PCT after rTMS for relapse prevention of depression

Since 2018, repetitive Transcranial Magnetic Stimulation (rTMS) is a first line
recommendation in the Netherlands for patients with Major Depressive Disorder
(MDD), not responding to at least two treatments. Most studies investigated
effectiveness up to 6 weeks after treatment, while relapse happens frequently
in a larger time frame and occurs in approx. 60-90 percent of patients with a
recurring course. MDD is a severe psychiatric illness with a high societal and
individual impact. Especially in our targeted refractory population, recurring
depressive episodes are seriously debilitating and suicide is not uncommon.
Relapse prevention is therefore of substantial importance, however literature
on (maintenance) therapy after successful rTMS treatment is scarce and of low
quality. For depression treated with psychotherapy and medication, Preventive
Cognitive Therapy (PCT; 8 sessions) is effective in reducing relapse risk. To
our knowledge, PCT after rTMS has never been investigated as a maintenance
strategy. In a larger randomised controlled trial, we aim to prolong rTMS
effects and decrease relapse risks in severely depressed patients by adding
Preventive Cognitive Therapy after response to effective rTMS treatment.
Prolonging the positive effects of rTMS and preventing these patients from
additional relapses will improve quality of life of patients and their
relatives and lower health care costs. In order to study the feasibility of
additional therapy in this patient population and to sufficiently power a large
RCT, we conduct the current study, , in which we compare treatment adherence of
20 patients who benefitted from rTMS who either receive face to face or online
PCT treatment. To monitor affective state for our secondary parameter, we use a
daily short form questionnaire.

This pilot study aims to establish the feasibility of offering PCT live or
online to MDD patients in remission due to rTMS by measuring treatment
adherence using descriptive data and daily affect. Results will be used to
improve patient compliance in a larger RCT investigating the effects of PCT
after rTMS.

Randomized controlled trial using 2 arms, a face to face PCT and a video call
PCT group will be compared. Patients are allocated to either the face to face
or video call PCT using a research randomization tool online (CASTOR), designed
for experimental research. Patients and researchers will not be blinded for the
conditions, however, questionnaires will be administered by a blinded research
assistant only involved for measurements. Data will be analyzed using
(repeated) linear mixed models in SPSS. If applicable, corrections will be
performed for skew data. We aim to describe results in 2 open access
publications, focusing on study design in preparation of an efficiency study
and first results and secondly on follow-up data. The outcome of the current
pilot study will be used to determine power analyses for a larger
cost-effective trial aimed to determine the beneficial effects of providing PCT
after rTMS.

PCT may prolong the effect of rTMS leading to a quick and long term effective
treatment method for chronically ill patients with high health care costs.
Combining these two forms of evidence based treatment for MDD may lead to lower
relapse rates and costs reduction. In this trial, half of the randomized
patients will receive PCT online via video call and half will receive PCT F2F
to study the feasibility of the add-on treatment for patients receiving rTMS.
All patients who receive rTMS treatment are psychotherapeutically treated
during rTMS treatment period as stated in the depression guideline. After
informed consent, patients are included in the current pilot study when
responding to rTMS and reaching at least 50% reduction of symptoms or remission
(scores 7 or lower) on the IDS self-report scale (Inventory of Depressive
Symptoms). Patients not responding will continue to receive regular
psychotherapy and will not be included in the current pilot study. PCT consists
of 8 weekly sessions of individual psychotherapy according to the protocol and
will be performed by a qualified Health care psychologist. PCT sessions via
videocall proved to be feasible in a former study by Brouwer et al. (2020) and
our study population may be supraregional due to the fact that rTMS treatment
is not widely offered in patient care. A short-form questionnaire (experience
sampling methodology) will be used to monitor daily positive and negative
affective states during the treatment period. All included patients will fill
in questionnaires regarding their depressive symptoms directly after rTMS when
reaching (partial) remission, directly after PCT, 3 months after PCT and 6
months after PCT. We will use the Hamilton depression rating scale (HDRS) and
the Inventory of Depressive Symptoms (IDS) to record depressive symptoms.

A potential benefit of participating in this study might be the beneficial
effects of PCT to prolong the effects of rTMS, although this is not established
yet. Beneficial effects are expected for future patients participating in a
larger RCT trail, since we gather information on best suited treatment options
and aim to lower the future burden of additional treatment for participating
patients. There will be some burden of participating in this study, which is
caused by filling in a daily short-form questionnaire about affect (5 min each
day) and follow-up questionnaires (+/- 60 min each measurement). In addition,
preventive cognitive training may not work causing you to potentially relapse
in your depression. As a result, there is a moderate risk associated with
participating in this study.