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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 -
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 -
Clinical Drug Investigation Apr 2021BACKGROUND AND OBJECTIVE: Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The... (Meta-Analysis)
Meta-Analysis
UNLABELLED
BACKGROUND AND OBJECTIVE: Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of safinamide administration compared to placebo in PD patients on multiple outcomes.
METHODS
PubMed, EMBASE, Cochrane CENTRAL, LILACS, and trial databases were searched up to 23 December 2020 for randomized controlled studies (RCTs) comparing safinamide to placebo, alone or as add-on therapy in PD. Data were extracted from literature and regulatory agencies. Primary outcomes were ON-time without troublesome dyskinesia, OFF-time, and Unified Parkinson's Disease Rating Scale (UPDRS) section III (UPDRS-III). Secondary outcomes included any dyskinesia rating scale (DRS), ON-time with troublesome dyskinesia, UPDRS-II, and Parkinson's Disease Questionnaire 39 (PDQ-39). In order to estimate mean difference (MD) and odds ratios with 95% confidence intervals (CI), generic inverse variance and Mantel-Haenszel methods were used for continuous and dichotomous variables, respectively. Analyses were performed grouping by PD with (PDwMF) or without (PDwoMF) motor fluctuations, safinamide dose, and concomitant dopaminergic treatment. Summary of findings with GRADE were performed.
RESULTS
Six studies with a total of 2792 participants were identified. In PDwMF patients, safinamide 100 mg as add-on to levodopa (L-dopa) significantly increased ON-time without troublesome dyskinesia (MD = 0.95 h; 95% CI from 0.41 to 1.49), reduced OFF-time (MD = - 1.06 h; 95% CI from - 1.60 to - 0.51), and improved UPDRS-III (MD = - 2.77; 95% CI from - 4.27 to - 1.28) with moderate quality of evidence. Similar results were observed for the 50 mg dose. However, the quality of evidence was moderate only for ON-time without troublesome dyskinesia, whereas for OFF-time and UPDRS-III was low. In PDwoMF patients taking a single dopamine agonist, safinamide 100 mg resulted in little to no clinically significant improvement in UPDRS-III (MD = - 1.84; 95% CI from - 3.19 to - 0.49), with moderate quality of evidence. Conversely, in PDwoMF patients, the 200 mg and 50 mg doses showed nonsignificant improvement in UPDRS-III, with very low and moderate quality of evidence, respectively. In PDwMF patients taking safinamide 100 mg or 50 mg, nonsignificant differences were observed for ON-time with troublesome dyskinesia and DRS, with high and low quality of evidence, respectively. In the same patients, UPDRS-II was significantly improved at the 100 mg and 50 mg dose, with high and moderate quality of evidence. In PDwoMF, UPDRS-II showed a little yet significant difference only at 100 mg, with low quality of evidence. PDQ-39 resulted significantly improved only with the 100 mg dose in PDwMF, with low quality of evidence.
CONCLUSION
Overall, safinamide is effective in PDwMF patients taking L-dopa both at 100 and 50 mg daily. Evidence for efficacy in early PD is limited. Further trials are needed to better evaluate the anti-dyskinetic properties of safinamide.
Topics: Alanine; Antiparkinson Agents; Benzylamines; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 33674954
DOI: 10.1007/s40261-021-01011-y -
Clinical NeuropharmacologyAcute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can...
OBJECTIVES
Acute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can impact morbidity. Glasgow Coma Scale (GCS) is the most widely used method of assessing the level of consciousness. Neurostimulants such as amantadine and modafinil are common pharmacologic agents that increase GCS in patients with brain trauma. This study aimed to compare the effectiveness of these 2 drugs.
METHODS
This systematic review obtained articles from Google Scholar, PubMed, Scopus, Embase, and MEDLINE databases. Extensive searches were conducted separately by 4 individuals in 3 stages. Ultimately, 16 clinical trials, cohort studies, case reports, and case series articles were obtained after reading the title, abstract, and full text and considering the exclusion criteria. The data of the final article were entered into the analysis table. This study was registered with PROSPERO (registration number CRD42022334409) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
Amantadine seems to be associated with a higher overall response rate. In contrast, modafinil is associated with the most remarkable change in GCS score during treatment. However, the number of clinical trials with high quality and sample size has not been satisfactory to compare the effectiveness of these 2 drugs and their potential side effects.
CONCLUSIONS
The authors recommend additional double-blind clinical trials are needed to be conducted with a larger sample size, comparing amantadine with modafinil to delineate the efficacy and adverse effects, both short and long term.
Topics: Humans; Modafinil; Consciousness; Brain Injuries, Traumatic; Amantadine; Brain Injuries; Randomized Controlled Trials as Topic
PubMed: 37962310
DOI: 10.1097/WNF.0000000000000577 -
The Cochrane Database of Systematic... May 2018Cerebral palsy occurs in up to 2.1 of every 1000 live births and encompasses a range of motor problems and movement disorders. One commonly occurring movement disorder... (Review)
Review
BACKGROUND
Cerebral palsy occurs in up to 2.1 of every 1000 live births and encompasses a range of motor problems and movement disorders. One commonly occurring movement disorder amongst those with cerebral palsy is dystonia: sustained or intermittent involuntary muscle spasms and contractions that cause twisting, repetitive movements and abnormal postures. The involuntary contractions are often very painful and distressing and cause significant limitations to activity and participation.Oral medications are often the first line of medical treatment for dystonia. Trihexyphenidyl is one such medication that clinicians often use to treat dystonia in people with cerebral palsy.
OBJECTIVES
To assess the effects of trihexyphenidyl in people with dystonic cerebral palsy, according to the World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) domains of impairment, activity and participation. We also assessed the type and incidence of adverse effects in people taking the drug.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, eight other databases and two trials registers in May 2017, and we checked reference lists and citations to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials comparing oral trihexyphenidyl versus placebo for dystonia in cerebral palsy. We included studies in children and adults of any age with dystonic cerebral palsy, either in isolation or with the associated movement disorders of spasticity, ataxia, chorea, athetosis and/or hypotonia. We included studies regardless of whether or not the study authors specified the method used to diagnose dystonia in their study population. Primary outcomes were change in dystonia and adverse effects. Secondary outcomes were: activity, including mobility and upper limb function; participation in activities of daily living; pain; and quality of life.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified one study, which was set in Australia, that met the inclusion criteria. This was a randomised, double-blind, placebo-controlled, cross-over trial in 16 children (10 boys and 6 girls) with predominant dystonic cerebral palsy and a mean age of 9 years (standard deviation 4.3 years, range 2 to 17 years). We considered the trial to be at low risk of selection, performance, detection, attrition, reporting and other sources of bias. We rated the GRADE quality of the evidence as low.We found no difference in mean follow-up scores for change in dystonia as measured by the Barry Albright Dystonia Scale (BADS), which assesses eight body regions for dystonia on a 5-point scale (0 = none to 4 = severe), resulting in a total score of 0 to 32. The BADS score was 2.67 points higher (95% confidence interval (CI) -2.55 to 7.90; low-quality evidence), that is, worse dystonia, in the treated group. Trihexyphenidyl may be associated with an increased risk of adverse effects (risk ratio 2.54, 95% CI 1.38 to 4.67; low-quality evidence).There was no difference in mean follow-up scores for upper limb function as measured by the Quality of Upper Extremity Skills Test, which has four domains that collectively assess 36 items (each scored 1 or 2) and produces a total score of 0 to 100. The score in the treated group was 4.62 points lower (95% CI -10.98 to 20.22; low-quality evidence), corresponding to worse function, than in the control group. We found low-quality evidence for improved participation (as represented by higher scores) in the treated group in activities of daily living, as measured by three tools: 18.86 points higher (95% CI 5.68 to 32.03) for the Goal Attainment Scale (up to five functional goals scored on 5-point scale (-2 = much less than expected to +2 = much more than expected)), 2.91 points higher (95% CI 1.01 to 4.82) for the satisfaction subscale of the Canadian Occupational Performance Measure (COPM; satisfaction with performance in up to five problem areas scored on a 10-point scale (1 = not satisfied at all to 10 = extremely satisfied)), and 2.24 points higher (95% CI 0.64 to 3.84) for performance subscale of the COPM (performance in up to five problem areas scored on a 10-point scale (1 = not able to do to; 10 = able to do extremely well)).The study did not report on pain or quality of life.
AUTHORS' CONCLUSIONS
At present, there is insufficient evidence regarding the effectiveness of trihexyphenidyl for people with cerebral palsy for the outcomes of: change in dystonia, adverse effects, increased upper limb function and improved participation in activities of daily living. The study did not measure pain or quality of life. There is a need for larger randomised, controlled, multicentre trials that also examine the effect on pain and quality of life in order to determine the effectiveness of trihexyphenidyl for people with cerebral palsy.
Topics: Adolescent; Anti-Dyskinesia Agents; Cerebral Palsy; Child; Child, Preschool; Dystonia; Female; Humans; Male; Trihexyphenidyl
PubMed: 29763510
DOI: 10.1002/14651858.CD012430.pub2 -
Brain Research Jan 2018The importance of circadian function in the aetiology, progression and treatment of Parkinson's disease is a topic of increasing interest to the scientific and clinical... (Review)
Review
The importance of circadian function in the aetiology, progression and treatment of Parkinson's disease is a topic of increasing interest to the scientific and clinical community. While clinical studies on this theme are relatively new and limited in number there are many preclinical studies which explore possible circadian involvement in Parkinson's disease and speculate as to the mechanism by which clinical benefit can be derived by manipulating the circadian system. The present review explores the sequelae of circadian related studies from a historical perspective and reveals mechanisms that may be involved in the aetiology and progression of the disease. A systematic review of these studies also sets the stage for understanding the basic neuroscientific approaches which have been applied and provides new direction from which circadian function can be explored.
Topics: Animals; Antiparkinson Agents; Circadian Rhythm; Drug Evaluation, Preclinical; Humans; Parkinson Disease
PubMed: 28958865
DOI: 10.1016/j.brainres.2017.09.027 -
Current Alzheimer Research 2023Alzheimer's disease (AD) ranks first among the causes of dementia worldwide. AD can develop a psychotic manifest at a significant rate. AD prognosis worsens by added...
Alzheimer's disease (AD) ranks first among the causes of dementia worldwide. AD can develop a psychotic manifest at a significant rate. AD prognosis worsens by added psychosis clinic. There is no treatment approved by the United States Food and Drug Administration (FDA) among antipsychotics for Alzheimer's disease Psychosis (ADP). However, pimavanserine, an atypical antipsychotic, has been approved by the FDA for Parkinson's psychosis. It is predicted that pimavanserin, a new antipsychotic, will fill an important gap in this area. In clinical trials, it appears to be effective in the treatment of delusions and hallucinations at psychosis in both Parkinson's and AD. In this systematic review, we evaluated the analysis of current literature data on pimavanserin used in ADP. We searched the existing literature on clinical studies on pimavanserin therapy used in ADP. Data were determined by systematically searching PubMed, MEDLINE, EMBASE, and Google Scholar until December 2022. A total of 35 citations were found and uploaded on the Mendeley program. Abstracts and full texts of literature data were examined. Pimavanserin was observed, and satisfactory results were obtained in treating ADP. Pimavanserin has a unique mechanism of action. Pimavanserin, an atypical antipsychotic drug, has a low affinity for 5-HT2C receptors and has selective 5-HT2A reverse agonist/antagonist action. Pimavanserin has no clinically significant affinity for dopaminergic, histaminergic, muscarinic or adrenergic receptors. This agent may also achieve significant positive results in resistant psychosis treatments.
Topics: United States; Humans; Psychotic Disorders; Alzheimer Disease; Parkinson Disease; Antipsychotic Agents; Urea
PubMed: 37641988
DOI: 10.2174/1567205020666230825124922 -
Neurological Sciences : Official... Apr 2024This analysis is the first systematic review and meta-analysis assessing occurrences of ICD in PD patients treated with oral DAs: ropinirole (ROP) and pramipexole (PRX).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This analysis is the first systematic review and meta-analysis assessing occurrences of ICD in PD patients treated with oral DAs: ropinirole (ROP) and pramipexole (PRX). This study compares the two oral DAs to a transdermal patch, rotigotine (RTG).
METHODS
We performed an extensive systematic search for eligible studies from PubMed, Embase, Cochrane Library, and Google Scholar. The data was analyzed by various software, including EndNote, Rayyan, PRISM, and RevMan. Two studies incorporating 658 patients collectively were assessed.
RESULTS
This meta-analysis shows a significant correlation between the usage of PRX (25.3%) or ROP (21.8%) and the development of ICD in PD patients. Compared to the transdermal patch, RTG, PRX was found to have a significant relative risk (P < 0.0001) of 3.46 (95% CI 2.07-5.76), and ROP was found to have a significant relative risk (P < 0.0001) of 2.98 (95% CI 1.77-5.02). The data collected shows RTG is approximately three times less likely to cause ICDs than oral PRX and ROP.
CONCLUSION
The present investigation provides insight into ICD occurrences with PRX, ROP, and RTG to allow physicians to make more informed decisions on risk versus reward when deciding how to treat a PD patient with these drugs. However, related to various disclosed limitations, our conclusion cannot provide definitive practice protocols.
Topics: Humans; Pramipexole; Parkinson Disease; Dopamine Agonists; Disruptive, Impulse Control, and Conduct Disorders; Antiparkinson Agents; Indoles; Tetrahydronaphthalenes; Thiophenes
PubMed: 38079019
DOI: 10.1007/s10072-023-07254-1 -
General Hospital Psychiatry 2022The present study aimed to systematically analyze the risk factors for RBD. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The present study aimed to systematically analyze the risk factors for RBD.
METHODS
A systematic review and meta-analysis of case-control studies, cohort studies, and cross-sectional studies derived from the articles published in eight electronic databases before December 1, 2021. The primary outcome was the odds ratio (OR) and 95% confidence interval (95% CI), and heterogeneity was quantified using I. Subgroup analyses and meta-regression were used to explore sources of heterogeneity. Egger's test and sensitivity analysis were performed. The PROSPERO ID number of the present study is CRD42021293942.
RESULTS
We identified 26 studies (44,230 subjects) among 2022 citations, and 13 factors were considered. Male sex (OR = 1.36, 95% CI = 1.13-1.64), smoking (OR = 1.37, 95% CI: 1.26-1.50), depression (OR = 2.06, 95% CI = 1.66-2.56), antidepressant use (OR = 2.36, 95% CI = 1.98-2.82), duration of neuropsychiatric disorders(OR = 1.43, 95% CI = 1.13-1.73), levodopa equivalent daily dose (LEDD, OR = 60.15, 95% CI = 23.95-96.35) and observable motor dysfunction (OR = 2.43, 95% CI = 0.65-4.22) were associated with a higher risk of RBD. Tertiary education and above (OR = 0.58, 95% CI = 0.35-0.96) was associated with a lower RBD risk. Men (OR = 1.40, 95% CI: 1.10-1.78, I = 0%, P = 0.005) and older individual (OR = 2.73, 95% CI: 1.03-4.43, I = 60%, P = 0.002) were more likely to have iRBD.
CONCLUSION
Six modifiable risk factors and one protective factor were associated with RBD. Further research is required to understand the mechanisms and to develop preventative strategies.
Topics: Male; Humans; Cross-Sectional Studies; REM Sleep Behavior Disorder; Levodopa; Risk Factors; Sleep
PubMed: 36375340
DOI: 10.1016/j.genhosppsych.2022.10.009 -
The Cochrane Database of Systematic... Jan 2018Antipsychotic (neuroleptic) medication is used extensively to treat people with serious mental illnesses. However, it is associated with a wide range of adverse effects,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic (neuroleptic) medication is used extensively to treat people with serious mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders. Because of this, many people treated with antipsychotic medication also receive anticholinergic drugs in order to reduce some of the associated movement side-effects. However, there is also a suggestion from animal experiments that the chronic administration of anticholinergics could cause tardive dyskinesia.
OBJECTIVES
To determine whether the use or the withdrawal of anticholinergic drugs (benzhexol, benztropine, biperiden, orphenadrine, procyclidine, scopolamine, or trihexylphenidyl) are clinically effective for the treatment of people with both antipsychotic-induced tardive dyskinesia and schizophrenia or other chronic mental illnesses.
SEARCH METHODS
We retrieved 712 references from searching the Cochrane Schizophrenia Group's Study-Based Register of Trials including the registries of clinical trials (16 July 2015 and 26 April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information.
SELECTION CRITERIA
We included reports identified in the search if they were controlled trials dealing with people with antipsychotic-induced tardive dyskinesia and schizophrenia or other chronic mental illness who had been randomly allocated to (a) anticholinergic medication versus placebo (or no intervention), (b) anticholinergic medication versus any other intervention for the treatment of tardive dyskinesia, or (c) withdrawal of anticholinergic medication versus continuation of anticholinergic medication.
DATA COLLECTION AND ANALYSIS
We independently extracted data from included trials and we estimated risk ratios (RR) with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The previous version of this review included no trials. We identified two trials that could be included from the 2015 and 2017 searches. They randomised 30 in- and outpatients with schizophrenia in the USA and Germany. Overall, the risk of bias was unclear, mainly due to poor reporting: allocation concealment was not described; generation of the sequence was not explicit; studies were not clearly blinded; and outcome data were not fully reported.Findings were sparse. One study reported on the primary outcomes and found that significantly more participants allocated to procyclidine (anticholinergic) had not improved to a clinically important extent compared with those allocated to isocarboxazid (MAO-inhibitor) after 40 weeks' treatment (1 RCT, n = 20; RR 4.20, 95% CI 1.40 to 12.58; very low quality evidence); that there was no evidence of a difference in the incidence of any adverse effects (1 RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence); or acceptability of treatment (measured by participants leaving the study early) (1 RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence). The other trial compared anticholinergic withdrawal with anticholinergic continuation and found no evidence of a difference in the incidence of acceptability of treatment (measured by participants leaving the study early) (1 RCT, n = 10; RR 2.14, 95% CI 0.11 to 42.52; very low quality evidence).No trials reported on social confidence, social inclusion, social networks, or personalised quality of life - outcomes designated important to patients. No studies comparing either i. anticholinergics with placebo or no treatment, or ii. studies of anticholinergic withdrawal, were found that reported on the primary outcome 'no clinically important improvement in TD symptoms and adverse events'.
AUTHORS' CONCLUSIONS
Based on currently available evidence, no confident statement can be made about the effectiveness of anticholinergics to treat people with antipsychotic-induced tardive dyskinesia. The same applies for the withdrawal of such medications. Whether the withdrawal of anticholinergics may benefit people with antipsychotic-induced TD should be evaluated in a parallel-group, placebo-controlled randomised trial, with adequate sample size and at least 6 weeks of follow-up.
Topics: Antipsychotic Agents; Biperiden; Cholinergic Antagonists; Dyskinesia, Drug-Induced; Humans; Isocarboxazid; Procyclidine; Randomized Controlled Trials as Topic; Schizophrenia; Withholding Treatment
PubMed: 29341071
DOI: 10.1002/14651858.CD000204.pub2