Clinical trial NCT04078438: Neurofeedback In Treatment Resistant Depression
Official title: Neurofeedback Treatment on Depressive Symptoms and Functional Recovery in Treatment-resistant Patients With Major Depressive Disorder: an Open-label Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Depression
Neurofeedback
Keywords: Treatment-resistant depression
Neurofeedback
Functional recovery
Lead sponsor: Yeungnam University Hospital
Sponsor class: OTHER
First posted: 2019-09-06
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The investigators evaluate the effects of neurofeedback as an augmentation treatment on depressive symptoms and functional recovery in patients with treatment-resistant depression (TRD).

TRD patients are assigned to the neurofeedback augmentation group and the medication-only (treatment as usual, TAU) group. The neurofeedback augmentation group underwent combined therapy comprising medication and 12-24 sessions of neurofeedback training for 12 weeks. To assess the serum levels of brain-derived neurotrophic factor (BDNF) in both groups, a pre- and post-treatment blood samples are obtained. Patients are evaluated using the Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), Clinical Global Impression-Severity (CGI-S), 5-level version of European Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D-5L), and Sheehan Disability Scale (SDS) at baseline, and at the 1-, 4-, and 12-week.

Detailed description: Major depressive disorder (MDD) is a severely disabling disorder resulting in the deterioration of daily function and lowering quality of life. The lifetime prevalence of depression is 10-15%, and the annual prevalence of MDD in the United States is approximately 7%. The World Health Organization has reported that MDD is expected to be the top disease in terms of global burden by 2030. Fifty percent of patients with depressive disorder have a chronic disease course, and 20% of such patients have insufficient responses to treatment despite the use of antidepressant medication. In addition, although antidepressants have been shown to be effective, residual symptoms may continue by stopping the medication early due to inconvenient side effects of the medication. Sixty percent of patients with depressive disorder have poorer executive function. Patients with depressive disorder are continuously affected by deficits in social functioning, such as interpersonal relationships and job adaptation, even if some of their symptoms are improved by medication. Therefore, various additional treatments other than antidepressant treatment have been tried to improve residual depressive symptoms and the remission rate.

Brain waves have been used to measure brain activity and previous studies have reported that different brain waves reflect different brain states, including moods. Neurofeedback is a type of electroencephalography (EEG) training that allows individuals to change the levels of particular types of brain waves displayed on a computer by operational conditioning. EEG studies showed that the neurofeedback is capable of generating long term changes in the spectral EEG topography, while neuroimaging studies represented the neuroplastic effects from neurofeedback treatment. Neurofeedback is an alternative approach that aims to help individuals alter brain activation without introducing electrical or magnetic activity, or pharmacological compounds into the brain, hence preventing the brain from becoming dependent on outside influences for better functioning. It is noninvasive method and there's no report of even minor side effects.

Neurofeedback may be considered a new augmentation treatment for patients with treatment-resistant depression (TRD), even after the use of antidepressants. Some studies have reported improvements in both depressive symptoms and executive function following neurofeedback treatment. A recent article insisted that neurofeedback treatment for depression as having "revealed promising effects in recent clinical trials". However, most such studies have been case reports or uncontrolled studies, and the mechanism underlying the treatment effects of neurofeedback are still unclear. In addition, there has been no study of neurofeedback on depressive symptoms and functional recovery in patients with TRD.

Brain-derived neurotrophic factor (BDNF) acts on certain neurons of the central nervous system and the peripheral nervous system. It helps support the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. Previous studies have suggested the presence of an etiological link between the development of depression and BDNF. However, no studies have examined the association between neurofeedback and changes in BDNF level.

The purpose of this pilot study was to evaluate the effects of neurofeedback as an augmentation treatment on depressive symptoms and functional recovery in patients with TRD. The investigators also aimed to identify the usefulness of BDNF as a biomarker for neurofeedback by examining changes in the BDNF level before vs. after treatment in the neurofeedback treatment and medication-only (treatment as usual, TAU) groups.

Eligibility criteria: Inclusion Criteria:

* Diagosis with MDD according to the DSM-IV-TR criteria for MDD, and especially treatment-resistant MDD (Hamilton Rating Scale for Depression \[HAM-D\] score ⩾14) despite adequate antidepressant therapy)

Exclusion Criteria:

* Psychosis
* Bipolar disorder
* Brain injury
* Clinically diagnosed neurological disorder
* Convulsive disorder
* Pregnancy

Primary outcomes:
measure: Changes in Hamilton Rating Scale for Depression [HAM-D] score at baselline and the 1-, 4-, and 12-week time points
timeFrame: at baseline, and at the 1-, 4-, and 12-week time points.
Secondary outcomes:
measure: Changes in Beck Depression Inventory- II (BDI-II) scores at baselline and the 1-, 4-, and 12-week time points
timeFrame: at baseline, and at the 1-, 4-, and 12-week time points.
measure: Changes in Sheehan Disability Scale (SDS) score at baselline and the 1-, 4-, and 12-week time points
timeFrame: at baseline, and at the 1-, 4-, and 12-week time points.
measure: Changes in Clinical Global Impression-Severity (CGI-S) at baselline and the 1-, 4-, and 12-week time points
timeFrame: at baseline, and at the 1-, 4-, and 12-week time points.
measure: Comparisons of serum brain-derived neurotrophic factor (BDNF) level between baseline and the 12-week time point among groups
timeFrame: at baseline, and 12-week time points.
measure: Type and number of adverse events
timeFrame: through study completion, an average of 12 weeks
measure: Changes in valuation of 5 level version of European Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D-5L) (converted tariff score)
timeFrame: at baseline, and at the 1-, 4-, and 12-week time points.
measure: Changes in response and remission rate of Hamilton Rating Scale for Depression [HAM-D] score
timeFrame: at baseline, and at the 1-, 4-, and 12-week time points.
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Hospital
Study officials:
affiliation: Yeungnam University Hospital
name: Eun-Jin Cheon, M.D., Ph.D
role: STUDY_DIRECTOR
References:
citation: Lee YJ, Lee GW, Seo WS, Koo BH, Kim HG, Cheon EJ. Neurofeedback Treatment on Depressive Symptoms and Functional Recovery in Treatment-Resistant Patients with Major Depressive Disorder: an Open-Label Pilot Study. J Korean Med Sci. 2019 Nov 4;34(42):e287. doi: 10.3346/jkms.2019.34.e287.