Repetitive Transcranial Magnetic Stimulation (rTMS) in youth with obsessive compulsive disorder (OCD) and/or Gilles de la Tourette syndrome (GTS): A feasibility study

Obsessive-compulsive disorder (OCD) is a serious psychiatric condition,
characterized by uncontrolled and recurring thoughts (obsessions), repetitive
behaviors (compulsions) or both. The lifetime prevalence of OCD is around 2-3%.
In about 45% of patients with OCD the symptoms already begin before the age of
18, and in 65% of all patients before the age of 25. OCD causes a lot of stress
and dysfunction in all forms of activities, and has negative impact on the
psychosocial development of patients and their families.
Current evidence-based treatment options include psychotherapy (cognitive
behavioral therapy; CBT) and antidepressant medication (such as selective
serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs)). In
current guidelines it*s recommended to first start CBT, and, if lack of
efficacy, add pharmacological treatment. Previous studies showed better
efficacy of these forms of treatment than placebo. Still, there is a group of
patients who doesn*t respond (enough) to CBT (whether or not in combination
with medication). Furthermore, medication itself is not always tolerated due to
side effects, or not wanted by the patient itself (and/or parents).

Gilles de la Tourette Syndrome (GTS) is a neurodevelopmental movement disorder
characterized by repetitive movements and vocalizations called tics. The
worldwide prevalence in children and adolescents is 0.77 - 1%. Also GTS is
known to negatively affect quality of life, not only at home, but also in
school and with friends and family. Treatment options for children with GTS are
limited. Two forms of behavioral therapy, habit reversal training (HRT) and
exposure and response prevention (ERP), are used. Different kinds of
medication, for example aripiprazole, can also be used, but carry a side effect
burden as well. Both forms of treatment have similarly results on the reduction
of tics. In about one third of the patients the symptom reduction is less than
50% to even minimal.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive
neuromodulatory technique that uses fluctuating extracranial magnetic fields to
generate cortical currents that focally stimulate the cerebral parenchyma by
depolarizing the neural cell membrane, leading to changes in the brain circuits
involved in psychiatric disorders. A coil is therefore placed on the patients
head. The efficacy of rTMS depends on multiple aspects, such as the location of
the target area (the dorsolateral prefrontal cortex is commonly used), and the
frequency that is been used (low-frequency versus high frequency). The total
number of needed sessions is not yet clear, with variating frequencies per week
and different durations in total weeks. Daily treatment for several weeks
although has shown its effect in several psychopathologies, such as
depression. In previous studies the possible side effects have been
investigated and seem to be minimal. Seizure is the most severe side effect of
rTMS, but had a very low incidence of occurring and seems to hardly only affect
patients with predisposing factors (on which can be screened on forehand).

The number and range of neuropsychiatric disorders that are treated by rTMS is
growing in the last years. In adults it has already been shown that rTMS is
effective for symptom reduction of OCD symptoms. Some small studies have also
suggested improvement of tic severity after use of rTMS in GTS. The research on
children and adolescents is limited. We therefore would like to perform a
feasibility study in youth aged 12 - 18 years with ODC and/or GTS, receiving
rTMS as add-on therapy next to their treatment-as-usual (TAU).

Primary Objective:
To explore the acceptability and feasibility of rTMS added to exposure with
response prevention and/or medication as an intervention in youth with OCD
and/or GTS.

Secondary Objective(s):
- To explore the effects of added rTMS on symptoms of OCD and GTS.
- To explore the safety (including side-effects and/or complications) of
added rTMS.
- To prepare a larger trial into the effectiveness of rTMS on symptoms OCD and
GTS, based on the results of this acceptability and feasibility study, and the
willingness to participate and time to include all patients in this feasibility
study.

This study will combine a qualitative study design and a randomized multiple
baseline single-case experimental design (SCED). The qualitative data from
interviews will be used to explore the acceptability and feasibility of rTMS.

The patients will be treated with a low frequency 1 Hz rTMS protocol on the
(pre)supplementary motor area (SMA). rTMS treatment will be given for 20 times,
once a day, 5 days/week, for 4 weeks. We will use several questionnaires
(C-YBOCS, YGTSS) every 5th rTMS session, and more questionnaires (SCARED,
CDI-2, EQ-5D-Y) and qualitative interviews pre- and post treatment.

The total duration of this feasibility study is 12 weeks. After informed
consent, a baseline phase of 2, 3 or 4 weeks will follow. After this, a total
of 20 rTMS sessions will take place on working days for 4 weeks. After the last
rTMS session, there is a follow-up phase of 4 weeks. Participating patients are
already in the clinical (day) clinic of Levvel Amsterdam. Each session includes
5 minutes of preparation, 25 minutes of stimulation, for a total of 40 minutes
per session. During the entire research period (maximum 12 weeks), a daily (on
weekdays) short assessment by the participant takes place, with a total of 120
minutes for 12 weeks. Psychometry is administered every fifth rTMS session,
with a total of 30 minutes for all questionnaires. The first baseline session
lasts (maximum) 1:30 hours, due to measurements and technical procedures,
psychometry, ECG and vital functions. The last two measurement moments (T5 at
the end of the 20th rTMS session, and T6 4 weeks after the last rTMS session)
last (maximum) 1:15 hours and 1:30 hours, respectively.
Questionnaires are also discussed with parents at three times (at the start, at
the end of rTMS and at the end of the entire study), lasting 0:45 - 1:00 hours.
During the entire research period (maximum 12 weeks), parents are also asked to
complete a daily short assessment via a digital application, lasting a total of
120 minutes.

The time burden for the participant is estimated at approximately 24 hours.
The time burden for the parent is estimated at a maximum of 5 hours.

The risks associated with rTMS are very low, as in previous studies rTMS is
shown as safe and non-invasive. Most common side-effects in adults are
neckpain/discomfort (±40%), local discomfort of the scalp (±39%), tension
headaches during and after stimulation (±28%) and dizziness. The discomfort and
pain mainly occur during the first sessions, and become less as the number of
treatments progresses. In earlier studies in children similar side-effects are
seen. Headache (±11,5%) and local discomfort of the scalp (2,5 - 12%) most
common, and less frequently fatigue and dizziness, which also disappear after
stopping rTMS.
The most severe, but extremely rare, side-effect is a seizure. The prevalence
is 0.08 of 1000 sessions and almost nihil when patients are medication free or
do not have a co-morbid neuro-logical disorder.