Music as an Intervention to Improve Hemodynamic Tolerability of Ketamine in Depression

NCT04701866 | Completed

• 1 other identifier: DOUGKMT01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the impact of music on patients receiving a course of intravenous (IV) ketamine for treatment-resistant depression (TRD), both unipolar and bipolar. The primary outcome is changes in in systolic blood pressure throughout each 40-minute infusion. Secondary outcomes include repeated measures of mood, anxiety, suicidality, and psychological/physical pain. Aspects of the treatment experience, with and without music, will also be explored.

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major; Unipolar Depression; Depression, Bipolar

Keywords

Treatment-Resistant Depression; Ketamine; Music; Hemodynamic Changes

Outcome Measures

Primary Outcomes (1)

• Changes in Systolic Blood Pressure

  For the primary outcome data analysis, we will adopt the generalized linear model (GLM) to investigate the change in systolic blood pressure (SBP) at 40 minutes versus at 0 minutes between intervention and control groups. Specifically, we treat the difference between the average of the triplicate SBP measurements (measured by a calibrated Welch Allyn Blood Pressure Device at 0 minutes and the average of the triplicate SBP measurements at 40 minutes at each infusion as the outcomes in the GLM, adjusting for covariates such as intervention, age and sex. The generalized estimating equation (GEE) technique is proposed to estimate the regression coefficients, and the corresponding variances are estimated by the sandwich estimators.

  From 0 to 40 minutes of each infusion.

Secondary Outcomes (25)

• Change From Baseline in MADRS Total Score to Last Treatment

  Baseline, Day 23

• Change From Baseline in MADRS Total Score to Follow-up

  Baseline, 1-month follow-up (8 weeks)

• Change From Baseline in Beck Depression Inventory (BDI-II) Total Score to Last Treatment

  Baseline, Day 23

• Change From Baseline in Beck Depression Inventory (BDI-II) Total Score to Follow-up

  Baseline, 1-month follow-up (8 weeks)

• Change From Baseline in Clinician-Rated Global Impression Improvement Score to Last Treatment

  Baseline, Day 23

Study Arms (2)

Music

EXPERIMENTAL

Music will be provided for participant's six 40 minute IV infusions of 0.5mg/kg ketamine administered over four weeks (biweekly for 2 weeks, then weekly for 2 weeks).

Other: Music

Usual Care

NO INTERVENTION

Participant's six 40 minute IV infusions of 0.5mg/kg ketamine administered over four weeks (biweekly for 2 weeks, then weekly for 2 weeks) will be administered as per usual care. That is, without music provided or permitted. Contact time with clinicians before, during, and after ketamine treatments will be matched.

Interventions

Music OTHER

Music will be provided via headphones during all 6 ketamine treatments, beginning at the commencement of each infusion and ending 55 minutes later. On the day of each infusion, before the treatment begins, clinicians will discuss music choices with participants in order to select amongst one of several options that have been designed for this purpose (length, genre, intensity, etc.).

Music

Eligibility Criteria

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

You may qualify if:

• Bipolar and unipolar depressive episode, current episode of depression (DSM-V) despite at least two adequate trials of Level 1-evidence psychiatric medications.
• No active substance use disorder (beyond nicotine use disorder);
• No contraindication of ketamine;
• Not of childbearing potential, defined as: Postmenopausal (defined as no menses for 12 months without an alternative medical cause). A high follicle stimulating hormone (FSH) level (\>40 IU/L or mIU/mL in the postmenopausal range) will be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy, however in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient;
• Permanently sterile: permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy.
• Female subjects of childbearing potential must have a negative urine pregnancy test at the beginning and be willing to use a highly effective method of contraception during the treatment and after the last ketamine infusion.
• Female subjects of childbearing potential must practice a highly effective method of contraception (failure rate of \<1percent per year when used consistently and correctly) beginning at least two weeks before and continued while receiving ketamine infusions;
• Male subjects who are sexually active with a woman of childbearing potential must agree to use a double-barrier method of contraception (eg, diaphragm or cervical/vault caps plus condom with spermicidal foam/gel/film/cream/suppository).
• Male subjects who are sexually active with a woman who is pregnant must agree to use a condom. Male subjects must also agree to not donate sperm during the treatment and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of ketamine;
• Abstention from consuming grapefruit juice (a potent 3A4 cytochrome inhibitor) on the day of the ketamine infusions as it may alter the metabolism of ketamine;
• Provision of written informed consent after reading the participant information handout;

You may not qualify if:

• Baseline blood pressure within normal limits, i.e. below 140/90 mmHg, when measured thrice in a quiet room.
• Significant hearing impairment not improved with hearing aids and/or sound amplification or unwillingness to listen to music during treatment;
• The subject's depressive symptoms have previously demonstrated non-response to esketamine or ketamine in the current major depressive episode;
• Known intellectual deficiency or autism spectrum disorder;
• Unable to accommodate regular visits to the Depressive Disorders Program at the Douglas Mental Health University Institute, Montreal, QC;
• Depression evaluated as secondary to stroke, cancer or other severe medical illnesses;
• Known risk factors for intracranial hemorrhage, including previous significant trauma, known aneurysm, or previous neurosurgery;
• Evidence of clinically relevant disease, e.g., renal or hepatic impairment, significant coronary artery disease (myocardial infarct within a year prior to initial randomization), cerebrovascular disease, viral hepatitis B or C, acquired immunodeficiency syndrome;
• A positive toxicology screen for drugs that are not prescribed;
• Unwilling, or unable to receive treating physician's agreement, or unable to hold benzodiazepines from the evening prior to the infusion of ketamine;
• Unwilling, or unable to receive treating physician's agreement, to discontinue any narcotic beginning a minimum of 5 drug half-lives prior to infusion;
• Unwilling, or unable to receive treating physician's agreement, to discontinue memantine (an NMDA antagonist) during infusions, beginning a minimum of 5 drug half-lives prior to infusions;
• Pregnant, lactating, or of childbearing potential and not willing to use an approved method of contraception during the ketamine infusion, as per above;
• A clinical finding that is unstable or that, in the opinion of the treating clinician(s), would be negatively affected by, or would affect, the medication (e.g., diabetes mellitus, unstable angina);
• Liver function tests AST and ALT three times the upper normal limit at screening.

Sponsors & Collaborators

• Douglas Mental Health University Institute: lead
• Réseau québécois sur le suicide, les troubles de l'humeur et les troubles associés: collaborator

Study Sites (2)

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Douglas Mental Health University Institute

Montreal, Quebec, H4H 1R3, Canada

Location

Related Publications (25)

• Weinberger AH, Gbedemah M, Martinez AM, Nash D, Galea S, Goodwin RD. Trends in depression prevalence in the USA from 2005 to 2015: widening disparities in vulnerable groups. Psychol Med. 2018 Jun;48(8):1308-1315. doi: 10.1017/S0033291717002781. Epub 2017 Oct 12.

  PMID: 29021005 BACKGROUND

• Demyttenaere K, Van Duppen Z. The Impact of (the Concept of) Treatment-Resistant Depression: An Opinion Review. Int J Neuropsychopharmacol. 2019 Feb 1;22(2):85-92. doi: 10.1093/ijnp/pyy052.

  PMID: 29961822 BACKGROUND

• Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. Lancet. 2013 May 11;381(9878):1672-82. doi: 10.1016/S0140-6736(13)60857-0.

  PMID: 23663953 BACKGROUND

• Pompili M, Gonda X, Serafini G, Innamorati M, Sher L, Amore M, Rihmer Z, Girardi P. Epidemiology of suicide in bipolar disorders: a systematic review of the literature. Bipolar Disord. 2013 Aug;15(5):457-90. doi: 10.1111/bdi.12087. Epub 2013 Jun 12.

  PMID: 23755739 BACKGROUND

• Grady SE, Marsh TA, Tenhouse A, Klein K. Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature. Ment Health Clin. 2018 Mar 23;7(1):16-23. doi: 10.9740/mhc.2017.01.016. eCollection 2017 Jan.

  PMID: 29955493 BACKGROUND

• Fukumoto K, Fogaca MV, Liu RJ, Duman C, Kato T, Li XY, Duman RS. Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine. Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):297-302. doi: 10.1073/pnas.1814709116. Epub 2018 Dec 17.

  PMID: 30559184 BACKGROUND

• De Kock M, Loix S, Lavand'homme P. Ketamine and peripheral inflammation. CNS Neurosci Ther. 2013 Jun;19(6):403-10. doi: 10.1111/cns.12104. Epub 2013 Apr 10.

  PMID: 23574634 BACKGROUND

• Chen MH, Li CT, Lin WC, Hong CJ, Tu PC, Bai YM, Cheng CM, Su TP. Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: A randomized, double-blind control study. Psychiatry Res. 2018 Nov;269:207-211. doi: 10.1016/j.psychres.2018.08.078. Epub 2018 Aug 21.

  PMID: 30153598 BACKGROUND

• Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.

  PMID: 25271445 BACKGROUND

• van Schalkwyk GI, Wilkinson ST, Davidson L, Silverman WK, Sanacora G. Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: Analysis of the Clinician Administered Dissociative State Scale. J Affect Disord. 2018 Feb;227:11-16. doi: 10.1016/j.jad.2017.09.023. Epub 2017 Sep 28.

  PMID: 29045915 BACKGROUND

• Conrad C, Niess H, Jauch KW, Bruns CJ, Hartl W, Welker L. Overture for growth hormone: requiem for interleukin-6? Crit Care Med. 2007 Dec;35(12):2709-13. doi: 10.1097/01.ccm.0000291648.99043.b9.

  PMID: 18074473 BACKGROUND

• Wiwatwongwana D, Vichitvejpaisal P, Thaikruea L, Klaphajone J, Tantong A, Wiwatwongwana A; Medscape. The effect of music with and without binaural beat audio on operative anxiety in patients undergoing cataract surgery: a randomized controlled trial. Eye (Lond). 2016 Nov;30(11):1407-1414. doi: 10.1038/eye.2016.160. Epub 2016 Oct 14.

  PMID: 27740618 BACKGROUND

• Merakou K, Varouxi G, Barbouni A, Antoniadou E, Karageorgos G, Theodoridis D, Koutsouri A, Kourea-Kremastinou J. Blood Pressure and Heart Rate Alterations through Music in Patients Undergoing Cataract Surgery in Greece. Ophthalmol Eye Dis. 2015 Jun 11;7:7-12. doi: 10.4137/OED.S20960. eCollection 2015.

  PMID: 26106264 BACKGROUND

• Bradt J, Dileo C. Music interventions for mechanically ventilated patients. Cochrane Database Syst Rev. 2014;2014(12):CD006902. doi: 10.1002/14651858.CD006902.pub3. Epub 2014 Dec 9.

  PMID: 25490233 BACKGROUND

• Metcalf CS, Huntsman M, Garcia G, Kochanski AK, Chikinda M, Watanabe E, Underwood T, Vanegas F, Smith MD, White HS, Bulaj G. Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs. Front Neurol. 2019 Mar 27;10:277. doi: 10.3389/fneur.2019.00277. eCollection 2019.

  PMID: 30972009 BACKGROUND

• Kaelen M, Barrett FS, Roseman L, Lorenz R, Family N, Bolstridge M, Curran HV, Feilding A, Nutt DJ, Carhart-Harris RL. LSD enhances the emotional response to music. Psychopharmacology (Berl). 2015 Oct;232(19):3607-14. doi: 10.1007/s00213-015-4014-y. Epub 2015 Aug 11.

  PMID: 26257162 BACKGROUND

• Kaelen M, Giribaldi B, Raine J, Evans L, Timmermann C, Rodriguez N, Roseman L, Feilding A, Nutt D, Carhart-Harris R. Correction to: The hidden therapist: evidence for a central role of music in psychedelic therapy. Psychopharmacology (Berl). 2018 May;235(5):1623. doi: 10.1007/s00213-018-4886-8.

  PMID: 29582103 BACKGROUND

• Fries GR, Walss-Bass C, Bauer ME, Teixeira AL. Revisiting inflammation in bipolar disorder. Pharmacol Biochem Behav. 2019 Feb;177:12-19. doi: 10.1016/j.pbb.2018.12.006. Epub 2018 Dec 24.

  PMID: 30586559 BACKGROUND

• Dakwar E, Anerella C, Hart CL, Levin FR, Mathew SJ, Nunes EV. Therapeutic infusions of ketamine: do the psychoactive effects matter? Drug Alcohol Depend. 2014 Mar 1;136:153-7. doi: 10.1016/j.drugalcdep.2013.12.019. Epub 2014 Jan 15.

  PMID: 24480515 BACKGROUND

• Niciu MJ, Shovestul BJ, Jaso BA, Farmer C, Luckenbaugh DA, Brutsche NE, Park LT, Ballard ED, Zarate CA Jr. Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression. J Affect Disord. 2018 May;232:310-315. doi: 10.1016/j.jad.2018.02.049. Epub 2018 Feb 17.

  PMID: 29501990 BACKGROUND

• Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Bond DJ, Frey BN, Sharma V, Goldstein BI, Rej S, Beaulieu S, Alda M, MacQueen G, Milev RV, Ravindran A, O'Donovan C, McIntosh D, Lam RW, Vazquez G, Kapczinski F, McIntyre RS, Kozicky J, Kanba S, Lafer B, Suppes T, Calabrese JR, Vieta E, Malhi G, Post RM, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018 Mar;20(2):97-170. doi: 10.1111/bdi.12609. Epub 2018 Mar 14.

  PMID: 29536616 BACKGROUND

• Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, Aan Het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Jun;71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62.

  PMID: 24740528 BACKGROUND

• Glue P, Neehoff S, Sabadel A, Broughton L, Le Nedelec M, Shadli S, McNaughton N, Medlicott NJ. Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study. J Psychopharmacol. 2020 Mar;34(3):267-272. doi: 10.1177/0269881119874457. Epub 2019 Sep 17.

  PMID: 31526207 BACKGROUND

• Greenway KT, Garel N, Dinh-Williams LL, Beaulieu S, Turecki G, Rej S, Richard-Devantoy S. Music as an Intervention to Improve the Hemodynamic Response of Ketamine in Depression: A Randomized Clinical Trial. JAMA Netw Open. 2024 Feb 5;7(2):e2354719. doi: 10.1001/jamanetworkopen.2023.54719.

  PMID: 38315489 DERIVED

• Garel N, Thibault Levesque J, Sandra DA, Lessard-Wajcer J, Solomonova E, Lifshitz M, Richard-Devantoy S, Greenway KT. Imprinting: expanding the extra-pharmacological model of psychedelic drug action to incorporate delayed influences of sets and settings. Front Hum Neurosci. 2023 Jul 18;17:1200393. doi: 10.3389/fnhum.2023.1200393. eCollection 2023.

  PMID: 37533588 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major; Depressive Disorder; Bipolar Disorder

Interventions

Music Therapy

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Sensory Art Therapies; Complementary Therapies; Therapeutics; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Stéphane Richard-Devantoy, MD, PhD

  Douglas Mental Health University Insitute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The primary investigator and outcome assessors will be masked throughout the trial. Participants and clinicians administering the ketamine treatments will not be masked, given the nature of the music intervention.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 8, 2021
• Study Start: January 11, 2021
• Primary Completion: August 24, 2022
• Study Completion: August 24, 2022
• Last Updated: October 4, 2022

Record last verified: 2022-10

Locations

CA (2)