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BMJ (Clinical Research Ed.) Dec 2010To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy. (Review)
Review
OBJECTIVE
To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy.
DESIGN
A review of all published cohort studies to identify key indications and a population based case-control study to test these indications.
SETTING
Review of PubMed, Web of Science, and Embase for papers about carbamazepine exposure in the first trimester of pregnancy and specific malformations, and the EUROCAT Antiepileptic Study Database, including data from 19 European population based congenital anomaly registries, 1995-2005.
PARTICIPANTS
The literature review covered eight cohort studies of 2680 pregnancies with carbamazepine monotherapy exposure, and the EUROCAT dataset included 98 075 registrations of malformations covering over 3.8 million births.
MAIN OUTCOME MEASURES
Overall prevalence for a major congenital malformation after exposure to carbamazepine monotherapy in the first trimester. Odds ratios for malformations with exposure to carbamazepine among cases (five types of malformation identified in the literature review) compared with two groups of controls: other non-chromosomal registrations of malformations and chromosomal syndromes.
RESULTS
The literature review yielded an overall prevalence for a major congenital malformation of 3.3% (95% confidence interval 2.7 to 4.2) after exposure to carbamazepine monotherapy in the first trimester. In 131 registrations of malformations, the fetus had been exposed to carbamazepine monotherapy. Spina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy (odds ratio 2.6 (95% confidence interval 1.2 to 5.3) compared with no antiepileptic drug), but the risk was smaller for carbamazepine than for valproic acid (0.2, 0.1 to 0.6). There was no evidence for an association with total anomalous pulmonary venous return (no cases with carbamazepine exposure), cleft lip (with or without palate) (0.2, 0.0 to 1.3), diaphragmatic hernia (0.9, 0.1 to 6.6), or hypospadias (0.7, 0.3 to 1.6) compared with no exposure to antiepileptic drugs. Further exploratory analysis suggested a higher risk of single ventricle and atrioventricular septal defect.
CONCLUSION
Carbamazepine teratogenicity is relatively specific to spina bifida, though the risk is less than with valproic acid. Despite the large dataset, there was not enough power to detect moderate risks for some rare major congenital malformations.
Topics: Abnormalities, Drug-Induced; Anticonvulsants; Carbamazepine; Case-Control Studies; Epilepsy; Europe; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Prevalence; Risk Factors
PubMed: 21127116
DOI: 10.1136/bmj.c6581 -
The Cochrane Database of Systematic... Dec 2015Topiramate is a newer broad-spectrum of antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Topiramate is a newer broad-spectrum of antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate monotherapy in people with JME.
OBJECTIVES
To determine the efficacy and tolerability of topiramate monotherapy in the treatment of JME.
SEARCH METHODS
We searched the Cochrane Epilepsy Group Specialized Register (2 November 2015), the Cochrane Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies CRSO, 2 November 2015), MEDLINE (Ovid, 2 November 2015), EMBASE (1 July 2015) and ClinicalTrials.gov (2 November 2015). In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) investigating topiramate monotherapy versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders or experiencing adverse events (AEs).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data.
MAIN RESULTS
We included three studies with 83 participants. For the efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate versus valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS or seizure-free. Concerning tolerability, we ranked AEDs associated with topiramate as moderate-to-severe, while we ranked 59% of AEDs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. We judged the quality of the evidence from the studies to be very low.
AUTHORS' CONCLUSIONS
This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but there were no more benefits of efficacy in topiramate compared with valproate. In the future, well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.
Topics: Adolescent; Anticonvulsants; Child; Fructose; Humans; Myoclonic Epilepsy, Juvenile; Randomized Controlled Trials as Topic; Seizures; Topiramate; Treatment Outcome; Valproic Acid; Young Adult
PubMed: 26695884
DOI: 10.1002/14651858.CD010008.pub2 -
Seizure Jul 2023The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS),... (Review)
Review
INTRODUCTION
The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS.
METHODS
We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748).
RESULTS
Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control.
CONCLUSIONS
AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option.
Topics: Humans; Down Syndrome; Epilepsy; Epilepsies, Myoclonic; Levetiracetam; Seizures; Alzheimer Disease; Electroencephalography; Anticonvulsants; Epilepsy, Generalized
PubMed: 37267668
DOI: 10.1016/j.seizure.2023.05.017 -
The Cochrane Database of Systematic... 2004Agitation affects up to 70% of older people with dementia. Valproic acid has been used for the past 10 years to control agitation in dementia, but no systematic review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Agitation affects up to 70% of older people with dementia. Valproic acid has been used for the past 10 years to control agitation in dementia, but no systematic review of the effectiveness of this drug has been published to date. The current study examines three randomized, placebo-controlled trials of the effect of valproic acid on older people with dementia who were agitated.
OBJECTIVES
To determine whether evidence supports the use of valproic acid in the treatment of agitation of people with dementia.
SEARCH STRATEGY
Trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 July 2003 using the terms ("agitat*" or "distur*" or "behavi*" or "aggress*") and "valproic" or "valproate" or "divalpro*." This Register contains articles from all major health care databases and many ongoing trials databases and is regularly updated. The reviewers contacted the authors of publications and drug companies manufacturing valproic acid for additional information.
SELECTION CRITERIA
Randomized, placebo-controlled trials with concealed allocation where agitation and dementia of participants were assessed
DATA COLLECTION AND ANALYSIS
1. Two reviewers extracted data from published trials. 2. Odds ratios of average differences were calculated. 3. Only "intention to treat" analyses were included. 4. Analysis compared participants treated with valproic acid with controls.
MAIN RESULTS
Meta-analysis of the pooled results of the included trials could not be performed because of the following problems. In Porsteinsson 2001, although the physicians having direct responsibility for patient care were blinded, a non-blinded physician, who had no direct contact with these physicians, adjusted divalproex sodium dosage on the basis of reports from blinded raters. Therefore, because the physician who controlled therapy knew which patients were receiving divalproex, the trial did not satisfy the criterion of concealed allocation. In Tariot 2001, 54% of the treated patients dropped out compared with 29% of control patients. Of all treated patients, 22% dropped out because of adverse effects, and the study had to be discontinued prematurely. The third trial (Sival 2002) had a cross-over design. No results from the first phase of the study were available, and although the statistical section stated, "the t-test for independent samples is used to analyze the two-period cross-over trial", because the samples were not independent - they are the same patients in the treatment and placebo groups - a question must be raised about the correctness of the analyses. The type of valproate used in the trials varied - one used short-acting sodium valproate, one long-acting divalproex sodium, and the third early-onset acting divalproex sodium. Average doses differed (480mg/d - 1000mg/d), as did duration of therapy (3 wks - 6 wks), and ways of evaluating patients and their response to therapy. A limited meta-analysis, pooling the results concerning adverse effects (Porsteinsson 2001, Tariot 2001) revealed the following: Sedation occurred more frequently in patients treated with valproic acid than in controls Urinary tract infection was more common among patients treated with valproic acid than controls Because of differences in identifying adverse effects it was not possible to pool other observations concerning adverse effects between the two studies that were examined.
REVIEWERS' CONCLUSIONS
The trials reviewed should be regarded as preliminary. Individual reports suggest that low dose sodium valproate is ineffective in treating agitation among demented patients, and that high dose divalproex sodium is associated with an unacceptable rate of adverse effects. More research on the use of valproate preparations for agitation of people with dementia is needed. On the basis of current evidence, valproate preparations cannot be recommended for the treatment of agitation in dementia.
Topics: Aged; Antimanic Agents; Dementia; Humans; Psychomotor Agitation; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 15106227
DOI: 10.1002/14651858.CD003945.pub2 -
The Canadian Journal of Hospital... 2022Status epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line... (Review)
Review
BACKGROUND
Status epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line treatment but fails to control SE in about one-third of patients. Levetiracetam may be used for SE that is refractory to benzodiazepine therapy.
OBJECTIVE
To examine, by means of a systematic review, the role of IV levetiracetam for the treatment of SE in adults.
DATA SOURCES
MEDLINE, Embase, CENTRAL, and CINAHL databases were searched, from inception to August 18, 2020.
STUDY SELECTION AND DATA EXTRACTION
Included in this review were prospective randomized controlled trials comparing levetiracetam with another antiepileptic drug, given with or after a benzodiazepine, in adult patients with SE. The primary outcome was cessation of SE. Quality of evidence was assessed with the Cochrane risk-of-bias tool. Characteristics of the included studies were reported using descriptive statistics.
DATA SYNTHESIS
Five studies compared IV levetiracetam with valproic acid, phenytoin (or its prodrug fosphenytoin), or both. All 5 studies found no statistically significant differences in efficacy or safety end points. There were numerically more cases of hypotension and respiratory failure with phenytoin, and more cases of psychiatric adverse effects (e.g., post-ictal psychosis) with levetiracetam.
CONCLUSIONS
Available evidence suggests that levetiracetam is as effective as valproic acid or phenytoin for the cessation of SE in adults. Other factors should therefore dictate the choice of antiepileptic drug for patients with SE, such as adverse effect profile, logistics of administration, drug cost, inclusion on hospital formularies, and drug availability.
PubMed: 34987263
DOI: 10.4212/cjhp.v75i1.3254 -
The Cochrane Database of Systematic... Jul 2008Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used; valproate is one of these.
OBJECTIVES
To review the effects of valproate for the treatment of schizophrenia and schizophrenia-like psychoses.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group's register (last update February 2007). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted a pharmaceutical company and authors of relevant studies in order to identify further trials.
SELECTION CRITERIA
We included all randomised controlled trials comparing valproate to antipsychotics or to placebo (or no intervention), whether as the sole agent or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We independently inspected citations and, where possible, abstracts, ordered papers and re-inspected and quality assessed these. Data were extracted independently by at least two reviewers. We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We analysed continuous data using weighted mean differences. Where possible we calculated the number needed to treat (NNT) or number needed to harm statistics.
MAIN RESULTS
The update search identified two further relevant studies, thus the review currently includes seven studies with a total of 519 participants. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With one exception the studies were small, short-term and incompletely reported. Adding valproate was as acceptable as adding placebo to antipsychotic drugs (6 RCT, n=270, RR leaving the study early 1.7 CI 0.9 to 3.2). No significant effect of valproate as an adjunct to antipsychotic medication on the participants' global state or the general mental state at the endpoint was evident. However, one study showed a quicker onset of action in the combination group (Casey 2003). A single small study found the participants in the valproate group to be less aggressive than the control group (n=30, WMD -3.8, CI -5.1 to -2.5). Participants receiving valproate more frequently experienced sedation than those in the placebo group. In a single small study valproate significantly reduced tardive dyskinesia (n=30, WMD -3.3, CI -4.9 to -1.7). The effects of valproate on important subgroups such as those with schizophrenia and aggressive behaviour or those with schizoaffective disorder are unknown.
AUTHORS' CONCLUSIONS
Based on currently available randomised trial-derived evidence, there are no data to support or to refute valproate as a sole agent for schizophrenia. There is some evidence for positive effects on aggression and tardive dyskinesia, but given that these results were based on only a single small study they cannot be considered robust. Given the paucity of the available database further large, simple well-designed and reported trials are necessary. Ideally these would focus on people with schizophrenia and aggression, on those with treatment resistant forms of the disorder and on those with schizoaffective disorders.
Topics: Antimanic Agents; Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Valproic Acid
PubMed: 18646098
DOI: 10.1002/14651858.CD004028.pub3 -
Neuro-oncology Mar 2023This systematic review provides updated insights, from the published literature in the past 5 years, based on the 2017 European Association of Neuro-Oncology (EANO)...
BACKGROUND
This systematic review provides updated insights, from the published literature in the past 5 years, based on the 2017 European Association of Neuro-Oncology (EANO) guidelines for palliative care in adults with malignant brain tumors. It provides an overview of palliative care options, including during the end-of-life phase for patients with malignant brain tumors.
METHODS
A systematic literature search was conducted from 2016 to 2021 focusing on four main topics: (1) symptom management, (2) caregiver needs, (3) early palliative care, and (4) care in the end-of-life phase. An international panel of palliative care experts in neuro-oncology synthesized the literature and reported the most relevant updates. A total of 140 articles were included.
RESULTS
New insights include that: Hippocampal avoidance and stereotactic radiosurgery results in a lower risk of neurocognitive decline in patients with brain metastases; levetiracetam is more efficacious in reducing seizures than valproic acid as first-line monotherapy antiseizure drug (ASD) in glioma patients; lacosamide and perampanel seem well-tolerated and efficacious add-on ASDs; and a comprehensive framework of palliative and supportive care for high-grade glioma patients and their caregivers was proposed. No pharmacological agents have been shown in randomized controlled trials to significantly improve fatigue or neurocognition.
CONCLUSIONS
Since the 2017 EANO palliative care guidelines, new insights have been reported regarding symptom management and end-of-life care, however, most recommendations remain unchanged. Early palliative care interventions are essential to define goals of care and minimize symptom burden in a timely fashion. Interventional studies that address pain, fatigue, and psychiatric symptoms as well as (the timing of) early palliative care are urgently needed.
Topics: Humans; Adult; Terminal Care; Brain Neoplasms; Glioma; Death; Fatigue
PubMed: 36271873
DOI: 10.1093/neuonc/noac216 -
The Cochrane Database of Systematic... 2004Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them valproate.
OBJECTIVES
To review the effects of valproate for the treatment of schizophrenia and schizophrenia-like psychoses.
SEARCH STRATEGY
The reviewers searched the Cochrane Schizophrenia Group's register (July 2002). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted a pharmaceutical company and authors of relevant studies in order to identify further trials.
SELECTION CRITERIA
All randomised controlled trials comparing valproate to antipsychotics or to placebo (or no intervention), whether as the sole agent or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using relative risks (RR) and the 95% confidence intervals (CI). Continuous data were analysed using weighted mean differences. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated.
MAIN RESULTS
Five studies with a total of 379 participants were included. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With one exception the studies were small, short-term and incompletely reported. Adding valproate was as acceptable as adding placebo to antipsychotic drugs (n=130, RR leaving the study early 1.6 CI 0.8 to 3.1). No significant effect of using valproate as an adjunct to antipsychotic medication on the participants' global state or general mental state at the endpoint studies was evident. However, one study showed a quicker onset of action in the combination group. Participants receiving valproate more frequently experienced sedation than those in the placebo group. The effects of valproate on important subgroups such as those with schizophrenia and aggressive behaviour or those with schizoaffective disorder are unknown.
REVIEWER'S CONCLUSIONS
Based on randomised trial-derived evidence which is currently available, there are no data to support or to refute the use of valproate as a sole agent for schizophrenia. There is some evidence for a more rapid improvement with valproate augmentation, but this effect vanished over time. Given this limited evidence, further large, simple well-designed and reported trials are necessary. These might focus on people with schizophrenia and violent episodes, on those with treatment resistant forms of the disorder and on people with schizoaffective disorders.
Topics: Antimanic Agents; Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Valproic Acid
PubMed: 14974054
DOI: 10.1002/14651858.CD004028.pub2 -
Clinical Pharmacokinetics Jul 2019Qualitative studies on drug-drug interactions (DDIs) between anticonvulsants and antibiotics report pharmacokinetic changes that may increase the clinical risks in terms... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Qualitative studies on drug-drug interactions (DDIs) between anticonvulsants and antibiotics report pharmacokinetic changes that may increase the clinical risks in terms of adverse drug reactions (ADRs) and efficacy. However, no studies have provided a systematic and quantitative analysis of anticonvulsant-antibiotic pharmacokinetic DDIs. To provide such indications, we systematically and critically reviewed the literature on anticonvulsant-antibiotic DDIs in terms of quantitative pharmacokinetic changes and related ADRs. We also investigated less-known interactions for the possible occurrence of clinically relevant events.
METHODS
We conducted a systematic review of all reports of DDIs between anticonvulsants and antibiotics assessing pharmacokinetic parameters published until 9 June 2017.
RESULTS
We were able to meta-analyse the effect of macrolides on carbamazepine area under the concentration-time curve from time zero to infinity [AUC] (+ 34.5 µg/mL*h, p = 0.005, n = 38), clearance (- 2.88 mL/min, p < 0.001, n = 46) and trough plasma concentration [Ct] (+ 8.0 µg/mL, p = 0.002, n = 23), and of carbapenems on valproic acid Ct (- 42.9 µg/mL, p < 0.001, n = 262). Pharmacokinetic parameters with other DDIs were insufficiently reported to allow a statistical analysis.
CONCLUSIONS
Therapeutic drug monitoring in patients receiving long-term antiepileptic therapies may help, in specific conditions, to improve safety while preserving efficacy. Such a procedure would also increase scientific information on how pharmacokinetic variations are associated with ADR occurrence, and possibly epileptological outcomes for those DDIs for which available information is suggestive of a relevant effect but is not yet sufficient to draw conclusions.
Topics: Anti-Bacterial Agents; Anticonvulsants; Drug Interactions; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 30406474
DOI: 10.1007/s40262-018-0720-z -
Clinical Toxicology (Philadelphia, Pa.) Oct 2021Valproic acid is a carboxylic acid derivative commonly prescribed for several types of seizure disorders or for acute manic episodes in patients with bipolar disorder....
INTRODUCTION
Valproic acid is a carboxylic acid derivative commonly prescribed for several types of seizure disorders or for acute manic episodes in patients with bipolar disorder. Several cases of valproate-induced pleural effusion have been reported, although the precise pathophysiological mechanism remains unknown.
OBJECTIVE
To describe the presentation of pleural effusion associated with valproate use and to categorize published case reports according to clinical, immunological, and pleural effusion cell type.
METHODS
PubMed/MEDLINE and Embase databases were systematically searched from January 1970 until November 2020 using the following search terms: "valproic acid" OR "valproate" OR "pleural fluid" OR "exudative effusion" OR "transudative effusion" OR "valproic lung adverse events". These searches yielded 171 references of which 135 articles were considered irrelevant, leaving 36 potentially relevant references which were carefully scrutinized. Twenty-eight cases of valproate-induced pleural effusion were identified after excluding two articles reporting five patients with lung parenchymal adverse reactions to treatment with valproic acid; two articles reporting three patients in whom the pleural effusion could not be attributed to valproic acid alone; one case discussing valproate therapy and fungal pleural effusion; and one describing a patient who suffered from severe cardiac failure. There were also two cases, in an abstract form, with pericardial and pleural effusion, but without any further informative details, and, thus, they were also excluded from this survey.
EXUDATIVE EOSINOPHILIC PLEURAL EFFUSION
This was the most common type of valproate-induced pleural effusion reported in 17 out of 28 cases (60.7%), with concurrent peripheral eosinophilia in ten. Acute hypersensitivity reaction, inflammation of the pleural cavity induced by the drug, drug toxicity, and damage to mesothelial cells due to oxidants, comprise the possible pivotal mechanisms.
EXUDATIVE LYMPHOCYTIC PLEURAL EFFUSION
This was reported in two cases, with concurrent pericardial effusion in one. Discontinuation of valproate led to resolution of the effusion, although the underlying pathophysiological mechanisms remain abstruse. Interestingly, a patient presented with recurrent pleural effusion characterized by transition from eosinophilic to lymphocytic predominance after readministration of valproate.
TRANSUDATIVE PLEURAL EFFUSION
Three out of 28 cases (10.7%) were characterized by neutrophilic transudative pleural effusion after long-term therapy with valproate, while concurrent pericardial effusion was also noted in two.
VALPROATE-INDUCED LUPUS ERYTHEMATOSUS WITH PLEURAL EFFUSION
Five patients receiving valproate therapy (17.9% out of the 28 cases) developed drug-induced lupus erythematosus with concurrent pleural effusion that was eosinophilic in three. All patients had positive antinuclear antibodies; anti-histone antibodies were positive in two.
CONCLUSIONS
Valproate-induced pleural effusion is rare, but patients receiving treatment with valproic acid who develop respiratory symptoms should be examined for valproate-induced pleural effusion.
Topics: Adolescent; Adult; Aged; Anticonvulsants; Eosinophilia; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Pleural Effusion; Prognosis; Risk Assessment; Risk Factors; Valproic Acid; Young Adult
PubMed: 34259092
DOI: 10.1080/15563650.2021.1945081