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• W3091567111 abstract "For over 10 years, electrical stimulation within the limbic corticosubcortical network has been evaluated for treating patients with severe obsessive-compulsive disorder (OCD) ( 1 Senova S. Clair A.-H. Palfi S. Yelnik J. Domenech P. Mallet L. Deep brain stimulation for refractory obsessive-compulsive disorder: Towards an individualised approach. Front Psychiatry. 2019; 10: 905 Crossref PubMed Scopus (23) Google Scholar ). High-frequency deep brain stimulation (DBS) of various targets has been tested, including the anteromedial part of the subthalamic nucleus (amSTN), nucleus accumbens (NAc), ventral capsule/ventral striatum, anterior limb of the internal capsule, bed nucleus of the stria terminalis, and inferior thalamic peduncle ( 1 Senova S. Clair A.-H. Palfi S. Yelnik J. Domenech P. Mallet L. Deep brain stimulation for refractory obsessive-compulsive disorder: Towards an individualised approach. Front Psychiatry. 2019; 10: 905 Crossref PubMed Scopus (23) Google Scholar ). So far, published data do not support superiority of any particular target, with a mean decrease of 45% in OCD severity for whichever target is stimulated and of about 25% in nonresponders ( 2 Kisely S. Hall K. Siskind D. Frater J. Olson S. Crompton D. Deep brain stimulation for obsessive-compulsive disorder: A systematic review and meta-analysis. Psychol Med. 2014; 44: 3533-3542 Crossref PubMed Scopus (56) Google Scholar , 3 Alonso P. Cuadras D. Gabriëls L. Denys D. Goodman W. Greenberg B.D. et al. Deep brain stimulation for obsessive-compulsive disorder: A meta-analysis of treatment outcome and predictors of response. PLoS One. 2015; 10e0133591 Crossref PubMed Scopus (178) Google Scholar ). A recent randomized double-blind crossover trial comparing the effects of amSTN or ventral capsule/ventral striatum DBS in 6 patients with severe OCD showed that both targets significantly reduced OCD symptoms 1 year after surgery, by 45% and 52.5%, respectively ( 4 Tyagi H. Apergis-Schoute A.M. Akram H. Foltynie T. Limousin P. Drummond L.M. et al. A randomised trial directly comparing ventral capsule and anteromedial subthalamic nucleus stimulation in obsessive compulsive disorder: Clinical and imaging evidence for dissociable effects. Biol Psychiatry. 2019; 85: 726-734 Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar ). Here, we tested the effects of amSTN, NAc, or caudate nucleus (CN) DBS in a randomized double-blind crossover trial (NCT01807403) in 8 patients (7 female/1 male; mean age = 42.5 ± 8.4 years) with severe and refractory OCD (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score at inclusion = 33.5 ± 4.31) (Figure 1A). The primary outcome was OCD severity measured using the Y-BOCS during 3 months of active DBS compared with OCD severity at inclusion (Figure 1A, B). We also assessed anxiety, depression, and quality of life (not shown). One patient (P06) prematurely ended the study at month 9 after attempting suicide; the patient’s OCD symptoms were unimproved during NAc or CN stimulation periods. The mean Y-BOCS score at the end of each double-blind active stimulation period was 24.1 ± 6.99 for amSTN DBS, 24.3 ± 6.21 for NAc DBS, and 28.4 ± 7.65 for CN DBS. During the randomized crossover periods, we found that Y-BOCS score was significantly decreased after active DBS of the amSTN (estimated marginal mean compared with baseline = 8.959 [SE = 1.955], p < .001), NAc (estimate = 8.561 [SE = 1.945], p < .001), and CN (estimate = 6.555 [SE = 1.855], p = .003). This corresponds to an average decrease of 25%, 22%, and 19%, with amSTN, NAc, and CN DBS, respectively. We found no significant differences in OCD severity between active DBS conditions during the randomized crossover period, nor when considering only the last visit of each double-blind phase (p > .10 for all comparisons) (Figure 1B). We did observe a significant decrease off DBS (sham) relative to inclusion (estimate = 7.158 [SE = 2.006], p = .003). We detected an order effect, whereby the stimulation benefit was larger after the first double-blind phase (estimate = 3.70 [SE = 1.55], p = .017). For 3 patients, the largest improvements were obtained with amSTN DBS, while this was observed with NAc DBS for 2 patients and with CN DBS for 1 patient. For 1 patient, amSTN DBS and NAc DBS were equivalent, and better than CN DBS. Anxiety, depression (Figure 1C), and quality of life were not significantly modified during the randomized crossover period. We tested for a lesioning effect but found no significant change in Y-BOCS score (Figure 1B) and anxiety, depression, and quality-of-life scores (not shown) after surgery (at month 3) relative to inclusion (p > .05 for all comparisons). At the end of the randomized period, patients were asked about which stimulation period they preferred. Six of 7 patients chose the amSTN, which we used for the following open phase. One patient chose the NAc, but we switched to amSTN DBS after 4 months owing to an absence of clear clinical benefit. At the end of the long-term follow-up period, all patients had amSTN DBS with a significant decrease in Y-BOCS score relative to inclusion (estimated marginal mean = 10.921 [SE = 2.004], p < .001). Three of 7 patients had >35% improvement, and 1 patient had a 27% improvement. We found a significant correlation between the open-phase stimulation of the amSTN and double-blind stimulation of the amSTN (Spearman’s r = .794, p = .0328). We also found a significant correlation between the open phase stimulation of the amSTN and double-blind stimulation of the CN (Spearman’s r = .833, p = .02). Overall, we observed 8 serious adverse events: 3 related to surgery (1 misplaced electrode [P01], and 2 infections [P02 and P05]); 3 related to amSTN DBS with postural instability, with falls in 1 patient (P02), and 1 patient with transient hypomanic status (P03); and 2 related to the disease, with increased anxiety in 1 patient (P08). Our study is the first to compare 3 distinct DBS targets in the same patients to treat severe and refractory OCD. Our Y-BOCS data suggest that amSTN DBS and NAc DBS are similarly effective for reducing OCD symptoms over a 3-month period of stimulation, with probably a weaker improvement with CN DBS. Despite this seemingly equivalent efficacy, almost all the patients blindly selected amSTN DBS when asked to identify the study period during which they felt the best in the double-blind phase, a complex subjective judgment that goes beyond standard psychopathological assessment of OCD symptomatology ( 5 de Haan S. Rietveld E. Stokhof M. Denys D. Effects of deep brain stimulation on the lived experience of obsessive-compulsive disorder patients: In-depth interviews with 18 patients. PLoS One. 2015; 10e0135524 Crossref PubMed Scopus (67) Google Scholar ). Consistent with our previous results ( 6 Mallet L. Polosan M. Jaafari N. Baup N. Welter M.-L. Fontaine D. et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008; 359: 2121-2134 Crossref PubMed Scopus (651) Google Scholar , 7 Mallet L. Du Montcel S.T. Clair A.-H. Arbus C. Bardinet E. Baup N. et al. Long-term effects of subthalamic stimulation in obsessive-compulsive disorder: Follow-up of a randomized controlled trial. Brain Stimul. 2019; 12: 1080-1082 Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar ), we observed a continuous and progressive improvement (66%) in OCD severity in 3 patients responsive to amSTN DBS in the long-term follow-up period, suggesting that time may be necessary for stimulation effects to manifest. However, amSTN DBS reduced OCD severity by <35% in 4 patients. Two of these patients had dysfunctional amSTN DBS electrodes, thus preventing accurate evaluation of the efficacy, although they also did not respond to NAc/CN DBS, despite in-depth testing during long-term follow-up (not shown). Interestingly, 1 of these 2 patients was the only hoarder of our sample, a condition identified as a resistance factor to neurosurgical approaches ( 8 Denys D. Mantione M. Figee M. van den Munckhof P. Koerselman F. Westenberg H. et al. Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. Arch Gen Psychiatry. 2010; 67: 1061-1068 Crossref PubMed Scopus (483) Google Scholar , 9 Gentil A.F. Lopes A.C. Dougherty D.D. Rück C. Mataix-Cols D. Lukacs T.L. et al. Hoarding symptoms and prediction of poor response to limbic system surgery for treatment-refractory obsessive-compulsive disorder: Clinical article. J Neurosurg. 2014; 121: 123-130 Crossref PubMed Scopus (15) Google Scholar ). Our results also suggest the possibility to determine responders from nonresponders quite early after stimulation initiation. Overall, our results confirm the significant improvement of OCD symptoms using DBS of different limbic deep brain structures for patients with severe and highly resistant OCD ( 1 Senova S. Clair A.-H. Palfi S. Yelnik J. Domenech P. Mallet L. Deep brain stimulation for refractory obsessive-compulsive disorder: Towards an individualised approach. Front Psychiatry. 2019; 10: 905 Crossref PubMed Scopus (23) Google Scholar ). Our limited sample size limits our ability to fully rule out order, sequence, and carryover effects. Further studies are needed to confirm our results and to identify the clinical features that predict DBS response in OCD patients, taking into account the relationship with the targeted structure ( 2 Kisely S. Hall K. Siskind D. Frater J. Olson S. Crompton D. Deep brain stimulation for obsessive-compulsive disorder: A systematic review and meta-analysis. Psychol Med. 2014; 44: 3533-3542 Crossref PubMed Scopus (56) Google Scholar , 3 Alonso P. Cuadras D. Gabriëls L. Denys D. Goodman W. Greenberg B.D. et al. Deep brain stimulation for obsessive-compulsive disorder: A meta-analysis of treatment outcome and predictors of response. PLoS One. 2015; 10e0133591 Crossref PubMed Scopus (178) Google Scholar , 4 Tyagi H. Apergis-Schoute A.M. Akram H. Foltynie T. Limousin P. Drummond L.M. et al. A randomised trial directly comparing ventral capsule and anteromedial subthalamic nucleus stimulation in obsessive compulsive disorder: Clinical and imaging evidence for dissociable effects. Biol Psychiatry. 2019; 85: 726-734 Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar ) and the effects of DBS on corticosubcortical network connectivity and activity ( 1 Senova S. Clair A.-H. Palfi S. Yelnik J. Domenech P. Mallet L. Deep brain stimulation for refractory obsessive-compulsive disorder: Towards an individualised approach. Front Psychiatry. 2019; 10: 905 Crossref PubMed Scopus (23) Google Scholar )." @default.
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• W3091567111 date "2021-11-01" @default.
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• W3091567111 title "Deep Brain Stimulation of the Subthalamic, Accumbens, or Caudate Nuclei for Patients With Severe Obsessive-Compulsive Disorder: A Randomized Crossover Controlled Study" @default.
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• W3091567111 doi "https://doi.org/10.1016/j.biopsych.2020.07.013" @default.
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