Cognitive behavioral therapy in patients with deep brain stimulation for obsessive-compulsive disorder: a matched controlled study.

BACKGROUND: Deep brain stimulation (DBS) is effective for refractory obsessive-compulsive disorder (OCD). Post-operative cognitive behavioral therapy (CBT) may augment the effects of DBS, but previous results are conflicting. Here, we investigated whether CBT augments the effect of DBS for OCD. METHOD: Patients with and without CBT following DBS of the ventral anterior limb of the internal capsule were included. First, we analyzed Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Hamilton Depression Rating Scale (HAM-D) scores before, during and after CBT in all patients with CBT. Second, we matched patients with and without CBT based on clinical baseline variables and initial response to DBS and compared the course of Y-BOCS and HAM-D scores over the same timeframe. RESULTS: In total, 36 patients with and 16 patients without CBT were included. Average duration of CBT was 10.4 months (s.d. 6.4). In the 36 patients with CBT, Y-BOCS scores decreased on average by 3.8 points (14.8%) from start until end of CBT (p = 0.043). HAM-D scores did not decrease following CBT. Second, 10 patients with CBT were matched to 10 patients without CBT. In both groups, Y-BOCS scores decreased equally from start until end of CBT or over a similar timeframe (10% in CBT group v. 13.1% in no-CBT group, p = 0.741). CONCLUSIONS: Obsessive-compulsive symptoms decreased over time in patients with and without post-operative CBT. Therefore, further improvement may be attributed to late effects of DBS itself. The present study emphasizes the need for prospective randomized controlled studies, examining the effects of CBT.

Cyclic versus continuous deep brain stimulation in patients with obsessive compulsive disorder: A randomized controlled trial.

BACKGROUND: Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is effective for refractory obsessive-compulsive disorder (OCD), but patients typically require high stimulation voltages and DBS comes with a risk for adverse events (AE). OBJECTIVE: The aim of the present study was to advance DBS for OCD by optimizing energy efficiency and minimize adverse events using a cyclic form of stimulation METHODS: This double blind, randomized crossover trial compares 2 weeks of continuous versus cyclic DBS (0.1 s ON, 0.2 s OFF) in 16 patients with OCD. We compared OCD symptoms (Yale-Brown Obsessive-Compulsive Scale, Y-BOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), AEs, battery life, cognitive performance and quality of life. RESULTS: Average Y-BOCS scores at baseline increased significantly with 5.5 points (p = 0.006) in the cyclic condition. Average HAM-D and HAM-A scores increased with 2.2 (p = 0.088) and 2.8 points (p = 0.018). The overall health scale of quality of life worsened during cyclic DBS (p = 0.044). Patients reported on average 3.3 AEs during continuous stimulation and 4.4 AEs during cyclic stimulation (p = 0.175), though stimulation-related AEs such as headache and concentration problems reduced during cyclic DBS. Battery usage during continuous DBS was 0.021 V per hour compared to 0.008 V per hour during cyclic DBS. CONCLUSION: Though specific stimulation-related AEs improved, cyclic stimulation (0.1 s ON, 0.2 s OFF) comes with a high relapse risk in patients with DBS for OCD. Cyclic DBS is no alternative for standard DBS treatment, but applicable in case of debilitating AEs.

Tractography-based versus anatomical landmark-based targeting in vALIC deep brain stimulation for refractory obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is effective for refractory obsessive-compulsive disorder (OCD). Retrospective evaluation showed that stimulation closer to the supero-lateral branch of the medial forebrain bundle (slMFB), within the vALIC, was associated with better response to DBS. The present study is the first to compare outcomes of DBS targeted at the vALIC using anatomical landmarks and DBS with connectomic tractography-based targeting of the slMFB. We included 20 OCD-patients with anatomical landmark-based DBS of the vALIC that were propensity score matched to 20 patients with tractography-based targeting of electrodes in the slMFB. After one year, we compared severity of OCD, anxiety and depression symptoms, response rates, time to response, number of parameter adjustments, average current, medication usage and stimulation-related adverse effects. There was no difference in Y-BOCS decrease between patients with anatomical landmark-based and tractography-based DBS. Nine (45%) patients with anatomical landmark-based DBS and 13 (65%) patients with tractography-based DBS were responders (BF10 = 1.24). The course of depression and anxiety symptoms, time to response, number of stimulation adjustments or medication usage did not differ between groups. Patients with tractography-based DBS experienced fewer stimulation-related adverse effects than patients with anatomical landmark-based DBS (38 vs 58 transient and 1 vs. 17 lasting adverse effects; BF10 = 14.968). OCD symptoms in patients with anatomical landmark-based DBS of the vALIC and tractography-based DBS of the slMFB decrease equally, but patients with tractography-based DBS experience less adverse effects.

Effectiveness and safety of deep brain stimulation for patients with refractory obsessive compulsive disorder and comorbid autism spectrum disorder; A case series.

BACKGROUND: Deep brain stimulation (DBS) is effective for patients with treatment refractory obsessive-compulsive disorder (OCD). Autism spectrum disorder (ASD) is present in up to a third of all patients with OCD, but it is unknown whether effectiveness of DBS for OCD also applies for patients with comorbid ASD. The present case series is the first to examine effectiveness on OCD symptoms and safety of DBS in patients with OCD and ASD specifically. METHODS: Six consecutive patients with treatment-refractory OCD and comorbid ASD received DBS of the ventral anterior limb of the internal capsule (vALIC) or medial forebrain bundle (MFB). We examined effectiveness of DBS on symptoms of OCD and depression with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Hamilton Depression Rating Scale (HAM-D), respectively. We included qualitative data to describe the course of treatment in individual patients with OCD and ASD. RESULTS: We found that DBS significantly decreased symptoms of OCD (p < .001) and depression (p = .007). Four out of six patients with OCD and comorbid ASD were responders (decrease ≥ 35% in Y-BOCS), one patient was partial-responder (decrease 25-35% in Y-BOCS) and one patient did not respond (decrease ≤ 25% in Y-BOCS). Serious adverse events were an infection of the DBS system, and a suicide attempt. CONCLUSIONS: Though present results are preliminary, DBS reduced symptoms of OCD and depression in patients with OCD and comorbid ASD. Comorbid ASD should therefore not be seen as a contra-indication for DBS in OCD.

Why Has Deep Brain Stimulation Had So Little Impact in Psychiatry?

Over two decades ago, the first scientific publication on deep brain stimulation (DBS) in psychiatry was published. The evidence for effectiveness of DBS for several psychiatric disorders has been steadily accumulating since the first report of DBS for Obsessive Compulsive Disorder (OCD) in 1999. However, the number of psychiatric patients treated with DBS is lagging behind, particularly in comparison with neurology. The number of patients treated with DBS for psychiatric indications worldwide probably does not exceed 500, compared to almost 300,000 patients with neurological disorders that have been treated with DBS within the same period of 20 years. It is not the lack of patients, knowledge, technology, or efficacy of DBS that hinders its development and application in psychiatry. Here, we discuss the reasons for the gap between DBS in neurology and in psychiatry, which seemed to involve the scientific and social signature of psychiatry.

Predicting Response to vALIC Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder.

Background: Deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) is effective in half of patients, but also is invasive and labor-intensive.Objective: Selecting probable responders beforehand would more optimally allocate treatment resources and prevent patients' disappointment. Some centers use clinical and demographic predictors to exclude patients from DBS treatment, but the evidence base remains uncertain.Methods: This observational cohort study examined the association of baseline demographic and disease characteristics with a 1-year prospective course of OCD and depressive symptoms in a cohort of 70 consecutive patients who received DBS of the ventral anterior limb of the internal capsule (vALIC-DBS) for OCD according to DSM-IV or DSM-5 criteria between April 2005 and October 2017. Baseline characteristics and symptom decrease were analyzed using Fisher exact tests and binary logistic regression to examine whether they could predict individual response (> 35% reduction in Yale-Brown Obsessive Compulsive Scale score and 50% reduction in Hamilton Depression Rating Scale score, respectively).Results: Insight into illness was the only significant predictor of individual response, with a positive predictive value of 84.4%, while the negative predictive value was 44.0% (b = 0.247, χ21 = 5.259, P = .022). Late-onset OCD was associated with more symptom decrease (ß = -0.29; 95% CI, -0.53 to -0.04; P = .023) and comorbid personality disorder with less symptom decrease over time (ß = 0.88; 95% CI -0.29 to 1.47; P = .004), but they could not significantly predict vALIC-DBS response. A later age at onset, comorbid personality disorder, and insight into illness were associated with clinical outcomes after vALIC-DBS, but predictive values were not large enough to facilitate clinical patient selection.Conclusions: Clinical and demographic factors cannot yet predict outcome and should not be used to exclude patients from treatment with vALIC-DBS. These first individual prediction analyses for vALIC-DBS response in OCD are important, given that some centers up until now still exclude patients based on clinical characteristics such as comorbid personality disorders.

Deep brain stimulation response in obsessive-compulsive disorder is associated with preoperative nucleus accumbens volume.

BACKGROUND: Deep brain stimulation (DBS) is a new treatment option for patients with therapy-resistant obsessive-compulsive disorder (OCD). Approximately 60% of patients benefit from DBS, which might be improved if a biomarker could identify patients who are likely to respond. Therefore, we evaluated the use of preoperative structural magnetic resonance imaging (MRI) in predicting treatment outcome for OCD patients on the group- and individual-level. METHODS: In this retrospective study, we analyzed preoperative MRI data of a large cohort of patients who received DBS for OCD (n = 57). We used voxel-based morphometry to investigate whether grey matter (GM) or white matter (WM) volume surrounding the DBS electrode (nucleus accumbens (NAc), anterior thalamic radiation), and whole-brain GM/WM volume were associated with OCD severity and response status at 12-month follow-up. In addition, we performed machine learning analyses to predict treatment outcome at an individual-level and evaluated its performance using cross-validation. RESULTS: Larger preoperative left NAc volume was associated with lower OCD severity at 12-month follow-up (pFWE < 0.05). None of the individual-level regression/classification analyses exceeded chance-level performance. CONCLUSIONS: These results provide evidence that patients with larger NAc volumes show a better response to DBS, indicating that DBS success is partly determined by individual differences in brain anatomy. However, the results also indicate that structural MRI data alone does not provide sufficient information to guide clinical decision making at an individual level yet.

Invasive and Non-invasive Neurostimulation for OCD.

It becomes increasingly clear that (non-)invasive neurostimulation is an effective treatment for obsessive-compulsive disorder (OCD). In this chapter we review the available evidence on techniques and targets, clinical results including a meta-analysis, mechanisms of action, and animal research. We focus on deep brain stimulation (DBS), but also cover non-invasive neurostimulation including transcranial magnetic stimulation (TMS). Data shows that most DBS studies target the ventral capsule/ventral striatum (VC/VS), with an overall 76% response rate in treatment-refractory OCD. Also TMS holds clinical promise. Increased insight in the normalizing effects of neurostimulation on cortico-striatal-thalamic-cortical (CSTC) loops - through neuroimaging and animal research - provides novel opportunities to further optimize treatment strategies. Advancing clinical implementation of neurostimulation techniques is essential to ameliorate the lives of the many treatment-refractory OCD patients.

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.

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.

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.

Is deep brain stimulation effective and safe for patients with obsessive compulsive disorder and comorbid bipolar disorder?

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Bipolar disorder (BD) is generally considered a contra-indication for DBS due to frequently reported transient impulsivity or (hypo)mania. OBJECTIVE: The present study is the first study to examine effectiveness and safety of DBS for patients with OCD and BD. METHODS: Five consecutive patients suffering from treatment-refractory OCD with comorbid BD (I or II) underwent DBS of the ventral anterior limb of the internal capsule (vALIC). We examined effectiveness of DBS on symptoms of OCD and depression, using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Hamilton Depression Rating Scale (HAM-D). We monitored side-effects, in particular DBS-induced (hypo)manic symptoms, using the Young mania rating scale (YMRS). RESULTS: Follow-up time ranged between 15 and 68 months. vALIC-DBS led to a significant improvement of OCD and depressive symptoms. Mean Y-BOCS score decreased from 36.8 (SD 2.4) to 22.4 (SD 9.4). Mean HAM-D score dropped from 24.2 (SD 8.6) to 16.5 (SD 11.3). Transient hypomanic symptoms were observed in 4 out of 5 patients and in 1 patient, hypomanic symptoms resolved by adjusting stimulation and medication. Changes in YMRS scores were not significant. Hypomanic symptoms did not result in admission or lasting adverse consequences. CONCLUSION: DBS effectively alleviates symptoms of OCD and depression in patients with OCD and BD but there is a large risk of developing transient hypomanic symptoms. Altogether, comorbid BD should not be considered as an absolute contra-indication for DBS in OCD patients with comorbid BD, but patients should be monitored carefully during optimization and follow-up of DBS.

The application of deep brain stimulation in the treatment of psychiatric disorders.

Deep brain stimulation (DBS) is a last-resort treatment for neurological and psychiatric disorders that are refractory to standard treatment. Over the last decades, the progress of DBS in psychiatry has been slower than in neurology, in part owing to the heterogenic symptomatology and complex neuroanatomy of psychiatric disorders. However, for obsessive-compulsive disorder (OCD) DBS is now an accepted treatment. This study first reviews clinical outcomes and mechanisms of DBS for OCD, and then discusses these results in an overview of current and future psychiatric applications, including DBS for mood disorders, Tourette's syndrome, addiction, anorexia nervosa, autism, schizophrenia, and anxiety disorders. In addition, it will focus on novel techniques that may enhance the application of DBS in psychiatry.