-
Movement Disorders Clinical Practice Sep 2023Continuous subcutaneous apomorphine infusion (CSAI) is one of the advanced therapies for Parkinson's disease (PD). (Review)
Review
BACKGROUND
Continuous subcutaneous apomorphine infusion (CSAI) is one of the advanced therapies for Parkinson's disease (PD).
METHODS
A systematic review of all published articles in English on CSAI for PD till January 30, 2022 was conducted.
RESULTS
A total of 82 articles met the search criteria. Publications included retrospective or prospective open-label observational studies, with a limited number of randomized control trials (RCT). Publications were highly heterogeneous and focused on different aspects of CSAI and included clinical audits, effects on cognition/behavior, axial symptoms, nocturnal issues, adverse events/reasons for discontinuation and comparison with other continuous dopaminergic therapies. CSAI was used in patients who presented severe motor fluctuations not resolved by oral therapy, poor candidates for deep brain stimulation (DBS) due to cognitive/behavioral issues or in those with DBS weaning effect. Recent studies have also shown that CSAI was useful for nocturnal usage in advanced PD, in addition to daytime utilization. Adverse effects were common and include skin lesions, sedation and nausea. Pump management difficulties and patient decisions were common reasons for therapy dropout, predominantly during the initial stages of the CSAI.
CONCLUSION
There is consistent agreement on the benefits of CSAI in reducing OFF periods and improving ON periods without troublesome dyskinesia and specific motor and non-motor symptoms. Although there is a paucity of RCTs, current data from almost 30 years of use suggests CSAI to be beneficial in advanced cases of PD.
Topics: Apomorphine; Parkinson Disease; Humans; Infusions, Subcutaneous; Antiparkinson Agents; Dopamine Agonists; Deep Brain Stimulation
PubMed: 37772305
DOI: 10.1002/mdc3.13810 -
Heliyon Mar 2024Despite existing evidence linking dyskinesia to levodopa, the primary treatment for Parkinson's, the dose-response relationship and risk factors remain uncertain. In... (Review)
Review
Despite existing evidence linking dyskinesia to levodopa, the primary treatment for Parkinson's, the dose-response relationship and risk factors remain uncertain. In this study, the risk for dyskinesia in patients with Parkinson's disease receiving levodopa was evaluated via meta-analysis and meta-regression approaches to examine dyskinesia risk factors more reliably and improve treatment strategies and patient care. The PubMed and Embase databases were searched to identify randomized controlled trials comparing levodopa with other anti-Parkinson's drugs published in English before June 31, 2023. The primary outcome was dyskinesia, and a risk of bias assessment was performed. In total, 24 studies met the inclusion criteria; 21 had a low risk of bias, and 3 had a high risk of bias. These studies included 4698 patients with Hoehn and Yahr Grade I-III Parkinson's disease. Our meta-analysis showed that the risk of dyskinesia was higher for levodopa than for other anti-Parkinson's drugs (odds ratio: 2.52 [95% confidence interval: 1.84-3.46]). Dyskinesia was not related to age (slope coefficient: 0.185 [0.095]; = 0.061), disease duration (slope coefficient: 0.011 [0.018]; = 0.566), or treatment duration (slope coefficient: 0.008 [0.007]; = 0.216). The mean levodopa equivalent dose (slope coefficient: 0.004 [0.001]; = 0.001) in the experimental group and the differences in drug doses between the experimental and control groups were correlated with the risk of dyskinesia. Results of randomized controlled trials supported an association between the levodopa dose and dyskinesia in patients with Parkinson's disease. Compared with levodopa users, users of other anti-Parkinson's drugs had a lower incidence of dyskinesia. Age, disease duration, and treatment duration were not correlated with dyskinesia. These findings suggest that anti-Parkinson's drugs other than levodopa, particularly in cases of early-stage Parkinson's disease, should be considered to reduce the risk of dyskinesia.
PubMed: 38515703
DOI: 10.1016/j.heliyon.2024.e27956 -
Neuropsychopharmacology Reports Mar 2024This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy,... (Meta-Analysis)
Meta-Analysis
AIM
This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants.
METHODS
Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non-response rate; the non-remission rate; all-cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain.
RESULTS
A literature search identified three double-blind, randomized, placebo-controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible-dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day.
CONCLUSIONS
Overall BRE showed similar utility to ARI and a good risk-benefit balance.
Topics: Humans; Aripiprazole; Depressive Disorder, Major; Japan; Psychomotor Agitation; Network Meta-Analysis; Weight Gain; Randomized Controlled Trials as Topic; Thiophenes; Quinolones
PubMed: 38219278
DOI: 10.1002/npr2.12414 -
BMJ Neurology Open 2024The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists...
BACKGROUND
The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs) and monoamine-oxidase B inhibitors (MAOB-Is) as adjunctive treatment to levodopa in patients with Parkinson's disease (PD) experiencing motor complications.
METHODS
In this systematic review and network meta-analysis, literature searches were performed in MEDLINE and Embase to identify eligible randomised controlled trials (RCTs) with a minimal follow-up of at least 4 weeks published in English between 1980 and 2021. RCTs were included if either a COMT-I, DRA or MAOB-I was evaluated as an adjunctive therapy to levodopa in patients with PD experiencing motor complications and dyskinesia. The main outcomes included daily off-medication time, motor and non-motor examination scales, and adverse events including dyskinesia.
RESULTS
74 RCTs reporting on 18 693 patients were included. All three studied drug classes decreased daily off-medication time compared with placebo (COMT-Is mean -0.8 hours (95% CI -1.0 to -0.6), DRAs -1.1 hours (95% CI -1.4 to -0.8), MAOB-Is -0.9 hours (95% CI -1.2 to -0.6)). Safety analysis showed an increased risk of dyskinesia for all three drug classes (COMT-Is OR 3.3 (95% CI 2.7 to 4.0), DRAs 3.0 (95% CI 2.5 to 3.5), MAOB-Is 1.6 (95% CI 1.2 to 2.2)). According to surface under the cumulative ranking curve scores, pramipexole IR was associated with the most favourable benefit-risk profile.
CONCLUSIONS
COMT-Is, DRAs and MAOB-Is effectively reduce motor complications and increase incidence of dyskinesia. In the network meta-analysis, adjunctive use of DRAs appeared most effective.
PubMed: 38352047
DOI: 10.1136/bmjno-2023-000573 -
General Hospital Psychiatry 2024This network meta-analysis assessed the efficacy, tolerability, and acceptability of second-generation antipsychotics (SGAs) for Parkinson's disease psychosis (PDP). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This network meta-analysis assessed the efficacy, tolerability, and acceptability of second-generation antipsychotics (SGAs) for Parkinson's disease psychosis (PDP).
METHODS
We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials investigating SGAs for PDP up to October 26, 2023.
RESULTS
We included 16 trials (N = 1252) investigating clozapine, melperone, olanzapine, pimavanserin, quetiapine, ulotaront, and placebo. In comparisons between SGAs and placebo, the findings were: i) Standardized mean differences, 95% confidence intervals (SMDs, 95%CIs), for psychotic-symptom reduction revealed the first rank of clozapine (-1.31, -1.73 to -0.89), the second rank of pimavanserin, with significant inferiority of quetiapine (SMD = 0.47, 0.02 to 0.92); ii) Mean differences (MDs, 95%CIs) for abnormal movement, as assessed by the Unified Parkinson's Disease Rating Scale - Part III, indicated that clozapine had the least motor side effects (-0.92, -2.75 to 0.91); iii) Risk ratios (RRs, 95% CIs) for adverse-effect dropout rates were lowest for melperone (1.02, 0.20 to 5.24); and iv) RRs (95% CIs) for all-cause dropout rates were lowest for clozapine (0.73, 0.42 to 1.25).
CONCLUSIONS
For patients with PDP, clozapine may substantially reduce psychotic symptoms with minimal abnormal movement, high acceptability, and moderate overall tolerability. Pimavanserin, not quetiapine, could be an alternative.
Topics: Humans; Antipsychotic Agents; Butyrophenones; Clozapine; Dyskinesias; Network Meta-Analysis; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Urea
PubMed: 38412585
DOI: 10.1016/j.genhosppsych.2024.02.008 -
Journal of the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
Journal of Neuroimmunology Dec 2023Huntington's disease (HD) is an autosomal dominant disease caused by an abnormally high number of CAG repeats at the huntingtin-encoding gene, HTT. This genetic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Huntington's disease (HD) is an autosomal dominant disease caused by an abnormally high number of CAG repeats at the huntingtin-encoding gene, HTT. This genetic alteration results in the expression of a mutant form of the protein (mHTT) and the formation of intracellular aggregates, inducing an inflammatory state within the affected areas. This dysfunction of inflammatory response leads to elevated levels of related inflammatory markers in both CNS tissue samples and body fluids. This study aims to investigate peripheral/blood concentrations of inflammatory molecules in HD.
METHODS
A search was conducted in MEDLINE, Scopus, Web of Science, and Embase databases until March 30th, 2023. Random-effect meta-analysis was used for exploring concentrations of inflammatory molecules in HD. Subgroup and sensitivity analyses were used to assess heterogeneity among the included studies. The study protocol has been registered in PROSPERO with the ID number CRD42022296078.
RESULTS
Ten studies were included in the meta-analysis. Plasma levels of Interleukin 6 (IL-6) and IL-10 were higher in HD compared to controls. Other biomarkers, namely, complement component C-reactive protein (CRP), C3, interferon-γ (IFN-γ), IL-1, IL-2, IL-8, and tumor necrosis factor-α (TNF-α), did not show any significant differences between the two groups. In addition, the subgroup analysis results established no significant differences in levels of these biomarkers in body fluids among premanifest and manifest HD patients.
CONCLUSION
The results of this study provide evidence for the presence of higher plasma levels of IL-6 and IL-10 in HD patients in comparison with healthy controls.
Topics: Humans; Huntington Disease; Interleukin-6; Interleukin-10; Biomarkers; Tumor Necrosis Factor-alpha; Huntingtin Protein
PubMed: 37984118
DOI: 10.1016/j.jneuroim.2023.578243 -
Clinical Genetics Aug 2023Huntington Disease (HD) is an incurable autosomal dominant single gene neurodegenerative disorder. Typical onset is between 30 and 40 years and characterised by motor... (Review)
Review
Huntington Disease (HD) is an incurable autosomal dominant single gene neurodegenerative disorder. Typical onset is between 30 and 40 years and characterised by motor difficulties, cognitive impairment, and behavioural and personality changes. The availability of reproductive testing means that affected and at-risk individuals can make reproductive decisions with genetic risk in mind. We aimed to summarise the literature on reproductive decision-making in the context of HD risk in terms of outcomes and the subjective experiences of at-risk individuals. Five databases were searched. Findings were synthesised using Framework analysis to identify common factors across results of quantitative and qualitative studies. Twenty five studies met inclusion criteria. Framework analysis identified the following key areas: 'The relationship between reproductive intentions and HD genetic risk', 'Views on assistive options', 'Complexity and challenges in reproductive decision-making', 'Actual reproductive outcomes', and 'Other factors influencing reproductive decision-making'. Quality of included studies was mixed. Reproductive decision making in the context of HD risk was found to be a complex and emotionally challenging process. Further research is required into reproductive decision-making and outcomes among those not utilising assistive options, and in developing a model of reproductive decision-making in HD.
Topics: Humans; Huntington Disease; Reproduction; Risk Factors; Decision Making
PubMed: 37095632
DOI: 10.1111/cge.14345 -
Neuropsychology Review Mar 2024Growing evidence points to a spectrum of non-motor symptoms, including cognitive difficulties that have a greater impact on functional outcomes and quality of life than... (Review)
Review
Growing evidence points to a spectrum of non-motor symptoms, including cognitive difficulties that have a greater impact on functional outcomes and quality of life than motor symptoms in cervical dystonia (CD). Some cognitive impairments have been reported; however, findings are inconsistent, and described across mixed groups of dystonia. The current review aimed to examine the evidence for cognitive impairments in CD. MEDLINE, EMBASE, PsychINFO and Web of Science databases were searched. Studies were included if they met the following criteria (i) cross-sectional or longitudinal studies of adults with CD, (ii) where the results of standardised measures of cognitive or neuropsychological function in any form were assessed and reported, (iii) results compared to a control group or normative data, and (iv) were published in English. Results are presented in a narrative synthesis. Twenty studies were included. Subtle difficulties with general intellectual functioning, processing speed, verbal memory, visual memory, visuospatial function, executive function, and social cognition were identified while language, and attention and working memory appear to be relatively spared. Several methodological limitations were identified that should be considered when interpreting the evidence to describe a specific profile of cognitive impairment in CD. Clinical and research implications are discussed.
Topics: Adult; Humans; Torticollis; Quality of Life; Cross-Sectional Studies; Cognition; Memory, Short-Term
PubMed: 36696021
DOI: 10.1007/s11065-022-09558-z -
Journal of Clinical Pharmacology Dec 2023Amiodarone is an antiarrhythmic drug with a significant adverse effect profile, including neurotoxicity. While ataxia, neuropathy, and tremors are more commonly seen... (Review)
Review
Amiodarone is an antiarrhythmic drug with a significant adverse effect profile, including neurotoxicity. While ataxia, neuropathy, and tremors are more commonly seen forms of amiodarone neurotoxicity, very few cases of nystagmus are reported. We report the case of an 86-year-old man who presented with abrupt-onset ataxia, dizziness, and inability to ambulate, 10 days after initiating amiodarone for atrial fibrillation. His examination revealed gaze-evoked nystagmus along with features of cerebellar dysfunction. After excluding other etiologies, amiodarone was stopped. His nystagmus resolved, and his ataxia improved within 48 h of stopping amiodarone. Due to the rarity of this drug-induced adverse effect, we performed a systematic review of available case reports in the literature (PubMed and Scopus) using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and presented our findings. Nystagmus is a rarely reported adverse effect of amiodarone, which can occur within days to months of starting the medication. Treatment includes stopping the drug and monitoring for resolution of nystagmus.
Topics: Aged, 80 and over; Humans; Male; Amiodarone; Anti-Arrhythmia Agents; Ataxia; Atrial Fibrillation; Dizziness; Drug-Related Side Effects and Adverse Reactions; Tremor; Case Reports as Topic
PubMed: 37571970
DOI: 10.1002/jcph.2330