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BMJ Open Jul 2017Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. (Meta-Analysis)
Meta-Analysis Review
Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis.
OBJECTIVES
Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding.
DESIGN AND SETTING
Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers.
PARTICIPANTS
29 cohort studies including 5100 infants/children.
INTERVENTIONS
Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group.
PRIMARY AND SECONDARY OUTCOME MEASURES
Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes.
RESULTS
The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control.
CONCLUSIONS
Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen.
TRIAL REGISTRATION NUMBER
PROSPERO database (CRD42014008925).
Topics: Anticonvulsants; Autistic Disorder; Bayes Theorem; Breast Feeding; Carbamazepine; Child; Epilepsy; Female; Humans; Lamotrigine; Observational Studies as Topic; Oxcarbazepine; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Triazines; Valproic Acid
PubMed: 28729328
DOI: 10.1136/bmjopen-2017-017248 -
The Cochrane Database of Systematic... Nov 2016There is evidence that certain antiepileptic drugs (AEDs) are teratogenic and are associated with an increased risk of congenital malformation. The majority of women... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is evidence that certain antiepileptic drugs (AEDs) are teratogenic and are associated with an increased risk of congenital malformation. The majority of women with epilepsy continue taking AEDs throughout pregnancy; therefore it is important that comprehensive information on the potential risks associated with AED treatment is available.
OBJECTIVES
To assess the effects of prenatal exposure to AEDs on the prevalence of congenital malformations in the child.
SEARCH METHODS
We searched the Cochrane Epilepsy Group Specialized Register (September 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 11), MEDLINE (via Ovid) (1946 to September 2015), EMBASE (1974 to September 2015), Pharmline (1978 to September 2015), Reprotox (1983 to September 2015) and conference abstracts (2010-2015) without language restriction.
SELECTION CRITERIA
We included prospective cohort controlled studies, cohort studies set within pregnancy registries and randomised controlled trials. Participants were women with epilepsy taking AEDs; the two control groups were women without epilepsy and women with epilepsy who were not taking AEDs during pregnancy.
DATA COLLECTION AND ANALYSIS
Three authors independently selected studies for inclusion. Five authors completed data extraction and risk of bias assessments. The primary outcome was the presence of a major congenital malformation. Secondary outcomes included specific types of major congenital malformations. Where meta-analysis was not possible, we reviewed included studies narratively.
MAIN RESULTS
We included 50 studies, with 31 contributing to meta-analysis. Study quality varied, and given the observational design, all were at high risk of certain biases. However, biases were balanced across the AEDs investigated and we believe that the results are not explained by these biases.Children exposed to carbamazepine (CBZ) were at a higher risk of malformation than children born to women without epilepsy (N = 1367 vs 2146, risk ratio (RR) 2.01, 95% confidence interval (CI) 1.20 to 3.36) and women with untreated epilepsy (N = 3058 vs 1287, RR 1.50, 95% CI 1.03 to 2.19). Children exposed to phenobarbital (PB) were at a higher risk of malformation than children born to women without epilepsy (N = 345 vs 1591, RR 2.84, 95% CI 1.57 to 5.13). Children exposed to phenytoin (PHT) were at an increased risk of malformation compared with children born to women without epilepsy (N = 477 vs 987, RR 2.38, 95% CI 1.12 to 5.03) and to women with untreated epilepsy (N = 640 vs 1256, RR 2.40, 95% CI 1.42 to 4.08). Children exposed to topiramate (TPM) were at an increased risk of malformation compared with children born to women without epilepsy (N = 359 vs 442, RR 3.69, 95% CI 1.36 to 10.07). The children exposed to valproate (VPA) were at a higher risk of malformation compared with children born to women without epilepsy (N = 467 vs 1936, RR 5.69, 95% CI 3.33 to 9.73) and to women with untreated epilepsy (N = 1923 vs 1259, RR 3.13, 95% CI 2.16 to 4.54). There was no increased risk for major malformation for lamotrigine (LTG). Gabapentin (GBP), levetiracetam (LEV), oxcarbazepine (OXC), primidone (PRM) or zonisamide (ZNS) were not associated with an increased risk, however, there were substantially fewer data for these medications.For AED comparisons, children exposed to VPA had the greatest risk of malformation (10.93%, 95% CI 8.91 to 13.13). Children exposed to VPA were at an increased risk of malformation compared with children exposed to CBZ (N = 2529 vs 4549, RR 2.44, 95% CI 2.00 to 2.94), GBP (N = 1814 vs 190, RR 6.21, 95% CI 1.91 to 20.23), LEV (N = 1814 vs 817, RR 5.82, 95% CI 3.13 to 10.81), LTG (N = 2021 vs 4164, RR 3.56, 95% CI 2.77 to 4.58), TPM (N = 1814 vs 473, RR 2.35, 95% CI 1.40 to 3.95), OXC (N = 676 vs 238, RR 3.71, 95% CI 1.65 to 8.33), PB (N = 1137 vs 626, RR 1.59, 95% CI 1.11 to 2.29, PHT (N = 2319 vs 1137, RR 2.00, 95% CI 1.48 to 2.71) or ZNS (N = 323 vs 90, RR 17.13, 95% CI 1.06 to 277.48). Children exposed to CBZ were at a higher risk of malformation than those exposed to LEV (N = 3051 vs 817, RR 1.84, 95% CI 1.03 to 3.29) and children exposed to LTG (N = 3385 vs 4164, RR 1.34, 95% CI 1.01 to 1.76). Children exposed to PB were at a higher risk of malformation compared with children exposed to GBP (N = 204 vs 159, RR 8.33, 95% CI 1.04 to 50.00), LEV (N = 204 vs 513, RR 2.33, 95% CI 1.04 to 5.00) or LTG (N = 282 vs 1959, RR 3.13, 95% CI 1.64 to 5.88). Children exposed to PHT had a higher risk of malformation than children exposed to LTG (N = 624 vs 4082, RR 1.89, 95% CI 1.19 to 2.94) or to LEV (N = 566 vs 817, RR 2.04, 95% CI 1.09 to 3.85); however, the comparison to LEV was not significant in the random-effects model. Children exposed to TPM were at a higher risk of malformation than children exposed to LEV (N = 473 vs 817, RR 2.00, 95% CI 1.03 to 3.85) or LTG (N = 473 vs 3975, RR 1.79, 95% CI 1.06 to 2.94). There were no other significant differences, or comparisons were limited to a single study.We found significantly higher rates of specific malformations associating PB exposure with cardiac malformations and VPA exposure with neural tube, cardiac, oro-facial/craniofacial, and skeletal and limb malformations in comparison to other AEDs. Dose of exposure mediated the risk of malformation following VPA exposure; a potential dose-response association for the other AEDs remained less clear.
AUTHORS' CONCLUSIONS
Exposure in the womb to certain AEDs carried an increased risk of malformation in the foetus and may be associated with specific patterns of malformation. Based on current evidence, LEV and LTG exposure carried the lowest risk of overall malformation; however, data pertaining to specific malformations are lacking. Physicians should discuss both the risks and treatment efficacy with the patient prior to commencing treatment.
Topics: Abnormalities, Drug-Induced; Anticonvulsants; Cardiovascular Abnormalities; Craniofacial Abnormalities; Epilepsy; Female; Humans; Infant, Newborn; Musculoskeletal Abnormalities; Neural Tube Defects; Pregnancy; Pregnancy Complications
PubMed: 27819746
DOI: 10.1002/14651858.CD010224.pub2 -
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 -
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 -
Progress in Neuro-psychopharmacology &... Jun 2023Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a...
OBJECTIVE
Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a series of matrices from combined samples of pregnant/breastfeeding women treated with anticonvulsants or lithium.
METHODS
We conducted a systematic literature search in PubMed/EMBASE for studies with concentrations of anticonvulsants/lithium from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal concentrations. When data from multiple studies were available, we calculated combined penetration ratios, weighting studies' mean by study size.
RESULTS
Ninety-one eligible studies for brivaracetam, carbamazepine, clonazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, lithium, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproate, vigabatrin and zonisamide were identified. For amniotic fluid, the highest penetration ratios were estimated for levetiracetam (mean 3.56, range 1.27-5.85, n = 2) and lowest for valproate (mean 0.11, range 0.02-1.02, n = 57). For umbilical cord plasma, oxcarbazepine had the highest ratio (mean 1.59, range 0.11-4.33, n = 12) with clonazepam having the lowest (mean 0.55, range 0.52-0.59, n = 2). For breast milk, the highest ratios were observed for oxcarbazepine (mean 3.75, range 0.5-7.0, n = 2), whereas the lowest were observed for valproate (mean 0.04, range 0.01-0.22, n = 121).
DISCUSSION
We observed substantial variability between anticonvulsants and lithium regarding their ability to enter fetal/newborn circulation. Assessing concentrations of anticonvulsants and lithium in maternal samples can provide a surrogate of fetal/infant exposure, although patterns of concentration-dependent effects for maternal/neonatal safety are lacking.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Anticonvulsants; Fetal Blood; Lithium; Maternal-Fetal Exchange; Milk, Human
PubMed: 36805301
DOI: 10.1016/j.pnpbp.2023.110733 -
Seizure May 2022Recent position papers and guidelines encourage women with epilepsy (WWE) to exclusively breastfeed their infants because the benefits to their infants outweigh the... (Review)
Review
BACKGROUND
Recent position papers and guidelines encourage women with epilepsy (WWE) to exclusively breastfeed their infants because the benefits to their infants outweigh the potential adverse effects caused by exposure to antiseizure medications (ASMs).
OBJECTIVE
The objectives of this review were: to evaluate concentrations of ASMs in breastmilk of lactating WWE, qualitatively synthesize evidence that can be used to estimate theoretical doses as estimated daily intake (EDI) and relative infant dose (RID) of ASMs, and to evaluate potential risks to infants as a result of exposure to ASMs from breastmilk.
METHODS
This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42020223645. The databases: MEDLINE/PubMed, EMBASE, CINAHL/EBSCO, COCHRANE, SpringerLink, ScienceDirect, Summon, WHO International Clinical Trials Registry Platform, and SCOPUS were systematically searched. A qualitative synthesis was adopted in this study.
RESULTS
A total of 15 records were included in this systematic review. The included studies reported levels of 8 ASMs in the breastmilk of WWE. The highest RIDs of carbamazepine, lamotrigine, primidone, phenobarbital, gabapentin, valproic acid, ethosuximide, levetiracetam, and topiramate were 3.70%, 36.33%, 4.96%, 3.15%, 4.37%, 1.90%, 31.49%, 12.50%, and 12.18%, respectively. Breastfeeding might be limited or even discontinued when signs of excessive sedation/drowsiness and/or poor weight gain are evident on infants exposed to primidone and phenobarbital, ethosuximide/primidone, or ethosuximide/phenobarbital.
CONCLUSIONS
Concentrations of ASMs can be detected in breastmilk of WWE and plasma/serum of infants exposed via breastmilk. Healthcare providers and WWE might use the findings of this study to make informed decisions on the safety of breastfeeding while taking ASMs.
Topics: Anticonvulsants; Breast Feeding; Epilepsy; Ethosuximide; Female; Humans; Infant; Lactation; Milk, Human; Phenobarbital; Primidone
PubMed: 35427849
DOI: 10.1016/j.seizure.2022.03.017 -
British Journal of Clinical Pharmacology Jun 2018Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in...
AIMS
Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates.
METHODS
Databases were searched up to and including September 2016. Studies were included based on PICO as follows: P: infants and neonates being treated with any medication, I: salivary TDM vs. C: traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data.
RESULTS
Twenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent/very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Any compound with an acid dissociation constant (pKa) within physiological range (pH 6-8) gave a more varied response.
CONCLUSION
There is significant potential for infantile saliva testing and in particular for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude, any compound with a pKa within physiological range (pH 6-8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.
Topics: Age Factors; Drug Monitoring; Humans; Infant; Infant, Newborn; Pharmaceutical Preparations; Pharmacokinetics; Predictive Value of Tests; Reproducibility of Results; Saliva
PubMed: 29442362
DOI: 10.1111/bcp.13553 -
Neurologia I Neurochirurgia Polska 2020Tremor is one of the most common movement disorders. It does not usually respond to first-line drug treatments (e.g. propranolol, primidone, anticholinergics, gabapentin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tremor is one of the most common movement disorders. It does not usually respond to first-line drug treatments (e.g. propranolol, primidone, anticholinergics, gabapentin and clonazepam) due to side effects and frequent dose limitations. Botulinum toxin type A (BoNT-A) has been widely used to treat tremor, but its efficacy and safety are uncertain.
AIMS
To evaluate the efficacy and safety of BoNT-A in the treatment of hand tremor.
METHODS
We searched the MEDLINE, EMBASE, PsycINFO and Cochrane Library databases for relevant randomised controlled trials of the effects of BoNT-A injections on tremors, up to 20 February 2020. A meta-analysis of comparative effects was performed using R studio software, and publication bias was examined using Egger's test.
RESULTS
Six studies examining a total of 245 participants with tremor were included in the meta-analysis. The primary outcome of meta-analysis showed no difference in clinical tremor scale scores between the BoNT-A group versus the placebo group (standardised mean difference (SMD): -0.42, 95% confidence interval (CI): -1.94 to 1.10; I2 = 96%). For clinical tremor scale scores, subgroup analyses suggested that the BoNT-A group may differ in terms of multiple sclerosis (MS) related tremor (SMD: -1.10; 95% CI: -2.17 to -0.04; I2 = 79%) compared to a placebo, but the difference did not exist in the outcome of essential tremor (ET) or hand tremor (MD: -1.31; 95% CI: -3.39; 1.31; I2 = 97%). Grip strength (MD: -1.25, 95% CI: -5.99 to 3.50, I2 = 97%) was slightly lower in the BoNT-A group, but the difference was not significant. The incidence of adverse events (AEs), including hand weakness (RR: 2.96, 95% CI: 1.40 to 6.24, I2 = 37%), was significantly greater in the BoNT-A group than in the placebo group. Two studies were assessed as having an overall low risk of bias.
CONCLUSIONS
Our study confirms that BoNT-A injections are unlikely to have an impact on patients with hand tremors. However, subgroup analysis suggested that BoNT-A injections could have possible benefits in MS-related tremor. While moderate to severe hand weakness AEs often limits their use in clinical practice, additional well-designed double-blind, placebo-controlled trials are needed to provide more robust conclusions.
Topics: Botulinum Toxins, Type A; Hand; Humans; Muscle Weakness; Tremor
PubMed: 33047784
DOI: 10.5603/PJNNS.a2020.0079