A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder

Abstract

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.

Fig. 1

Coronal brain atlas slices showing the location of the center of all 58 cathodes at 12 months follow-up (26 patients). Contacts are depicted with different symbols, according to the patient’s Y-BOCS improvement at 12 months follow-up (versus preoperative baseline): ● indicates less than 25% improvement, ▲ 25–35%, ■ 35–65% and ⋆ more than 65% improvement. One subject was excluded because, although the neurostimulator was on at Month 12, it was unclear for what actual duration the therapy had been delivered, due to low impedance. Note that three patients were stimulated with two or three contacts per hemisphere, whereas one patient was only stimulated with one active contact on the right side. All 22 other patients were stimulated bilaterally, with one cathode in each hemisphere. In the top left corner of each slice, the position anterior (−) or posterior (+) to the anterior commissure is specified. For each coronal slice, the right and left hemispheres are depicted adjacently, in accordance with the radiological convention (right hemisphere shown on the left side and vice versa). Instead of displaying complete coronal slices, a detailed window is shown, dorsally bordered by the corpus callosum and ventrally extending 10 mm below the intercommissural plane, as indicated in the bottom left panel. In addition, a sagittal view of the brain with indication of the relevant coronal slices is shown. ac anterior commissure, Ac nucleus accumbens, AIC anterior limb of the internal capsule, AM anteromedial thalamic nucleus, BST bed nucleus of the stria terminalis, cc corpus callosum, Cd caudate nucleus, EGP external globus pallidus, Fa fasciculosus nucleus, FCd fundus region of caudate nucleus, FLV frontal horn of lateral ventricle, FPu fundus region of putamen, fx fornix, IC internal capsule, IGP internal globus pallidus, ITP inferior thalamic peduncle, LH lateral hypothalamic area, lml lateral medullary lamina of globus pallidus, LS lateral septal nucleus; LV lateral ventricle, mfb medial forebrain bundle, mml medial medullary lamina of globus pallidus, MPO medial preoptic nucleus, Pa paraventricular hypothalamic nucleus, PRt prereticular zone, Pu putamen, PV paraventricular thalamic nucleus, Rt reticular thalamic nucleus, SCGP supracapsular part of globus pallidus, st stria terminalis, VA ventral anterior thalamic nucleus, 3V third ventricle. Images are adapted from Mai’s Atlas of the Human Brain [43]

Fig. 2

Frequency distribution of the individual patients’ Y-BOCS Total scores at each visit. Total n = 31 enrolled patients. Stimulation status: white = on bilateral, black = off, hatched = on unilateral. X-axis: Y-BOCS total score; Y-axis: count of patients

Fig. 3

Efficacy measurements’ changes across visits. n = 30 implanted patients. The blue circles and solid lines represent all patients. On the MADRS plot, the green squares and dotted line represent the 9 patients with baseline MDD. Scr screening visit, BL baseline visit, PS parameter selection visit. Error bars represent ± 1 standard error. Y-BOCS Yale–Brown Obsessive-Compulsive Scale, MADRS Montgomery-Åsberg Depression Rating Scale, GAF Global Assessment of Functioning, EQ-5D EuroQol group-5 Dimensional, YMRS Young Mania Rating Scale, CGI-I Clinician Global Impressions of Improvement, CGI-S Clinician Global Impressions of Severity