*4.1. E*ff*ectiveness*

The two studies that assessed the e ffects of CBT added on to DBS both support its e ffectiveness. In the study by Denys et al., CBT was responsible for significant additional reduction of 22% on the Y-BOCS after optimal stimulation settings were achieved [14]. In the study by Tyagi et al., there was a trend for an additional improvement of 35% on the Y-BOCS (*p* = 0.09). Whereas this was not statistically significant, there is a clear trend towards significance for this finding and it constitutes a clinically relevant improvement. In our opinion the lack of a statistical significance may well be due to a power problem because of the very low number of included patients (*n* = 6). So contrary to the authors, who present this as a negative outcome, we consider this study in support of postoperative CBT.

In theory, the e ffectiveness of CBT may also depend on the preoperative cognitive state of the patient, as well as on the potential cognitive side e ffects of DBS. Whereas in patients with Parkinson's disease, cognitive side e ffects of DBS—especially of the subthalamic nucleus—have been associated with reduced processing speed and working memory [22], there is little evidence of any detrimental effect of DBS—of any target—on the cognitive performance of OCD patients [23]. Studies that do report on neuropsychological measures report no relevant change in cognitive performance after DBS [24], and in one case even an improvement in cognitive flexibility for STN DBS but not for VC/VS DBS [15]. None of the included papers report on problems administering CBT due to cognitive side e ffects.

There has been some discussion on whether the e ffects of CBT may depend on the DBS target. Mantione et al. sugges<sup>t</sup> that the e ffect of CBT in their study may be specific to stimulation of the NA, since NA DBS has a profound e ffect on anxiety and depression, as opposed to, e.g., DBS of the STN, which reduces compulsions without significant e ffects on mood and anxiety [11]. However, in the study by Tyagi et al., the additional improvement in patients with STN and VC/VS DBS is in the same range, if not larger than in the study by Mantione et al. [15]. Based on these scarce data, we expect CBT to be e ffective as add-on treatment to DBS in therapy-resistant OCD patients, irrespective of the stimulation target. However, only further studies comparing the e ffectiveness of CBT in OCD patients with di fferent DBS stimulation targets can reveal a potential target related e ffect of CBT.
