Optimizing Deep Brain Stimulation Parameters in Obsessive-Compulsive Disorder.

OBJECTIVES: Deep brain stimulation (DBS) is an innovative and effective treatment for patients with therapy-refractory obsessive-compulsive disorder (OCD). DBS offers unique opportunities for personalized care, but no guidelines on how to choose effective and safe stimulation parameters in patients with OCD are available. Our group gained relevant practical knowledge on DBS optimization by treating more than 80 OCD patients since 2005, the world's largest cohort. The article's objective is to share this experience. MATERIALS AND METHODS: We provide guiding principles for optimizing DBS stimulation parameters in OCD and discuss the neurobiological and clinical basis. RESULTS: Adjustments in stimulation parameters are performed in a fixed order. First, electrode contact activation is determined by the position of the electrodes on postoperative imaging. Second, voltage and pulse width are increased stepwise, enlarging both the chance of symptom reduction and of inducing side effects. Clinical evaluation of adjustments in stimulation parameters needs to take into account: 1) the particular temporal sequence in which the various OCD symptoms and DBS side-effects change; 2) the lack of robust response predictors; 3) the limited sensitivity of the Yale-Brown Obsessive-Compulsive Scale to assess DBS-induced changes in OCD symptoms; and 4) a patient's fitness for additional cognitive-behavioral therapy (CBT). CONCLUSIONS: Decision-making in stimulation parameter optimization needs to be sensitive to the particular time-courses on which various symptoms and side effects change.

Impulsivity and decision-making in obsessive-compulsive disorder after effective deep brain stimulation or treatment as usual.

OBJECTIVE: Impulsivity and impaired decision-making have been proposed as obsessive-compulsive disorder (OCD) endophenotypes, running in OCD and their healthy relatives independently of symptom severity and medication status. Deep brain stimulation (DBS) targeting the ventral limb of the internal capsule (vALIC) and the nucleus accumbens (Nacc) is an effective treatment strategy for treatment-refractory OCD. The effectiveness of vALIC-DBS for OCD has been linked to its effects on a frontostriatal network that is also implicated in reward, impulse control, and decision-making. While vALIC-DBS has been shown to restore reward dysfunction in OCD patients, little is known about the effects of vALIC-DBS on impulsivity and decision-making. The aim of the study was to compare cognitive impulsivity and decision-making between OCD patients undergoing effective vALIC-DBS or treatment as usual (TAU), and healthy controls. METHODS: We used decision-making performances under ambiguity on the Iowa Gambling Task and reflection impulsivity on the Beads Task to compare 20 OCD patients effectively treated with vALIC-DBS, 40 matched OCD patients undergoing effective TAU (medication and/or cognitive behavioural therapy), and 40 healthy subjects. Effective treatment was defined as at least 35% improvement of OCD symptoms. RESULTS: OCD patients, irrespective of treatment modality (DBS or TAU), showed increased reflection impulsivity and impaired decision-making compared to healthy controls. No differences were observed between OCD patients treated with DBS or TAU. CONCLUSION: OCD patients effectively treated with vALIC-DBS or TAU display increased reflection impulsivity and impaired decision-making independent of the type of treatment.

Deep brain stimulation for obsessive-compulsive disorders: long-term analysis of quality of life.

OBJECTIVE: To evaluate the long-term effects of deep brain stimulation (DBS) on quality of life (QOL) in therapy-refractory obsessive-compulsive disorder (OCD) patients. DESIGN: 16 patients who met Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV) criteria for OCD and were considered therapy-refractory were treated with DBS. Patients were assessed 1 month before device implantation (T0), at 8 months of active stimulation (T1) and at 3-5 years of active stimulation (T2). QOL was measured with the WHO Quality of Life Scale-Brief Version (WHOQOL-BREF) that covers physical, psychological, social and environmental domains. The study was conducted between April 2005 and January 2011 at the Academic Medical Center, Amsterdam, The Netherlands. RESULTS: At T1 and T2, we found significant improvement (p<0.05) in the general score and in the physical, psychological and environmental domains of WHOQOL-BREF. Between T1 and T2, the physical and psychological domains improved further (p<0.05). At T2, the general score improved by a total of 90%, the physical and psychological domains both improved by 39.5% and the environmental domain improved by 16%. The social domain did not change between baseline and follow-up assessments. CONCLUSIONS: In line with symptom improvement, patient's QOL improved in the general score and in three of the four WHOQOL-BREF domains. This suggests that the improvement caused by DBS is not limited to symptom reduction alone, but also has a positive influence on patients' perception of their physical, psychological, environmental and global QOL. CLINICAL TRIAL REGISTRATION: http://isrctn.org identifier: ISRCTN23255677.

Efficacy and quality of life after 6-9 years of deep brain stimulation for depression.

BACKGROUND: Given the invasiveness of deep brain stimulation (DBS), the effect should prove to be stable over the long-term and translate into an improvement of quality of life (QOL). OBJECTIVE: To study the effectiveness and QOL up to nine years after the DBS surgery. METHODS: We treated 25 adult patients with major depression with DBS of the ventral anterior limb of the internal capsule (vALIC). We followed them up naturalistically for 6-9 years after surgery (mean: 7.7 [SD:1.5] years), including a randomized crossover phase after the first year comparing sham with active DBS. Symptom severity was quantified using the Hamilton Depression Scale with response defined as a ≥50% decrease of the score compared to baseline. Quality of life was measured using the WHOQOL-BREF, assessing 5 domains (general, physical, psychological, social, environmental). RESULTS: Intention-to-treat response rates remained mostly stable from Year 3 to last follow-up (Year 3, 5 and 6: 40%; Year 4: 36%; Last observation: 44%). General, physical, psychological (all P < 0.001) and the environmental (P = 0.02) domain scores increased during DBS optimization and remained stable over the long term. No statistically significant changes were detected on the social domain. Patients scored significantly higher during active than sham DBS on the psychological, social and environmental domains, and trended towards a higher score on the general and physical domains. CONCLUSION: This study shows continued efficacy of vALIC DBS in depression, which translates into an improvement of QOL providing further support for DBS as a durable treatment for TRD.

Long-term Outcome of Deep Brain Stimulation of the Ventral Part of the Anterior Limb of the Internal Capsule in a Cohort of 50 Patients With Treatment-Refractory Obsessive-Compulsive Disorder.

BACKGROUND: Deep brain stimulation (DBS) is an effective intervention for patients with severe treatment-refractory obsessive-compulsive disorder (OCD). Our aim was to examine long-term effectiveness and tolerability of DBS and its impact on functioning and well-being. METHODS: Fifty patients with severe treatment-refractory OCD received DBS of the ventral part of the anterior limb of the internal capsule and were followed for at least 3 years following implantation (mean 6.8 ± 3 years). Primary effectiveness was assessed by change in Yale-Brown Obsessive Compulsive Scale scores. Secondary effectiveness measures included Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, World Health Organization Quality of Life Scale-Brief Version, Global Assessment of Functioning, and a scale assessing functioning in work, family, and social life. Adverse effects of DBS were examined with a structured interview (n = 38). RESULTS: At long-term follow-up, OCD symptoms decreased by 39% (p < .001), and half of the patients were responders (≥35% decrease of Yale-Brown Obsessive Compulsive Scale score). Anxiety and depressive symptoms decreased significantly, with reductions of 48% and 50%, respectively. The World Health Organization Quality of Life Scale-Brief Version general score improved significantly, as did 3 of 4 subdomains. Both clinician- and patient-rated functioning improved substantially (p < .001). The unemployment rate decreased from 78% at baseline to 58% at last follow-up (z = -1.90, p = .058), and 21 patients stopped or decreased psychotropic medication (z = -2.887, p = .004). Long-term adverse effects included cognitive complaints and fatigue. Serious adverse events included 1 suicide attempt, related to comorbid depression. CONCLUSIONS: Our results provide evidence that DBS of the ventral part of the anterior limb of the internal capsule is effective and tolerable for treatment-refractory OCD in the long term and improves functioning and overall well-being.

Efficacy of Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Refractory Obsessive-Compulsive Disorder: A Clinical Cohort of 70 Patients.

OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment option for patients with refractory obsessive-compulsive disorder (OCD). However, clinical experience with DBS for OCD remains limited. The authors examined the tolerability and effectiveness of DBS in an open study of patients with refractory OCD. METHODS: Seventy consecutive patients, including 16 patients from a previous trial, received bilateral DBS of the ventral anterior limb of the internal capsule (vALIC) between April 2005 and October 2017 and were followed for 12 months. Primary effectiveness was assessed by the change in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from baseline until the 12-month follow-up. Response was defined by a ≥35% decrease in Y-BOCS score, partial response was defined by a 25%-34% decrease, and nonresponse was defined by a <25% decrease. Secondary effectiveness measures were the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D). RESULTS: Y-BOCS, HAM-A, and HAM-D scores all decreased significantly during the first 12 months of DBS. Twelve months of DBS resulted in a mean Y-BOCS score decrease of 13.5 points (SD=9.4) (40% reduction; effect size=1.5). HAM-A scores decreased by 13.4 points (SD=9.7) (55%; effect size=1.4), and HAM-D scores decreased by 11.2 points (SD=8.8) (54%; effect size=1.3). At the 12-month follow-up, 36 of the 70 patients were categorized as responders (52%), 12 patients as partial responders (17%), and 22 patients as nonresponders (31%). Adverse events included transient symptoms of hypomania, agitation, impulsivity, and sleeping disorders. CONCLUSIONS: These results confirm the effectiveness and safety of DBS of the vALIC for patients with treatment-refractory OCD in a regular clinical setting.

Cost-effectiveness of deep brain stimulation versus treatment as usual for obsessive-compulsive disorder.

BACKGROUND: Deep Brain Stimulation (DBS) is effective for obsessive-compulsive disorder (OCD), but requires expensive medical procedures. To date, no study has examined the cost-effectiveness of DBS for OCD. OBJECTIVE: To perform the first economic evaluation of DBS for therapy refractory OCD. METHODS: We conducted a 2-year prospective, open cost-effectiveness study, comparing DBS (n = 17) with treatment as usual (TAU) (n = 11), with cost per Quality-Adjusted-Life-Year (QALY) as outcome measure. Apart from the base-case, or primary analysis, we conducted two practice-based scenarios: (1) standard care scenario, without research and innovation costs, and (2) rechargeable scenario, in which we assume the use of a rechargeable battery. Base-case and both scenarios were extrapolated to four years to estimate long-term cost-effectiveness. RESULTS: Compared to TAU, DBS provides an additional 0.26 QALY (SD = 0.16). Median cost per QALY gained is estimated at €141,446 for base-case, €115,916 for standard care and €65,394 for the rechargeable scenario. Extending the time-horizon to four years results in a median cost per QALY of €80,313 for base-case, €69,287 for standard care, and turned out to be cost-saving at €4678 per QALY for the rechargeable scenario. Assuming a willingness to pay threshold of €80,000/QALY, DBS, under base-case and standard care had 25% and 35% probability of being more cost-effective than TAU. With the rechargeable scenario and in all scenarios extrapolated to four years, the probability of cost-effectiveness was equal or higher than TAU. CONCLUSIONS: This study indicates DBS for OCD is cost-effective in the long-term, especially when rechargeable batteries are taken into account.

Rebound of affective symptoms following acute cessation of deep brain stimulation in obsessive-compulsive disorder.

BACKGROUND: Deep brain stimulation (DBS) is regarded as an effective way to treat refractory obsessive-compulsive disorder (OCD). Little is known about the effects of DBS cessation following a longer period of stimulation. OBJECTIVE: To determine the relapse and rebound effects of psychiatric symptoms, and their impact on Quality of Life (QoL) following acute cessation of DBS in OCD patients. METHODS: We included 16 out of 32 patients who were treated with DBS between April 2005 and January 2011 at the Academic Medical Center, Amsterdam. After treatment for at least one year, patients entered a 1-week phase in which DBS was switched off. We evaluated psychiatric symptoms and QoL at three time points: before DBS surgery (pre-DBS), following at least one year of DBS treatment (DBS-on) and following 1 week of DBS off (DBS-off). Psychiatric symptoms were assessed with the Yale-Brown obsessive-compulsive disorder scale (Y-BOCS), the Hamilton anxiety rating scale (HAM-A) and the Hamilton depression rating scale (HAM-D). QoL was assessed using the World Health Organization QOL scale (WHOQOL-Bref). RESULTS: Switching from DBS-on to DBS-off, Y-BOCS scores increased with 50%, HAM-A scores with 80% and HAM-D scores with 83%. In the DBS-off period, HAM-A and HAM-D scores exceeded pre-surgery levels with approximately 40%, suggesting a rebound phenomenon. Furthermore, a deterioration of physical and psychological QoL to levels comparable with pre-surgery was found during DBS-off. CONCLUSION: Acute DBS cessation causes a relapse of obsessions and compulsions and a rebound of anxiety and depression. Additionally, improvements on QoL disappear.

Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder.

Little is known about the underlying neural mechanism of deep brain stimulation (DBS). We found that DBS targeted at the nucleus accumbens (NAc) normalized NAc activity, reduced excessive connectivity between the NAc and prefrontal cortex, and decreased frontal low-frequency oscillations during symptom provocation in patients with obsessive-compulsive disorder. Our findings suggest that DBS is able to reduce maladaptive activity and connectivity of the stimulated region.