Deep Brain Stimulation in Chronic Treatment refractory Drug Dependence: A Pilot Study

Addiction is a chronic relapsing brain disease with severe negative
consequences for patients, their environment and society as a whole.
Fortunately, a large number of effective interventions is currently available
and many patients can be adequately treated. However, like in most other
chronic diseases, not all patients respond favourably and additional treatments
are needed to help those chronically addicted, treatment refractory patients.
As a consequence, many treatment refractory patients remain devoid of effective
treatment.

Recently Deep Brain Stimulation has been applied for treatment refractory
psychiatric disorders. Deep Brain Stimulation (DBS) is an adjustable,
reversible, non-destructive intervention using a surgically implanted medical
device, similar to a pacemaker, to deliver carefully controlled electrical
pulses to precisely targeted areas of the brain. There is compelling evidence
from both experimental human studies that DBS of the NcAcc is potentially
effective in the treatment of patients with a substance use disorder.

Until now, the safety and efficacy of DBS for treating substance use disorders
has not been examined. Therefore, the present pilot study aims to test the
feasibility, safety and potential efficacy of nucleus accumbens (NcAcc) DBS in
chronic, treatment-refractory heroin and/or cocaine dependent patients. In
addition, the study aims to understand to changes in brain function related to
NcAcc DBS and the relationship between these changes and treatment outcome
using functional Magnetic Resonance Imaging (fMRI) and Single Photon Emission
Computed Tomography

The aims of the study are (1) to establish the feasibility, safety, and
potential efficacy of NcAcc DBS in patients with a chronic, treatment
refractory heroin and/or cocaine addiction; (2) to explore functional effects
of NcAcc DBS in terms of brain activation patterns in response to
(neurocognitive) challenges related to addiction and relapse using functional
MRI (fMRI) and to study the association between these effects and clinical
outcome parameters; (3) to explore the functional effects of DBS in terms of
changes in striatal dopamine D2 binding using SPECT and to study the
association between these changes and clinical outcome parameters.

It is a pilot study in which the subjective craving and illicit drug use will
be compared over time during different time points in the research.

Neuroimaging study:
Patients will be compared within a randomized double blind within subject study
design over two time points in which the stimulator is either on or off. The
changes in D2 receptor binding and alterations in BOLD response will be
compared over these time points.

The intervention of this study will be Deep Brain Stimulation (DBS) in the
Nucleus Accumbens (NcAcc) in all participants. Deep Brain Stimulation is an
adjustable, reversible, non-destructive intervention using a surgically
implanted medical device to deliver carefully controlled electrical pulses to
precisely targeted areas of the brain. The stimulation can be programmed and
adjusted non-invasively (without surgery) by a trained clinician to maximize
symptom control and minimize side effects. The NcAcc has been chosen because
both animal and human studies indicate that this location is promising for DBS
treatment of addiction and because this location has shown to be safe in DBS
studies among humans with other psychiatric disorders such as anxiety,
depression, and OCD. In addition, the AMC has ample experience with NcAcc DBS,
since more than 20 patients with OCD have been treated following the same
protocol.

The greatest burden on the patient during this study is the intervention
itself, including (full) detoxification, surgery and the establishment of a new
lifestyle without the use of illicit drugs. During the various phases of the
study, the time burden on the patient varies from 4 hours in the 1 week surgery
phase, through 8 hours in the 8 weeks preparatory phase to almost 20 hours
during the 12 week double blind phase. With the exception of the neuroimaging
assessments, none of the assessments are very cumbersome. Moreover, none of the
assessments is very painful or carries a serious health risk. For the SPECT
scans the total radiation dose for each [123I]IBZM scan is 4.8 mSv. Because
every patient will get 2 SPECT scans the total radiation dose is 9.6 mSv. This
lies below the maximum dose allowed for scientific research (10 mSv/year).
Potential risks involved in DBS include the risks associated with the surgical
procedures, including the small risk (< 1%) of intracranial haemorrhage or
infection and the associated neurological consequences. In addition, some
patients may experience temporary but unpleasant sensations around the
subcutaneously implanted stimulator and the cables form the stimulator to the
electrodes. Finally, some patients may show some temporary neurological
symptoms (e.g. eye movement abnormalities) that generally disappear
spontaneously or after some fine-tuning of the stimulator.