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| 2. |
- Wikell, Cecilia, et al.
(författare)
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Effects on drug disposition, brain monoamines and behavior after chronic treatment with the antidepressant venlafaxine in rats with experimental hepatic encephalopathy
- 2002
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Ingår i: European Neuropsychopharmacology. - 0924-977X .- 1873-7862. ; 12:4, s. 327-336
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic hepatic encephalopathy (HE) may present affective symptoms and antidepressant drug treatment in this condition is not uncommon. The present microdialysis study investigated treatment with the chronic antidepressant venlafaxine (VEN) in experimental HE with regard to tentative changes in pharmacokinetic and/or pharmacodynamic parameters. Three weeks after portacaval shunt (PCS) or sham operation in rats, VEN (10 mg/kg daily) was administered by implanted osmotic minipumps. VEN treatment for 14 days resulted in higher concentrations of VEN in PCS rats than in sham controls in serum and brain compartments, and the VEN levels in serum and brain were strongly inter-correlated. The serum N-desmethylvenlafaxine concentration did not differ between the groups, but correlated with the serum VEN levels. The other VEN metabolites were below the quantification limits. VEN treatment for 9-12 days significantly stimulated locomotion and rearing in the open field in sham controls, but failed to do so in the PCS rats. The concentrations of noradrenaline, dopamine, 5-HT, and 5-HIAA in neocortical dialysates were higher in PCS than in sham rats after 14 days of VEN treatment, but the elevations reached statistical significance only in the case of dopamine and 5-HIAA. In summary, there were significant pharmacokinetic and pharmacodynamic alterations in rats with experimental HE as compared to controls. The described experimental HE model may be useful for continued pharmacokinetic/pharmacodynamic interaction studies to unravel the pathophysiological consequences of HE on the CNS. Copyright ⌐ 2002 Elsevier Science B.V.
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- Brikell, I., et al.
(författare)
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ADHD medications and the risk of epileptic seizures : a pharmacoepidemiological study using nationwide register data
- 2017
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 27:Suppl. 4, s. S1113-S1114
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Attention-deficit/hyperactivity disorder (ADHD) affects 10–30% of children with epilepsy, making it one of the most common comorbidities in epilepsy. Stimulant medications are first line pharmacological treatment of ADHD, yet there areconcerns regarding the safety of stimulant treatment in patients with comorbid ADHD and epilepsy. This is due to the long held view that stimulants may lower the seizure threshold and increase seizure frequency [1]. Evidence for such an effect are however inconsistent and largely based on studies with small sample sizes, highly selected patient populations and observational studies that have not sufficiently addressed issues of confounding [2]. The aim of this pharmacoepidemiological register based study wastherefore to estimate the risk of seizures in relation to ADHD medication use in a population based cohort of individuals with a history of seizures.Methods: Using Swedish national registers, we identified a cohort of 62,361 individuals (48% female) born in Sweden between 1960 and 2004, with at least one seizure episode according to ICD codes. Each individual was followed from January 1st 2006, their first seizure or age five, up until December 31st 2013 or death, whichever came first. We identified periods of ADHD medication use (methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine, and atomoxetine) from the Swedish National Prescribed Drug Register. A period was defined as on-medication when two consecutive prescriptions where no more than 183 days apart, and off-medication if more than 183 daysapart. We obtained information on medical visit for unplanned seizures events from the Swedish National Patient register using ICD codes. We estimated the population level association between ADHD medications and the rate of seizures during medicated and non-medication periods using a cox proportional hazards regression model. To adjust for individual-specific confounding that may influence both seizure risk and the likelihood of receiving ADHD medication, we used a stratified Cox regression model to estimate the rate of seizures during medicated and non-medicated periods, within the same individual.Preliminary Result: A total of 59,749 seizure events occurred during 361,501 person years of follow-up. ADHD medications were not associated with the rate of seizures at the population level (HR = 1.06, 95%CI 0.91–1.23). In the within-individual analysis, ADHD medication periods were associated with a reduced rate of seizures (HR = 0.70, 95%CI 0.62–0.79), compared to non-medicated periods. Estimates did not differ across sex, nor in age restricted analyses including only ages 5 and 20 years. All analyses were adjusted for age as a time-varying covariate. Population level analyses were additionally adjusted for sex.Conclusions: Our findings suggest that ADHD medications are not associated with an increased risk of seizures. Rather, results from the within-individual analysis, which adjusts for factors that are constant within the individual, such as genetic factors and underlying disorder severity, suggest a protective effect of ADHD medication treatment on seizure rates. Next, we will study the effect of concurrent antiepileptic medication use and whether the observed effect differs by stimulant and non-stimulant ADHD medications. We will also further investigate possible mechanisms contributing to the observed protective effect of ADHD medications on seizure rates.References[1] Williams, A.E., Giust, J.M., Kronenberger, W.G., Dunn, D.W., 2016. Epilepsy and attention-deficit hyperactivity disorder: links, risks, and challenges. Neuropsychiatr Dis Treat 12, 287–296.[2] Ravi, M., Ickowicz, A., 2016. Epilepsy, Attention-Deficit/Hyperactivity Disorder and Methylphenidate: Critical Examination of Guiding Evidence. Journal of the Canadian Academy of Child and Adolescent Psychiatry 25 (1), 50.
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| 5. |
- Evers, Kathinka
(författare)
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Philosophical challenges for neuroethics
- 2008
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Ingår i: European Neuropsychopharmacology. - 0924-977X .- 1873-7862. ; 18:Suppl. 4, s. S202-S202
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Tidskriftsartikel (refereegranskat)abstract
- Neuroethics is an area concerned with the possible benefitsand dangers of modern research on the brain. Researchers inneuroethics have focused mainly on applied neuroethics, suchas ethical issues involved in neuroimaging techniques, cognitiveenhancement, or neuropharmacology (Illes 2006). Another important,less prevalent, scientific approach is fundamental neuroethics:how knowledge of the brain’s functional architecture and itsevolution can deepen our understanding of identity, consciousnessand intentionality, including the development of moral thoughtand judgment (Evers 2008). The relevance of neuroscience tounderstanding moral judgment depends on the theoretical viewthat is taken on the brain. A modern, dynamic view of thebrain may provide a fruitful theoretical framework for neuroethicsthrough its high explanatory value in regard to the evolution andnature of moral judgment under the aspects of subjective evaluation,free will and personal or public responsibility (Evers 2007).Informed materialism is a model based on the notion that all theelementary cellular processes of brain networks are grounded onphysico-chemical mechanisms and adopts an evolutionary viewof consciousness as a biological function of neuronal activities,but describes the brain as an autonomously active, projective andvariable system in which emotions and values are incorporated asnecessary constraints. Dynamic processes of evaluation and theemotional systems involved in their genesis are basic properties ofour brains: we are neurobiologically predisposed to develop thesecomplex and diverse systems of moral and other values enablingus to establish appropriate relationships in our social, cultural andphysical environments.
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| 9. |
- Lundmark, Jöns, et al.
(författare)
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The effect of paroxetine on cerebrospinal fluid concentrations of neurotransmitter metabolites in depressed patients
- 1994
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Ingår i: European Neuropsychopharmacology. - 0924-977X .- 1873-7862. ; 4:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the effect of the selective serotonin reuptake inhibiting drug (SSRI), paroxetine, on cerebrospinal fluid concentrations of neurotransmitter metabolites in depressed patients. 5-Hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured at baseline and after 3 weeks of treatment with 30 mg paroxetine daily. In line with similar studies on other SSRIs, influence on both the serotonin and noradrenaline metabolite was found. The mechanism behind the action of paroxetine on both 5-HIAA and MHPG is assumed to be an expression of the linkage between the serotonergic and noradrenergic systems in the brain. A frequently reported correlation between 5-HIAA and HVA was also found. The analysis of paroxetine in CSF proves the transportation of the drug into the central nervous system.
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| 10. |
- Nordin, Conny, 1944-, et al.
(författare)
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CSF taurine level is influenced by plasma cholesterol and the CYP2D6 phenotype
- 2003
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Ingår i: European Neuropsychopharmacology. - 0924-977X .- 1873-7862. ; 13:5, s. 333-335
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Tidskriftsartikel (refereegranskat)abstract
- Eight healthy male volunteers, lumbar-punctured before and during simvastatin treatment, were phenotyped for CYP2D6 analysis of the debrisoquine metabolic ratio (the ratio between the urinary recovery of debrisoquine and its 4-hydroxy metabolite) after a single oral dose of debrisoquine. The mean cerebrospinal fluid concentrations of cholesterol and taurine did not differ before and during treatment. During (but not before) treatment taurine in the CSF correlated with the debrisoquine metabolic ratio (r=-0.93, P=0.0007) Our results might indicate an influence of CYP2D6 on the level of taurine in the CSF that was secondary to the change in plasma cholesterol. ⌐ 2003 Elsevier B.V./ECNP. All rights reserved.
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