Neurorestorative Effects of Electroconvulsive Therapy (ECT) in Patients With Severe Late Life Depression

NCT02667353 | Completed DMC

• 1 other identifier: S53144
• Study Type: interventional
• Target: 110
• Locations: 0 countries
• Sites: N/A

Brief Summary

To study the potential neurorestorative effects of electroconvulsive therapy (ECT) in depressed patients by measuring brain derived neurotrophic factor (BDNF) serum levels and hippocampal volumes in severely depressed patients receiving ECT.

Conditions

Depression

Keywords

electroconvulsive; hippocampus; elderly; working mechanism

Outcome Measures

Primary Outcomes (3)

• change in hippocampal volume as assessed by manual delineation following an initial automatic segmentation

  Hippocampal volumes were normalized using the following equation: normalised hippocampal volume = original hippocampal volume - linear regression coefficient x (total intracranial volume - mean total intracranial volume). The coefficient was derived from a linear regression of total intracranial volume and original hippocampal volume. Total intracranial volume was obtained from an automated segmentation of grey matter, white matter and cerebrospinal fluid. Intra-rater reliability was determined using randomly selected scans segmented at two time-points at least one month apart. The intra-class correlation coefficient (Cronbach's alfa) was 0.96 for the left hippocampus and 0.95 for the right hippocampus.

  6 months

• change in brain derived neurotrophic factor as assessed by the Emax Immuno Assay system

  Blood samples were taken between 07:30 am and 09:30 am after an overnight fast. Serum was immediately separated and stored at -85 °celcius until assayed. BDNF protein levels were measured using the Emax Immuno Assay system from Promega according to the manufacturer's protocol (Madison, United States of America), in one laboratory (Maastricht University). Undiluted serum was acid treated as this reliably increased the detectable BDNF in a dilution-dependent way. Greiner Bio-One high affinity 96-well plates were used. Serum samples were diluted 100 times, and the absorbency was read in duplicate using a Bio-Rad (Hercules, United States of America) Benchmark microplate reader at 450 nm.

  4 weeks

• change of mood as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS)

  The MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The questionnaire includes questions on the following symptoms: apparent sadness; reported sadness; inner tension; reduced sleep; reduced appetite; concentration difficulties; lassitude; inability to feel; pessimistic thoughts; suicidal thoughts.

  up to 1 year

Secondary Outcomes (2)

• change of cognition as assessed by the mini mental state examination

  up to 1 year

• change of psychomotor symptoms as assessed by the CORE (not an acronym)

  up to 1 year

Study Arms (1)

electroconvulsive therapy

OTHER

only one arm in this study: patients who are treated with electroconvulsive therapy and have been given anesthesia with etomidate and succinylcholine

Procedure: ECT; Drug: Etomidate; Drug: Succinylcholine

Interventions

ECT PROCEDURE

ECT was administered twice a week with a constant-current brief-pulse device (Thymatron, System IV). Motor and electroencephalographic seizures were monitored to ensure adequate duration and quality. Subjects were all treated with right unilateral (RUL) ECT with stimulus intensity 6 times the initial seizure threshold (ST), as determined by empirical dose titration at the first treatment, until remission (Montgomery-Åsberg Depression Rating Scale (MADRS) (27) \< 10 in two consecutive ratings with a week interval). Subjects who failed to respond right unilateral ECT after the sixth treatment were switched to bitemporal ECT (1.5x seizure threshold).

Also known as: electroconvulsive therapy

electroconvulsive therapy

Etomidate DRUG

Anesthesia was achieved with intravenous administration of etomidate (0.2mg/kg).

Also known as: anesthetic

electroconvulsive therapy

Succinylcholine DRUG

Anesthesia was achieved with intravenous administration of succinylcholine (1mg/kg).

Also known as: muscle relaxant

electroconvulsive therapy

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are considered suitable after they were diagnosed as having severe depression according to Diagnostic and Statistical Manual IV (DSM-IV criteria) and were above 55 years of age.

You may not qualify if:

• another major psychiatric illness, (a history of) a major neurological illness (including Parkinson's disease, stroke, and dementia) and metal implants precluding Magnetic Resonance Imaging (MRI).
• Subjects were included at the University Psychiatric Center Katholieke Universiteit Leuven (KU Leuven), Belgium and Geestelijke Gezondheidszorg in Geest (GGZinGeest), Amsterdam, the Netherlands. The project is part of the project Mood Disorders in Elderly and Electroconvulsive therapy (MODECT).

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• VU University of Amsterdam: collaborator

Related Publications (20)

• Bolwig TG. How does electroconvulsive therapy work? Theories on its mechanism. Can J Psychiatry. 2011 Jan;56(1):13-8. doi: 10.1177/070674371105600104.

  PMID: 21324238 BACKGROUND

• Bocchio-Chiavetto L, Zanardini R, Bortolomasi M, Abate M, Segala M, Giacopuzzi M, Riva MA, Marchina E, Pasqualetti P, Perez J, Gennarelli M. Electroconvulsive Therapy (ECT) increases serum Brain Derived Neurotrophic Factor (BDNF) in drug resistant depressed patients. Eur Neuropsychopharmacol. 2006 Dec;16(8):620-4. doi: 10.1016/j.euroneuro.2006.04.010. Epub 2006 Jun 6.

  PMID: 16757154 BACKGROUND

• Bolwig TG, Madsen TM. Electroconvulsive therapy in melancholia: the role of hippocampal neurogenesis. Acta Psychiatr Scand Suppl. 2007;(433):130-5. doi: 10.1111/j.1600-0447.2007.00971.x.

  PMID: 17280579 BACKGROUND

• Chen AC, Shin KH, Duman RS, Sanacora G. ECS-Induced mossy fiber sprouting and BDNF expression are attenuated by ketamine pretreatment. J ECT. 2001 Mar;17(1):27-32. doi: 10.1097/00124509-200103000-00006.

  PMID: 11281511 BACKGROUND

• Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006 Jun 15;59(12):1116-27. doi: 10.1016/j.biopsych.2006.02.013. Epub 2006 Apr 21.

  PMID: 16631126 BACKGROUND

• Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003 Jan 24;112(2):257-69. doi: 10.1016/s0092-8674(03)00035-7.

  PMID: 12553913 BACKGROUND

• Fisman M, Rabheru K, Hegele RA, Sharma V, Fisman D, Doering M, Appell J. Apolipoprotein E polymorphism and response to electroconvulsive therapy. J ECT. 2001 Mar;17(1):11-4. doi: 10.1097/00124509-200103000-00003.

  PMID: 11281508 BACKGROUND

• Marano CM, Phatak P, Vemulapalli UR, Sasan A, Nalbandyan MR, Ramanujam S, Soekadar S, Demosthenous M, Regenold WT. Increased plasma concentration of brain-derived neurotrophic factor with electroconvulsive therapy: a pilot study in patients with major depression. J Clin Psychiatry. 2007 Apr;68(4):512-7. doi: 10.4088/jcp.v68n0404.

  PMID: 17474805 BACKGROUND

• Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382.

  PMID: 444788 BACKGROUND

• Newton SS, Collier EF, Hunsberger J, Adams D, Terwilliger R, Selvanayagam E, Duman RS. Gene profile of electroconvulsive seizures: induction of neurotrophic and angiogenic factors. J Neurosci. 2003 Nov 26;23(34):10841-51. doi: 10.1523/JNEUROSCI.23-34-10841.2003.

  PMID: 14645477 BACKGROUND

• Nordanskog P, Dahlstrand U, Larsson MR, Larsson EM, Knutsson L, Johanson A. Increase in hippocampal volume after electroconvulsive therapy in patients with depression: a volumetric magnetic resonance imaging study. J ECT. 2010 Mar;26(1):62-7. doi: 10.1097/YCT.0b013e3181a95da8.

  PMID: 20190603 BACKGROUND

• Oudega ML, van Exel E, Wattjes MP, Comijs HC, Scheltens P, Barkhof F, Eikelenboom P, de Craen AJ, Beekman AT, Stek ML. White matter hyperintensities, medial temporal lobe atrophy, cortical atrophy, and response to electroconvulsive therapy in severely depressed elderly patients. J Clin Psychiatry. 2011 Jan;72(1):104-12. doi: 10.4088/JCP.08m04989blu. Epub 2010 Aug 24.

  PMID: 20816035 BACKGROUND

• Sapolsky RM. Depression, antidepressants, and the shrinking hippocampus. Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12320-2. doi: 10.1073/pnas.231475998. No abstract available.

  PMID: 11675480 BACKGROUND

• Segi-Nishida E, Warner-Schmidt JL, Duman RS. Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11352-7. doi: 10.1073/pnas.0710858105. Epub 2008 Aug 5.

  PMID: 18682560 BACKGROUND

• Steffens DC, Byrum CE, McQuoid DR, Greenberg DL, Payne ME, Blitchington TF, MacFall JR, Krishnan KR. Hippocampal volume in geriatric depression. Biol Psychiatry. 2000 Aug 15;48(4):301-9. doi: 10.1016/s0006-3223(00)00829-5.

  PMID: 10960161 BACKGROUND

• UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet. 2003 Mar 8;361(9360):799-808. doi: 10.1016/S0140-6736(03)12705-5.

  PMID: 12642045 BACKGROUND

• Vaidya VA, Siuciak JA, Du F, Duman RS. Hippocampal mossy fiber sprouting induced by chronic electroconvulsive seizures. Neuroscience. 1999 Mar;89(1):157-66. doi: 10.1016/s0306-4522(98)00289-9.

  PMID: 10051225 BACKGROUND

• Wagenmakers MJ, Oudega ML, Klaus F, Wing D, Orav G, Han LKM, Binnewies J, Beekman ATF, Veltman DJ, Rhebergen D, van Exel E, Eyler LT, Dols A. BrainAge of patients with severe late-life depression referred for electroconvulsive therapy. J Affect Disord. 2023 Jun 1;330:1-6. doi: 10.1016/j.jad.2023.02.047. Epub 2023 Feb 27.

  PMID: 36858270 DERIVED

• Wagenmakers MJ, Oudega ML, Bouckaert F, Rhebergen D, Beekman ATF, Veltman DJ, Sienaert P, van Exel E, Dols A. Remission Rates Following Electroconvulsive Therapy and Relation to Index Episode Duration in Patients With Psychotic Versus Nonpsychotic Late-Life Depression. J Clin Psychiatry. 2022 Aug 10;83(5):21m14287. doi: 10.4088/JCP.21m14287.

  PMID: 35950901 DERIVED

• Carlier A, Rhebergen D, Veerhuis R, Schouws S, Oudega ML, Eikelenboom P, Bouckaert F, Sienaert P, Obbels J, Stek ML, van Exel E, Dols A. Inflammation and Cognitive Functioning in Depressed Older Adults Treated With Electroconvulsive Therapy: A Prospective Cohort Study. J Clin Psychiatry. 2021 Aug 10;82(5):20m13631. doi: 10.4088/JCP.20m13631.

  PMID: 34383393 DERIVED

MeSH Terms

Conditions

Depression

Interventions

Electroconvulsive Therapy; Etomidate; Anesthetics; Succinylcholine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Choline; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Succinates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Onium Compounds

Study Officials

• Mathieu Vandenbulcke, MD PhD

  Universitaire Ziekenhuizen KU Leuven

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2016
• First Posted: January 28, 2016
• Study Start: June 1, 2011
• Primary Completion: June 1, 2014
• Study Completion: December 1, 2015
• Last Updated: January 28, 2016

Record last verified: 2016-01