Continuation Electroconvulsive Therapy (C-ECT) for Relapse Prevention in Major Depression

Continuation Electroconvulsive Therapy Associated With Pharmacotherapy Versus Pharmacotherapy Alone for Relapse Prevention in Major Depression. A Clinical, Controlled, Prospective and Randomized Trial

OBJECTIVES:

To evaluate the comparative efficacy and security of Continuation Electroconvulsive Therapy associated with pharmacotherapy versus pharmacotherapy alone in the prevention of depressive relapse.

METHODS:

Demographic and clinical variables will be collected and side effects scales and neurocognitive battery will be performed. Variables of efficacy: relapse percentage in both groups in one year (primary variable); time without relapse. Main variable of security: occurrence of side effects and neurocognitive performance.

DESIGN: Randomized controlled clinical trial.

SAMPLE:

104 outpatients diagnosed with unipolar depression (DSM-IV-R criteria) who had remitted with a course of bilateral ECT. They will be randomized to two groups of treatment.

SETTING: Psychiatry Department at Bellvitge University Hospital.

ANALYSIS: Descriptive analysis of clinical variables; survive analysis and Cox model of regression.

Study Overview

• Status: Terminated
• Conditions: Depression
• Intervention / Treatment: Device: C-ECT; Drug: PHARMACOTHERAPY

Detailed Description

Major Depressive Disorder (MDD) is a severe psychiatric disorder that affects more than 6 million people in our country and has a life prevalence of 8.9% for men and 16. 5% for women (Haro et al, 2007). Besides, in recent decades, its incidence is increasing (Kessler et al, 2004). MDD has high recurrence rates and 25% of the cases develop chronification. Moreover it can occur at any age leading to severe disability. The majority of studies published in this field demonstrated the efficacy of antidepressant treatment in a short or medium-term basis, but there is a lack of long-term clinical trials regarding antidepressant efficacy and published ones present methodological problems. At present, a line of fundamental research in therapeutics includes pragmatic studies because they can answer crucial and specific questions in clinical practice. Therefore, the aim of this project is to conduct a pragmatic, parallel, randomized trial with 2 treatment arms to answer a key question of great interest to psychiatrists: Is it more effective to extend the use of ECT as maintenance therapy (together with drug therapy) rather than just using drug therapy in patients that previously required an acute ECT course for a depressive episode? This study is a controlled randomized clinical trial that starts after the remission of the acute depressive episode. Once patients have clinically remitted they will be randomized in two groups:

1. C-ECT together with pharmacotherapy (same treatment used in the acute episode).
2. Maintenance pharmacotherapy treatment (same treatment used in the acute episode).

Consolidation treatment with ECT will be considered finished after 9 months of being started, at which time patients will stay only on the pharmacological treatment they already had. The study will be completed within 15 months of patient inclusion (six months after the end of C-ECT). Patient assessment and follow-up will be conducted by participant researchers. Blind rater will conduct clinical and adverse effects ratings. A neuropsychologist will conduct neuropsychological assessments.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge, IDIBELL
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• MDD diagnosis by DSM IV-TR.
• ECT requirement during acute episode. Therapeutic indication will be based on clinical criteria, following APA guidelines. During the acute episode, patients will be controlled by the usual clinical care team.
• Complete clinical remission (HDRS < or = 7 across two weeks).
• Appropriate intellectual level that allows adequate communication.
• Women of childbearing potential must use contraceptive methods.
• Signed Consent form.
• Other axis I or II diagnosis by DSM-IV-TR, except for nicotine dependence.
• To be in maintenance ECT program.
• To receive ECT during the previous three months of the acute episode.
• Pregnancy or breastfeeding.

Exclusion Criteria:

• Other axis I or II diagnosis by DSM-IV-TR, except for nicotine dependence.
• To be in maintenance ECT program.
• To receive ECT during the previous three months of the acute episode.
• Pregnancy or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: C-ECT and Pharmacotherapy; Consolidation treatment with ECT will be considered finished after 9 months of being started, at which time patients will stay only on the pharmacological treatment they already had. The study will be completed within 15 months of patient inclusion (six months after the end of C-ECT). Patient assessment and follow-up will be conducted by participant researchers. Blind rater will conduct clinical and adverse effects ratings. A neuropsychologist will conduct neuropsychological assessments.	Device: C-ECT; C-ECT will be administered through a Thrymatron System IV device (Somatics, LLC, ISO 13485:2003). Electrode placement will be bilateral and energy administered during consolidation treatment will be same used in the acute episode. C-ECT will be given weekly for the first month, fortnightly for the following two months and monthly during the next 6 months. A total of 14 C-ECT sessions will be given over 9 months of treatment. Pharmacotherapy will remain unchanged since the acute episode to the end of the study. Drugs will be obtained as usually from the National Health System and will be prescribed according to data sheet and it will have a duration of 15 months.; Other Names: Thrymatron System IV device (Somatics, LLC, ISO 13485:2003).; Pharmacotherapy:; Antidepressants:; - Venlafaxine 75-225 mg/d. N06AX16; - Duloxetine 60-120 mg/d. N06AX21; - Imipramine 100-300 mg/d. N06AA02; - Clomipramine 75-225 mg/d. N06AA04; - Nortriptyline 75-200 mg/d. 906AA10; - Sertraline 50-200 mg/d. N06AB06; -Fluoxetine 20-40 mg/d. N06AB03; - Citalopram 20-60 mg/d. N06AB04; - Paroxetine 20-40 mg/d. N06AB05; - Escitalopram 10-20 mg/d. N06AB10; - Mirtazapine 15-45 mg/d. N06AX11; - Mianserin 10-60 mg/d. 906AX03; - Trazadone 50-200 mg/d. 906AX05; - Reboxetin 2-12 mg/d. N06AX18; Antipsychotic drugs; - Olanzapine 2'5-20 mg/d. N05AH03; - Risperidone 0'5-9 mg/d. N05AX08; - Quetiapine 50-600 mg/d. N05AH04; - Aripiprazole 5-30 mg/d. N05AX12; Lithium: 200-1200 mg/d. 905AN01; Anxyiolitics:; - Diazepam 2'5-50 mg/d. N05BA01; - Clorazepate 5-50 mg/d. N05BA05; - Lorazepam 1-10 mg/d. N05BA06
ACTIVE_COMPARATOR: Pharmacotherapy; Pharmacotherapy will remain unchanged since the acute episode to the end of the study. Psychotropics will be obtained as usually from the National Health System and will be prescribed according to data sheet.	Drug: PHARMACOTHERAPY; Pharmacotherapy will remain unchanged since the acute episode to the end of the study. Psychotropics will be obtained as usually from the National Health System and will be prescribed according to data sheet and will have a 15 month duration.; Other Names: Pharmacotherapy:; Antidepressants:; - Venlafaxine 75-225 mg/d. N06AX16; - Duloxetine 60-120 mg/d. N06AX21; - Imipramine 100-300 mg/d. N06AA02; - Clomipramine 75-225 mg/d. N06AA04; - Nortriptyline 75-200 mg/d. 906AA10; - Sertraline 50-200 mg/d. N06AB06; -Fluoxetine 20-40 mg/d. N06AB03; - Citalopram 20-60 mg/d. N06AB04; - Paroxetine 20-40 mg/d. N06AB05; - Escitalopram 10-20 mg/d. N06AB10; - Mirtazapine 15-45 mg/d. N06AX11; - Mianserin 10-60 mg/d. 906AX03; - Trazadone 50-200 mg/d. 906AX05; - Reboxetin 2-12 mg/d. N06AX18; Antipsychotic drugs; - Olanzapine 2'5-20 mg/d. N05AH03; - Risperidone 0'5-9 mg/d. N05AX08; - Quetiapine 50-600 mg/d. N05AH04; - Aripiprazole 5-30 mg/d. N05AX12; Lithium: 200-1200 mg/d. 905AN01; Anxyiolitics:; - Diazepam 2'5-50 mg/d. N05BA01; - Clorazepate 5-50 mg/d. N05BA05; - Lorazepam 1-10 mg/d. N05BA06

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale 21 items (HDRS-21)	HDRS-21 will measure the relapse year in each group. Relapse will be defined as the reappearance of relevant symptoms after resolutin of the acute episode, measured by a scoring in HDRS-21 between 15-17 over two following measures or a HDRS>18 score in a single measure.	One year. HDRS will be assessed in each follow-up visit (weekly the first month, fortnightly the second and third month, monthly the following 6 months and quarterly at 12 and 15 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-Mental State Examination (MMSE 35)	Assessment of general cognitive status.	Basal, at 8 months and 12 months
UKU - Adverse effects rating scales	Qualitiative measure of side effects in each treatment group.	Every assessment (weekly, fortnightly, monthly and quarterly) till the month 15 of the follow-up.
Demographical Data Memory (MEDABI-20)	Descriptive measure of cogntive status.	Basal, at 8 months and 12 months
Rey Figure	Measure of visual perception, concentration and memory.	Basal, at 8 months and 12 months
Trail Making Test A	Measure of attention and cognitive flexibility.	Basal, at 8 months and 12 months
Trail Making Test B	Measure of attention and cognitive flexibility.	Basal, at 8 months and 12 months
Stroop Test	Measure of selective attention, cognitive flexibility and processing speed as well as executive function.	Basal, at 8 months and 12 months
Direct and inverse digits (WAIS, Weschler Adults Intelligence Sacle).	Measure of general intelligence and attention	Basal
Vocabulary WAIS (Weschler Adults Intelligence Scale)	Measure of general intelligence	Basal
Frequency Hospitalization Quotient	Measure of number of hospitalization per year.	One year
Hospital Day Quotient (HDQ)	Number of days hospitalized per year.	One year

Collaborators and Investigators

• Sponsor: Hospital Universitari de Bellvitge
• Investigators: Principal Investigator: Mikel Urretavizcaya Sarachaga, MD, PhD, Hospital Universitari de Bellvitge, IDIBELL; Principal Investigator: Èrika Martínez Amorós, MD, Corporacion Parc Tauli

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: February 28, 2011
• First Submitted That Met QC Criteria: February 28, 2011
• First Posted (ESTIMATE): March 1, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): August 31, 2015
• Last Update Submitted That Met QC Criteria: August 28, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Depression; Efficacy; Drug therapy; Prevention; Pharmacotherapy; Electroconvulsive therapy; Consolidation ECT
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Antidepressive Agents, Tricyclic; Antimanic Agents; Cytochrome P-450 CYP2D6 Inhibitors; Serotonin 5-HT3 Receptor Antagonists; Neuromuscular Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Adrenergic Uptake Inhibitors; Adrenergic alpha-Antagonists; Muscle Relaxants, Central; Antiparkinson Agents; Anti-Dyskinesia Agents; Adrenergic alpha-2 Receptor Antagonists; Olanzapine; Aripiprazole; Sertraline; Duloxetine Hydrochloride; Citalopram; Clomipramine; Paroxetine; Quetiapine Fumarate; Risperidone; Diazepam; Lithium Carbonate; Dexetimide; Venlafaxine Hydrochloride; Mirtazapine; Nortriptyline; Fluoxetine; Lorazepam; Antidepressive Agents; Antipsychotic Agents; Imipramine; Mianserin; Clorazepate Dipotassium
• Other Study ID Numbers: TECHUB2007