Depression
Conditions
Keywords
Depression,, ECT,, rTMS,, Right prefrontal,, antidepressive efficacy
Brief summary
The aim of the present study is to investigate in which degree low frequency right prefrontal rTMS used ad add-on may potentiate the antidepressant effect of unilateral ECT and accelerate remission . To investigate the correlation between blood concentration of specific inflammation makers and change in depressive symptoms during treatment
Detailed description
ECT is a well-established and effective method for the treatment of severe depression. During the last decades, rTMS has appeared as a potential new non-invasive antidepressant method, which may be a potential alternative to ECT due to fewer side effects. Both methods expose the brain to an electric current. But while ECT is associated with global cerebral stimulation elicited by an epileptic seizure, rTMS implies non-convulsive focal stimulation through a time varying magnetic field. Thus, the antidepressant effect of rTMS does not depend on seizure activity and consequently requires no anesthesia. In addition, rTMS seems not to be associated with cognitive disturbances. Previous research indicates that the antidepressant effect of rTMS is associated with specific stimulation of the dorsolateral prefrontal cortex. The majority of clinically controlled studies have used high frequency stimulation of the left frontal cortex (1-4). Few have used right prefrontal low frequency rTMS, which has less side effects, such as local discomfort and a lower risk of releasing epileptic seizures, than high frequency stimulation (5-10). Both models have been used with varying results. Meta-analysis of the antidepressant effect of rTMS (11,x) have found a modest, statistically significant antidepressant effect but generally definite conclusions on the antidepressant effect of rTMS has been difficult to draw, probably because of small and selected study populations, varying ways of stimulation and other confounding factors in the clinical setting. The important clinical question of whether rTMS may substitute ECT in the treatment of depression has almost exclusively been elucidated in studies using high frequency stimulation of the left frontal cortex. Some of these suggest that the effectiveness of rTMS is equal to that of ECT in non-delusional patients (12-19). However, a recent investigation has compared the antidepressant efficacy and side effects of right prefrontal low frequency rTMS with ECT. In this study the mean Hamilton total 17-item (HAM-D score) scores were reduced significantly over time in both groups (ECT: p\<0.001, rTMS: p\<0.001); but ECT was more effective than rTMS on a short term after 3 weeks of treatment. The outcome did not point to right frontal low frequency rTMS as a first line substitute for ECT, but it might have place in the treatment of depression as add on to other types of treatment. ECT is normally administered 3 times a week for 3-4 weeks. Daily treatment sessions might accelerate remission, but is impossible because of cognitive side effects. However, rTMS seems not to be associated with reduction in cognitive performance and might potentiate the antidepressant efficacy of ECT. Therefore the investigators have found it clinical interesting to investigate in which degree low frequency right prefrontal rTMS used ad add-on may potentiate the antidepressant effect of unilateral ECT and accelerate remission . In addition we want to investigate te correlation between change in depressive symptoms and -blood concentration of specific inflammation CNS- makers
Interventions
DEVICELow frequency (1 hz) rTMS, as add-on to ECT
Right prefrontal Low frequency (1 hz) repetitive transcranial magnetic stimulation as add-on to ECT.
DEVICESham-rTMS
Right prefrontal Low frequency (1 hz) sham-stimulation using af double blind placebo coil as add-on to ECT.
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Patients admitted to the Psychiatric Hospital of Aarhus * Patients referred for ECT * Age 18-80 years * Moderate or severely depressed patients (ICD-10(DSM-IV) * HAM-D score (17-item) ≥20 and/or Ham-D subscale ≥10.
Exclusion criteria
* Organic brain disease * Epilepsy or disposition to epilepsy * Metallic objects in chest or brain * Cardiac pacemaker * Somatic diseases associated with brain dysfunction * Pregnancy * Severe agitation or delirium * Alcohol or drug dependence (ICD-10) * Use of coercive measures * The patient does not wish to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission | 7 weeks | The Hamilton (17 -item) Rating Scale for Depression is a clinician-administered assessement scale, that contains 17 items pertaining to symptoms of depression experienced over the past week. The total range is 0-52.Higher scores mean a worse outcomeRemission is defined by a Hamilton 17-item total score \< 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response | 7 weeks | The Hamilton (17 -item) Rating Scale for Depression is a clinician-administered assessement scale, that contains 17 items pertaining to symptoms of depression experienced over the past week. The total range is 0-52.Higher scores mean a worse outcome. Response is defined by a reduction in the Hamilton 17 item score of \>= 50% |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Right prefrontal Low frequency (1 hz) repetitive transcranial magnetic stimulation, administered with 2 sessions each week
Low frequency (1 hz) rTMS, as add-on to ECT: Right prefrontal Low frequency (1 hz) repetitive transcranial magnetic stimulation as add-on to ECT. | 18 |
| Sham-rTMS Sham right prefrontal rTMS 2 times a week
Sham-rTMS: Right prefrontal Low frequency (1 hz) sham-stimulation using af double blind placebo coil as add-on to ECT. | 17 |
| Total | 35 |
Baseline characteristics
| Characteristic | Low Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) | Sham-rTMS | Total |
|---|---|---|---|
| Age, Continuous | 50 years | 47 years | 49 years |
| Antidepressant drug treatment | 18 Participants | 16 Participants | 34 Participants |
| Hamilton depression scale score Hamilton depression rating scale (17-item) | 24 units on a scale | 26 units on a scale | 25 units on a scale |
| Hamilton depression scale score Hamilton depression rating scale (6-item) | 13 units on a scale | 13 units on a scale | 13 units on a scale |
| Hamilton depression scale score Major Depression inventory | 45 units on a scale | 41 units on a scale | 43 units on a scale |
| number of patients with bipolar depressive | 1 Participants | 6 Participants | 7 Participants |
| number of patients with melancholic depression | 16 Participants | 13 Participants | 29 Participants |
| number of patients with psychotic depression | 2 Participants | 3 Participants | 5 Participants |
| Number of patients with Severe depression | 15 Participants | 17 Participants | 32 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Denmark | 18 participants | 17 participants | 35 participants |
| Sex: Female, Male Female | 13 Participants | 12 Participants | 25 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 4 / 12 | 3 / 14 |
| serious Total, serious adverse events | 1 / 12 | 0 / 14 |
Outcome results
Primary
Remission
The Hamilton (17 -item) Rating Scale for Depression is a clinician-administered assessement scale, that contains 17 items pertaining to symptoms of depression experienced over the past week. The total range is 0-52.Higher scores mean a worse outcomeRemission is defined by a Hamilton 17-item total score \< 8.
Time frame: 7 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Frequency rTMS | Remission | 7 Participants |
| Sham-rTMS | Remission | 10 Participants |
p-value: 0.3Chi-squared
Secondary
Response
The Hamilton (17 -item) Rating Scale for Depression is a clinician-administered assessement scale, that contains 17 items pertaining to symptoms of depression experienced over the past week. The total range is 0-52.Higher scores mean a worse outcome. Response is defined by a reduction in the Hamilton 17 item score of \>= 50%
Time frame: 7 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Frequency rTMS | Response | 11 Participants |
| Sham-rTMS | Response | 13 Participants |