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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 -
Neurotherapeutics : the Journal of the... Jan 2014Tremor is a hyperkinetic movement disorder characterized by rhythmic oscillations of one or more body parts. It can be disabling and may impair quality of life. Various... (Review)
Review
Tremor is a hyperkinetic movement disorder characterized by rhythmic oscillations of one or more body parts. It can be disabling and may impair quality of life. Various etiological subtypes of tremor are recognized, with essential tremor (ET) and Parkinsonian tremor being the most common. Here we review the current literature on tremor treatment regarding ET and head and voice tremor, as well as dystonic tremor, orthostatic tremor, tremor due to multiple sclerosis (MS) or lesions in the brainstem or thalamus, neuropathic tremor, and functional (psychogenic) tremor, and summarize main findings. Most studies are available for ET and only few studies specifically focused on other tremor forms. Controlled trials outside ET are rare and hence most of the recommendations are based on a low level of evidence. For ET, propranolol and primidone are considered drugs of first choice with a mean effect size of approximately 50 % tremor reduction. The efficacy of topiramate is also supported by a large double-blind placebo-controlled trial, while other drugs have less supporting evidence. With a mean effect size of about 90 % deep brain stimulation in the nucleus ventralis intermedius or the subthalamic nucleus may be the most potent treatment; however, there are no controlled trials and it is reserved for severely affected patients. Dystonic limb tremor may respond to anticholinergics. Botulinum toxin improves head and voice tremor. Gabapentin and clonazepam are often recommended for orthostatic tremor. MS tremor responds only poorly to drug treatment. For patients with severe MS tremor, thalamic deep brain stimulation has been recommended. Patients with functional tremor may benefit from antidepressants and are best be treated in a multidisciplinary setting. Several tremor syndromes can already be treated with success. But new drugs specifically designed for tremor treatment are needed. ET is most likely covering different entities and their delineation may also improve treatment. Modern study designs and long-term studies are needed.
Topics: Amines; Anticonvulsants; Botulinum Toxins; Cyclohexanecarboxylic Acids; Deep Brain Stimulation; Fructose; Gabapentin; Humans; Topiramate; Tremor; gamma-Aminobutyric Acid
PubMed: 24142589
DOI: 10.1007/s13311-013-0230-5 -
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 -
BMJ Clinical Evidence May 2007Essential tremor is one of the most common movement disorders throughout the world, with prevalence in the general population of 0.4-3.9%. Although most people with... (Review)
Review
INTRODUCTION
Essential tremor is one of the most common movement disorders throughout the world, with prevalence in the general population of 0.4-3.9%. Although most people with essential tremor are only mildly affected, those who seek medical care are disabled to some extent, and most are socially handicapped by the tremor.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of drug treatments in people with essential tremor of the hand? We searched: Medline, Embase, The Cochrane Library and other important databases up to December 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 41 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding mirtazepine to other antitremor drugs; benzodiazepines; beta-blockers other than propranolol; botulinum A toxin-haemagglutinin complex; calcium channel blockers; carbonic anhydrase inhibitors; clonidine; flunarizine; gabapentin; isoniazid; Phenobarbital; primidone; propranolol; and topiramate.
Topics: Double-Blind Method; Essential Tremor; Humans; Primidone; Propranolol; Tremor
PubMed: 19454072
DOI: No ID Found -
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 -
Canadian Medical Association Journal Jul 1964Although sneezing is a particularly common symptom, there are surprisingly few references to this subject in the medical literature. Many of these references are...
Although sneezing is a particularly common symptom, there are surprisingly few references to this subject in the medical literature. Many of these references are shrouded in superstition and unscientific theory. Preparation of this report was stimulated by an interesting example of severe uncontrollable non-allergic paroxysmal sneezing which was carefully investigated with regard to both physical and psychological factors. A further example of paroxysms of sneezing occurring in a patient with temporal lobe seizures is also discussed with particular reference to the control of the sneezing episodes in association with anticonvulsant medication and control of the epileptic attacks. In addition, the neurophysiological mechanisms of sneezing are reviewed and the specific neurological references to the subject are discussed in relation to physiological and clinical data. At times the symptom of sneezing would appear to reflect some unknown disorder which may have central and possibly cortical affiliations.
Topics: Anticonvulsants; Child; Child Psychiatry; Epilepsy; Epilepsy, Temporal Lobe; Humans; Hydantoins; Methamphetamine; Phenobarbital; Primidone; Sneezing; Temporal Lobe
PubMed: 14180524
DOI: No ID Found -
Indian Journal of Dermatology,... 2011Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine... (Review)
Review
Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.
Topics: Anticonvulsants; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Incidence; Male; Pharmaceutical Preparations; Prognosis; Risk Assessment; Severity of Illness Index; Syndrome; Time Factors
PubMed: 21220873
DOI: 10.4103/0378-6323.74964