86 Chapter 4 Another limitation is the variation in stimulation targets between the studies. Nevertheless, heterogeneity was low, suggesting that the different stimulation sites have comparable effects. Furthermore, the overall risk of bias of the included studies was moderate to serious. This could be improved by adding an independent assessor to the study. Also the quality of evidence was considered moderate for the more objective primary outcome, and low for the subjective outcome measurements. The pooled results showed statistically large effects suggesting clinical relevance, however more parameters should be taken into account to allow the conclusion of relevant clinical functional improvement. It is important to note that our meta-analysis showed a large beneficial effect of DBS on BMI, however not all patients reached BMI in a normal range at the end of the follow-up. Also, three included studies reported only somatic adverse events related to surgery or stimulation. Only one study reported psychiatric adverse events related to DBS (15). Finally, no international consensus has been reached on the definition of response to treatment or remission in anorexia nervosa in general, and of response to DBS in AN in particular. The included studies used heterogeneous definitions of response to DBS, therefore responder rates could not be determined. This study again emphasizes the need for such a consensus, as this would allow clinicians to assess the efficacy of this procedure. A major strength of this study was that it is the first meta-analysis of the effect of DBS in treatment-refractory AN. Thereby, we provide an overall estimate of the size of the effect and the strength and quality of the evidence for the efficacy of DBS in treatment-refractory AN. Research implications Results from this meta-analyse provide several new inroads for future research. A first point of focus are the differences and similarities of the diverse DBS targets that have been applied. Studies might focus on clinical and biological differences in effects, e.g. by applying advanced clinical phenotyping and diverse biological assessments including advanced (connectomic) neuroimaging. A second issue is prediction of response to improve patient selection. It would be helpful to identify factors that may predict response to DBS treatment in AN, and test whether the predictive value is strong enough for clinical implementation (46). A third aspect is the combination with psychotherapy. DBS studies in psychiatry for other indications suggested that DBS may improve the response to psychotherapeutic interventions. It would be worthwhile to test whether this is also the case for AN-patients, and whether psychotherapy may increase the effectiveness of DBS.
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