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- Antonini, Angelo, et al.
(författare)
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Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson’s Disease : A Systematic Review and Bayesian Network Meta-analysis
- 2022
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Ingår i: CNS Drugs. - : Springer Science and Business Media LLC. - 1172-7047 .- 1179-1934. ; 36:12, s. 1269-1283
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson’s disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD. Methods: A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson’s Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson’s Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness. Results: A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5–70.9 years, duration of PD was 9.1–15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL. Conclusions: This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.
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- Ardura-Fabregat, A., et al.
(författare)
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Targeting Neuroinflammation to Treat Alzheimer’s Disease
- 2017
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Ingår i: CNS Drugs. - : Springer Science and Business Media LLC. - 1172-7047 .- 1179-1934. ; 31:12, s. 1-26
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Forskningsöversikt (refereegranskat)abstract
- Over the past few decades, research on Alzheimer’s disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intra-neuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as danger-associated molecular patterns, that—upon engagement of pattern recognition receptors—induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on Neuroinflammation 2016, provides an overview of our current understanding of AD-related immune processes. We describe the principal cellular and molecular players in inflammation as they pertain to AD, examine modifying factors, and discuss potential future therapeutic targets.
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- Bang Madsen, Kathrine, et al.
(författare)
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Attention-Deficit Hyperactivity Disorder (ADHD) Medication Use Trajectories Among Women in the Perinatal Period
- 2024
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Ingår i: CNS Drugs. - : Adis International Ltd.. - 1172-7047 .- 1179-1934. ; 38, s. 301-314
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An increasing number of women of reproductive age are treated with attention-deficit hyperactivity disorder (ADHD) medication; however, patterns of ADHD medication use for women in the perinatal period have not been well described.OBJECTIVE: This study aimed to describe ADHD medication use patterns from 1 year before pregnancy to 1 year after delivery, and to describe sociodemographic characteristics and clinical features by medication trajectories.METHODS: The population-based cohort study included pregnancies in Denmark between 1997 and 2020, from the Medical Birth Register, by women who filled at least one prescription for ADHD medication from 12 months before pregnancy until 12 months after delivery. We applied group-based trajectory modeling to classify women into subgroups based on the identification of heterogeneous ADHD medication treatment patterns, and described the characteristics associated with these groups.RESULTS: Overall, we included 4717 pregnancies leading to liveborn singletons by 4052 mothers with a mean (standard deviation) age of 27.5 (5.6) years. We identified four treatment trajectories across pregnancy and the postpartum period: continuers (23.3%), discontinuers (41.8%), interrupters who ceased filling prescriptions during pregnancy but resumed postpartum (17.2%), and postpartum initiators (17.7%). Continuers were older at the time of conception, gave birth in more recent years, were more likely to smoke during pregnancy, and used other psychotropic medications during pregnancy. A large proportion of continuers used methylphenidate (89.1%) compared with the other groups (75.9-84.1%) and had switched ADHD medication type during the whole period (16.4% vs. 7.4-14.8%).CONCLUSION: We found that approximately 60% of women discontinued or interrupted their ADHD medication around pregnancy, and those who continued differed in sociodemographic and clinical factors that may reflect more severe ADHD.
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- Ben-Menachem, Elinor, 1945, et al.
(författare)
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A Phase II Randomized Trial to Explore the Potential for Pharmacokinetic Drug-Drug Interactions with Stiripentol or Valproate when Combined with Cannabidiol in Patients with Epilepsy
- 2020
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Ingår i: Cns Drugs. - : Springer Science and Business Media LLC. - 1172-7047 .- 1179-1934. ; 34:6, s. 661-672
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Tidskriftsartikel (refereegranskat)abstract
- Background In recent randomized, placebo-controlled, phase III trials, highly purified cannabidiol demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut syndrome or Dravet syndrome. It is anticipated that antiepileptic drugs such as stiripentol and valproate will be administered concomitantly with cannabidiol. Objectives This trial evaluated the effect of cannabidiol on steady-state pharmacokinetics of stiripentol or valproate in patients with epilepsy, and the safety and tolerability of cannabidiol. Methods This phase II, two-arm, parallel-group, double-blind, randomized, placebo-controlled trial recruited male and female patients with epilepsy aged 16-55 years. Patients receiving a stable dose of stiripentol or valproate were randomized 4:1 to receive concomitant double-blind cannabidiol or placebo. Patients received plant-derived, highly purified cannabidiol medicine (Epidiolex(R) in the USA; Epidyolex(R) in the EU; 100 mg/mL oral solution) at a dose of 20 mg/kg/day from day 12 to 26, following a 10-day dose-escalation period. Blood samples for pharmacokinetic evaluations were collected on days 1 and 26 before stiripentol/valproate dosing and up to 12 h postdose. Treatment-emergent adverse events (AEs) were recorded. Results In total, 35 patients were recruited to the stiripentol arm (n = 14) or the valproate arm (n = 21). Both the safety and the pharmacokinetic populations of the stiripentol arm comprised 14 patients (2 placebo; 12 cannabidiol). The safety population of the valproate arm comprised 20 patients (4 placebo; 16 cannabidiol; one withdrew before receiving treatment); the pharmacokinetic population comprised 15 patients (3 placebo; 12 cannabidiol). Concomitant cannabidiol led to a small increase in stiripentol exposure (17% increase in maximum observed plasma concentration [C-max]; 30% increase in area under the concentration-time curve over the dosing interval [AUC(tau)]). Concomitant cannabidiol also had little effect on valproate exposure (13% decrease in C-max; 17% decrease in AUC(tau)) or its metabolite, 2-propyl-4-pentenoic acid (4-ene-VPA) (23% decrease in C-max; 30% decrease in AUC(tau)). All changes in exposure are expressed as the dose-normalized geometric mean (CV%) day 26 to day 1 ratio. The most common AE was diarrhea; most AEs were mild. Two patients discontinued cannabidiol because of serious AEs (rash [n = 1] in the stiripentol arm; hypertransaminasemia [n = 1] in the valproate arm). A separate in vitro study investigated the bidirectional effect of cannabidiol, or its metabolite 7-carboxy-cannabidiol, on valproate plasma protein binding; no change in plasma protein binding was observed for either compound. Conclusions The clinical relevance of the increase in stiripentol exposure is unknown; patients receiving cannabidiol and stiripentol concomitantly should be monitored for adverse reactions as individual patient responses may vary. Coadministration of cannabidiol did not affect the pharmacokinetics of valproate or its metabolite, 4-ene-VPA, in adult patients with epilepsy. Safety results were consistent with the known safety profile of cannabidiol at a dose of 20 mg/kg/day. Clinicaltrials.gov: NCT02607891.
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- Bäckström, Torbjörn, et al.
(författare)
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The role of hormones and hormonal treatments in premenstrual syndrome
- 2003
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Ingår i: CNS Drugs. - 1172-7047 .- 1179-1934. ; 17:5, s. 325-342
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Tidskriftsartikel (refereegranskat)abstract
- Premenstrual syndrome (PMS) is a menstrual cycle-linked condition with both mental and physical symptoms. Most women of fertile age experience cyclical changes but consider them normal and not requiring treatment. Up to 30% of women feel a need for treatment. The aetiology is still unclear, but sex steroids produced by the corpus luteum of the ovary are thought to be symptom provoking, as the cyclicity disappears in anovulatory cycles when a corpus luteum is not formed. Progestogens and progesterone together with estrogen are able to induce similar symptoms as seen in PMS. Symptom severity is sensitive to the dosage of estrogen. The response systems within the brain known to be involved in PMS symptoms are the serotonin and GABA systems. Progesterone metabolites, especially allopregnanolone, are neuroactive, acting via the GABA system in the brain. Allopregnanolone has similar effects as benzodiazepines, barbiturates and alcohol; all these substances are known to induce adverse mood effects at low dosages in humans and animals. SSRIs and substances inhibiting ovulation, such as gonadotrophin-releasing hormone (GnRH) agonists, have proven to be effective treatments. To avoid adverse effects when high dosages of GnRH agonists are used, add-back hormone replacement therapy is recommended. Spironolactone also has a beneficial effect, although not as much as SSRIs and GnRH agonists.
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| 10. |
- Cardona Cano, Sebastian, et al.
(författare)
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Role of ghrelin in the pathophysiology of eating disorders: Implications for pharmacotherapy
- 2012
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Ingår i: CNS Drugs. - : Springer Science and Business Media LLC. - 1172-7047 .- 1179-1934. ; 26, s. 281-296
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Forskningsöversikt (refereegranskat)abstract
- Ghrelin is the only known circulating orexigenic hormone. It increases food intake by interacting with hypothalamic and brainstem circuits involved in energy balance, as well as reward-related brain areas. A heightened gut-brain ghrelin axis is an emerging feature of certain eating disorders such as anorexia nervosa and Prader-Willi syndrome. In common obesity, ghrelin levels are lowered, whereas post-meal ghrelin levels remain higher than in lean individuals. Agents that interfere with ghrelin signalling have therapeutic potential for eating disorders, including obesity. However, most of these drugs are only in the preclinical phase of development. Data obtained so far suggest that ghrelin agonists may have potential in the treatment of anorexia nervosa, while ghrelin antagonists seem promising for other eating disorders such as obesity and Prader-Willi syndrome. However, large clinical trials are needed to evaluate the efficacy and safety of these drugs. © 2012 Adis Data Information BV. All rights reserved.
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