*4.4. Adverse E*ff*ects*

The safety of SCC-DBS was subsequently assessed following the initial results of the e fficacy of DBS in treating TRD. In 2008, McNeely et al. conducted a trial on six patients with an average of 5.6 years of current MDE. They found that mood was significantly improved during the 1-year DBS treatment without serious cognitive deterioration [73]. Moreines et al. found that DBS treatment in both unipolar and bipolar TRD patients with at least 2 years of current MDE improved executive functions and stabilized their memory [76]. Similarly, SCC-DBS for 6 months followed by depression treatment in patients with MDD, who had increased negative emotional processing and/or reduced positive emotions, resulted in reduced negative emotional bias [53]. Martín-Blanco et al. reported that a 52-year-old female had a seizure after 5 weeks of DBS. As severe MDD may predispose patients to seizures, the authors recommended that patients should be evaluated for seizures before administering DBS and parameters might need to be adjusted to within safe ranges [52]. In a study in 2017 by McInerney et al. on 20 unipolar TRD patients with an average of 6.9 years of MDE, they reported that 11 patients responded at the end of the 12-month DBS without further deterioration of cognitive functions. They also found a correlation between verbal fluency and mood improvement, which could be predictive of the DBS response [14]. The side e ffects reported in this review range from mild symptoms, such as headaches, dizziness and gastrointestinal irritation [43,66], to more severe e ffects including suicidal ideation and device malfunction [15,67]. This reporting should not discourage the development of therapies. Indeed, many treatments including serotonin-selective reuptake inhibitors

have severe side e ffects, including increased fractures and suicidal ideations [77,78]. In the study of therapies, it is important to report these side e ffects and to note that these therapies are administered by a professional, whose role is to detect and modulate the therapies accordingly.
