| 1. |
- Hansen, Cerine C., et al.
(författare)
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Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs : Focus on Topiramate, Levetiracetam, and Perampanel
- 2018
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Ingår i: Behavioural Neurology. - : Hindawi Limited. - 0953-4180 .- 1875-8584. ; 2018
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Forskningsöversikt (refereegranskat)abstract
- Antiepileptic drugs (AEDs) are effective against seizures, but their use is often limited by adverse effects, among them psychiatric and behavioral ones including aggressive behavior (AB). Knowledge of the incidence, risk factors, and the underlying mechanisms of AB induced by AEDs may help to facilitate management and reduce the risk of such side effects. The exact incidence of AB as an adverse effect of AEDs is difficult to estimate, but frequencies up to 16% have been reported. Primarily, levetiracetam (LEV), perampanel (PER), and topiramate (TPM), which have diverse mechanisms of action, have been associated with AB. Currently, there is no evidence for a specific pharmacological mechanism solely explaining the increased incidence of AB with LEV, PER, and TPM. Serotonin (5-HT) and GABA, and particularly glutamate (via the AMPA receptor), seem to play key roles. Other mechanisms involve hormones, epigenetics, and "alternative psychosis" and related phenomena. Increased individual susceptibility due to an underlying neurological and/or a mental health disorder may further explain why people with epilepsy are at an increased risk of AB when using AEDs. Remarkably, AB may occur with a delay of weeks or months after start of treatment. Information to patients, relatives, and caregivers, as well as sufficient clinical follow-up, is crucial, and there is a need for further research to understand the complex relationship between AED mechanisms of action and the induction/worsening of AB.
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| 2. |
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| 3. |
- Olsson, Patrik, et al.
(författare)
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Quality of life after switching to generic levetiracetam – A prospective comparative study
- 2019
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Ingår i: Epilepsy and Behavior. - : Elsevier BV. - 1525-5069 .- 1525-5050. ; 96, s. 169-174
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundImproved quality of life (QoL) is one of the most important objectives in the treatment of epilepsy. Recent prospective, clinical studies proved no significant differences between brand antiepileptic drugs (AEDs) and their generic equivalents in terms of seizure control, pharmacokinetics, or safety. In this study, we focused on possible changes in QoL and adverse events in connection with generic substitution of levetiracetam (LEV).MethodsThis was a prospective, naturalistic, two-cohort, twin-center study. After a baseline period of 10 weeks, outpatients with epilepsy on stable treatment with Keppra® either continued on this brand (reference group, n = 16) or switched to generic LEV (1A Pharma®) (study group, n = 16) for an eight-week study period. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and an adverse events' questionnaire were administered at inclusion, after baseline, and at the end of the study period. The study protocol included a close clinical follow-up with repeated LEV serum concentration measurements and nurse-led outpatient visits.ResultsClinically relevant improvements in overall QOLIE-31 scores according to minimally important change (MIC) estimates were seen in both groups. QOLIE-31 subscales in both groups showed significantly less worry about seizures at the end of the study compared to scores at inclusion (study group: p = 0.01; reference group: p = 0.02). No significant deterioration in QoL or adverse events were observed following generic substitution. No switchbacks occurred.ConclusionsWe found reduced seizure worries over time among people with epilepsy allocated to either generic switch or continued treatment with brand LEV. We hypothesize that the nurse-led structured follow-up had an impact on seizure worries and switchback rates because of reduced nocebo effects. Further studies on generic AED substitution, focusing on psychological outcome measures, are warranted to test this supposition.
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| 4. |
- Olsson, Patrik, et al.
(författare)
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Widespread skeptic attitudes among people with epilepsy toward generic antiseizure drugs – A Swedish survey study
- 2021
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Ingår i: Epilepsy and Behavior. - : Elsevier BV. - 1525-5050. ; 114
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore associations between the characteristics of people with epilepsy (PWE) and their attitudes toward generic substitution of antiseizure drugs (ASDs) in epilepsy. Methods: This was a cross-sectional survey study directed at adults with epilepsy using selected brand drugs: Keppra®, Lamictal®, Lyrica® or Topimax®. Symptoms of anxiety and depression, sense of self-efficacy, and beliefs about medicines were assessed. Caregivers were asked to answer for persons with intellectual or communicative difficulties. Results: The total response rate was 41% (n = 178). Almost half (46%) of subjects stated that they would oppose generic substitution (Gen-NEG) if suggested by their neurologist, while 71% would worry about adverse effects and/or increased seizure frequency after a putative switch. Age ≥50 increased the odds of being Gen-NEG (adjusted OR: 2.20, 95% CI: 1.18–4.11). Negative associations with both Gen-NEG and worriers were found for education level of high-school diploma or above, employment/studies, and prior experience of generic ASD switch. The proportion of worriers was much higher among caregivers (21/22) compared to subjects with epilepsy (106/156). Conclusion: High proportions of PWE express concerns regarding generic substitution of ASDs. The elderly and caregivers seem to express particular concerns. Identifying ways to diminish negative outcomes and worries in connection with a switch is an important future field of research in order to ensure high quality, cost-effective health care for the most vulnerable people in our societies.
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| 5. |
- Reimers, Arne, et al.
(författare)
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An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy
- 2019
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Ingår i: Expert Opinion on Pharmacotherapy. - : Informa UK Limited. - 1465-6566 .- 1744-7666. ; 20:8, s. 909-915
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: About 70 million people worldwide are estimated to suffer from epilepsy. Despite a large variety of old and new antiepileptic drugs on the market, about 30% of people with epilepsy do not become seizure-free with medical treatment. This is a major individual and public health burden. Most of these difficult-to-treat patients are having focal seizures. Zonisamide is effective against focal seizures in adults and children and, thus, a therapeutic option for such patients. Its safety profile needs special attention. Areas covered: Herein, the authors discuss the pharmacology, clinical efficacy and the adverse effects of zonisamide. The article is derived from clinical trial data, long-term studies, meta-analyses, review articles, text books, webpages, and official license information. Expert opinion: Zonisamide has proven to be efficacious in focal epilepsy in children and adults, although it is not more effective than carbamazepine or other antiepileptic drugs. It is also effective in generalized epilepsy and in several other conditions of the CNS. Its safety profile may prevent it from becoming a first-line drug for focal epilepsy or any other indication.
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| 6. |
- Reimers, Arne, et al.
(författare)
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Cognitive Safety is Largely Ignored in Clinical Drug Trials : A Study of Registered Study Protocols
- 2024
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Ingår i: Drug Safety. - 0114-5916. ; 47:1, s. 23-28
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: The number of reports on suspected drug-induced memory impairment submitted to the US Food and Drug Administration increased 30-fold from 2000 to 2022. Drugs are the most common cause of reversible dementia. However, there is very little research on drug-induced cognitive impairment. The aim of this study was to investigate if and how an assessment of cognitive safety was included in recent, registered, controlled, clinical drug trials. Methods: The clinical trials registry (www.clinicaltrials.gov) was searched for randomized controlled clinical trials with available study protocols. After excluding irrelevant trials such as surgical procedures, local or short-term treatment, and dietary supplements, 803 trials were included in this study. The protocols were manually reviewed for information on if, and how, cognitive safety had been assessed. Trial drugs were categorized into those targeting the central nervous system or not, as well as older and newer drugs. Methods used for the assessment of cognitive function were categorized into questionnaires, screening instruments, and neuropsychological tests. If the trial results were published, we examined whether the publication contained any data on cognitive safety that had emerged from the trial. Results: The start dates of the screened trials ranged from 31 July, 2009, to 4 April, 2021. Out of the 803 trials, 52 (6.5%) actively assessed cognitive safety. The remaining trials relied solely on spontaneous reporting. Of 429 trials studying a new drug, 32 (7.5%) actively assessed cognitive safety. One hundred and fifty-eight trials examined drugs intended to, or known to have, pharmacological effects on the central nervous system. Of these, 21 (13.5%) assessed cognitive safety. Most of the trials that assessed cognitive safety used either crude screening tools or questionnaires. Conclusions: Cognitive safety is largely ignored by recent controlled clinical trials. This applies even to trials assessing new drugs and trials assessing central nervous system drugs. There is an urgent need for drug manufacturers, regulatory authorities, and the medical profession to address the cognitive safety of drugs.
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| 7. |
- Reimers, Arne, et al.
(författare)
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Impact of generic substitution on levetiracetam serum concentration : A prospective study in an outpatient setting
- 2017
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Ingår i: Epilepsy Research. - : Elsevier BV. - 1872-6844 .- 0920-1211. ; 134, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Switching patients from a branded antiepileptic drug (AED) to a generic is often challenging. Several studies have shown that considerable proportions of patients report deteriorated seizure control or increased adverse effects, enforcing a switchback to the original drug. Since tolerability and seizure control usually correlate with AED serum concentrations, we examined the fluctuation of levetiracetam (LEV) serum concentrations in patients with epilepsy before and after generic substitution.METHODS: This was an 18-week, naturalistic, open, prospective, two-center study. After a baseline period of 10 weeks, 33 outpatients on stable treatment with branded LEV (Keppra(®)) either continued with this product or were switched overnight to a generic LEV preparation (1A Pharma) for an eight-week study period. Throughout the study, patients were monitored with bi-weekly LEV serum concentration measurements and seizure diaries.RESULTS: 16 out of 33 patients were switched to a generic LEV product. No switchbacks were seen. LEV dose, LEV serum concentrations, fluctuation index and concentration/dose-ratio (C/D-ratio) were not significantly different within-group (baseline vs. study period) or between-group. Large within-subject variability in serum concentrations was seen in both groups. None of the patients that were seizure-free before inclusion experienced seizures while on the generic LEV product.CONCLUSIONS: Our results show equal fluctuation of LEV serum concentrations with branded LEV and the generic LEV. Most importantly, within-subject variability was much larger than the small, non-significant differences between brands.
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| 8. |
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| 9. |
- Reimers, Arne, et al.
(författare)
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The emerging role of omega-3 fatty acids as a therapeutic option in neuropsychiatric disorders
- 2019
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Ingår i: Therapeutic advances in psychopharmacology. - : SAGE Publications. - 2045-1253 .- 2045-1261. ; 9
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Forskningsöversikt (refereegranskat)abstract
- The prevalence of neurologic and psychiatric diseases has been increasing for decades and, given the moderate therapeutic efficacy and safety profile of existing pharmacological treatments, there is an urgent need for new therapeutic approaches. Nutrition has recently been recognized as an important factor for the prevention and treatment of neuropsychiatric disorders. The omega-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play critical roles in neuronal cell function and neurotransmission as well as inflammatory and immune reactions that are involved in neuropsychiatric disease states. A large number of experimental and epidemiological studies provide a strong basis for interventional clinical trials that assessed the clinical efficacy of n-3 PUFAs in various neurological and psychiatric disorders. Most of these trials found beneficial effects of dietary supplementation with EPA and DHA, and no serious safety concerns have emerged. This review gives an introduction to recent findings on the clinical efficacy of n-3 PUFAs in various neuropsychiatric disorders and the underlying biochemical mechanisms. In addition, the reader will be enabled to identify common methodological weaknesses of clinical studies on n-3 PUFAs, and suggestions for the design of future studies are given.
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| 10. |
- Shirzadi, Maryam, et al.
(författare)
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Rash during lamotrigine treatment is not always drug hypersensitivity a retrospective cohort study among children and adults
- 2021
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Ingår i: Seizure. - : Elsevier BV. - 1059-1311. ; 89, s. 12-18
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Cutaneous adverse drug reactions (cADRs) are a major cause of lamotrigine (LTG) discontinuation. Remarkable variation in their reported incidence suggests confounders and diverse terms and definitions. The aim of this study was to identify immunological cADRs and to throw light on classification and differential diagnoses in children and adults. Methods Hospital records of 2683 patients with epilepsy (1897 adults, 786 children) were retrospectively screened. Of these, 403 patients (236 adults, 167 children) with first time exposure to LTG were reviewed. Skin reactions were categorized into possible or probable cADRs due to LTG hypersensitivity, and other skin reactions (OSRs) unlikely to be caused by this mechanism. Results 29 of 403 patients (7.2%) reported emergent skin symptoms within 3 months of treatment with LTG of which 20 (5%: 5.9% adults, 3.6% children) were categorized as possible or probable cADRs. Concomitant infection appeared to be present in several cases, particularly in children. OSRs were found in 4.2% of the children using LTG, compared to 0.8% of the adults (p = 0.04). Conclusions Rash during the early phase of LTG treatment is not always drug hypersensitivity. Whenever skin symptoms occur, other potential causes should receive attention to avoid needless discontinuation, particularly in children. However, when early symptoms and signs of severe cADRs are suspected, LTG should promptly be discontinued.
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