Depression and Parkinson's Disease: Biological Therapies

2017 ◽  
Vol 41 (S1) ◽  
pp. S770-S770
Author(s):  
B. Mures ◽  
N.G. Lluis ◽  
A.P. Iñigo ◽  
M.H. German ◽  
T.G. Miriam ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Psychiatric Morbidity ◽  
Beneficial Effects ◽  
The Core ◽  
Previous Diagnosis ◽  
Medication Side ◽  
Dopaminergic Psychosis ◽  
Competing Interest ◽  
Motor Improvement

Introduction.Depression occurs in approximately 40% of patients with Parkinson's disease. Parkinson's disease is commonly associated with psychiatric morbidity, which includes depression, anxiety, and dopaminergic psychosis. These compound the patient's predicament. Fortunately, a variety of effective treatments are available.Objective.The purpose of this e-poster is to provide an update of the research regarding depression in Parkinson's disease.Methods.Describe a case report. A 56-year-old man, with previous diagnosis of Parkinson's disease. We used SSRIs, but they was not enough to successful treatment so we decided to use ECT.Results.Our patient failed to respond to medication or develop intolerable medication side effects. Electroconvulsive therapy (ECT) should be considered for this group of patients. Contrary to popular belief, ECT is a widely used and safe treatment for depression when medication fails. ECT has been shown to be effective and safe in PD for treating both depression and dopaminergic psychosis. Several studies also report varying periods of motor improvement following ECT in PD. A study is currently underway at UBC to examine this phenomenon in a controlled setting. ECT improves depression, may permit a reduction in antidepressant medications, and has intrinsic antiparkinsonian properties.Conclusions.ECT, has repeatedly been shown to have beneficial effects in PD, but has never gained acceptance as a clinical treatment option. We review the literature on the use of ECT in PD, pointing out that ECT has beneficial effects on both the core motor symptoms of PD as well as the commonly occurring psychiatric comorbidities.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Blinded SAPS-PD Assessment After 10 Weeks of Pimavanserin Treatment for Parkinson’s Disease Psychosis

2020 ◽  
Vol 10 (4) ◽  
pp. 1389-1396
Author(s):  
Stuart H. Isaacson ◽  
Bruce Coate ◽  
James Norton ◽  
Srdjan Stankovic
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Controlled Trial ◽  
Previous Treatment ◽  
Open Label ◽  
Beneficial Effects ◽  
The Core ◽  
Open Label Extension ◽  
Core Study ◽  
Burden Scale

Background: Parkinson’s disease psychosis (PDP) is a common nonmotor symptom that affects up to 60% of patients. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, is approved for treating hallucinations and delusions associated with PDP. Objective: Evaluate the efficacy and tolerability of pimavanserin in an open-label extension (OLE) study. Methods: Patients completing a pivotal 6-week placebo-controlled trial (Core Study) could enroll in the OLE. All patients pimavanserin 34 mg once daily, blinded to previous treatment allocation. Prespecified blinded assessments at Week 4 were the Scale for the Assessment of Positive Symptoms (SAPS) PD version and SAPS H + D scales, Caregiver Burden Scale (CBS), and Clinical Global Impression (CGI) Improvement and Severity scales. Results: Of 171 who entered the OLE, 148 (87%) completed Week 4. Among patients who received placebo in the Core Study, mean (SD) change from OLE baseline to OLE Week 4 for the SAPS-PD was – 3.4 (6.3); p < 0.0001. Mean change from Core Study baseline to OLE Week 4 for SAPS-PD was similar among prior pimavanserin- and placebo-treated patients (–6.9 vs. –6.3). Improvement was similar with CGI-I, CGI-S, CBS, and SAPS-H + D in patients previously treated with placebo. Adverse events occurred in 92 (53.8%) patients during the 4-week OLE. Conclusion: Improvements at OLE Week 4 from pretreatment baseline were similar with placebo and pimavanserin in the Core Study. The beneficial effects observed with pimavanserin in the 6-week Core Study were maintained for 4 weeks in the blinded OLE, supporting the durability of response with pimavanserin 34 mg for PDP over 10 weeks.

scholarly journals Electrode Location in a Microelectrode Recording-Based Model of the Subthalamic Nucleus Can Predict Motor Improvement After Deep Brain Stimulation for Parkinson’s Disease

2019 ◽  
Vol 9 (3) ◽  
pp. 51 ◽  
Author(s):  
Rens Verhagen ◽  
Lo Bour ◽  
Vincent Odekerken ◽  
Pepijn van den Munckhof ◽  
P. Schuurman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Anatomical Variation ◽  
Patient Specific ◽  
One Year ◽  
Motor Improvement ◽  
Deep Brain

Motor improvement after deep brain stimulation (DBS) in the subthalamic nucleus (STN) may vary substantially between Parkinson’s disease (PD) patients. Research into the relation between improvement and active contact location requires a correction for anatomical variation. We studied the relation between active contact location relative to the neurophysiological STN, estimated by the intraoperative microelectrode recordings (MER-based STN), and contralateral motor improvement after one year. A generic STN shape was transformed to fit onto the stereotactically defined MER sites. The location of 43 electrodes (26 patients), derived from MRI-fused CT images, was expressed relative to this patient-specific MER-based STN. Using regression analyses, the relation between contact location and motor improvement was studied. The regression model that predicts motor improvement based on levodopa effect alone was significantly improved by adding the one-year active contact coordinates (R2 change = 0.176, p = 0.014). In the combined prediction model (adjusted R2 = 0.389, p < 0.001), the largest contribution was made by the mediolateral location of the active contact (standardized beta = 0.490, p = 0.002). With the MER-based STN as a reference, we were able to find a significant relation between active contact location and motor improvement. MER-based STN modeling can be used to complement imaging-based STN models in the application of DBS.

The beneficial effects of subthalamic nucleus stimulation on manipulative finger force control in Parkinson's disease

2005 ◽  
Vol 193 (2) ◽  
pp. 427-436 ◽  
Author(s):  
Dennis A. Nowak ◽  
Helge Topka ◽  
Stephen Tisch ◽  
Marwan Hariz ◽  
Patricia Limousin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subthalamic Nucleus ◽  
Force Control ◽  
Finger Force ◽  
Beneficial Effects ◽  
Subthalamic Nucleus Stimulation

scholarly journals Neuroprotection and Functional Recovery Associated with Decreased Microglial Activation Following Selective Activation of mGluR2/3 Receptors in a Rodent Model of Parkinson's Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Hugh Chan ◽  
Helen Paur ◽  
Anthony C. Vernon ◽  
Virginia Zabarsky ◽  
Krishna P. Datla ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Recovery ◽  
Metabotropic Glutamate Receptor ◽  
Glutamate Excitotoxicity ◽  
Nigrostriatal System ◽  
Antiinflammatory Action ◽  
Metabotropic Glutamate ◽  
Beneficial Effects ◽  
6 Hydroxydopamine

Clinical trials have demonstrated positive proof of efficacy of dual metabotropic glutamate receptor 2/3 (mGluR2/3) agonists in both anxiety and schizophrenia. Importantly, evidence suggests that these drugs may also be neuroprotective against glutamate excitotoxicity, implicated in the pathogenesis of Parkinson's disease (PD). However, whether this neuroprotection also translates into functional recovery is unclear. In the current study, we examined the neuroprotective efficacy of the dual mGluR2/3 agonist, 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), and whether this is accompanied by behavioral recovery in a rodent 6-hydroxydopamine (6-OHDA) model of PD. We now report that delayed post lesion treatment with 2R,4R-APDC (10 nmol), results in robust neuroprotection of the nigrostriatal system, which translated into functional recovery as measured by improved forelimb use asymmetry and reduced (+)-amphetamine-induced rotation compared to vehicle treated animals. Interestingly, these beneficial effects were associated with a decrease in microglial markers in the SNc, which may suggest an antiinflammatory action of this drug.

scholarly journals Emulated Clinical Trials from Longitudinal Real-World Data Efficiently Identify Candidates for Neurological Disease Modification: Examples from Parkinson’s Disease

2020 ◽  
Author(s):  
Daphna Laifenfeld ◽  
Chen Yanover ◽  
Michal Ozery-Flato ◽  
Oded Shaham ◽  
Michal Rozen-Zvi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Real World ◽  
Late Onset ◽  
Real World Data ◽  
World Data ◽  
Healthcare Data ◽  
Beneficial Effects ◽  
Disease Modifying

AbstractReal-world healthcare data hold the potential to identify therapeutic solutions for progressive diseases by efficiently pinpointing safe and efficacious repurposing drug candidates. This approach circumvents key early clinical development challenges, particularly relevant for neurological diseases, concordant with the vision of the 21stCentury Cures Act. However, to-date, these data have been utilized mainly for confirmatory purposes rather than as drug discovery engines. Here, we demonstrate the usefulness of real-world data in identifying drug repurposing candidates for disease-modifying effects, specifically candidate marketed drugs that exhibit beneficial effects on Parkinson’s disease (PD) progression. We performed an observational study in cohorts of ascertained PD patients extracted from two large medical databases, Explorys SuperMart (N=88,867) and IBM MarketScan Research Databases (N=106,395); and applied two conceptually different, well-established causal inference methods to estimate the effect of hundreds of drugs on delaying dementia onset as a proxy for slowing PD progression. Using this approach, we identified two drugs that manifested significant beneficial effects on PD progression in both datasets: rasagiline, narrowly indicated for PD motor symptoms; and zolpidem, a psycholeptic. Each confers its effects through distinct mechanisms, which we explored via a comparison of estimated effects within the drug classification ontology. We conclude that analysis of observational healthcare data, emulating otherwise costly, large, and lengthy clinical trials, can highlight promising repurposing candidates, to be validated in prospective registration trials, for common, late-onset progressive diseases for which disease-modifying therapeutic solutions are scarce.

GOCOVRI® (amantadine) extended-release capsules in Parkinson's disease

2021 ◽  
Author(s):  
Thomas Müller
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Extended Release ◽  
Motor Behavior ◽  
Brain Delivery ◽  
Antiviral Compound ◽  
Once Daily ◽  
Beneficial Effects ◽  
Central Monoamine ◽  
Preventive Effects

Amantadine is an old, antiviral compound, which moderately improves motor behavior in Parkinson's disease. Its current resurgence results from an innovative, delayed uptake and extended release amantadine hydrochloride capsule, given at bedtime once daily. It is the only approved compound for reduction of involuntary movements, so called dyskinesia, in fluctuating orally levodopa treated patients. It additionally ameliorates ‘off’-intervals characterized by impaired motor behavior. These beneficial effects result from higher and more continuous brain delivery of amantadine. Future clinical research is warranted on preventive effects of this amantadine capsule combined with enzyme blockers of central monoamine oxidase B and peripheral catechol-O-methyltransferase on motor complications in orally levodopa treated patients, as all these pharmacological principles support the concept of continuous dopamine substitution.

scholarly journals Aerobic Exercise and Healthy Nutrition as Neuroprotective Agents for Brain Health in Patients with Parkinson’s Disease: A Critical Review of the Literature

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 380
Author(s):  
Davide Maria Cammisuli ◽  
Ubaldo Bonuccelli ◽  
Simona Daniele ◽  
Claudia Martini ◽  
Jonathan Fusi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Aerobic Exercise ◽  
Cognitive Outcomes ◽  
Neuroprotective Agents ◽  
Brain Health ◽  
Beneficial Effects ◽  
Healthy Nutrition ◽  
Different Levels

Parkinson’s disease (PD) is characterized by motor and nonmotor features that have an influence on patients’ quality of life at different levels. To date, some evidences have arisen on the effectiveness of physical trainings and nutrients intake in ameliorating functional and cognitive outcomes in PD patients. Physical activity is effective in improving both motor and nonmotor features and recent epidemiological investigations have revealed the pivotal role that dietary patterns may play in reducing the risk of PD highlighting the pathogenesis of the neurodegeneration. Specifically, aerobic exercise shows beneficial effects in improving motor functions and executive control in PD patients, as well as proper nutrition may help in improving neuroprotective agents counteracting neurodegeneration and allows patients to better interact with the medication. Our narrative review critically focused on aerobic exercise and nutrition in PD in order to point out the best prescriptions for brain health of affected patients. Implications for a therapeutic plan and rehabilitation for these patients are also discussed.

scholarly journals Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Rayul Wi ◽  
Young Cheul Chung ◽  
Byung Kwan Jin ◽  
Lihua Duan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Significant Loss ◽  
Glial Activation ◽  
Dopamine Neurons ◽  
Pcr Analysis ◽  
Beneficial Effects ◽  
Nigrostriatal Dopamine ◽  
Nigrostriatal Dopamine Neurons

The present study examined whether crosstalk between cannabinoid (CB) and transient potential receptor vanilloid type 1 (TRPV1) could contribute to the survival of nigrostriatal dopamine neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). MPTP induced a significant loss of nigrostriatal dopamine neurons and glial activation in the substantia nigra (SN) and striatum (STR) as visualized by tyrosine hydroxylase (TH) or macrophage antigen complex-1 (MAC-1) or glial fibrillary acidic protein (GFAP) immunocytochemistry, respectively. RT-PCR analysis shows the upregulation of inducible nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α in microglia in the SN in vivo, indicating the activation of the inflammatory system. By contrast, treatment with capsaicin (a specific TRPV1 agonist) increased the survival of dopamine neurons in the SN and their fibers and dopamine levels in the STR in MPTP mice. Capsaicin neuroprotection is accompanied by inhibiting MPTP-induced glial activation and production of inflammatory cytokines. Treatment with AM251 and AM630 (CB1/2 antagonists) abolished capsaicin-induced beneficial effects, indicating the existence of a functional crosstalk between CB and TRPV1. Moreover, treatment with anandamide (an endogenous agonist for both CB and TRVP1) rescued nigrostriatal dopamine neurons and reduced gliosis-derived neuroinflammatory responses in MPTP mice. These results suggest that the cannabinoid and vanilloid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with neuroinflammation.

scholarly journals Pallidotomy after chronic deep brain stimulation

2013 ◽  
Vol 35 (5) ◽  
pp. E5 ◽  
Author(s):  
Kristian J. Bulluss ◽  
Erlick A. Pereira ◽  
Carole Joint ◽  
Tipu Z. Aziz
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Full Time ◽  
Progressive Dementia ◽  
Deep Brain Stimulator ◽  
Beneficial Effects ◽  
Unilateral Pallidotomy ◽  
Deep Brain

Recent publications have demonstrated that deep brain stimulation for Parkinson's disease still exerts beneficial effects on tremor, rigidity, and bradykinesia for up to 10 years after implantation of the stimulator. However with the progression of Parkinson's disease, features such as cognitive decline or “freezing” become prominent, and the presence of an implanted and functioning deep brain stimulator can impose a profound burden of care on the clinical team and family. The authors describe their experience in treating 4 patients who underwent removal of the implanted device due to either progressive dementia requiring full-time nursing or due to infection, and who subsequently underwent a unilateral pallidotomy.

Sign in / Sign up

Export Citation Format

Share Document