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BMJ Clinical Evidence Dec 2013About 10% of seizures in children with epilepsy are typical absence seizures. Absence seizures have a significant impact on quality of life. (Review)
Review
INTRODUCTION
About 10% of seizures in children with epilepsy are typical absence seizures. Absence seizures have a significant impact on quality of life.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for typical absence seizures in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2013 (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), the European Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 18 RCTs or systematic reviews of RCTs 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: clonazepam, ethosuximide, gabapentin, lamotrigine, and valproate.
Topics: Acute Disease; Anticonvulsants; Child; Epilepsy, Absence; Ethosuximide; Evidence-Based Medicine; Humans; Quality of Life; Seizures; Treatment Outcome; Valproic Acid
PubMed: 24351614
DOI: No ID Found -
Acta Psychiatrica Scandinavica May 2022Clozapine is the most effective medication for treatment-refractory schizophrenia, but it is associated with severe cardiac adverse events including myocarditis and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Clozapine is the most effective medication for treatment-refractory schizophrenia, but it is associated with severe cardiac adverse events including myocarditis and cardiomyopathy. To aid treatment decision-making for clinicians, patients and their carers, we conducted a systematic review and meta-analysis to identify potential risk factors for clozapine-induced myocarditis and cardiomyopathy.
METHODS
A systematic search was conducted of PubMed, Embase, CINAHL, Web of Science, Cochrane and PsycInfo for studies reporting myocarditis and cardiomyopathy among people on clozapine and potential risk factors. We calculated pooled effect sizes on risk factors using a random-effects meta-analytic model. Risk of publication bias was assessed using the Newcastle-Ottawa scale.
RESULTS
Seven studies met the inclusion criteria, of which six studies had quantitative data included in the meta-analysis. The odds of clozapine-induced myocarditis increased with concurrent sodium valproate use (k = 6, n = 903, pooled OR 3.58, 95% CI 1.81-7.06), but were not significantly greater with the use of quetiapine, lithium or selective serotonin reuptake inhibitors. Our qualitative review identified conflicting results reported for increasing age and higher clozapine dose as risk factors for myocarditis. No other factors, including genetic risk, sex, ethnicity, smoking, alcohol, substance abuse or cardiometabolic disease, were associated with greater odds of myocarditis. No risk factors for cardiomyopathy were identified in the literature.
CONCLUSION
Concurrent use of sodium valproate increases the odds of clozapine-induced myocarditis. Thus, clinicians should consider the temporary cessation of sodium valproate during the initial titration phase of clozapine.
Topics: Antipsychotic Agents; Cardiomyopathies; Clozapine; Humans; Myocarditis; Risk Factors; Valproic Acid
PubMed: 35067911
DOI: 10.1111/acps.13398 -
Canadian Family Physician Medecin de... Apr 2006Increasing numbers of pregnant patients are treated with valproic acid, not just for epilepsy, but also for psychiatric conditions. Are there teratogenic risks other... (Review)
Review
QUESTION
Increasing numbers of pregnant patients are treated with valproic acid, not just for epilepsy, but also for psychiatric conditions. Are there teratogenic risks other than the risk of spina bifida?
ANSWER
It has now become evident that valproic acid might cause more than just neural tube defects (NTDs). In a systematic review of all cohort studies intended to answer this question, higher rates of major malformations (and not just NTDs) were found in most studies. The calculated relative risk was 2.59 when compared with other antiepileptic drugs and was 3.77 when compared with risk in the general population. There is compelling evidence that the risk is dose dependent. The risks appear to begin increasing at doses of 600 mg/d and to become more prominent at doses above 1000 mg/d.
Topics: Abnormalities, Drug-Induced; Anticonvulsants; Antimanic Agents; Developmental Disabilities; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Pregnancy; Valproic Acid
PubMed: 16639967
DOI: No ID Found -
CNS Drugs Oct 2022Psychotropic drugs are a heterogenous group of treatments prescribed for many psychiatric disorders, often for long periods. Their effects on the kidney and its...
BACKGROUND AND OBJECTIVE
Psychotropic drugs are a heterogenous group of treatments prescribed for many psychiatric disorders, often for long periods. Their effects on the kidney and its functioning are complex and a source of significant research and debate. This article aims to review recent evidence of the acute and chronic kidney adverse events of diverse psychotropes.
METHODS
A systematic search of randomized controlled trials and large observational studies (n ≥ 100) reporting the effects of psychotropic drugs on the kidney was conducted. The MEDLINE, PsycInfo, and EMBASE databases from 2011 to 2021, inclusive, were broadly searched with few restrictions and no prespecified outcomes. Two or more independent reviewers assessed and summarized all eligible studies, including risks of bias and levels of evidence.
RESULTS
In all, 1999 abstracts were screened for eligibility and 47 articles were included, which examined lithium (33), antiepileptics (10), antipsychotics (13), and antidepressants (9). No studies examining kidney adverse effects of other psychotropes, such as benzodiazepines, met inclusion criteria. Study populations were adult (8), geriatric (9), and mixed (30). Lithium was almost unanimously associated with (1) chronic kidney disease and (2) nephrogenic diabetes insipidus in methodologically diverse studies. The most supported risk factors for declining kidney functioning with lithium were advanced age, duration of lithium treatment, acute lithium toxicity, female sex, medications with known renal interactions, diabetes mellitus/hyperglycemia, and overall medical comorbidity. Supratherapeutic lithium concentrations are both the causes and consequences of acute kidney injury. Once significant chronic kidney disease has developed, four studies found that replacing lithium with other mood stabilizers does not slow progression, and the evolution to end-stage kidney disease is rare overall with modern practices. Compared to lithium, fewer studies examined antipsychotics and antiepileptics but found relatively less direct kidney harms. Antidepressants were not associated with acute or chronic kidney harms.
CONCLUSIONS
Despite the heterogeneity of findings, owing to varying methodologies and research challenges, recent studies strongly suggest that lithium is associated with an increased risk of chronic kidney disease and nephrogenic diabetes insipidus, especially in older adults and long-term lithium users. Clinicians should balance the harms of lithium against its established benefits, and ensure adequate monitoring and management of comorbidities in all patients. Weaker evidence suggests that antiepileptics such as valproate and antipsychotics result in comparatively less harm to the kidney than lithium, but warrant monitoring because of multiple direct and indirect mechanisms for potential kidney adverse events. Antidepressants do not have clear kidney adverse effects and appear safe (though potentially less effective) in the setting of kidney disease. Other classes of psychotropic drugs have received little research interest. Further research is warranted, particularly into specific antiepileptics and antipsychotics, and careful attention should be paid to mitigating important sources of bias such as confounding by indication.
Topics: Aged; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Diabetes Insipidus, Nephrogenic; Female; Humans; Kidney; Lithium; Lithium Compounds; Psychotropic Drugs; Renal Insufficiency, Chronic; Valproic Acid
PubMed: 36161425
DOI: 10.1007/s40263-022-00952-y -
The Cochrane Database of Systematic... Nov 2021Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME).... (Review)
Review
BACKGROUND
Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. This is an update of a Cochrane Review first published in 2015, and last updated in 2019.
OBJECTIVES
To evaluate the efficacy and tolerability of topiramate in the treatment of JME.
SEARCH METHODS
For the latest update, we searched the Cochrane Register of Studies (CRS Web) on 26 August 2021, and MEDLINE (Ovid 1946 to 26 August 2021). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) investigating topiramate versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders and proportion of participants 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 of the studies.
MAIN RESULTS
We included three studies with a total of 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or greater reduction in primarily generalized tonic-clonic seizures (PGTCS), compared with participants in the placebo group (RR 4.00, 95% CI 1.08 to 14.75; 1 study, 22 participants; very low-certainty evidence). There were no significant differences between topiramate and valproate for participants responding with a 50% or greater reduction in myoclonic seizures (RR 0.88, 95% CI 0.67 to 1.15; one study, 23 participants; very-low certainty evidence) or in PGTCS (RR 1.22, 95% CI 0.68 to 2.21; one study, 16 participants, very-low certainty evidence), or participants becoming seizure-free (RR 1.13, 95% CI 0.61 to 2.11; one study, 27 participants; very-low certainty evidence). Concerning tolerability, we ranked AEs associated with topiramate as moderate to severe, while we ranked 59% of AEs linked to valproate as severe complaints (2 studies, 61 participants; very low-certainty evidence). Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. Overall we judged all three studies to be at high risk of attrition bias and at unclear risk of reporting bias. We judged the studies to be at low to unclear risk of bias for the remaining domains (selection bias, performance bias, detection bias and other bias). We judged the overall certainty of the evidence for the outcomes as very low using the GRADE approach.
AUTHORS' CONCLUSIONS
We have found no new studies since the last version of this review was published in 2019. 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 has no clear benefits over valproate in terms of efficacy. Well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.
Topics: Anticonvulsants; Humans; Myoclonic Epilepsy, Juvenile; Randomized Controlled Trials as Topic; Seizures; Topiramate; Valproic Acid
PubMed: 34817852
DOI: 10.1002/14651858.CD010008.pub5 -
BMC Neurology Jun 2023Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs. (Meta-Analysis)
Meta-Analysis
The efficacy and safety of metoclopramide in relieving acute migraine attacks compared with other anti-migraine drugs: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Many drugs are prescribed in relieving acute migraine attacks, we aim to compare metoclopramide with other antimigraine drugs.
METHODS
We searched online databases like PubMed, Cochrane Library, Scopus, and Web of Science till June 2022 for RCTs that compared metoclopramide alone with placebo or active drugs. The main outcomes were the mean change in headache score and complete headache relief. The secondary outcomes were the rescue medications need, side effects, nausea and recurrence rate. We qualitatively reviewed the outcomes. Then, we performed the network meta-analyses (NMAs) when it was possible. which were done by the Frequentist method using the MetaInsight online software.
RESULTS
Sixteen studies were included with a total of 1934 patients: 826 received metoclopramide, 302 received placebo, and 806 received other active drugs. Metoclopramide was effective in reducing headache outcomes even for 24 h. The intravenous route was the most chosen route in the included studies and showed significant positive results regarding headache outcomes; however, the best route whether intramuscular, intravenous, or suppository was not compared in the previous studies. Also, both 10 and 20 mg doses of metoclopramide were effective in improving headache outcomes; however, there was no direct comparison between both doses and the 10 mg dose was the most frequently used dosage. In NMA of headache change after 30 min or 1 h, metoclopramide effect came after granisetron, ketorolac, chlorpromazine, and Dexketoprofen trometamol. Only granisetron's effect was significantly higher than metoclopramide's effect which was only significantly higher than placebo and sumatriptan. In headache-free symptoms, only prochlorperazine was non-significantly higher than metoclopramide which was higher than other medications and showed significantly higher effects only with placebo. In rescue medication, metoclopramide's effect was only non-significantly lower than prochlorperazine and chlorpromazine while its effect was higher than other drugs and showed higher significant effects only than placebo and valproate. In the recurrence rate, studies showed no significant difference between metoclopramide and other drugs. Metoclopramide significantly decreased nausea more than the placebo. Regarding side effects, metoclopramide showed a lower incidence of mild side effects than pethidine and chlorpromazine and showed a higher incidence of mild side effects than placebo, dexamethasone, and ketorolac. The reported extrapyramidal symptoms with metoclopramide were dystonia or akathisia.
CONCLUSION
A dose of 10 mg IV Metoclopramide was effective in relieving migraine attacks with minimal side effects. Compared to other active drugs, it only showed a lower significant effect compared with granisetron regarding headache change while it showed significantly higher effects only with placebo in both rescue medication needs and headache-free symptoms and valproate in only rescue medication need. Also, it significantly decreased headache scores more than placebo and sumatriptan. However, more studies are needed to support our results.
Topics: Humans; Metoclopramide; Sumatriptan; Network Meta-Analysis; Prochlorperazine; Chlorpromazine; Granisetron; Valproic Acid; Ketorolac; Randomized Controlled Trials as Topic; Migraine Disorders; Nausea; Headache
PubMed: 37291500
DOI: 10.1186/s12883-023-03259-7 -
BMJ Clinical Evidence Jan 2008About 10% of seizures in children with epilepsy are typical absence seizures. Absence seizures have a significant impact on quality of life. (Review)
Review
INTRODUCTION
About 10% of seizures in children with epilepsy are typical absence seizures. Absence seizures have a significant impact on quality of life.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for typical absence seizures in children? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2007 (BMJ 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 16 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: clonazepam, ethosuximide, gabapentin, lamotrigine, and valproate.
Topics: Acute Disease; Anticonvulsants; Child; Epilepsy, Absence; Ethosuximide; Evidence-Based Medicine; Humans; Incidence; Quality of Life; Valproic Acid
PubMed: 19450342
DOI: No ID Found -
The Cochrane Database of Systematic... Nov 2016Many 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, and valproate is one of these.
OBJECTIVES
To examine whether:1. valproate alone is an effective treatment for schizophrenia and schizoaffective psychoses; and2. valproate augmentation of antipsychotic medication is an effective treatment for the same illnesses.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (July 2002; February 2007; July 2012; March 04, 2016). We also contacted pharmaceutical companies 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 people with schizophrenia 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. At least two review authors independently extracted data. We analysed dichotomous data using risk ratio (RR) and its 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their 95% CI. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table.
MAIN RESULTS
The 2012 update search identified 19 further relevant studies, most of which were from China. Thus the review currently includes 26 studies with a total of 2184 participants. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With the exception of two studies, the studies were small, the participants and personnel were not blinded (neither was outcome assessment), and most were short-term and incompletely reported.For this update we prespecified seven main outcomes of interest: clinical response (clinically significant response, aggression/agitation), leaving the study early (acceptability of treatment, overall tolerability), adverse events (sedation, weight gain) and quality of life.Adding valproate to antipsychotic treatment resulted in more clinically significant response than adding placebo to antipsychotic drugs (14 RCTs, n = 1049, RR 1.31, 95% CI 1.16 to 1.47, I = 12%, low-quality evidence). However, this effect was removed after excluding open RCTs in a sensitivity analysis. In terms of acceptability of treatment (measured by the number of participants leaving the study early due to any reason) valproate was just as acceptable as placebo (11 RCTs, n = 951, RR 0.76, 95% CI 0.47 to 1.24, I = 55%). Also overall tolerability (measured by the number of participants leaving the study early for adverse events) between valproate and placebo was similar (6 RCTs, n = 974, RR 1.33, 95% CI 0.90 to 1.97, I = 0).Participants in the valproate group were found to be less aggressive than the control group based on the Modified Overt Aggression Scale (3 RCTs, n = 186, MD -2.55, 95% CI -3.92 to -1.19, I = 82%, very low-quality evidence). Participants receiving valproate more frequently experienced sedation (8 RCTs, n = 770, RR 1.38, 95% CI 1.07 to 1.79, I = 0, low-quality evidence) but were no more likely to gain weight than those receiving placebo (4 RCTs, n = 427, RR 1.17, 95% CI 0.76 to 1.82, I = 0, low-quality evidence). No study reported on the important outcome of quality of life.
AUTHORS' CONCLUSIONS
There is limited evidence, based on a number of trials, that the augmentation of antipsychotics with valproate may be effective for overall clinical response, and also for specific symptoms, especially in terms of excitement and aggression. However, this evidence was entirely based on open RCTs. Moreover, valproate was associated with a number of adverse events among which sedation and dizziness appeared significantly more frequently than in the control groups. Further randomised studies which are blinded are necessary before any clear recommendation can be made. Ideally these would focus on people with schizophrenia and aggression, on those with treatment-resistant forms of the illness and on those with schizoaffective disorders.
Topics: Antimanic Agents; Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Valproic Acid
PubMed: 27884042
DOI: 10.1002/14651858.CD004028.pub4 -
European Neuropsychopharmacology : the... Oct 2016Breast milk is considered the best source of nutrients and provides much better protection than immune modified milk. However, the postpartum period is a phase of... (Review)
Review
Breast milk is considered the best source of nutrients and provides much better protection than immune modified milk. However, the postpartum period is a phase of increased risk for all women to experience psychiatric symptoms and recurrences or new episodes of bipolar disorder (BD), especially in those who have discontinued treatment. This is a systematic review of the risks and benefits of mood stabilizers and antipsychotics during breastfeeding as they relate to the health and well-being of mothers and their infants. Evidence-based treatment advice for women with BD during lactation is also provided. This systematic review has been conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. We included studies examining the exposure and the effects of antipsychotics and mood stabilizers used to treat BD on infants during breastfeeding clearly reporting the estimated amount of drug or effects on infants. The final selection included 56 studies. The available data supports the use of lithium as a possible treatment option during breastfeeding. Carbamazepine and valproic acid are also considered relatively safe. Lamotrigine can be used but at the lowest doses and considered for individual cases. Among the antipsychotics, quetiapine and olanzapine should be considered as first-line treatment options. Risperidone may be compatible with breastfeeding under medical supervision. Clozapine and amisulpiride are currently contraindicated. Long-term outcome studies evaluating the infant׳s health and psychosocial and cognitive functioning are needed.
Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Breast Feeding; Female; Humans; Infant, Newborn; Milk, Human; Postpartum Period
PubMed: 27568278
DOI: 10.1016/j.euroneuro.2016.08.008 -
Epilepsy & Behavior : E&B Jun 2022New-onset movement disorders have been frequently reported in association with the use of antiseizure medications (ASMs). The frequency of specific motor manifestations... (Review)
Review
New-onset movement disorders have been frequently reported in association with the use of antiseizure medications (ASMs). The frequency of specific motor manifestations and the spectrum of their semiology for various ASMs have not been well characterized. We carried out a systematic review of literature and conducted a search on CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and Scopus from inception to April 2021. We compiled the data for all currently available ASMs using the conventional terminology of movement disorders. Among 5123 manuscripts identified by the search, 437 met the inclusion criteria. The largest number of reports of abnormal movements were in association with phenobarbital, valproic acid, lacosamide, and perampanel, and predominantly included tremor and ataxia. The majority of attempted interventions for all agents were discontinuation of the offending drug or dose reduction which led to the resolution of symptoms in most patients. Familiarity with the movement disorder phenomenology previously encountered in relation with specific ASMs facilitates early recognition of adverse effects and timely institution of targeted interventions.
Topics: Anticonvulsants; Humans; Lacosamide; Movement Disorders; Phenobarbital; Valproic Acid
PubMed: 35483204
DOI: 10.1016/j.yebeh.2022.108693