- Riluzole effectively treats psychotic symptoms and improves cognition in 22q11.2 deletion syndrome: A clinical case. [Journal Article]
- EJEur J Med Genet 2019 Jun 20; :103705
- 22q11.2 deletion syndrome (22q11DS) is a genetic disorder caused by a hemizygous microdeletion on the long arm of chromosome 22 and is associated with a high risk for psychosis and cognitive impairme…
22q11.2 deletion syndrome (22q11DS) is a genetic disorder caused by a hemizygous microdeletion on the long arm of chromosome 22 and is associated with a high risk for psychosis and cognitive impairment. One of the genes located in the deleted region of 22q11DS is Proline Dehydrogenase (PRODH) which is important for conversion of proline to glutamate. Glutamate is the primary excitatory neurotransmitter and is involved in the pathophysiology of psychosis as well as in cognition. Excessive concentrations are toxic. Possibly, neuroprotective drugs modulating glutamatergic neurotransmission could be effective in treating psychotic symptoms and cognitive enhancement in patients with 22q11DS. Riluzole is a potent anti-glutamatergic drug that reduces glutamatergic neurotransmission. Here we report acute (single dose) and long-term effects of riluzole on glutamate and GABA levels in the anterior cingulate cortex (ACC) and striatum (measured with magnetic resonance spectroscopy, 1H-MRS) as well as on psychotic symptoms and cognitive functioning in a medication-free 23-year old woman with 22q11DS. Patient presented with frequent auditory and visual hallucinations and mild paranoid ideas. The 1H-MRS measurements showed that after a single dose riluzole (50 mg), glutamate in the ACC and striatum was reduced whereas striatal GABA increased compared to baseline. Strikingly, hallucinations and paranoia disappeared. Therefore, riluzole treatment was initiated and patient was followed up after 18 months of treatment. At follow-up, patient reported no hallucinations or paranoia and several cognitive functions were improved. Furthermore, glutamate concentrations in the ACC and striatum decreased whereas GABA concentrations increased in the striatum but decreased in the ACC. These results suggests that riluzole may be an effective treatment option for psychotic symptoms and cognitive enhancement in 22q11DS. Results warrant replication in a bigger sample.
- Treatment of amphetamine abuse/use disorder: a systematic review of a recent health concern. [Journal Article]
- DARUDaru 2019 Jun 21
- CONCLUSIONS: A review of trials indicates that pharmacological treatments and BCBT in a research setting outperform control conditions in treating amphetamines abuse and associated harms. Large-scale studies should determine if both treatments can be effective in clinical settings.
- Pharmacoeconomic Review Report: Edaravone (Radicava): (Mitsubishi Tanabe Pharma Corporation): Indication: For the treatment of Amyotrophic Lateral Sclerosis (ALS) [BOOK]
- BOOKCanadian Agency for Drugs and Technologies in Health: Ottawa (ON)
- Edaravone (Radicava) is indicated for the treatment of adult patients with amyotrophic lateral sclerosis (ALS). Edaravone is available as a 30 mg/100 mL solution for infusion. It is administered intr…
Edaravone (Radicava) is indicated for the treatment of adult patients with amyotrophic lateral sclerosis (ALS). Edaravone is available as a 30 mg/100 mL solution for infusion. It is administered intravenously as 60 mg infusions over 60 minutes daily for 10 days out of a 14-day period, followed by a 14-day drug-free period. In the first month of treatment, edaravone is administered for 14 days (rather than 10). The submitted price is $1,424 per 60 mg, or $1,424 per patient daily and $185,182 per patient annually ($190,880 in the first year of treatment). The manufacturer submitted a cost-effectiveness analysis based on a Markov state–transition model comparing current standard of care (interdisciplinary supportive care plus riluzole) with edaravone plus current standard of care. In standard of care, 85% of patients were concurrently taking riluzole, the only disease-modifying treatment currently available for ALS. The manufacturer assumed that all patients, at any stage of the disease, were eligible for edaravone therapy and that edaravone slowed disease progression at all stages of the disease. The model did not assume a direct treatment effect on disease-specific mortality. The analysis was run over a 20-year time horizon using a three-month cycle length. The analysis adopted a Canadian public health care system perspective. The manufacturer’s analysis indicated that edaravone is not cost-effective compared with standard of care, with an incremental cost-effectiveness ratio of $1,957,200 per quality-adjusted life-year (QALY) gained.
- The emergence of new antidepressants for clinical use: Agomelatine paradox versus other novel agents. [Review]
- IRIBRO Rep 2019; 6:95-110
- This study was designed with the rational aim of discussing the emerging antidepressant agents that are likely to bring positive landmark, tremendous improvement and significant impact to the managem…
This study was designed with the rational aim of discussing the emerging antidepressant agents that are likely to bring positive landmark, tremendous improvement and significant impact to the management of patients with depression disorders. It also elaborates on the Agomelatine paradox vis-a-vis the other novel antidepressant agents. The emerging antidepressants are: selective monoamine oxidase inhibitors (MAOIs) such as bifemelane, pirlindole, toloxatone, selegiline, rasagiline and safinamide; serotonin-norepinephrine reuptake inhibitors (SNRIs) such as ansofaxine, nefopam and levomilnacipran; norepinephrine reuptake inhibitors (NRIs) such as Reboxetine, viloxazine, teniloxazine (also known as sulfoxazine or sufoxazine), and atomoxetine; Vilazodone (a serotonin 5-HT1A autoreceptor partial agonist with serotonin reuptake inhibition [SPARI]); Vortioxetine (a serotonin receptors antagonist with serotonin reuptake inhibition [SARI]); atypical antipsychotics such as olanzapine, quetiapine, risperidone, lurasidone, aripiprazole and brexpiprazole; N-methyl-d-aspartate (NMDA)-glutamatergic neurotransmission system blockers such as ketamine, CP-101,606 (traxoprodil), GLYX-13 (rapastinel), NRX-1074 (Apimostinel) and Riluzole. While Agomelatine (a melatonergic MT 1 and MT 2 receptors agonist and a selective serotonergic 5-HT 2B and 5-HT 2C receptors antagonist [MASSA]) remains a paradoxical agent that doesn't fit into any of the currently available classes of antidepressant agents and its pharmacological properties also deemed it unfit and inappropriate to be classified into another separate novel class of antidepressants contrary to the reports published in previous reference literatures. Lastly, this review remarkably advocates for the incorporation of the atypical antipsychotics and NMDA-glutamatergic ionoceptor blockers as new member classes of the antidepressant agents because of their clinically significant roles in the management of depression disorders.
- Effectiveness assessment of riluzole in the prevention of oxaliplatin-induced peripheral neuropathy: RILUZOX-01: protocol of a randomised, parallel, controlled, double-blind and multicentre study by the UNICANCER-AFSOS Supportive Care intergroup. [Journal Article]
- BOBMJ Open 2019 Jun 09; 9(6):e027770
- Most patients (>70%) experience acute neuropathic symptoms shortly after oxaliplatin infusions. These symptoms are not always resolved between infusions. Overall, 30%-50% of patients suffer from chro…
Most patients (>70%) experience acute neuropathic symptoms shortly after oxaliplatin infusions. These symptoms are not always resolved between infusions. Overall, 30%-50% of patients suffer from chronic oxaliplatin-induced peripheral neuropathy (OIPN). This cumulative and dose-dependent sensory neuropathy limits compliance or results in oxaliplatin-based chemotherapies to be substituted with less neurotoxic agents. These treatment changes impair clinical outcomes, and may be associated with comorbidities, such as distress, depression and anxiety. Currently, no drug used to prevent or treat OIPN is sufficiently effective to be used routinely in clinical practice. There is, thus, an unmet therapeutic need to reduce the intensity of and/or prevent OIPN. We hypothesised that riluzole would be an excellent candidate to address this public health issue. Riluzole is approved for treating amyotrophic lateral sclerosis. In animals, there is a beneficial effect on sensorimotor and pain disorders, as well as related comorbidities, after repeated administration of oxaliplatin. In humans, riluzole has shown neuroprotective, anxiolytic and antidepressive effects.
- Proteostasis and ALS: protocol for a phase II, randomised, double-blind, placebo-controlled, multicentre clinical trial for colchicine in ALS (Co-ALS). [Journal Article]
- BOBMJ Open 2019 May 30; 9(5):e028486
- Disruptions of proteasome and autophagy systems are central events in amyotrophic lateral sclerosis (ALS) and support the urgent need to find therapeutic compounds targeting these processes. The heat…
Disruptions of proteasome and autophagy systems are central events in amyotrophic lateral sclerosis (ALS) and support the urgent need to find therapeutic compounds targeting these processes. The heat shock protein B8 (HSPB8) recognises and promotes the autophagy-mediated removal of misfolded mutant SOD1 and TDP-43 fragments from ALS motor neurons (MNs), as well as aggregating species of dipeptides produced in C9ORF72-related diseases. In ALS-SOD1 mice and in human ALS autopsy specimens, HSPB8 is highly expressed in spinal cord MNs that survive at the end stage of disease. Moreover, the HSPB8-BAG3-HSP70 complex maintains granulostasis, which avoids conversion of dynamic stress granules (SGs) into aggregation-prone assemblies. We will perform a randomised clinical trial (RCT) with colchicine, which enhances the expression of HSPB8 and of several autophagy players, blocking TDP-43 accumulation and exerting crucial activities for MNs function.
- Clinical characteristics of a large cohort of US participants enrolled in the National Amyotrophic Lateral Sclerosis (ALS) Registry, 2010-2015. [Journal Article]
- ALAmyotroph Lateral Scler Frontotemporal Degener 2019 May 26; :1-8
- CONCLUSIONS: These data show how ALS clinical characteristics differ widely in a large cohort of participants preceding diagnosis and reflect variations in disease onset, progression, and prognosis. Better characterization of symptom onset may assist clinicians in diagnosing ALS sooner, which could lead to earlier therapeutic interventions.
- Neuroprotective properties of RT10, a fraction isolated from Parawixia bistriata spider venom, against excitotoxicity injury in neuron-glia cultures. [Journal Article]
- JVJ Venom Anim Toxins Incl Trop Dis 2019; 25:e148818
- CONCLUSIONS: RT10 fraction exhibits neuroprotective effects against L-Glu excitotoxicity in neuron-glia cultured in vitro.
- Sialorrhea in patients with ALS: current treatment options. [Journal Article]
- DNDegener Neurol Neuromuscul Dis 2019; 9:19-26
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor neuron, which selectively affects it both at central (first motor-neuron) and peripheral level (second mot…
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of the motor neuron, which selectively affects it both at central (first motor-neuron) and peripheral level (second motor-neuron). The disease shows up at a mean age of 56 years and the most affected are males. Although ALS may start as a bulbar or spinal disease, with the progression of the disease typically both become evident. Pharmacological approved treatments for ALS are still limited and include riluzole and edaravone which improve survival over time. Despite this, ALS leads to progressive muscle involvement and requires a complex multidisciplinary approach to manage increasing disability which goes beyond motor neurons. Sialorrhea is, amongst others, one of the most disabling symptoms in ALS. The complexity in managing saliva is due to a muscular spasticity and to a scarce palatino-lingual muscles control, rather than to an overproduction of saliva. These features could increase the risk of aspiration pneumonia and limit the use of noninvasive mechanical ventilation. We reviewed the treatment for sialorrhea in ALS patients that are available at this time, emphasizing pros and cons for each approach. Our purpose is to create a practical tool for the diagnosis, in order to facilitate the quantification and management of sialorrhea in everyday practice.
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- Estimating Amyotrophic Lateral Sclerosis and Motor Neuron Disease Prevalence in Portugal Using a Pharmaco-Epidemiological Approach and a Bayesian Multiparameter Evidence Synthesis Model. [Journal Article]
- NNeuroepidemiology 2019 May 22; :1-11
- CONCLUSIONS: Overall, and even though we must account for the limitations of the indirect methods and models used for prevalence estimation, we probably have a very high ALS/MND prevalence in Portugal. It would be important to create registries, particularly in rare diseases, for better organization and distribution of healthcare services and resources, particularly at the level of ventilatory support.