Publications by authors named "Donald Malone"

Article Synopsis
  • The ELEKT-D trial explored whether intravenous ketamine is as effective as ECT for patients with treatment-resistant depression (TRD), finding that ketamine is noninferior to ECT in this group.
  • This secondary analysis aimed to identify which clinical features might predict better outcomes with either ketamine or ECT in treating TRD.
  • The study involved 365 participants from five U.S. medical centers, comparing treatment responses based on various baseline factors, such as depression severity and cognitive function, using advanced statistical methods.
View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Automated measurement of affective behavior in psychopathology has been limited primarily to screening and diagnosis. While useful, clinicians more often are concerned with whether patients are improving in response to treatment. Are symptoms abating, is affect becoming more positive, are unanticipated side effects emerging? When treatment includes neural implants, need for objective, repeatable biometrics tied to neurophysiology becomes especially pressing.

View Article and Find Full Text PDF

(Reprinted with permission from 12:175. Copyright © 2018 Widge, Malone, and Dougherty).

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Objective: Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive-compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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 16 weeks. Data were analysed at the individual and group levels.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

The success of device-based research in the clinical neurosciences has overshadowed a critical and emerging problem in the biomedical research environment in the United States. Neuroprosthetic devices, such as deep brain stimulation (DBS), have been shown in humans to be promising technologies for scientific exploration of neural pathways and as powerful treatments. Large device companies have, over the past several decades, funded and developed major research programs.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

Although antidepressant drugs do not differ much in their efficacy rates, the particular characteristics of one drug may make it a better choice in a given patient. This article provides insight into the art of prescribing antidepressants in primary care, with recommendations for prescribing for patients with chronic pain, sexual dysfunction, anxiety, chronic fatigue syndrome, fibromyalgia, severe insomnia, old age, diabetes, and heart problems.

View Article and Find Full Text PDF

Background: Chronic neuropathic pain in thalamic pain syndrome remains intractable. Its poor response is ascribed to destruction of the integrated neuromatrix in experience of pain. Deep brain stimulation is a promising technique to modulate activity of implicated structures.

View Article and Find Full Text PDF

Background: Major depressive disorder is a common and disabling illness and is the leading cause of disability worldwide. Despite aggressive medical, behavioral, and electroconvulsive therapies, a significant number of patients remain refractory to treatment. Deep brain stimulation (DBS) has proven efficacy in neurobehavioral disorders and, in a general sense, works by modulation of corticostriatopallidothalamocortical circuits implicated in these disorders.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF