A Naturalistic Study of Ketamine for Treatment Resistant Mood Disorders (GDKet)

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.

Study Overview

• Status: Completed
• Conditions: Bipolar Depression; Major Depressive Disorder; Treatment Resistant Depression; Ketamine
• Intervention / Treatment: Drug: Ketamine

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 Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Poland
  • Gdańsk, Poland, 80-952
    • Department of Psychiatry, Medical University of Gdańsk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Inpatients with TRD referred to the tertiary-reference unit for mood disorders

Description

Inclusion Criteria:

1. Major depressive disorder (MDD) or bipolar disorder (BD) diagnosis as provided by DSM-5 criteria
2. 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)

Exclusion Criteria:

1. Pregnancy and lactation
2. Hypersensitivity to ketamine
3. Uncontrolled hypertension
4. Other uncontrolled somatic diseases that may impact safety per investigators judgement

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	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	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	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	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	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	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline through week 5

Collaborators and Investigators

• Sponsor: Medical University of Gdansk

Publications and helpful links

General Publications

• Wlodarczyk 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.
• Wlodarczyk 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2019
• Primary Completion (Actual): July 4, 2022
• Study Completion (Actual): July 4, 2022

Study Registration Dates

• First Submitted: January 2, 2020
• First Submitted That Met QC Criteria: January 10, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: major depressive disorder; ketamine; bipolar depression; treatment resistant depression; multiple series
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Bipolar Disorder; Mood Disorders; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: NKBBN/172-674/2019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No