Neuroimaging, Neuropsychological, Quality of life effects and costs of Deep Brain Stimulation in Treatment-refractory patients with Major Depressive Disorder

In any given 1-year period, 5.8 percent of the Dutch population suffers from
Major Depressive Disorder (MDD). This has huge consequences on a psychological,
social and economical level for the patients, persons who care about them and
society. A recent World Health Organization report predicts that MDD will be
the leading cause of disability and premature death in the industrial world by
the year 2020. Without treatment, ten percent of people suffering from severe
MDD will commit suicide. Although de majority of the patients with MDD benefits
from treatment with pharmacological, psychotherapeutic and/or Electro
convulsion therapy (ECT) there is a group of patients(up to 15%) for whom
multiple interventions will be unhelpful and will have significant depression.
For this group of refractory MDD patients, neurosurgery is a last resort.
Several methods are used, but all have in common that they are irreversible.
Recently Deep Brain Stimulation (DBS) has been used as a potentially *non-
destructive* alternative to ablative neurosurgery. Although their have only
been results published from studies with small groups of patients, the first
results look promising.
The department of psychiatry of the AMC will start to assess DBS on 26
treatment refractory patients suffering from MDD. The protocol of this study
has been approved by the METC (METC number 08/207). In this protocol the
additional study is described. This study aims to explore the effects of DBS on
a neurological, neuropsychological, quality of life and economical level.
Information on these effects is essential for further optimisation and
provision of the DBS treatment in the Netherlands.

Amendement:
The D2-receptor binding of patients with treatment-resistant depression (TRD)
will be compared with healthy controls. This information is needed to getter a
better understanding of the pathofysiology in TRD, in order to develop more
effective treatment of this patient group.

The study has 3 substudies with each their separate goals:
Neuroimaging part:
1. To determine the effects of DBS on D2 receptor binding.
2. To determine alterations in cerebral perfusion associated with deep brain
stimulation (DBS).

Neuropsychological part:
1. To evaluate the neuropsychological safety of treatment with deep brain
stimulation.
-effects of surgery on cognitive functioning
-effects of short and long term stimulation on cognitive functioning
2. The comparison of the effects on cognitive functioning induced by DBS
relative to ECT and treatment as usual.

Quality of life and economic evaluation:
1. To compare quality of life between DBS, ECT and treatment as usual (TAU).
2. To determine the cost-effectiveness of DBS in comparison with ECT and TAU.

Amendement:
This additional study has one objecitve:
1.To determine the difference in D2 receptor binding between treatment
resistant MDD-patients and healthy, never depressed controls.

Neuroimaging study:
Prospective longitudinal cohort study. Comparing D2 receptor binding and
alterations in cerebral perfusion of DBS in TRD with healthy controls.

Neuropsychological study:
Prospective longitudinal cohort study, comparing cognitive effects of DBS
operation and treatment in TRD patients with: TRD patients who are treated with
ECT, TRD patients who are treated as usual and healthy controls.

Quality of life and cost-effectiveness study:
Prospective longitudinal cohort study, comparing QOL effects and healtcare
utillisation of TRD patients with DBS with: TRD patients who are treated with
ECT and TRD patients who are treated as usual.

Amendement:
Cross-sectional descriptive study in which D2 receptor binding in patients with
TRD will be compared with healthy, never depressed controls. This will be done
with [123I]IBZM SPECT imaging.

DBS and healthy control group:
Patients* will undergo 3 times a SPECT scan and 4 times a fMRI scan. Besides
that they will have 6 moments where they participate in the neuropsychological
research and 5 times where they have to fill in the QOL and resource
utilisation questionnaires.

ECT group:
Patients will have to conduct the neuropsychological research 6 times and at 5
times they will have to fill in the QOL and resource utilisation questionnaires.

MDD control group:
Patients will have to conduct the neuropsychological research 6 times and at 5
times they will have to fill in the QOL and resource utilisation questionnaires.

All the researches will be planned so subjects will have to visit the AMC
maximum 7 times (DBS group, healty controls) and 6 times (ECT and MDD group).

Amendement:
The control group will undergo a SPECT scan 1 time.