and oral ketamine for treatment-resistant mood disorders. The investigators intend to explore questions regarding optimal dose, treatment frequency and duration.
- Being tested
- Ketamine
- Keywords
- treatment resistant depression, bipolar depression, ketamine, multiple series, major depressive disorder
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Bipolar Disorder, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Ketamine will be infused (slow IV infusions of ketamine (0.5 mg/kg) over 40 minutes) twice weekly over a period of 4 weeks) Ketamine will be given in intranasal spray twice weekly over a period of 4 weeks Ketamine will be given orally (solution 2.0mg/kg, 2.5mg/kg) twice weekly over a period of 4 weeks.
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events assessed by Clinical-Administered Dissociative Symptoms Scale (CADSS)
Incidence of adverse events will be assessed by Clinician-Administered Dissociative Symptoms Scale (change from baseline to each measure). Higher values represent a worse severity, but not necessarily outcome. The Clinical-Administered Dissociative Symptoms Scale has 23-items based on dissociative symptoms during the assessment. Each item is scored 0 (normal) to 4 (severe symptoms) with overall score ranges from 0 (normal) to 92 (severe symptoms). Total number of assessments:18 times
Measured: Baseline through week 5
Incidence of adverse events assessed by 4-items positive symptoms subscale of Brief Psychiatric Rating Scale (BPRS)
Incidence of adverse events will be assessed by 4-items positive symptoms subscale of Brief Psychiatric Rating Scale (change from baseline to each measure). Higher values represent a worse severity but not necessarily outcome. The 4-item positive symptoms subscale of Brief Psychiatric Rating Scale has 4-items based on conceptual disorganization, suspiciousness, hallucination and unusual thought content. Each item is scored 0 (normal) to 6 (severe symptoms) with overall score ranges from 0 (normal) to 24 (severe symptoms). Total number of assessments:18 times
Measured: Baseline through week 5
Incidence of adverse events assessed by body temperature (oral measurements)
Incidence of adverse events assessed by body temperature (oral measurement) in Celsius degree - change from baseline to each measure. A normal range is from 36.2 to 38.0 Celsius degrees; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
Measured: Baseline through week 5
Incidence of adverse events assessed by blood pressure
Incidence of adverse events assessed by blood pressure (after the participant has rested for at least 5 minutes) in mmHg - change from baseline to each measure. A normal range for systolic blood pressure is from 90 to 140 mmHg, for diastolic blood pressure is from 50 to 90 mmHg; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
Measured: Baseline through week 5
Incidence of adverse events assessed by respiration rate
Incidence of adverse events assessed by respiration rate in a breath number per minute - change from baseline to each measure. A normal range for respiration is from 12 to 16 breaths per minute; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
Measured: Baseline through week 5
Incidence of adverse events assessed by pulse
Incidence of adverse events assessed by pulse (beats per minute [bpm]) - change from baseline to each measure. A normal range for pulse is from 60 to 90 bpm; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
Measured: Baseline through week 5
Incidence of adverse events assessed by blood oxygen saturation
Incidence of adverse events assessed by blood oxygen saturation in percentage - change from baseline to each measure. A normal range for blood oxygen saturation is from 95 to 100 percentage; measurements under 95% are clinically significant. The total number of measurements: 44 times
Measured: Baseline through week 5
Incidence of adverse events assessed by weight
Incidence of adverse events assessed by weight in kilograms- change from baseline to each measure. Gain weight for 7% baseline weight is clinically significant. Total numbers of assessments: 2. Weight and height will be combined to report BMI in kg/m^2
Measured: Baseline and week 5
Incidence of adverse events assessed by height
Incidence of adverse events assessed by height in meters. Total numbers of assessments: 1. Weight in kilograms and height in meters will be combined to report BMI in kg/m^2
Measured: Baseline
Secondary outcomes (1)
Change in severity of depression symptoms assessed by Montgomery-Asberg Depression Rating Scale (MADRS)
Change in severity of depression symptoms from baseline to each measure. Higher values represent a worse severity, but not necessarily outcome. The MADRS has 10-items which are based on mood symptoms over the past 7 days. Each item is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).
Measured: Baseline through week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start4 Dec 2019
- Primary completion4 Jul 2022
- Study completion4 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- More trials run by Medical University of GdanskThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (actual)
- Target duration
- 1 Week
Sponsor and investigators
- Lead sponsor
- Medical University of Gdansk
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maria Galuszko-Wegielnik, Medical University of Gdansk
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04226963
- Sponsor's protocol ID
- NKBBN/172-674/2019
- Acronym
- GDKet
- Status last verified
- Sep 2023
- First submitted
- 2 Jan 2020
- Last updated
- 28 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kwasny A, Wilkowska A, Pastuszak M, Pastuszak K, Cubala WJ. Treatment-emergent psychiatric adverse events in patient-reported outcomes during ketamine use for major depressive disorder: a retrospective analysis. Pharmacol Rep. 2026 Aug;78(4):1292-1300. doi: 10.1007/s43440-026-00867-1. Epub 2026 May 20.
PubMed 42159864Kachlik Z, Cubala WJ, Walaszek M, Pastuszak M, Pastuszak K, Kwasny A. Nonresponse to Ketamine in Treatment-Resistant Bipolar Depression. Neuropsychopharmacol Rep. 2025 Sep;45(3):e70038. doi: 10.1002/npr2.70038.
PubMed 40879542Wlodarczyk A, Cubala WJ, Galuszko-Wegielnik M, Szarmach J. Dissociative symptoms with intravenous ketamine in treatment-resistant depression exploratory observational study. Medicine (Baltimore). 2021 Jul 23;100(29):e26769. doi: 10.1097/MD.0000000000026769.
PubMed 34398056Wlodarczyk A, Cubala WJ, Galuszko-Wegielnik M, Szarmach J. Central nervous system-related safety and tolerability of add-on ketamine to antidepressant medication in treatment-resistant depression: focus on the unique safety profile of bipolar depression. Ther Adv Psychopharmacol. 2021 May 19;11:20451253211011021. doi: 10.1177/20451253211011021. eCollection 2021.
PubMed 34046159
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Naturalistic Study of Ketamine for Treatment Resistant Mood Disorders: Gdansk Depression Ketamine Project
- ClinicalTrials.gov ID
- NCT04226963
- Acronym / sponsor ID
- GDKet / NKBBN/172-674/2019
- Keywords
- treatment resistant depression, bipolar depression, ketamine, multiple series, major depressive disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Medical University of GdanskUniversity, hospital or other
- Study start
- 4 Dec 2019 (actual)
- Primary completion
- 4 Jul 2022 (actual)
- Study completion
- 4 Jul 2022 (actual)
- First posted
- 13 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to openly test the long-term safety, tolerability and effectiveness of repeated administration of IV, nasal spray and oral ketamine for treatment-resistant mood disorders.
Detailed description
Current pharmacological treatments for depression prove unsatisfactory efficacy with a proportion of subjects demonstrating treatment-resistant depression (TRD). The observation applies both to major depressive disorder (MDD) as well as bipolar I depression. There is growing evidence that the glutamatergic system plays a role in the pathophysiology and treatment of depression. Discovery of rapid, although transient antidepressant effect of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist used in a single sub-anaesthetic intravenous dose in unipolar, bipolar and treatment-resistant patients provides evidence for a glutamatergic antidepressant. Subsequent studies confirmed this effect in repeated doses. Further research demonstrated that repeated ketamine infusions result in sustainable antidepressant effect with both, twice-weekly and thrice-weekly administration schedules. However, the worsening of depression may occur after infusions are completed. Given the risk of relapses, there is a definite need for the development of new strategies to maintain the beneficial effects of ketamine treatment. In the present study, the investigators aim to openly assess the safety, tolerability, and effectiveness of repeated, individually tailored IV, nasal spray and oral ketamine for treatment-resistant mood disorders. The investigators intend to explore questions regarding optimal dose, treatment frequency and duration.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Week
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Inpatients with TRD referred to the tertiary-reference unit for mood disorders
Key inclusion criteria (2 listed)
- Major depressive disorder (MDD) or bipolar disorder (BD) diagnosis as provided by DSM-5 criteria
- TRD defined as the patient does not reach remission within the 8 week trial of an antidepressant or combination at a therapeutic dose of at least two trials of first-line evidence-based treatments and/or electroconvulsive therapy (ECT)
Key exclusion criteria (4 listed)
- Pregnancy and lactation
- Hypersensitivity to ketamine
- Uncontrolled hypertension
- Other uncontrolled somatic diseases that may impact safety per investigators judgement
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineKetamine will be infused (slow IV infusions of ketamine (0.5 mg/kg) over 40 minutes) twice weekly over a period of 4 weeks) Ketamine will be given in intranasal spray twice weekly over a period of 4 weeks Ketamine will be given orally (solution 2.0mg/kg, 2.5mg/kg) twice weekly over a period of 4 weeks. | Drug | – |
Primary outcome
Incidence of adverse events assessed by Clinical-Administered Dissociative Symptoms Scale (CADSS)
Time frame: Baseline through week 5
Incidence of adverse events will be assessed by Clinician-Administered Dissociative Symptoms Scale (change from baseline to each measure). Higher values represent a worse severity, but not necessarily outcome. The Clinical-Administered Dissociative Symptoms Scale has 23-items based on dissociative symptoms during the assessment. Each item is scored 0 (normal) to 4 (severe symptoms) with overall score ranges from 0 (normal) to 92 (severe symptoms). Total number of assessments:18 times
Incidence of adverse events assessed by 4-items positive symptoms subscale of Brief Psychiatric Rating Scale (BPRS)
Time frame: Baseline through week 5
Incidence of adverse events will be assessed by 4-items positive symptoms subscale of Brief Psychiatric Rating Scale (change from baseline to each measure). Higher values represent a worse severity but not necessarily outcome. The 4-item positive symptoms subscale of Brief Psychiatric Rating Scale has 4-items based on conceptual disorganization, suspiciousness, hallucination and unusual thought content. Each item is scored 0 (normal) to 6 (severe symptoms) with overall score ranges from 0 (normal) to 24 (severe symptoms). Total number of assessments:18 times
Incidence of adverse events assessed by body temperature (oral measurements)
Time frame: Baseline through week 5
Incidence of adverse events assessed by body temperature (oral measurement) in Celsius degree - change from baseline to each measure. A normal range is from 36.2 to 38.0 Celsius degrees; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
Incidence of adverse events assessed by blood pressure
Time frame: Baseline through week 5
Incidence of adverse events assessed by blood pressure (after the participant has rested for at least 5 minutes) in mmHg - change from baseline to each measure. A normal range for systolic blood pressure is from 90 to 140 mmHg, for diastolic blood pressure is from 50 to 90 mmHg; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
Incidence of adverse events assessed by respiration rate
Time frame: Baseline through week 5
Incidence of adverse events assessed by respiration rate in a breath number per minute - change from baseline to each measure. A normal range for respiration is from 12 to 16 breaths per minute; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
Incidence of adverse events assessed by pulse
Time frame: Baseline through week 5
Incidence of adverse events assessed by pulse (beats per minute [bpm]) - change from baseline to each measure. A normal range for pulse is from 60 to 90 bpm; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
Incidence of adverse events assessed by blood oxygen saturation
Time frame: Baseline through week 5
Incidence of adverse events assessed by blood oxygen saturation in percentage - change from baseline to each measure. A normal range for blood oxygen saturation is from 95 to 100 percentage; measurements under 95% are clinically significant. The total number of measurements: 44 times
Incidence of adverse events assessed by weight
Time frame: Baseline and week 5
Incidence of adverse events assessed by weight in kilograms- change from baseline to each measure. Gain weight for 7% baseline weight is clinically significant. Total numbers of assessments: 2. Weight and height will be combined to report BMI in kg/m^2
Incidence of adverse events assessed by height
Time frame: Baseline
Incidence of adverse events assessed by height in meters. Total numbers of assessments: 1. Weight in kilograms and height in meters will be combined to report BMI in kg/m^2
1 secondary outcome
Change in severity of depression symptoms assessed by Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Baseline through week 5
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Derived from this study: PubMed 42159864Kwasny A, Wilkowska A, Pastuszak M, Pastuszak K, Cubala WJ. Treatment-emergent psychiatric adverse events in patient-reported outcomes during ketamine use for major depressive disorder: a retrospective analysis. Pharmacol Rep. 2026 Aug;78(4):1292-1300. doi: 10.1007/s43440-026-00867-1. Epub 2026 May 20.
- Derived from this study: PubMed 40879542Kachlik Z, Cubala WJ, Walaszek M, Pastuszak M, Pastuszak K, Kwasny A. Nonresponse to Ketamine in Treatment-Resistant Bipolar Depression. Neuropsychopharmacol Rep. 2025 Sep;45(3):e70038. doi: 10.1002/npr2.70038.
- Derived from this study: PubMed 34398056Wlodarczyk A, Cubala WJ, Galuszko-Wegielnik M, Szarmach J. Dissociative symptoms with intravenous ketamine in treatment-resistant depression exploratory observational study. Medicine (Baltimore). 2021 Jul 23;100(29):e26769. doi: 10.1097/MD.0000000000026769.
- Derived from this study: PubMed 34046159Wlodarczyk A, Cubala WJ, Galuszko-Wegielnik M, Szarmach J. Central nervous system-related safety and tolerability of add-on ketamine to antidepressant medication in treatment-resistant depression: focus on the unique safety profile of bipolar depression. Ther Adv Psychopharmacol. 2021 May 19;11:20451253211011021. doi: 10.1177/20451253211011021. eCollection 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Treatment Resistant Depression and Bipolar Depression, run by Medical University of Gdansk at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events assessed by Clinical-Administered Dissociative Symptoms Scale (CADSS) (time frame: Baseline through week 5). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04226963, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.