Clinical trial NCT04226963: A Naturalistic Study of Ketamine for Treatment Resistant Mood Disorders
Official title: A Naturalistic Study of Ketamine for Treatment Resistant Mood Disorders: Gdansk Depression Ketamine Project
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Treatment Resistant Depression
Bipolar Depression
Ketamine
Major Depressive Disorder
Keywords: treatment resistant depression
bipolar depression
ketamine
multiple series
major depressive disorder
Lead sponsor: Medical University of Gdansk
Sponsor class: OTHER
First posted: 2020-01-13
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Inpatients with TRD referred to the tertiary-reference unit for mood disorders

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events assessed by Clinical-Administered Dissociative Symptoms Scale (CADSS)
timeFrame: Baseline through week 5
measure: Incidence of adverse events assessed by 4-items positive symptoms subscale of Brief Psychiatric Rating Scale (BPRS)
timeFrame: Baseline through week 5
measure: Incidence of adverse events assessed by body temperature (oral measurements)
timeFrame: Baseline through week 5
measure: Incidence of adverse events assessed by blood pressure
timeFrame: Baseline through week 5
measure: Incidence of adverse events assessed by respiration rate
timeFrame: Baseline through week 5
measure: Incidence of adverse events assessed by pulse
timeFrame: Baseline through week 5
measure: Incidence of adverse events assessed by blood oxygen saturation
timeFrame: Baseline through week 5
measure: Incidence of adverse events assessed by weight
timeFrame: Baseline and week 5
measure: Incidence of adverse events assessed by height
timeFrame: Baseline
Secondary outcomes:
measure: Change in severity of depression symptoms assessed by Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Baseline through week 5
Other outcomes:
Locations:
city: Gdańsk
country: Poland
facility: Department of Psychiatry, Medical University of Gdańsk
Study officials:
References:
citation: 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.
citation: 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.