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JAMA Neurology Aug 2021Enzyme-inducing antiseizure medications (eiASMs) have been hypothesized to be associated with long-term risks of cardiovascular disease.
IMPORTANCE
Enzyme-inducing antiseizure medications (eiASMs) have been hypothesized to be associated with long-term risks of cardiovascular disease.
OBJECTIVE
To quantify and model the putative hazard of cardiovascular disease secondary to eiASM use.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study covered January 1990 to March 2019 (median [IQR] follow-up, 9 [4-15], years). The study linked primary care and hospital electronic health records at National Health Service hospitals in England. People aged 18 years or older diagnosed as having epilepsy after January 1, 1990, were included. All eligible patients were included with a waiver of consent. No patients were approached who withdrew consent. Analysis began January 2021 and ended August 2021.
EXPOSURES
Receipt of 4 consecutive eiASMs (carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide, or topiramate) following an adult-onset (age ≥18 years) epilepsy diagnosis or repeated exposure in a weighted cumulative exposure model.
MAIN OUTCOMES AND MEASURES
Three cohorts were isolated, 1 of which comprised all adults meeting a case definition for epilepsy diagnosed after 1990, 1 comprised incident cases diagnosed after 1998 (hospital linkage date), and 1 was limited to adults diagnosed with epilepsy at 65 years or older. Outcome was incident cardiovascular disease (ischemic heart disease or ischemic or hemorrhagic stroke). Hazard of incident cardiovascular disease was evaluated using adjusted propensity-matched survival analyses and weighted cumulative exposure models.
RESULTS
Of 10 916 166 adults, 50 888 (0.6%) were identified as having period-prevalent cases (median [IQR] age, 32 [19-50] years; 16 584 [53%] female), of whom 31 479 (62%) were diagnosed on or after 1990 and were free of cardiovascular disease at baseline. In a propensity-matched Cox proportional hazards model adjusted for age, sex, baseline socioeconomic status, and cardiovascular risk factors, the hazard ratio for incident cardiovascular disease was 1.21 (95% CI, 1.06-1.39) for those receiving eiASMs. The absolute difference in cumulative hazard diverges by more than 1% and greater after 10 years. For those with persistent exposure beyond 4 prescriptions, the median hazard ratio increased from amedian (IQR) of 1.54 (1.28-1.79) when taking a relative defined daily dose of an eiASM of 1 to 2.38 (1.52-3.56) with a relative defined daily dose of 2 throughout a maximum of 25 years’ follow-up compared with those not receiving an eiASM. The hazard was elevated but attenuated when restricting analyses to incident cases or those diagnosed when older than 65 years.
CONCLUSIONS AND RELEVANCE
The hazard of incident cardiovascular disease is higher in those receiving eiASMs. The association is dose dependent and the absolute difference in hazard seems to reach clinical significance by approximately 10 years from first exposure.
Topics: American Medical Association; Periodicals as Topic; United States
PubMed: 34081094
DOI: 10.1001/jamaneurol.2021.2135 -
The Cochrane Database of Systematic... Apr 2017Essential tremor (ET) is one of the most common movement disorders. The management is primarily based on pharmacological agents and in clinical practice propranolol and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Essential tremor (ET) is one of the most common movement disorders. The management is primarily based on pharmacological agents and in clinical practice propranolol and primidone are considered the first-line therapy. However, these treatments can be ineffective in 25% to 55% of people and are frequently associated with serious adverse events (AEs). For these reasons, it is worthwhile evaluating other treatments for ET. Topiramate has been suggested as a potentially useful agent for the treatment of ET but there is uncertainty about its efficacy and safety.
OBJECTIVES
To assess the efficacy and safety of topiramate in the treatment of ET.
SEARCH METHODS
We carried out a systematic search without language restrictions to identify all relevant trials in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to January 2017), Embase (January 1988 to January 2017), National Institute for Health and Care Excellence (1999 to January 2017), ClinicalTrials.gov (1997 to January 2017) and World Health Organization International Clinical Trials Registry Platform (ICTRP; 2004 to January 2017). We searched BIOSIS Citation Index (2000 to January 2017) for conference proceedings. We handsearched grey literature and the reference lists of identified studies and reviews.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of topiramate versus placebo/open control or any other treatments. We included studies in which the diagnosis of ET was made according to accepted and validated diagnostic criteria. We excluded studies conducted in people presenting with secondary forms of tremor or reporting only neurophysiological parameters to assess outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently collected and extracted data using a data collection form. We assessed the risk of bias and the quality of evidence. We used a fixed-effect meta-analysis for data synthesis.
MAIN RESULTS
This review included three trials comparing topiramate to placebo (309 participants). They were all at high overall risk of bias. The quality of evidence ranged from very low to low. Compared to placebo, participants treated with topiramate showed a significant improvement in functional disability and an increased risk of withdrawal (risk ratio (RR) 1.78, 95% confidence interval (CI) 1.23 to 2.60). There were more AEs for topiramate-treated participants, particularly paraesthesia, weight loss, appetite decrease and memory difficulty.
AUTHORS' CONCLUSIONS
This systematic review highlighted the presence of limited data and very low to low quality evidence to support the apparent efficacy and the occurrence of treatment-limiting AEs in people with ET treated with topiramate. Further research to assess topiramate efficacy and safety on ET is needed.
Topics: Activities of Daily Living; Anticonvulsants; Essential Tremor; Fructose; Humans; Patient Dropouts; Publication Bias; Randomized Controlled Trials as Topic; Topiramate
PubMed: 28409827
DOI: 10.1002/14651858.CD009683.pub2 -
CMAJ : Canadian Medical Association... Nov 2017
Topics: Adrenergic beta-Antagonists; Aging; Essential Tremor; Humans; Primidone
PubMed: 29109210
DOI: 10.1503/cmaj.170128 -
The Cochrane Database of Systematic... Oct 2016Essential tremor is one of the most common movement disorders. Treatment primarily consists of pharmacological agents. While primidone and propranolol are... (Review)
Review
BACKGROUND
Essential tremor is one of the most common movement disorders. Treatment primarily consists of pharmacological agents. While primidone and propranolol are well-established treatments in clinical practice, they may be ineffective in 25% to 55% of patients and can produce serious adverse events in a large percentage of them. For these reasons, it is worth evaluating the treatment alternatives for essential tremor. Some specialists have suggested that pregabalin could be a potentially useful agent, but there is uncertainty about its efficacy and safety.
OBJECTIVES
To assess the effects of pregabalin versus placebo or other treatment for essential tremor in adults.
SEARCH METHODS
We performed a systematic search without language restrictions to identify all relevant trials up to December 2015. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, NICE, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We handsearched grey literature and examined the reference lists of identified studies and reviews.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of pregabalin versus placebo or any other treatments. We included studies in which the diagnosis of ET was made according to accepted and validated diagnostic criteria. We excluded studies conducted in patients presenting secondary forms of tremor or reporting only neurophysiological parameters to assess outcomes.
DATA COLLECTION AND ANALYSIS
Two reviewers independently collected and extracted data using a data collection form. We assessed the risk of bias of the body of evidence, and we used inverse variance methods to analyse continuous outcomes and measurement scales. We compared the mean difference between treatment groups, and we combined results for dichotomous outcomes using Mantel-Haenszel methods and risk differences We used Review Manager software for data management and analysis.
MAIN RESULTS
We only found one study eligible for this review (22 participants). We assessed the risk of bias for most domains as unclear. We graded the overall quality of evidence as very low. Compared to placebo, patients treated with pregabalin showed no significant improvement of motor tasks on the 36-point subscale of the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (MD -2.15 points; 95% CI -9.16 to 4.86) or on the 32-point functional abilities subscale of the TRS (MD -0.66 points; 95% CI -2.90 to 1.58).The limited evidence showed no difference in study withdrawal (Mantel-Haenszel RD -0.09; 95% CI -0.48 to 0.30) and presentation of adverse events between pregabalin and placebo (Mantel-Haenszel RD 0.18; 95% CI -0.13 to 0.50).
AUTHORS' CONCLUSIONS
The effects of pregabalin for treating essential tremor are uncertain because the quality of the evidence is very low. One small study did not highlight any effect of this treatment; however, the high risk of bias and the lack of other studies on this topic limit further conclusion.
Topics: Adult; Anticonvulsants; Essential Tremor; Humans; Middle Aged; Pregabalin; Randomized Controlled Trials as Topic; Upper Extremity
PubMed: 27763691
DOI: 10.1002/14651858.CD009682.pub2 -
The Cochrane Database of Systematic... Aug 2017Essential tremor (ET) is one of the most common movement disorders. The treatment is primarily based on pharmacological agents. Although primidone and propranolol are... (Review)
Review
BACKGROUND
Essential tremor (ET) is one of the most common movement disorders. The treatment is primarily based on pharmacological agents. Although primidone and propranolol are well established treatments in clinical practice, they can be ineffective in 25% to 55% of patients, and can produce serious adverse events in a large percentage of them. For these reasons, it may be worthwhile evaluating the treatment alternatives for ET. Zonisamide has been suggested as a potentially useful agent for the treatment of ET but there is uncertainty about its efficacy and safety.
OBJECTIVES
To assess the effect on functional abilities and the safety profile of zonisamide in adults with essential tremor (ET).
SEARCH METHODS
We carried out a systematic search, without language restrictions to identify all relevant trials. We searched CENTRAL, MEDLINE, Embase, NICE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) to January 2017. We searched BIOSIS Citation Index (2000 to January 2017) for conference proceedings. We handsearched grey literature and examined the reference lists of identified studies and reviews.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of zonisamide versus placebo or any other treatment. We included studies in which the diagnosis of ET was made according to accepted and validated diagnostic criteria. We excluded studies conducted in patients presenting secondary forms of tremor or reporting only neurophysiological parameters to assess outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently collected and extracted data using a data collection form. We assessed the risk of bias and the quality of evidence.We used inverse variance methods for continuous outcomes and measurement scales. We compared differences between treatment groups as mean differences. We combined results for dichotomous outcomes using Mantel-Haenszel methods and obtained risk differences to compare treatment groups. We used Review Manager 5 software for data management and analysis.
MAIN RESULTS
We only considered one study eligible for this review (20 participants). Assessments of risk of bias for most domains were unclear or low. Adverse events were only reported in participants from the zonisamide group, making it possible that they were aware of treatment group assignment. We are uncertain as to the effects of zonisamide on motor tasks (mean difference (MD) -0.00, 95% confidence interval (CI) -1.51 to 1.51, very low-quality evidence) and functional disabilities (MD -0.30, 95% CI -1.23 to 0.63, very low-quality evidence) when compared with placebo. Three participants in the zonisamide group (30%) and two participants in the placebo group (20%) discontinued the treatment and withdrew from the study for any reason (very low-quality evidence), however the increased risk of withdrawal in the zonisamide group was statistically non-significant (risk difference (RD) 0.1, 95% CI -0.28 to 0.48). Six participants in the zonisamide group (60%) and none of the participants in the placebo group (0%) developed adverse events (AEs), with a RD of 0.60 (95% CI 0.28 to 0.92; very low quality evidence). The most common AEs, experienced with zonisamide treatment, were headache, nausea, fatigue, sleepiness, and diarrhoea. Quality of life was not assessed in the study included.
AUTHORS' CONCLUSIONS
Based on currently available data, there is insufficient evidence to assess the efficacy and safety of zonisamide treatment for ET.
Topics: Anticonvulsants; Essential Tremor; Humans; Isoxazoles; Randomized Controlled Trials as Topic; Zonisamide
PubMed: 28836659
DOI: 10.1002/14651858.CD009684.pub2 -
The Cochrane Database of Systematic... Dec 2015Essential tremor (ET) is one of the most common movement disorders. Treatment is based primarily on pharmacological agents. On this basis, although primidone and... (Review)
Review
BACKGROUND
Essential tremor (ET) is one of the most common movement disorders. Treatment is based primarily on pharmacological agents. On this basis, although primidone and propranolol are well-established treatments in clinical practice, they could be ineffective in 25% to 55% of patients and can produce serious adverse events (AEs) in a large percentage of individuals. For these reasons, evaluating treatment alternatives for ET may be a worthwhile pursuit. Alprazolam has been suggested as a potentially useful agent for treatment of individuals with ET, but its efficacy and safety are uncertain.
OBJECTIVES
PrimaryTo assess the efficacy and safety of alprazolam in the treatment of individuals with ET. SecondaryTo examine effects of alprazolam treatment on the quality of life of people with ET.
SEARCH METHODS
We carried out a systematic search without language restrictions to identify all relevant trials. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to September 2015), EMBASE (January 1988 to September 2015), the National Institute for Health and Care Excellence (NICE) (1999 to September 2015), ClinicalTrials.gov (1997 to September 2015) and the World Health Organiza tion (WHO) International Clinical Trials Registry Platform (ICTRP) (2004 to September 2015). We handsearched grey literature and examined the reference lists of identified studies and reviews.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of alprazolam versus placebo or any other treatment. We included studies in which ET was diagnosed according to accepted and validated diagnostic criteria. We excluded studies that included patients presenting with secondary forms of tremor or reporting only neurophysiological parameters for the pur p ose of assessing outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently collected and extracted data using a data collection form. We assessed risk of bias and the body of evidence. We used inverse variance methods for continuous outcomes and measurement scales. We compared differences between treatment groups as mean differences. We used Review Manager software for management and analysis of data.
MAIN RESULTS
We included in this review one trial that compared alprazolam versus placebo (24 participants). It was judged to have high overall risk of bias. We graded the overall quality of evidence as very low. Compared with those given placebo, participants treated with alprazolam showed a significant reduction in tremor severity (mean difference (MD) -0.75, 95% confidence interval (CI) -0.83 to -0.67). Nine alprazolam-treated participants (75%) developed AEs, mainly represented by sedation (50%), constipation (17%) and dry mouth (9%). No participants in the alprazolam group and no p articipants in the placebo group discontinued treatment and dropped out of the study.
AUTHORS' CONCLUSIONS
Currently available data reveal evidence insufficient for assessment of the efficacy and safety of alprazolam treatment for individuals with ET.
Topics: Adult; Aged; Alprazolam; Anticonvulsants; Constipation; Essential Tremor; Humans; Middle Aged; Randomized Controlled Trials as Topic; Xerostomia
PubMed: 26638213
DOI: 10.1002/14651858.CD009681.pub2 -
Toxins Nov 2017Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the... (Review)
Review
Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one's ability to perform daily tasks becomes impaired. Oral therapies, including propranolol and primidone, can be effective in the management of essential tremor, although adverse effects can limit their use and about 50% of individuals lack response to oral pharmacotherapy. Locally administered botulinum toxin injection has become increasingly useful in the management of essential tremor. Targeting of select muscles with botulinum toxin is an area of active research, and muscle selection has important implications for toxin dosing and functional outcomes. The use of anatomical landmarks with palpation, EMG guidance, electrical stimulation, and ultrasound has been studied as a technique for muscle localization in toxin injection. Earlier studies implemented a standard protocol for the injection of (predominantly) wrist flexors and extensors using palpation and EMG guidance. Targeting of muscles by selection of specific activators of tremor (tailored to each patient) using kinematic analysis might allow for improvement in efficacy, including functional outcomes. It is this individualized muscle selection and toxin dosing (requiring injection within various sites of a single muscle) that has allowed for success in the management of tremors.
Topics: Botulinum Toxins; Electric Stimulation; Electromyography; Extremities; Humans; Tremor
PubMed: 29125566
DOI: 10.3390/toxins9110365 -
Neurological Research and Practice Oct 2022Slow orthostatic tremor is an extremely rare movement disorder with relatively low-frequency tremor (< 13 Hz) in the legs and trunk, which is evoked by standing....
Slow orthostatic tremor is an extremely rare movement disorder with relatively low-frequency tremor (< 13 Hz) in the legs and trunk, which is evoked by standing. There is still much controversy regarding its precise etiology. Here we present a 57 year-old female patient with a slow orthostatic tremor variant who experienced progressive gait disturbances since six years due to isolated trunk tremor. Potential symptomatic causes of tremor and other neurological co-morbidities were excluded through an exenstive clinical, laboratoy and imaging work-up. Subsequently, a combined treatment with propranolol and primidone was started, which resulted in almost complete resolution of the trunk tremor. Given that the slow trunk tremor in this patient almost completely resolved after therapy with a low-dose propranolol and primidone, considered first line drugs for the treatment of essential tremor, this case illustrates that isolated orthostatic trunk tremor may occur as a rare variant of essential tremor.
PubMed: 36244974
DOI: 10.1186/s42466-022-00216-6 -
Cureus May 2024Essential tremors (ETs) commonly manifest as involuntary shaking of the hands that disrupt daily activities. These tremors involve the central motor network of the... (Review)
Review
Essential tremors (ETs) commonly manifest as involuntary shaking of the hands that disrupt daily activities. These tremors involve the central motor network of the cerebellum, thalamus, and cortical networks, leading to different clinical phenotypes. The goal of this review was to establish evidence-based recommendations for effective care and simplify decisions for those dealing with ET. For this narrative literature review, we conducted a thorough search using core keywords such as "essential tremor" and "therapy." From the 27 selected articles, relevant data were presented regarding pathophysiology, medications, and other treatment options, with necessary supplemental data such as side effects and use cases. This paper examines treatments for ET, including commonly prescribed medications such as propranolol and primidone; invasive treatments such as deep brain stimulation, focused ultrasound thalamotomy, transcranial magnetic stimulation, and some surgical methods; and non-invasive methods such as the neuromodulation technique of transcutaneous afferent patterned stimulation. Overall, this study presents a synthesized understanding of the currently available modalities for managing ETs. It is intended to guide care providers in choosing the best possible method to contain symptoms.
PubMed: 38826876
DOI: 10.7759/cureus.59451 -
Tremor and Other Hyperkinetic Movements... 2021There are few medications for the treatment of essential tremor (ET). One of these, primidone, which is one of only two front-line agents, is associated with... (Review)
Review
BACKGROUND
There are few medications for the treatment of essential tremor (ET). One of these, primidone, which is one of only two front-line agents, is associated with considerable adverse drug reactions (ADRs). It is unclear why some primidone-treated ET patients develop ADRs whereas others do not, and why these ADRs seem to be more prevalent in ET patients than primidone-treated patients with epilepsy.
OBJECTIVE
To review several possible explanations underlying the above-referenced differences.
METHODS
A literature search was conducted in PubMed in October 2021. Studies reporting the ADRs of primidone in different neurological conditions were comprehensively reviewed.
DISCUSSION
Although there were no head-to-head data, a review of the previous studies on ET and epilepsy patients indicates that the former is relatively more intolerant to primidone. Moreover, not all ET patients develop ADR of similar nature or severity. We discuss several potential mechanisms for this variability in the intolerance to primidone. These include: (i) older age (ET vs. epilepsy patients), (ii) cross-tolerance to primidone in patients with epilepsy, (iii) neurobiological (GABA-related) abnormalities associated with ET.
CONCLUSION
We speculate that there are several possible explanations for primidone intolerance in ET. These possibilities should be tested in future studies, and we propose the roadmap for designing these studies. It is of value to obtain detailed insight into these complex issues because primidone remains one of the few frontline anti-tremor medications in ET. Answers to issues we have raised in this article could facilitate more customized formulation of primidone in ET patients.
Topics: Aged; Essential Tremor; Humans; Primidone; Tremor
PubMed: 35070493
DOI: 10.5334/tohm.672