Cognitive and psychiatric outcomes in the GALAXY trial: effect of anaesthesia in deep brain stimulation.

BACKGROUND: This study aims: (1) To compare cognitive and psychiatric outcomes after bilateral awake versus asleep subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson's disease (PD). (2) To explore the occurrence of psychiatric diagnoses, cognitive impairment and quality of life after surgery in our whole sample. (3) To validate whether we can predict postoperative cognitive decline. METHODS: 110 patients with PD were randomised to receive awake (n=56) or asleep (n=54) STN DBS surgery. At baseline and 6-month follow-up, all patients underwent standardised assessments testing several cognitive domains, psychiatric symptoms and quality of life. RESULTS: There were no differences on neuropsychological composite scores and psychiatric symptoms between the groups, but we found small differences on individual tests and cognitive domains. The asleep group performed better on the Rey Auditory Verbal Learning Test delayed memory test (f=4.2, p=0.04), while the awake group improved on the Rivermead Behavioural Memory Test delayed memory test. (f=4.4, p=0.04). The Stroop III score was worse for the awake group (f=5.5, p=0.02). Worse scores were present for Stroop I (Stroop word card) (f=6.3, p=0.01), Stroop II (Stroop color card) (f=46.4, p<0.001), Stroop III (Stroop color-word card) (f=10.8, p=0.001) and Trailmaking B/A (f=4.5, p=0.04). Improvements were seen on quality of life: Parkinson's Disease Questionnaire-39 (f=24.8, p<0.001), and psychiatric scales: Hamilton Depression Rating Scale (f=6.2, p=0.01), and Hamilton Anxiety Rating Scale (f=5.5, p=0.02). CONCLUSIONS: This study suggests that the choice between awake and asleep STN DBS does not affect cognitive, mood and behavioural adverse effects, despite a minor difference in memory. STN DBS has a beneficial effect on quality of life, mood and anxiety symptoms. TRIAL REGISTRATION NUMBER: NTR5809.

A Multicenter Retrospective Chart Review on the Effectiveness and Tolerability of Electroconvulsive Therapy in Adolescents and Young Adults With Major Depressive Disorder or Bipolar Depression.

BACKGROUND: Major depressive disorder and bipolar depression in adolescents and young adults are prevalent and major contributors to the global burden of disease, whereas effective interventions are limited. Available evidence is insufficient to assess effectiveness and tolerability of electroconvulsive therapy in depressed adolescents and young adults. METHODS: A retrospective chart review was conducted in patients with major depressive disorder or bipolar depression who underwent electroconvulsive therapy from 2001 to 2021 in 12 centers in the Netherlands. Patients were classified as young (15-25 years) and older adults (26-80 years). Primary outcome was effectiveness, expressed as response (≥50% reduction in rating scale score compared with baseline) and remission. Rating scale scores were cross-sectionally assessed at baseline and at the end of the index course. Outcomes of remitters were included in responders. Secondary outcome was occurrence of subjective cognitive impairment and adverse events. Long-term outcomes were not available. RESULTS: In the young (n = 57) and older adult (n = 41) group, 40.4% and 56.1% (P = 0.153) of patients achieved response and 28.1% and 39.0% (P = 0.281) remission, respectively. Subjective cognitive impairment (80.5% vs 56.3%; P = 0.001) and transient cardiac arrhythmia (14.6% vs 2.8%; P = 0.020) were reported significantly more frequently in the older adult group. CONCLUSIONS: Despite significantly more comorbidity of personality disorders, autism spectrum disorders, and anxiety disorders, effectiveness in the young was similar to the older adults. Tolerability was even superior in the young, despite significantly more bilateral treatment. Electroconvulsive therapy could be considered a viable treatment option in depressed adolescents and young adults.

Deep brain stimulation normalizes amygdala responsivity in treatment-resistant depression.

Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is a promising intervention for treatment-resistant depression (TRD). However, the working mechanisms of vALIC DBS in TRD remain largely unexplored. As major depressive disorder has been associated with aberrant amygdala functioning, we investigated whether vALIC DBS affects amygdala responsivity and functional connectivity. To investigate the long-term effects of DBS, eleven patients with TRD performed an implicit emotional face-viewing paradigm during functional magnetic resonance imaging (fMRI) before DBS surgery and after DBS parameter optimization. Sixteen matched healthy controls performed the fMRI paradigm at two-time points to control for test-retest effects. To investigate the short-term effects of DBS de-activation after parameter optimization, thirteen patients additionally performed the fMRI paradigm after double-blind periods of active and sham stimulation. Results showed that TRD patients had decreased right amygdala responsivity compared to healthy controls at baseline. Long-term vALIC DBS normalized right amygdala responsivity, which was associated with faster reaction times. This effect was not dependent on emotional valence. Furthermore, active compared to sham DBS increased amygdala connectivity with sensorimotor and cingulate cortices, which was not significantly different between responders and non-responders. These results suggest that vALIC DBS restores amygdala responsivity and behavioral vigilance in TRD, which may contribute to the DBS-induced antidepressant effect.

Patient specific intracranial neural signatures of obsessions and compulsions in the ventral striatum.

Objective. Deep brain stimulation is a treatment option for patients with refractory obsessive-compulsive disorder. A new generation of stimulators hold promise for closed loop stimulation, with adaptive stimulation in response to biologic signals. Here we aimed to discover a suitable biomarker in the ventral striatum in patients with obsessive compulsive disorder using local field potentials.Approach.We induced obsessions and compulsions in 11 patients undergoing deep brain stimulation treatment using a symptom provocation task. Then we trained machine learning models to predict symptoms using the recorded intracranial signal from the deep brain stimulation electrodes.Main results.Average areas under the receiver operating characteristics curve were 62.1% for obsessions and 78.2% for compulsions for patient specific models. For obsessions it reached over 85% in one patient, whereas performance was near chance level when the model was trained across patients. Optimal performances for obsessions and compulsions was obtained at different recording sites.Significance. The results from this study suggest that closed loop stimulation may be a viable option for obsessive-compulsive disorder, but that intracranial biomarkers are patient and not disorder specific.Clinical Trial:Netherlands trial registry NL7486.

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.

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.

Augmenting neurocognitive remediation therapy to Preventive Cognitive Therapy for partially remitted depressed patients: protocol of a pragmatic multicentre randomised controlled trial.

INTRODUCTION: Major depressive disorder (MDD) affects 163 million people globally every year. Individuals who experience subsyndromal depressive symptoms during remission (ie, partial remission of MDD) are especially at risk for a return to a depressive episode within an average of 4 months. Simultaneously, partial remission of MDD is associated with work and (psycho)social impairment and a lower quality of life. Brief psychological interventions such as preventive cognitive therapy (PCT) can reduce depressive symptoms or relapse for patients in partial remission, although achieving full remission with treatment is still a clinical challenge. Treatment might be more effective if cognitive functioning of patients is targeted as well since cognitive problems are the most persisting symptom in partial remission and predict poor treatment response and worse functioning. Studies show that cognitive functioning of patients with (remitted) MDD can be improved by online neurocognitive remediation therapy (oNCRT). Augmenting oNCRT to PCT might improve treatment effects for these patients by strengthening their cognitive functioning alongside a psychological intervention. METHODS AND ANALYSIS: This study will examine the effectiveness of augmenting oNCRT to PCT in a pragmatic national multicentre superiority randomised controlled trial. We will include 115 adults partially remitted from MDD with subsyndromal depressive symptoms defined as a Hamilton Depression Rating Scale score between 8 and 15. Participants will be randomly allocated to PCT with oNCRT, or PCT only. Primary outcome measure is the effect on depressive symptomatology over 1 year. Secondary outcomes include time to relapse, cognitive functioning, quality of life and healthcare costs. This first dual approach study of augmenting oNCRT to PCT might facilitate full remission in partially remitted individuals as well as prevent relapse over time. ETHICS AND DISSEMINATION: Ethical approval was obtained by Academic Medical Center, Amsterdam. Outcomes will be made publicly available. TRIAL REGISTRATION NUMBER: NL9582.

The neurobiology of treatment-resistant depression: A systematic review of neuroimaging studies.

Treatment-resistant depression (TRD) is a debilitating condition associated with higher medical costs, increased illness burden, and reduced quality of life compared to non-treatment-resistant major depressive disorder (MDD). The question arises whether TRD can be considered a distinct MDD sub-type based on neurobiological features. To answer this question we conducted a systematic review of neuroimaging studies investigating the neurobiological differences between TRD and non-TRD. Our main findings are that patients with TRD show 1) reduced functional connectivity (FC) within the default mode network (DMN), 2) reduced FC between components of the DMN and other brain areas, and 3) hyperactivity of DMN regions. In addition, aberrant activity and FC in the occipital lobe may play a role in TRD. The main limitations of most studies were related to inherent confounding factors for comparing TRD with non-TRD, such as differences in disease chronicity/severity and medication history. Future studies may use prospective longitudinal neuroimaging designs to delineate which effects are present in treatment-naive patients and which effects are the result of disease progression.

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.

Deep brain stimulation versus ablative surgery for treatment-refractory obsessive-compulsive disorder: A meta-analysis.

OBJECTIVE: Ablative surgery (ABL) and deep brain stimulation (DBS) are last-resort treatment options for patients suffering from treatment-refractory obsessive-compulsive disorder (OCD). The aim of this study was to conduct an updated meta-analysis comparing the clinical outcomes of the ablative procedures capsulotomy and cingulotomy and deep brain stimulation. METHODS: We conducted a PubMed search to identify all clinical trials on capsulotomy, cingulotomy, and DBS. Random effects meta-analyses were performed on 38 articles with a primary focus on efficacy in reducing OCD symptoms as measured by a reduction in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score and the responder rate (≥35% reduction in Y-BOCS score). RESULTS: With responder rates of 48% and 53% after 12-16 months and 56% and 57% at last follow-up for ABL and DBS, respectively, and large effect sizes in the reduction in Y-BOCS scores, both surgical modalities show effectiveness in treating refractory OCD. Meta-regression did not show a statistically significant difference between ABL and DBS regarding these outcomes. Regarding adverse events, a statistically significant higher rate of impulsivity is reported in studies on DBS. CONCLUSION: This meta-analysis shows equal efficacy of ABL and DBS in the treatment of refractory OCD. For now, the choice of intervention should, therefore, rely on factors such as risk of developing impulsivity, patient preferences, and experiences of psychiatrist and neurosurgeon. Future research should provide more insight regarding differences between ABL and DBS and response prediction following direct comparisons between the surgical modalities, to enable personalized and legitimate choices between ABL and DBS.

Apathy Induced by Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis.

Apathy, the loss of motivation, is a common problem in Parkinson's disease (PD) and often observed following deep brain stimulation (DBS) of the subthalamic nucleus (STN). The aim of this meta-analysis was to determine the occurrence of apathy following STN DBS in literature. Relevant articles were searched in PubMed/Medline, SCOPUS, EMBASE, and Web of Sciences electronic databases. Studies were included if they reported apathy scores pre- and post-DBS or the cross-sectional difference between PD patients receiving STN DBS and patients receiving medication only. Thirty-three articles were included in the meta-analyses from 6,658 screened articles by two authors independently. A total of 1,286 patients were included with a mean age (±standard deviation [SD]) of 58.4 ± 8.5 years and a disease duration of 11.0 ± 5.8 years. The apathy score measured by means of the Apathy Evaluation Scale (AES), Starkstein Apathy Scale (SAS), and the Lille Apathy Rating Scale (LARS) was significantly higher after DBS than pre-operatively (g = 0.34, 95% confidence interval [CI] = 0.19-0.48, P < 0.001). An equal, significant difference in severity of apathy was found between STN DBS and medication only (g = 0.36, 95% CI = 0.03-0.65; P = 0.004). Statistical heterogeneity was moderately high, but the effects stood strong after multiple analyses and were independent of tapering off dopaminergic medication. The findings of this meta-analysis indicate that apathy is increased after STN DBS compared to the pre-operative state and to medication only (systematic review registration number: PROSPERO CRD42019133932). © 2020 Universiteit van Amsterdam. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

Cognitive behavioral therapy for misophonia: A randomized clinical trial.

BACKGROUND: Patients with misophonia suffer from anger or disgust confronted with specific sounds such as smacking or breathing. Avoidance of cue-related situations results in social isolation and significant functional impairment. This is the first randomized, controlled cognitive behavioral therapy (CBT) trial for misophonia, evaluating the short- and long-term efficacy. METHODS: The evaluator-blinded, randomized clinical trial was conducted from May 2017 until December 2018 at an academic outpatient clinic. Misophonia patients were randomly assigned to 3 months of weekly group-CBT or a waiting list and tested at baseline, 3 months (following CBT or waiting list), 6 months (after cross-over), and 15/18 months (1-year follow-up). CBT consisted of task concentration and arousal reduction, positive affect labeling, and stimulus manipulation. Co-primary outcomes were symptom severity assessed by the Amsterdam Misophonia Scale-Revised (AMISOS-R) and improvement on the Clinical Global Impression-Improvement (CGI-I). Secondary outcomes were self-assessed ratings of general psychopathology (Symptom Checklist-90-Revised [SCL-90-R]) and quality of life (five-dimensional EuroQol [EQ5-D], Sheehan Disability Scale [SDS], WHO Quality of Life-BREF [WHOQoL-BREF]). RESULTS: In all, 54 out of 71 patients were included (mean age, 33.06 [SD, 14.13] years; 38 women [70.4%]) and 46 (85%) completed the study. In the randomized phase, CBT resulted in statistically significant less misophonia symptoms in the short-term (-9.7 AMISOS-R; 95% CI, -12.0 to -7.4; p < .001, d = 1.97). The CBT group had an observed clinical improvement (CGI-I < 3) in 37% compared to 0% in the waiting list group (p < .001). The effect of CBT was maintained at 1-year follow-up on primary and secondary outcomes. CONCLUSIONS: This first randomized control trial shows both short-term and long-term efficacy of CBT for misophonia.

Distance to white matter trajectories is associated with treatment response to internal capsule deep brain stimulation in treatment-refractory depression.

BACKGROUND: Deep brain stimulation (DBS) is an innovative treatment for treatment-refractory depression. DBS is usually targeted at specific anatomical landmarks, with patients responding to DBS in approximately 50% of cases. Attention has recently shifted to white matter tracts to explain DBS response, with initial open-label trials targeting white matter tracts yielding much higher response rates (>70%). OBJECTIVE/HYPOTHESIS: Our aim was to associate distance to individual white matter tracts around the stimulation target in the ventral anterior limb of the internal capsule to treatment response. METHODS: We performed diffusion magnetic resonance tractography of the superolateral branch of the medial forebrain bundle and the anterior thalamic radiation in fourteen patients that participated in our randomized clinical trial. We combined the tract reconstructions with the postoperative images to identify the DBS leads and estimated the distance between tracts and leads, which we subsequently associated with treatment response. RESULTS: Stimulation closer to both tracts was significantly correlated to a larger symptom decrease (r = 0.61, p = 0.02), suggesting that stimulation more proximal to the tracts was beneficial. Biophysical modelling indicated that 37.5% of tracts were even outside the volume of activated tissue. There was no difference in lead placement with respect to anatomical landmarks, which could mean that differences in treatment response were driven by individual differences in white matter anatomy. CONCLUSIONS: Our results suggest that deep brain stimulation of the ventral anterior limb of the internal capsule could benefit from targeting white matter bundles. We recommend acquiring diffusion magnetic resonance data for each individual patient.

Long-term deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression.

OBJECTIVE: Deep brain stimulation (DBS) reduces depressive symptoms in approximately 40%-60% of patients with treatment-resistant depression (TRD), but data on long-term efficacy and safety are scarce. Our objective was to assess the efficacy and safety of DBS targeted at the ventral anterior limb of the internal capsule (vALIC) in 25 patients with TRD during a 1-year, open-label, maintenance period, which followed a 1-year optimisation period. METHODS: Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Montgomery-Asberg Depression Rating Scale (MADRS) and self-reported Inventory of Depressive Symptomatology (IDS-SR). Primary outcomes were response rate (≥50% HAM-D-17 score reduction) after the maintenance phase, approximately 2 years after DBS surgery, and changes in depression scores and occurrence of adverse events during the maintenance phase. RESULTS: Of 25 operated patients, 21 entered and 18 completed the maintenance phase. After the maintenance phase, eight patients were classified as responder (observed response rate: 44.4%; intention-to-treat: 32.0%). During the maintenance phase, HAM-D-17 and MADRS scores did not change, but the mean IDS-SR score decreased from 38.8 (95% CI 31.2 to 46.5) to 35.0 (95% CI 26.1 to 43.8) (p=0.008). Non-responders after optimisation did not improve during the maintenance phase. Four non-DBS-related serious adverse events occurred, including one suicide attempt. CONCLUSIONS: vALIC DBS for TRD showed continued efficacy 2 years after surgery, with symptoms remaining stable after optimisation as rated by clinicians and with patient ratings improving. This supports DBS as a viable treatment option for patients with TRD. TRIAL REGISTRATION NUMBER: NTR2118.

Treatment-resistant depression and suicidality.

BACKGROUND: Thirty percent of patients with treatment-resistant depression (TRD) attempt suicide at least once during their lifetime. However, it is unclear what the attempted and completed suicide incidences are in TRD patients after initiating a treatment, and whether specific treatments increase or decrease these incidences. METHODS: We searched PubMed systematically for studies of depressed patients who failed at least two antidepressant therapies and were followed for at least three months after initiating a treatment. We estimated attempted and completed suicide incidences using a Poisson meta-analysis. Given the lack of controlled comparisons, we used a meta-regression to estimate whether these incidences differed between treatments. RESULTS: We included 30 studies investigating suicidality in 32 TRD samples, undergoing deep brain stimulation (DBS, n = 9), vagal nerve stimulation (VNS, n = 9), electroconvulsive therapy (ECT, n = 5), treatment-as-usual (n = 3), capsulotomy (n = 2), cognitive behavioral therapy (n = 2), ketamine (n = 1), and epidural cortical stimulation (n = 1). The overall incidence of completed suicides was 0.47 per 100 patient years (95% CI: 0.22-1.00), and of attempted suicides 4.66 per 100 patient years (95% CI: 3.53-6.23). No differences were found in incidences following DBS, VNS or ECT. LIMITATIONS: Suicidality is poorly recorded in many studies limiting the number of studies available. CONCLUSIONS: The completed and attempted suicide incidences are high (0.47 and 4.66 per 100 patient years respectively), but these incidences did not differ between three end of the line treatments (DBS, VNS or ECT). Given the high suicide risk in TRD patients, clinical trials should consider suicidality as an explicit outcome measure.

Episodic memory following deep brain stimulation of the ventral anterior limb of the internal capsule and electroconvulsive therapy.

BACKGROUND: Electroconvulsive Therapy (ECT) and Deep Brain Stimulation (DBS) are effective treatments for patients with treatment-resistant depression (TRD). However, a common side effect of ECT is autobiographical memory loss (e.g., personal experiences), whereas the impact of DBS on autobiographical memories has never been established. OBJECTIVE: Comparing autobiographical memories following DBS and ECT. METHODS: In two hospitals in The Netherlands, we interviewed 25 TRD patients treated with DBS of the ventral anterior limb of the internal capsule (vALIC), 14 TRD patients treated with ECT and 22 healthy controls (HC) with the Autobiographical Memory Inventory - Short Form (AMI-SF) in a prospective, longitudinal study between March 2010 and August 2016. Patients treated with DBS were interviewed before surgery, after surgery, and twice during treatment over 122.7 (SD: ±22.2) weeks. Patients treated with ECT were tested before ECT, after six right unilateral (RUL) ECT sessions and twice following ECT over 65.1 (±9.3) weeks. Controls were tested four times over 81.5 (±15.6) weeks. RESULTS: Compared to HC, the AMI-SF score decreased faster in both TRD groups (P < 0.001). More specifically, AMI-SF score decreased in a comparable rate as HC after DBS surgery, but decreased more during treatment. The AMI-SF decrease in the ECT group was larger than both the DBS and HC groups. CONCLUSIONS: Both ECT and vALIC DBS result in a faster autobiographical memory decline compared to HC. DBS might have a negative impact on autobiographical memories, although less so than ECT. Future work should dissect whether DBS or characteristics of TRD cause this decline.

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.