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BACKGROUND: Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain. METHODS: We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT. During an initial 3-week treatment phase, patients received either ECT three times per week or ketamine (0.5 mg per kilogram of body weight over 40 minutes) twice per week. The primary outcome was a response to treatment (i.e., a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report; scores range from 0 to 27, with higher scores indicating greater depression). The noninferiority margin was -10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. After the initial treatment phase, the patients who had a response were followed over a 6-month period. RESULTS: A total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24.2; P<0.001 for the noninferiority of ketamine to ECT). ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test-Revised, -0.9±1.1 in the ketamine group vs. -9.7±1.2 in the ECT group; scores range from -300 to 200, with higher scores indicating better function) with gradual recovery during follow-up. Improvement in patient-reported quality-of-life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation. CONCLUSIONS: Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis. (Funded by the Patient-Centered Outcomes Research Institute; ELEKT-D ClinicalTrials.gov number, NCT03113968.).
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Antidepresivos , Trastorno Depresivo Resistente al Tratamiento , Terapia Electroconvulsiva , Ketamina , Humanos , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/terapia , Terapia Electroconvulsiva/efectos adversos , Ketamina/administración & dosificación , Ketamina/efectos adversos , Ketamina/uso terapéutico , Calidad de Vida , Resultado del Tratamiento , Antidepresivos/administración & dosificación , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Trastorno Depresivo Resistente al Tratamiento/diagnóstico , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/terapia , Administración Intravenosa , Trastornos PsicóticosRESUMEN
OBJECTIVE: Deep brain stimulation (DBS) for pain has largely been implemented in an uncontrolled manner to target the somatosensory component of pain, with research leading to mixed results. We have previously shown that patients with poststroke pain syndrome who were treated with DBS targeting the ventral striatum/anterior limb of the internal capsule (VS/ALIC) demonstrated a significant improvement in measures related to the affective sphere of pain. In this study, we sought to determine how DBS targeting the VS/ALIC modifies brain activation in response to pain. MATERIALS AND METHODS: Five patients with poststroke pain syndrome who were blinded to DBS status (ON/OFF) and six age- and sex-matched healthy controls underwent functional magnetic resonance imaging (fMRI) measuring blood oxygen level-dependent activation in a block design. In this design, each participant received heat stimuli to the affected or unaffected wrist area. Statistical comparisons were performed using fMRI z-maps. RESULTS: In response to pain, patients in the DBS OFF state showed significant activation (p < 0.001) in the same regions as healthy controls (thalamus, insula, and operculum) and in additional regions (orbitofrontal and superior convexity cortical areas). DBS significantly reduced activation of these additional regions and introduced foci of significant inhibitory activation (p < 0.001) in the hippocampi when painful stimulation was applied to the affected side. CONCLUSIONS: These findings suggest that DBS of the VS/ALIC modulates affective neural networks.
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Estimulación Encefálica Profunda , Estriado Ventral , Humanos , Cápsula Interna/diagnóstico por imagen , Imagen por Resonancia Magnética , DolorRESUMEN
Poststroke pain syndrome (PSPS) is an often intractable disorder characterized by hemiparesis associated with unrelenting chronic pain. Although traditional analgesics have largely failed, integrative approaches targeting affective-cognitive spheres have started to show promise. Recently, we demonstrated that deep brain stimulation (DBS) of the ventral striatal area significantly improved the affective sphere of pain in patients with PSPS. In the present study, we examined whether electrophysiological correlates of pain anticipation were modulated by DBS that could serve as signatures of treatment effects. We recorded event-related fields (ERFs) of pain anticipation using magnetoencephalography (MEG) in 10 patients with PSPS preoperatively and postoperatively in DBS OFF and ON states. Simple visual cues evoked anticipation as patients awaited a painful (PS) or nonpainful stimulus (NPS) to the nonaffected or affected extremity. Preoperatively, ERFs showed no difference between PS and NPS anticipation to the affected extremity, possibly due to loss of salience in a network saturated by pain experience. DBS significantly modulated the early N1, consistent with improvements in affective networks involving restoration of salience and discrimination capacity. Additionally, DBS suppressed the posterior P2 (aberrant anticipatory anxiety) while enhancing the anterior N1 (cognitive and emotional regulation) in responders. DBS-induced changes in ERFs could potentially serve as signatures for clinical outcomes. NEW & NOTEWORTHY We examined the electrophysiological correlates of pain affect in poststroke pain patients who underwent deep brain stimulation (DBS) targeting the ventral striatal area under a randomized, controlled trial. DBS significantly modulated early event-related components, particularly N1 and P2, measured with magnetoencephalography during a pain anticipatory task, compared with baseline and the DBS-OFF condition, pointing to possible mechanisms of action. DBS-induced changes in event-related fields could potentially serve as biomarkers for clinical outcomes.
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Síndromes de Dolor Regional Complejo/terapia , Cuerpo Estriado/fisiopatología , Estimulación Encefálica Profunda/métodos , Accidente Cerebrovascular/complicaciones , Adulto , Anticipación Psicológica , Síndromes de Dolor Regional Complejo/etiología , Potenciales Evocados , Femenino , Humanos , Magnetoencefalografía , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The experience with deep brain stimulation (DBS) for pain is largely based on uncontrolled studies targeting the somatosensory pathways, with mixed results. We hypothesized that targeting limbic neural pathways would modulate the affective sphere of pain and alleviate suffering. METHODS: We conducted a prospective, double-blinded, randomized, placebo-controlled, crossover study of DBS targeting the ventral striatum/anterior limb of the internal capsule (VS/ALIC) in 10 patients with poststroke pain syndrome. One month after bilateral DBS, patients were randomized to active DBS or sham for 3 months, followed by crossover for another 3-month period. The primary endpoint was a ≥50% improvement on the Pain Disability Index in 50% of patients with active DBS compared to sham. This 6-month blinded phase was followed by an 18-month open stimulation phase. RESULTS: Nine participants completed randomization. Although this trial was negative for its primary and secondary endpoints, we did observe significant differences in multiple outcome measures related to the affective sphere of pain (eg, Montgomery-Åsberg Depression Rating Scale, Beck Depression Inventory, Affective Pain Rating Index of the Short-Form McGill Pain Questionnaire). Fourteen serious adverse events were recorded and resolved. INTERPRETATION: VS/ALIC DBS to modulate the affective sphere of pain represents a paradigm shift in chronic pain management. Although this exploratory study was negative for its primary endpoint, VS/ALIC DBS demonstrated an acceptable safety profile and statistically significant improvements on multiple outcome measures related to the affective sphere of pain. Therefore, we believe these results justify further work on neuromodulation therapies targeting the affective sphere of pain. Ann Neurol 2017;81:653-663.
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Dolor Crónico , Estimulación Encefálica Profunda/métodos , Cápsula Interna , Neuralgia , Evaluación de Resultado en la Atención de Salud , Accidente Cerebrovascular/complicaciones , Estriado Ventral , Adulto , Dolor Crónico/etiología , Dolor Crónico/psicología , Dolor Crónico/terapia , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuralgia/etiología , Neuralgia/psicología , Neuralgia/terapia , Dimensión del Dolor , Estudios ProspectivosRESUMEN
BACKGROUND: We report the neuropsychological outcome of 25 patients with treatment-resistant major depressive disorder (TRD) who participated in an Institutional Review Board (IRB)-approved randomised double-blind trial comparing active to sham deep brain stimulation (DBS) in the anterior limb of the ventral capsule/ventral striatum (VC/VS). METHODS: Participants were randomised to active (n=12) versus sham (n=13) DBS for 16â weeks. Data were analysed at the individual and group levels. Group differences were analysed using repeated measures ANOVAs. Relationships between depression severity and cognition were examined using partial correlations. The false discovery rate method controlled for multiple analyses. RESULTS: No significant interactions comparing active versus sham stimulation over time were evident. Change in depression was unrelated to change in neuropsychological measures. Twenty patients declined by ≥1 SD on at least one measure (41.3% of declines occurred in active group participants; 63.0% in older participants regardless of stimulation status). Twenty-two patients exhibited improvements >1 SD on neuropsychological measures (47.7% in the active group; 63.1% in younger participants). CONCLUSIONS: These data suggest that VC/VS DBS in patients with TRD does not significantly affect neuropsychological function. Age at surgery, regardless of stimulation status, may be related to cognitive outcome at the individual patient level. TRIAL REGISTRATION NUMBER: NCT00837486; Results.
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Cognición/fisiología , Estimulación Encefálica Profunda , Trastorno Depresivo Resistente al Tratamiento/terapia , Estriado Ventral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Resultado del TratamientoRESUMEN
BACKGROUND: Neurostimulation as a treatment option for refractory neuropsychiatric disorders has been increasingly utilized in recent years. For patients with such refractory disorders who have often failed to respond to various medical interventions, deep brain stimulation (DBS) has emerged as a promising treatment modality. DBS is a reversible and adjustable form of brain stimulation (also known as functional neurosurgery) in which desired brain structures (or circuits) are given focal electric stimulation via electrodes that are implanted in the brain tissue during a surgical procedure. It has been utilized among various psychiatric and neurological illnesses, in particular headache disorders. This article reviews the most relevant data regarding DBS for psychiatric and primary headache disorders. METHODS: Authors conducted a detailed literature search of Medline/PubMed database and studies that used DBS for the treatment of refractory neuropsychiatric disorders were reviewed. Response, remission, and safety measures of these studies were obtained. RESULTS: Despite the advancement in DBS treatment, the number of randomized controlled studies remains very limited due to ethical and methodological difficulties of setting up invasive procedures of this magnitude. So at present, DBS represents a modality used only in the most refractory patients. CONCLUSION: Current data support DBS as a promising treatment option for neuropsychiatric disorders that do not respond to conventional treatments; however, it is clear that more research and patient volume is needed to demonstrate its efficacy in treating these conditions. The use of functional imaging to understand the pathophysiology of these disorders has been crucial for the utilization of DBS.
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Estimulación Encefálica Profunda/métodos , Trastornos de Cefalalgia/terapia , Trastornos Mentales/terapia , Bases de Datos Bibliográficas/estadística & datos numéricos , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Deep brain stimulation (DBS) has shown promise as a treatment for severe, highly treatment-refractory obsessive-compulsive disorder (OCD) or major depressive disorder (MDD). We describe the neuropsychological outcome in 21 patients (10 OCD and 11 MDD) who received DBS in the anterior limb of the internal capsule/ventral striatum (VC/VS). METHODS: All patients completed a preoperative and postoperative neuropsychological battery. Average duration of DBS stimulation was 8.91 months (SD = 4.63) at the time of follow-up testing. Data were analyzed using practice-effect-corrected change scores. RESULTS: No significant cognitive declines were seen. There were significant improvements in prose passage recall after chronic DBS. The cognitive improvements were not related to change in severity of OCD, depression or global impairment. CONCLUSIONS: This preliminary study suggests that VC/VS DBS does not result in cognitive declines. The observations that verbal memory improved are consistent with current theories on the role of the VS in the memory, but require replication in larger studies.
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Ganglios Basales/fisiopatología , Estimulación Encefálica Profunda , Trastorno Depresivo Mayor/terapia , Cápsula Interna/fisiopatología , Trastorno Obsesivo Compulsivo/terapia , Adulto , Trastorno Depresivo Mayor/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/fisiopatología , Resultado del TratamientoRESUMEN
OBJECTIVES: To review the current state of cerebral stimulation for neuropathic pain and to propose that cerebral stimulation should aim also at the affective sphere of chronic pain rather than solely focusing on the primary sensory-discriminative sphere. METHODS: The past and current goals of cerebral stimulation are reviewed as well as its limitations. A novel deep brain stimulation approach is proposed to evaluate this conceptual shift from somatosensory to affective sphere of pain targeting. APPROACH: Thalamic and other central pain syndromes are typically intractable to current treatment methods, including cerebral neuromodulation of somatosensory pathways, leading to long-term distress and disability. Our modern understanding of chronic pain pathophysiology is based largely on the neuromatrix theory, where cognitive, affective, and sensory-discriminative spheres contribute equally to the overall pain experience. During the last decade, the safety and feasibility of chronic stimulation of neural pathways related to mood and affect has been explored with promising results. Here, we propose a novel approach to modulate the affective sphere of chronic pain by targeting similar networks in patients with treatment-refractory central pain. Our primary goal is not to produce (or measure) analgesia, but rather to modulate the affective burden of chronic pain. DISCUSSION: Cerebral neuromodulation for neuropathic pain has had limited efficacy thus far. Shifting our aim to neural networks related to the affective sphere of pain may allow us to reduce pain conditioning and pain-related disability. Our ultimate goal is to promote rehabilitation from chronic pain-social and occupational.
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Síntomas Afectivos/terapia , Estimulación Encefálica Profunda/métodos , Neuralgia/terapia , Síntomas Afectivos/fisiopatología , Animales , Encéfalo/fisiopatología , Dolor Crónico/fisiopatología , Dolor Crónico/terapia , Humanos , Neuralgia/fisiopatologíaRESUMEN
OBJECTIVE: Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress. DESIGN: The ASSFN convened a meeting on June 3, 2022 in Atlanta, Georgia and included leaders from the fields of neurology, neurosurgery, and psychiatry along with colleagues from industry, government, ethics, and law. The goal was to review the current state of the field, assess for advances or setbacks in the interim six years, and suggest a future path forward. The participants focused on five areas of interest: interdisciplinary engagement, regulatory pathways and trial design, disease biomarkers, ethics of psychiatric surgery, and resource allocation/prioritization. The proceedings are summarized here. CONCLUSION: The field of surgical psychiatry has made significant progress since our last expert meeting. Although weakness and threats to the development of novel surgical therapies exist, the identified strengths and opportunities promise to move the field through methodically rigorous and biologically-based approaches. The experts agree that ethics, law, patient engagement, and multidisciplinary teams will be critical to any potential growth in this area.
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Estimulación Encefálica Profunda , Trastornos Mentales , Neurocirugia , Psicocirugía , Humanos , Estados Unidos , Procedimientos Neuroquirúrgicos , Trastornos Mentales/cirugíaRESUMEN
OBJECTIVE: The underlying hypothesis of our work is that specific clinical neuropsychiatric benefits can be achieved by selective activation of specific axonal pathways during deep brain stimulation (DBS). As such, the goal of this study was to develop a method for identifying axonal pathways whose activation is most likely necessary for achieving therapeutic benefits during DBS. EXPERIMENTAL DESIGN: Our approach combined clinical data, diffusion tensor tractography, and computer models of patient-specific neurostimulation to identify particular axonal pathways activated by DBS and determine their correlations with individual clinical outcome measures. We used this method to evaluate a cohort of seven treatment-resistant depression patients treated with DBS of the ventral anterior internal capsule and ventral striatum (VC/VS). PRINCIPAL OBSERVATIONS: Clinical responders exhibited five axonal pathways that were consistently activated by DBS. All five pathways coursed lateral and medial to the VS or dorsal and lateral to the nucleus accumbens; however, details of their specific trajectories differed. Similarly, one common pathway was identified across nonresponders. CONCLUSIONS: Our method and preliminary results provide important background for studies aiming to expand scientific characterization of neural circuitry associated with specific psychiatric outcomes from DBS. Furthermore, identification of pathways linked to therapeutic benefit provides opportunities to improve clinical selection of surgical targets and stimulation settings for DBS devices.
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Axones , Mapeo Encefálico , Estimulación Encefálica Profunda , Depresión/patología , Vías Nerviosas/citología , Adulto , Ensayos Clínicos como Asunto , Simulación por Computador , Depresión/terapia , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Resultado del Tratamiento , Adulto JovenRESUMEN
Major depressive disorder is a serious medical illness which is responsible for considerable morbidity and disability. Despite decades of research, the neural basis for depression is still incompletely understood. In this review, evidence from neuroimaging, neuropsychiatric and brain stimulations studies are explored to answer the question regarding the localization of depression in the brain. Neuroimaging studies indicate that although many regions of the brain have been repeatedly implicated in the pathophysiology of depression, not many consistent findings have been found until present. In recent times, the focus of neuroimaging has shifted from regional brain abnormalities to circuit level connectivity abnormalities. However, connectivity models are inherently more complicated, and the validity of these models remains to be tested. Neuropsychiatric studies of illnesses such as Parkinson's disease and stroke provide promising clues regarding areas involved in depression, but again consistent findings are rare. Similarly, stimulation of a variety of brain regions and circuits has been reported as being effective in depression. Therefore, the current knowledge indicates that the pathophysiology of depression may be distributed across many brain regions and circuits. In future studies, this distributed nature of depression needs to be further investigated, primary and secondary areas affected need to be identified, and new paradigms to explain complex mental functions need to be explored.
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Encéfalo/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Terapia por Estimulación Eléctrica/métodos , Neuroimagen/métodos , Mapeo Encefálico , Trastorno Depresivo Mayor/terapia , Humanos , Enfermedad de Huntington/fisiopatología , Enfermedad de Parkinson/fisiopatologíaRESUMEN
OBJECTIVE: Past neuroimaging work has suggested that increased activation to cognitive and emotional tasks and decreased connectivity in frontal regions are related to cognitive inefficiency in depression; normalization of these relationships has been associated with successful treatment. The present study investigated brain function before and after electroconvulsive therapy (ECT) in patients with major depressive disorder (MDD) and demonstrated the effect of treatment on cortical activation patterns. METHODS: Six ECT-naive patients with depression (mean ± SD age, 39.0 ± 5.4 years) were treated with ECT. Within 1 week before and 1 to 3 weeks after ECT, the patients underwent a magnetic resonance imaging session with functional magnetic resonance image scanning during working memory and affective tasks and during rest. Changes in voxelwise statistical maps of brain response to each task in regions identified to be relevant from past studies of depression were compared with changes in depression severity as measured by the Hamilton Depression Rating Score. Changes in functional connectivity between brain regions were also compared with changes in depression severity. RESULTS: Activation during both tasks was generally found to be decreased after ECT. Remission of depression was significantly associated with reduced affective deactivation after ECT in the orbitofrontal cortex (P = 0.03). Whole-brain functional connectivity of the anterior cingulate cortex showed a consistent increase in connectivity to the right dorsolateral prefrontal cortex and posterior cingulate cortex after ECT. CONCLUSIONS: These results suggest that successful ECT for MDD is associated with decreased activation to cognitive and emotional tasks and an increase in resting connectivity.
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Encéfalo/fisiopatología , Depresión/fisiopatología , Depresión/terapia , Terapia Electroconvulsiva , Adulto , Mapeo Encefálico , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/psicología , Emociones/fisiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiología , Pruebas Neuropsicológicas , Corteza Prefrontal/fisiología , Corteza Prefrontal/fisiopatología , Escalas de Valoración PsiquiátricaRESUMEN
Obsessive-compulsive disorder (OCD), a leading cause of disability, affects ~1-2% of the population, and can be distressing and disabling. About 1/3 of individuals demonstrate poor responsiveness to conventional treatments. A small proportion of these individuals may be deep brain stimulation (DBS) candidates. Candidacy is assessed through a multidisciplinary process including assessment of illness severity, chronicity, and functional impact. Optimization failure, despite multiple treatments, is critical during screening. Few patients nationwide are eligible for OCD DBS and thus a multi-center approach was necessary to obtain adequate sample size. The study was conducted over a six-year period and was a NIH-funded, eight-center sham-controlled trial of DBS targeting the ventral capsule/ventral striatum (VC/VS) region. There were 269 individuals who initially contacted the sites, in order to achieve 27 participants enrolled. Study enrollment required extensive review for eligibility, which was overseen by an independent advisory board. Disabling OCD had to be persistent for ≥5 years despite exhaustive medication and behavioral treatment. The final cohort was derived from a detailed consent process that included consent monitoring. Mean illness duration was 27.2 years. OCD symptom subtypes and psychiatric comorbidities varied, but all had severe disability with impaired quality of life and functioning. Participants were randomized to receive sham or active DBS for three months. Following this period, all participants received active DBS. Treatment assignment was masked to participants and raters and assessments were blinded. The final sample was consistent in demographic characteristics and clinical features when compared to other contemporary published prospective studies of OCD DBS. We report the clinical trial design, methods, and general demographics of this OCD DBS sample.
RESUMEN
Major depressive disorder (MDD) is the most common mental illness and the leading cause of disability worldwide. Electroconvulsive therapy (ECT) is the most effective treatment for MDD and the gold-standard therapy for treatment-resistant depression (TRD), yet it remains underutilized due to factors such as limited availability, stigma, and concerns about cognitive side effects. Ketamine has emerged as the first rapid-acting antidepressant and shows robust short-term efficacy in clinical trials, but there are concerns about its long-term safety and efficacy. While response rates are similar between ECT and ketamine in clinical trials, these treatments have never been compared head-to-head in a sufficiently large, well-powered randomized study. Here we describe the study protocol for ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression (ELEKT-D), a non-inferiority, comparative effectiveness trial. Patients with TRD seeking clinical treatment are randomized (1:1) to receive ECT (thrice weekly) or intravenous ketamine (twice weekly) for 3-5â¯weeks. The primary outcome is the proportion of responders in each group at the end of study visit, as measured by a patient-reported outcome measure (Quick Inventory of Depressive Symptomatology-Self Report). The study is powered such that the non-inferiority margin allows for ketamine to retain 90% of the ECT treatment effect, with a projected sample size of 400 patients (200 per group). Secondary outcomes include remission rates, depression severity, cognitive functioning, quality of life, adverse events, and tolerability. The results of the ELEKT-D study will have important implications for patient choice, clinical practice, and health insurance policies.
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Trastorno Depresivo Resistente al Tratamiento/terapia , Terapia Electroconvulsiva/métodos , Ketamina/uso terapéutico , Adulto , Anciano , Antidepresivos/uso terapéutico , Cognición , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Terapia Electroconvulsiva/efectos adversos , Estudios de Equivalencia como Asunto , Femenino , Humanos , Ketamina/administración & dosificación , Ketamina/efectos adversos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
(Reprinted with permission from Frontiers of Neuroscience, 12:175. Copyright © 2018 Widge, Malone, and Dougherty).
RESUMEN
Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial "failures" are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this "valley of disillusionment," DBS may be nearing a "slope of enlightenment." Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.
RESUMEN
Deep brain stimulation (DBS) of the anterior limb of the internal capsule has been shown to be beneficial in the short term for obsessive-compulsive disorder (OCD) patients who exhaust conventional therapies. Nuttin et al, who published the first DBS for OCD series, found promising results using a capsule target immediately rostral to the anterior commissure extending into adjacent ventral capsule/ventral striatum (VC/VS). Published long-term outcome data are limited to four patients. In this collaborative study, 10 adult OCD patients meeting stringent criteria for severity and treatment resistance had quadripolar stimulating leads implanted bilaterally in the VC/VS. DBS was activated openly 3 weeks later. Eight patients have been followed for at least 36 months. Group Yale-Brown Obsessive Compulsive Scale (YBOCS) scores decreased from 34.6+/-0.6 (mean+/-SEM) at baseline (severe) to 22.3+/-2.1 (moderate) at 36 months (p < 0.001). Four of eight patients had a > or =35% decrease in YBOCS severity at 36 months; in two patients, scores declined between 25 and 35%. Global Assessment of Functioning scores improved from 36.6+/-1.5 at baseline to 53.8+/-2.5 at 36 months (p < 0.001). Depression and anxiety also improved, as did self-care, independent living, and work, school, and social functioning. Surgical adverse effects included an asymptomatic hemorrhage, a single seizure, and a superficial infection. Psychiatric adverse effects included transient hypomanic symptoms, and worsened depression and OCD when DBS was interrupted by stimulator battery depletion. This open study found promising long-term effects of DBS in highly treatment-resistant OCD.
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Estimulación Encefálica Profunda/métodos , Trastorno Obsesivo Compulsivo/terapia , Resultado del Tratamiento , Adulto , Análisis de Varianza , Ansiedad/etiología , Ansiedad/terapia , Cuerpo Estriado/fisiopatología , Cuerpo Estriado/efectos de la radiación , Depresión/etiología , Depresión/terapia , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/complicaciones , Trastorno Obsesivo Compulsivo/patología , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Adverse effects of antidepressant drugs can decrease compliance and delay recovery. It is therefore crucial to consider potential side effects when choosing an antidepressant. Although there is no perfect antidepressant that works quickly and is completely free of adverse reactions, newer antidepressants are safer, better tolerated, and associated with a lower rate of noncompliance.
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Antidepresivos/efectos adversos , Antidepresivos/farmacocinética , HumanosRESUMEN
BACKGROUND: Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published. METHODS: Thirty patients with TRD participated in a sham-controlled trial of DBS at the ventral capsule/ventral striatum target for TRD. Patients were randomized to active versus sham DBS treatment in a blinded fashion for 16 weeks, followed by an open-label continuation phase. The primary outcome measure was response, defined as a 50% or greater improvement on the Montgomery-Åsberg Depression Rating Scale from baseline. RESULTS: There was no significant difference in response rates between the active (3 of 15 subjects; 20%) and control (2 of 14 subjects; 14.3%) treatment arms and no significant difference between change in Montgomery-Åsberg Depression Rating Scale scores as a continuous measure upon completion of the 16-week controlled phase of the trial. The response rates at 12, 18, and 24 months during the open-label continuation phase were 20%, 26.7%, and 23.3%, respectively. CONCLUSION: The results of this first randomized controlled study of DBS for the treatment of TRD did not demonstrate a significant difference in response rates between the active and control groups at the end of the 16-week controlled phase. However, a range of 20% to 26.7% of patients did achieve response at any time during the open-label continuation phase. Future studies, perhaps utilizing alternative study designs and stimulation parameters, are needed.