The Antidepressant Efficacy of Low Frequency rTMS as add-on

The Antidepressive Effect of Low Frequency Right Prefrontal Repetitive Transcranial Magnetic Stimulation as add-on to Antidepressant Drug Treatment. A Blinded, Placebo Controlled Randomised Study.

rTMS has appeared a potential new non-invasive antidepressant method, which implies non-convulsive focal stimulation of the brain through a time varying magnetic field. ). Research on rTMS reports of minimal side effects of the method . The majority of clinically controlled studies have used high frequency stimulation of the left frontal cortex .

Fewer studies have used right prefrontal, which has less side effects, such as local discomfort and a lower risk of releasing epileptic seizures, than high frequency stimulation .Both stimulus models has been shown to have statistically significant antidepressant effect and recent research clearly indicates that low frequency rTMS of the right prefrontal cortex i associated with an antidepressant effect at the same level as the high frequency model. Therefore the investigators want to examine the antidepressant effect of a specific rTMS low frequency model in a clinical setting using a placebo controlled, randomized double blind design.

Study Overview

• Status: Withdrawn
• Conditions: Depression
• Intervention / Treatment: Device: Right prefrontal low frequency rTMS; Other: Sham-rTMS

Detailed Description

rTMS has appeared a potential new non-invasive antidepressant method, which implies non-convulsive focal stimulation of the brain through a time varying magnetic field. ). RTMS is based on the principle of electromagnetism. An electromagnetic coil placed on the scalp produces a time-varying magnetic field that penetrates the scalp and skull unattenuated and gives rise to a current in the proximity of the cerebral cortex as well as functionally connected parts of the brain. Research on rTMS reports of minimal side effects of the method Previous research indicates that the antidepressant effect of rTMS is associated with specific stimulation of the dorsolateral prefrontal cortex. The stimulus frequency has shown to play a key role in the mechanisms of action of rTMS. Previous animal studies have shown that low frequency rTMS is associated with long term inhibition of neuronal activity (long term depression), while high frequency stimulation is followed by prolonged activation (long term potentiation). To some extent, this differential effect of different frequencies is reflected in human studies (REF).

The majority of clinically controlled studies have used high frequency stimulation of the left frontal cortex , which has been approved by the USA FDA (1) and later in EU for the treatment of depression.

Fewer studies have used right prefrontal, which has less side effects, such as local discomfort and a lower risk of releasing epileptic seizures, than high frequency stimulation . In addition low frequency rTMS is generally less time-consuming. Both stimulus models has been shown to have a modest, statistically significant antidepressant effect and recent research clearly indicates that low frequency rTMS of the right prefrontal cortex i associated with an antidepressant effect at the same level as the high frequency model. The issue indicates that low frequency due to the more advantagous side effect profile should be the stimulus model of choice in a clinical setting.

Therefore the investigators want to examine the antidepressant effect of a specific rTMS low frequency model in a clinical setting using a placebo controlled, randomized double blind design.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Out-patients referred to Aarhus University Hospital, Risskov
2. Moderate-severe uni- and bipolar depression according to ICD-10
3. Age 18-80 years

Exclusion Criteria:

1. Organic brain disease.
2. Epileptic seizure < 2 years
3. Patients with implanted metal parts in the brain or chest
4. Patients with pacemaker
5. Medical diseases with cerebral impact
6. Serious suicidal danger

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Right prefrontal low frequency rTMS.; Right prefrontal low frequency rTMS (1Hz). A treatment session each day in four weeks apart from weekends. Each session is administered with 2 pulse trains of 180 sec with a 2 min interval	Device: Right prefrontal low frequency rTMS; A treatment session each day in four weeks apart from weekends. Each session is administered with 2 pulse trains of 180 sec with a 2 min interval
Placebo Comparator: Sham-rTMS; Right prefrontal rTMS sham treatment. A treatment session each day in four weeks apart from weekends. Each session is administered with 2 pulse trains of 180 sec with a 2 min interval	Other: Sham-rTMS; Right prefrontal rTMS sham treatment. A treatment session each day in four weeks apart from weekends. Each session is administered with 2 pulse trains of 180 sec with a 2 min interval

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
remission	the number of patients obtaining a Hamilton-17 item total score of < 8	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response	the number of patients obtaining a reduction in the 17-item score on the Hamilton scale for depression of >= 50%	8 weeks
Cognitive function	Psychological testing of cognitive functions	8 weeks

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Poul Erik Buchholtz, MD, Aarhus University Hospital, Risskov

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: November 15, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): November 29, 2017
• Last Update Submitted That Met QC Criteria: November 28, 2017
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: AMB-TMS-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No