Fade away: Targeting negative schemas with electroconvulsive therapy

In part II (Chapter 2) of this thesis, we describe a systematic review of studies combining structural and functional neuroimaging in major depressive disorder (MDD). Only fourteen multimodal studies were identified, despite the extensive neuroimaging work that has been done over the past two decades. The multimodal neuroimaging studies showed no robust relationship between abnormalities in brain structure and brain function in MDD. The most consistent finding was that reduced gray or white matter integrity was associated with enhanced neural activity or connectivity in the default mode network (DMN). However, the number of studies was small, and the patient groups and neuroimaging methods appeared heterogeneous. Conclusions based on these studies were therefore premature.

During the recruitment period of patients for our prospective randomized clinical trial (RCT), we noticed that inclusion of our pre-defined patient group went very slow. Clinically, our impression was that treatment-resistant MDD-patients were sparsely referred for ECT. Therefore, we conducted an investigation of the application of ECT in The Netherlands (Chapter 3). We quantified the use of ECT in non-psychotic patients with persistent depressive episodes (i.e., > two years of duration) using data from the Dutch Healthcare Authority (NZa). Therewith, we established that only 1.2% of these patients in The Netherlands received ECT. Because according to the current clinical guidelines, ECT could have been considered in 26% of this group, we concluded that referral for ECT stagnates in our daily practice. This finding is alarming, because ECT is effective in patients with treatment-resistant as well as persistent variants of MDD. Reasons for underusing ECT are speculative, although influence of negative stigma may be expected. Also, exposure to - and experience with - ECT of psychiatrists (or residents in training) may be quite low, because within the >250 Dutch institutions for specialized mental health care (‘S-GGZ-instellingen’) only around 33 ECT-centers exist. This may lead to insufficient knowledge about ECT and - consequently – less recommendation of this treatment option to patients and their significant others.

In part III (chapter 4), we report on our RCT to enhance treatment efficacy and to reduce relapse-rate after ECT. In our study (n=66), we treated patients with an emotional memory reactivation intervention (EMR) or control condition just before the ECT-sessions. We found no evidence that this innovative strategy resulted in higher efficacy of ECT nor in a reduced relapse-rate after the ECT-course. A possible explanation of this negative finding was that our EMR cues, as well as the chosen detailed personalized emotional memory scripts, were not suitable (enough) to reactivate the underlying negative cognitive schemas. Although the observed strong emotions, that were experienced in patients after our EMR interventions, suggested a certain amount of reactivation, we did not evaluate specifically whether the personalized emotional memory had been weakened after a successful ECT-course. Despite that our experimental EMR intervention did not have an extra effect on response-rate nor relapse-rate, we once more confirmed that ECT was an effective treatment, even in patients suffering very severe and persistent MDD.

Cognitive psychotherapeutic treatments for MDD focus on the weakening of negative thoughts or negative schemas. In Chapter 5 it was shown that ECT (i.e., a biological treatment modality pur sang), very interestingly, also changed negative cognitive schemas in MDD-patients. After the ECT-course, patients reported significantly fewer negative thoughts and it seemed that change in negative cognitive schemas mediated depressive symptom improvement. Again, no additional effect of the EMR intervention prior to ECT-sessions was found, specifically not regarding the negative schemas. To our knowledge, this is the first study to show that ECT is able to change negative cognitive schemas in MDD-patients. Although the stigma around ECT remains large and its working mechanisms are still unclear, the efficacy of ECT in treating patients with (persistent) MDD is evident. This thesis adds to our current knowledge about ECT-efficacy, because it shows that not only improvement on vital depressive symptoms is established, but also negative thoughts may diminish after a course of ECT.