Schema-ECT: A novel treatment for severe depression

Electroconvulsive therapy (ECT) is often considered a last treatment option for
otherwise treatment resistant depression. Unfortunately, approximately 50% of
patients do not respond sufficiently (Heijnen et al., 2010). Furthermore, of
the patients who respond initially, 40-80% relapse within half a year (Sackeim
et al., 2001). We hypothesize that suboptimal efficacy of ECT could be due to
insufficient modulation of negative cognitive schemas, which are relative
stable representations of prior knowledge and experiences. These negative
schemas distort the perception of new experiences in a maladaptive manner, and
focus one*s thoughts on negative aspects of oneself. Cognitive theories of
depression hold that these negative schemas play an important role in the
development, maintenance and recurrence of depression (Beck and Clark, 1988).
We recently found that memories can be weakened by applying ECT shortly after
reactivation of a memory (Kroes et al., 2013). This suggests that reactivation
of negative schemas just prior to ECT may also weaken those schemas. According
to the cognitive theory of depression this will lead to the recovery from
depression and will additionally reduce the risk to relapse, but this has not
yet been investigated. Here, we aim to investigate the efficacy of *schema-ECT*
and hypothesize that repeated reactivation of depressive schemas prior to ECT
weakens negative schemas, increases the efficacy of the ECT course, and reduces
the relapse rate after the reduction of the ECT session frequency or
discontinuing ECT. In addition to our main aim, we will investigate how the
response to ECT influences brain function and structure using MRI and MRS to
gain further understanding of the neural mechanisms that underlie the ECT
response and in addition to the MR scans take blood samples from the venous
catheter to analyze whether biomarkers can predict treatment response.

Our primary objectives are to determine whether schema-ECT increases the
remission rate of a course of ECT, reduces the relapse rate, and weakens
negative schemas. Our secondary objectives are to assess the neurobiological
mechanisms underlying the response to ECT using neuroimaging and blood
biomarkers and to identify neurobiological biomarkers that can predict
treatment response.

A randomized controlled trial (RCT) is used to determine schema-ECT efficacy.
The influence of response to ECT on neuroimaging and blood biomarkers will be
determined using a longitudinal, parallel group design, for which we will
compare ECT responders to non-responders.

Patients will be randomized to schema-ECT or control-ECT, stratified for
research center. Schema-ECT consists of reactivation of depressive schemas
using the arrow-down technique that is used in cognitive-behavioral therapy
(CBT). In the control condition, patients will be interviewed about details
that are also of clinical relevance but are not expected to activate depressive
schemas (e.g., their medical record, diet, exercise). ECT is performed
according to the national guidelines, which consists of a minimum of 6 biweekly
sessions until remission or a plateau in response is achieved.

The burden of ineffectively treated depression is high. The burden of ECT is
considerable but is warranted because of successful treatment, and its risk can
be considered negligible. Importantly, only the regular ECT-population will be
recruited. The additional burden for participating in this study is minimal and
the additional risk can be considered negligible. Because the treatment under
investigation is expected to increase the efficacy of ECT, patients may
directly benefit from participating in this study. The additional burden for
participating in the neuroimaging study can be considered minimal, and the
additional risk for eligible candidates is negligible. The additional burden
for blood sampling from the venous catheter that is already placed as part of
the ECT procedure can be considered minimal and the risk negligible.