Clinical trial NCT04027452: Electroconvulsive Therapy for Traumatic Memories
Official title: Electroconvulsive Therapy for Traumatic Memories: A Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post Traumatic Stress Disorder
Depression
Keywords: electroconvulsive therapy
post traumatic stress disorder
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
First posted: 2019-07-22
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will investigate whether ECT treatment can reduce the effect of traumatic memories if those memories are recalled immediately prior to the ECT sessions. Participants will be randomized to either a recall of a traumatic memory or a neutral non-traumatic memory prior to their ECT sessions.

Detailed description: Traumatic events contribute to the genesis of disorders such as post-traumatic stress disorder (PTSD) and depression, and memories of the event can cause ongoing distress. Short-term episodic memories are encoded by the hippocampus and gradually become consolidated through reciprocal connections with the cortex, resulting in long-term memories being stored in a distributed network throughout the cerebral cortex. There are no effective treatments currently for specifically targeting traumatic memories and reducing the distress they cause.

ECT is the most effective treatment for improving mood in patients with depression and there is new evidence emerging that suggests ECT can also improve PTSD symptoms independently of co-morbid depression. In addition, the main side-effect of ECT is memory loss, specifically for autobiographical details surrounding the course of ECT, but not typically affecting long-term episodic memory, nor procedural memories. Memories stored in the hippocampus are vulnerable to disruption by ECT because they rely on synaptic changes that are mediated by relatively unstable modifications in AMPA receptor and metabotropic glutamate receptor density. The investigators propose to exploit this feature of ECT, which normally is considered an undesirable side-effect of treatment, in an attempt to selectively reduce traumatic memories and the distress associated with them.

The investigators propose to recruit patients referred for ECT for treatment-resistant depression, who also have traumatic memories that are causing distress. These patients will be asked to write two narratives, one of the traumatic memory, and the other of a trivial, non-traumatic remote event. Patients will then be asked to listen to an audio recording of either the traumatic memory or the neutral memory (control group) immediately before their ECT sessions. The severity of the traumatic memory related symptoms will be assessed before and after the course of ECT using the Modified PTSD Symptom Scale (MPSS-SR) and the Clinician Administered PTSD Scale for DSM-5 (CAPS-5). Data will be analyzed by comparing the change in overall MPSS-SR scores and CAPS-5 scores pre- and post-ECT between the experimental and control groups. Physiological data will also be collected at each ECT session during the time the participant is listening to the audio recordings. Heart rate and skin conductance will be measured prior to and during listening of the traumatic or non-traumatic memory, in order to determine if there is a change associated with a stress response, and whether this response normalizes in association with reduction of PTSD symptoms with treatment.

Eligibility criteria: Inclusion Criteria:

1. Patient referred and accepted for ECT treatment at CAMH
2. Presence of traumatic memories
3. Able to write about their traumatic experience(s)
4. Capable of informed consent to participate in this study
5. Age 18 or greater
6. MPSS-SR re-experiencing score (items 1-4, 17) ≥ 20

Exclusion Criteria:

1. History of neurological or developmental disorder, including seizures
2. ECT treatment already started

Primary outcomes:
measure: Change in Modified PTSD Symptom Scale (MPSS-SR) score
timeFrame: Baseline, after ECT treatment course (an average of 4 weeks), and at 3 month follow up
measure: Change in Clinician Administered PTSD Scale for DSM-5 (CAPS-5) score
timeFrame: Baseline, after ECT treatment course (an average of 4 weeks), and at 3 month follow up
Secondary outcomes:
measure: Change in heart rate
timeFrame: Change of heart rate from 0-30 seconds of the audio recording to heart rate from 90-120 seconds of the audio recording.
measure: Skin conductance
timeFrame: Change of skin conductance from 0-30 seconds of the audio recording to skin conductance from 90-120 seconds of the audio recording.
measure: Change in The Quick Inventory of Depressive Symptomatology (Self-Report)
timeFrame: Baseline, after ECT treatment course (an average of 4 weeks), and at 3 month follow up
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Albert HC Wong, MD, FRCPC, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tang VM, Trought K, Gicas KM, Kozak M, Josselyn SA, Daskalakis ZJ, Blumberger DM, Voineskos D, Knyahnytska Y, Pasricha S, Chung Y, Zhou Y, Isserles M, Wong AHC. Electroconvulsive therapy with a memory reactivation intervention for post-traumatic stress disorder: A randomized controlled trial. Brain Stimul. 2021 May-Jun;14(3):635-642. doi: 10.1016/j.brs.2021.03.015. Epub 2021 Mar 27.