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Der Nervenarzt May 2023Until now the long-term consequences of the medical treatment for bipolar disorder have barely been examined, especially the consequences with respect to cognitive... (Review)
Review
BACKGROUND
Until now the long-term consequences of the medical treatment for bipolar disorder have barely been examined, especially the consequences with respect to cognitive impairment and dementia. Some studies show signs that some treatment options have a better effect on the brain than others. This review summarizes the current state of research.
OBJECTIVE
The effects of long-term consequences of lithium, valproic acid, carbamazepine and antipsychotic agents on the development of dementia or cognitive impairments in patients with bipolar disorder were investigated.
METHODS
A systematic literature search was carried out in the PubMed data base from May to July 2022.
RESULTS
The majority of studies showed that lithium has a neuroprotective effect and can lower the risk of developing dementia, whereas an increased risk was found in patients taking valproic acid. There are only very few studies that deal with antipsychotic medication and the long-term consequences concerning dementia.
CONCLUSION
Lithium should be recommended for the long-term treatment of bipolar disorder. Valproic acid should not or carefully be used as it can affect the risk of developing dementia. With respect to antipsychotics there is no recommendation as more studies are needed to evaluate the long-term consequences.
Topics: Humans; Antipsychotic Agents; Bipolar Disorder; Valproic Acid; Lithium; Carbamazepine; Benzodiazepines; Dementia; Cognition; Antimanic Agents
PubMed: 36922444
DOI: 10.1007/s00115-023-01454-y -
Developmental Neuroscience 2020Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by repetitive behaviours, cognitive rigidity/inflexibility, and social-affective...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by repetitive behaviours, cognitive rigidity/inflexibility, and social-affective impairment. Unfortunately, few pharmacological treatments exist to alleviate these socio-behavioural impairments. Prenatal administration of valproic acid (VPA) has become an accepted animal model of ASD and has been extensively used to explore new pharmacotherapies in rodents. We conducted a systematic review of the behavioural impairments induced by the VPA model in rodents, with specific reference to 3 core socio-behavioural alterations associated with ASD: repetitive behaviours, cognitive rigidity/inflexibility, and social-affective impairment. We systematically reviewed studies attempting to alleviate these core behavioural alterations using pharmacological means. We include 132 studies exploring the prenatal effects of VPA in rodents. Gestational exposure to VPA in rodents has significant effects on rodent-equivalent measures of the 3 core behavioural traits characteristic of ASD in humans, inducing social impairments, repetitive behaviour, and cognitive rigidity/inflexibility after birth. This model's validity has seen it used to test potential drug treatments for ASD and is likely to continue doing so. We conclude the rodent VPA model may be suitable to examine future therapeutic interventions for ASD, providing an overview of the progress made so far.
Topics: Animals; Anticonvulsants; Autistic Disorder; Behavior, Animal; Disease Models, Animal; Humans; Rodentia; Social Behavior; Valproic Acid
PubMed: 32810856
DOI: 10.1159/000509109 -
The Cochrane Database of Systematic... Apr 2017Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic... (Review)
Review
BACKGROUND
Topiramate is a newer broad-spectrum 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. This is an updated version of the original Cochrane Review published in Issue 12, 2015.
OBJECTIVES
To evaluate the efficacy and tolerability of topiramate monotherapy in the treatment of JME.
SEARCH METHODS
For the latest update, on 21 February 2017 we searched Cochrane Epilepsy's Specialized Register, CENTRAL, MEDLINE, and ClinicalTrials.gov. We also searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted study 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 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
Since the last version of this review we found no new studies. 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: 28434203
DOI: 10.1002/14651858.CD010008.pub3 -
Seizure Oct 2021We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted... (Review)
Review
BACKGROUND
We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted side effects of ASMs with a particular attention to hair loss, hirsutism, acne, and gingival hyperplasia.
METHODS
This systematic review was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE, and Google Scholar from the inception to 25 March, 2021 were systematically searched. These key words (title/abstract) were used: "hair loss" OR "hirsutism" OR "acne" OR "gingival hyperplasia" AND "seizure" OR "epilepsy" OR "anriseizure" OR "antiepileptic". The exclusion criteria included: non-original studies, articles not in English, and animal studies.
RESULTS
The primary search yielded 3938 studies; 127 studies were related to the topic and were included in the current systematic review. The most robust evidence on cosmetic adverse effects of ASMs were related to phenytoin (causing gingival hyperplasia, hirsutism, and acne) and valproate (causing hair loss and hirsutism); however, many other ASMs were also implicated in causing these cosmetic adverse effects.
CONCLUSION
Antiseizure medications may be associated with various cosmetic adverse effects. Phenytoin and valproate are the most notorious ASMs in this regard; but, other ASMs have also been implicated in causing hair loss, hirsutism, acne, and gingival hyperplasia. Physicians should pay more attention to these significant adverse effects that may affect a patient's facial attractiveness, quality of life, and emotional state.
Topics: Animals; Anticonvulsants; Epilepsy; Humans; Phenytoin; Quality of Life; Valproic Acid
PubMed: 34052629
DOI: 10.1016/j.seizure.2021.05.010 -
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 -
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 -
British Journal of Clinical Pharmacology May 2018Population pharmacokinetics is an essential tool that helps guide individualized dosing regimens. The aims of this systematic review are to provide knowledge concerning...
AIMS
Population pharmacokinetics is an essential tool that helps guide individualized dosing regimens. The aims of this systematic review are to provide knowledge concerning population pharmacokinetics of valproic acid (VPA) and to identify factors influencing VPA pharmacokinetic variability.
METHODS
PubMed and Embase databases were systematically searched from inception to June, 2017. Relevant articles from reference lists were also included. All population pharmacokinetic studies of VPA conducted in humans and that employed a nonlinear mixed effect modelling approach were included in this review.
RESULTS
Twenty-six studies were included in this review. Most studies characterized VPA pharmacokinetics as a one-compartment model. Three studies reported a two-compartment model. Body weight, dose and age were significant predictors for VPA volume of distribution (V ). The estimated V for one-compartment models ranged from 8.4 to 23.3 l. For two-compartment models, peripheral volumes of distribution ranged from 4.08 to 42.1 l. Frequently reported significant predictors for VPA clearance (CL ) included body weight, VPA dose, concomitant medications, gender and age. The estimated CL ranged from 0.206 to 1.154 l h and the inter-individual variability ranged from 13.40 to 35.90%. Two studies reported population pharmacokinetics/pharmacodynamics of VPA in patients with epilepsy. Seventeen studies evaluated the performance of their final models.
CONCLUSIONS
Significant predictors influencing VPA pharmacokinetics as well as model methodologies are highlighted in this review. For clinical application, CL could be predicted using body weight, VPA dose, concomitant medications, gender or age. For future research, there is a knowledge gap regarding population pharmacokinetics/pharmacodynamics of VPA in a population other than epileptic patients.
Topics: Anticonvulsants; Humans; Models, Biological; Valproic Acid
PubMed: 29328514
DOI: 10.1111/bcp.13510 -
The Cochrane Database of Systematic... Feb 2022Seizures after stroke are an important clinical problem and may result in poor outcomes. The indications of antiepileptic drugs (AEDs) for seizure prophylaxis after... (Review)
Review
BACKGROUND
Seizures after stroke are an important clinical problem and may result in poor outcomes. The indications of antiepileptic drugs (AEDs) for seizure prophylaxis after stroke remain unclear. This is an updated version of the Cochrane Review previously published in 2014.
OBJECTIVES
To assess the effects of AEDs for the primary and secondary prevention of seizures after stroke. For primary prevention, we aimed to assess whether AEDs reduce the likelihood of seizures in people who have a stroke but do not have a seizure. For secondary prevention, we aimed to assess whether AEDs reduce the likelihood of further seizures in people who have a stroke and at least one post-stroke seizure.
SEARCH METHODS
We searched the following databases on 9 March 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to March 08, 2021). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organisation International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy and Stroke. We also checked the reference lists of articles retrieved from these searches.
SELECTION CRITERIA
We selected randomised and quasi-randomised controlled studies that recruited participants with a clinical diagnosis of stroke, either ischaemic or haemorrhagic. We excluded studies that only recruited participants with subarachnoid haemorrhage, subdural haemorrhage, extradural haemorrhage, or other non-stroke diagnoses such as tumour- or infection-related infarction or haemorrhage. We also excluded studies that recruited only participants who had undergone neurosurgery. We included participants of all ages suffering any seizure type who were assigned to AEDs or placebo groups.
DATA COLLECTION AND ANALYSIS
In accordance with standard methodological procedures expected by The Cochrane Collaboration, two review authors independently assessed trials for inclusion before evaluating trial risk of bias and extracting relevant data. The primary outcome assessed was the proportion of participants who experienced seizures in the follow-up period. We presented results as summary risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. Where we had sufficient data, we calculated random-effects (Mantel-Haenszel) meta-analyses for dichotomous outcomes; otherwise, we reported results narratively. We used the I statistic to analyse statistical heterogeneity. We planned to use funnel plots to assess publication bias in meta-analyses with at least 10 included studies. We used the GRADE approach to assess the certainty of the evidence.
MAIN RESULTS
Two studies with a total of 856 subjects were included. AEDs were not shown to be effective in primary prophylaxis of post-stroke seizure (RR 0.65, 95% CI 0.34 to 1.26; 2 studies, 856 participants; moderate-certainty evidence). The first study was a randomised double-blind study comparing valproic acid with placebo for primary seizure prevention up to one year after stroke. The study included 72 adults with intracerebral haemorrhage. There was no difference in the risk of post-stroke seizures (RR 0.88, 95% CI 0.35 to 2.16) or of death (RR 1.20, 95% CI 0.40 to 3.58). The second study was a substudy on the use of diazepam in acute stroke. It was a randomised double-blind study, comparing a three-day diazepam treatment versus placebo for primary seizure prevention up to three months after stroke in 784 adults with acute stroke. There was no evidence of a difference in the risk of post-stroke seizures for all stroke or subgroups of haemorrhagic or ischaemic stroke (RR for all stroke 0.47, 95% CI 0.18 to 1.22). In a subgroup analysis of anterior circulation cortical infarcts, primary prophylaxis with diazepam was associated with a reduced risk of post-stroke seizures (RR 0.21, 95% CI 0.05 to 0.95). Risks of mortality did not differ between the diazepam and the placebo group at two weeks (RR 0.84, 95% CI 0.56 to 1.26) and three months follow-up (RR 0.95, 95% CI 0.72 to 1.26). We assessed both studies to be at a low overall risk of bias. Using the GRADE approach, we assessed the overall certainty of the evidence as low to moderate.
AUTHORS' CONCLUSIONS
There is insufficient evidence to support the routine use of AEDs on the primary and secondary prevention of seizures after stroke. Further well-conducted studies are warranted for this important clinical problem.
Topics: Adult; Anticonvulsants; Brain Ischemia; Humans; Randomized Controlled Trials as Topic; Secondary Prevention; Seizures; Stroke
PubMed: 35129214
DOI: 10.1002/14651858.CD005398.pub4 -
Seizure Mar 2016Warnings of L-carnitine induced seizures are recorded on product monographs and pharmacy databases, without any referenced literature. This medication can potentially... (Review)
Review
OBJECTIVE
Warnings of L-carnitine induced seizures are recorded on product monographs and pharmacy databases, without any referenced literature. This medication can potentially improve the hospital course in those patients with valproic acid (VPA) induced hyperammonemic encephalopathy, but may be withheld because of this warning. The goal was to perform an extensive systematic review of the literature to document the incidence of levocarnitine (L-carnitine) induced seizures in those patients on VPA therapy.
METHODS
Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to June 2015), and reference lists of relevant articles were searched. The strength of evidence was to be adjudicated using both the Oxford and GRADE methodology by two independent reviewers.
RESULTS
We failed to identify a single study implicating L-carnitine supplementation leading to seizures in any patient on VPA therapy. This contradicts all quoted, but unsubstantiated, concerns on product monographs and pharmacy databases related to seizure induction/propagation with L-carnitine supplementation.
CONCLUSION
There is no literature available to support claims of L-carnitine induced seizures during supplementation in patients on VPA therapy for seizures. This contradicts quoted, but not referenced, concerns on the product monograph. In patients suffering from hypocarnitinemia or hyperammonemic encephalopathy while on VPA, L-carnitine supplementation can be considered knowing there is no data to support seizure propagation or induction with administration of this supplement.
Topics: Anticonvulsants; Carnitine; Databases, Factual; Humans; Seizures; Valproic Acid
PubMed: 26889779
DOI: 10.1016/j.seizure.2016.01.020 -
Acta Psychiatrica Scandinavica Sep 2021Polypharmacy is common in maintenance treatment of bipolar illness, but proof of greater efficacy compared to monotherapy is assumed rather than well known. We... (Review)
Review
OBJECTIVES
Polypharmacy is common in maintenance treatment of bipolar illness, but proof of greater efficacy compared to monotherapy is assumed rather than well known. We systematically reviewed the evidence from the literature to provide recommendations for clinical management and future research.
METHOD
A systematic review was conducted on the use of polypharmacy in bipolar prophylaxis. Relevant papers published in English through 31 December 2019 were identified searching the electronic databases MEDLINE, Embase, PsycINFO, and the Cochrane Library.
RESULTS
Twelve studies matched inclusion criteria, including 10 randomized controlled trials (RCTs). The best drug combination in prevention is represented by lithium + valproic acid which showed a significant effect on time to mood relapses (HR = 0.57) compared to valproic acid monotherapy, especially for manic episodes (HR = 0.51). The effect was significant in terms of time to new drug treatment (HR = 0.51) and time to hospitalization (HR = 0.57). A significant reduction in the frequency of mood relapses was also reported for lithium + valproic acid vs. lithium monotherapy (RR=0.12); however, the trial had a small sample size. Lamotrigine + valproic acid reported significant efficacy in prevention of depressive episodes compared to lamotrigine alone.
CONCLUSIONS
The literature to support a generally greater efficacy with polypharmacy in bipolar illness is scant and heterogeneous. Within that limited evidence base, the best drug combination in bipolar prevention is represented by lithium + valproic acid for manic, but not depressive episodes. Clinical practice should focus more on adequate monotherapy before considering polypharmacy.
Topics: Antimanic Agents; Bipolar Disorder; Humans; Lithium Compounds; Polypharmacy; Valproic Acid
PubMed: 33960396
DOI: 10.1111/acps.13312