Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.302
Filtrar
3.
Bol. latinoam. Caribe plantas med. aromát ; 18(5): 459-479, sept. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1008268

RESUMO

Neuronal cell damage is often caused by prolonged misuse of Methylphenidate (MPH). Topiramate (TPM) carries neuroprotective properties but its assumed mechanism remains unclear. The present study evaluates in vivo role of various doses of TPM and its mechanism against MPH-induced motor activity and related behavior disorder. Thus, we used domoic acid (DOM), bicuculline (BIC), Ketamine (KET), Yohimibine (YOH) and Haloperidole (HAL) as AMPA/kainite, GABAA, NMDA, ɑ2 adrenergic and D2 of dopamine receptor antagonists respectively. Open Field Test (OFT), Elevated Plus Maze (EPM) and Forced Swim Test (FST) were used to study motor activity, anxiety and depression level. TPM (100 and 120 mg/kg) reduced MPH-induced rise and inhibited MPH-induced promotion in motor activity disturbance, anxiety and depression. Pretreatment of animals with KET, HAL, YOH and BIC inhibited TPM- improves anxiety and depression through the interacting with Dopaminergic, GABAA, NMDA and ɑ2-adrenergic receptors.


El daño a las células neuronales a menudo es causado por el uso prolongado de metilfenidato (MPH). El topiramato (TPM) tiene propiedades neuroprotectoras, pero su mecanismo de acción no es claro. El presente estudio evalúa el papel in vivo de varias dosis de TPM y su mecanismo contra la actividad motora inducida por MPH y el trastorno de comportamiento relacionado. Utilizamos ácido domoico (DOM), bicuculina (BIC), ketamina (KET), yohimbina (YOH) y haloperidol (HAL), así como antagonistas AMPA/kainato, GABAA, NMDA, ɑ2-adrenérgico y D2 dopaminérgicos, respectivamente. Se utilizaron las pruebas de campo abierto (OFT), elevación de laberinto (EPM) y natación forzada (FST) para estudiar la actividad motora, la ansiedad y el nivel de depresión. El TPM (100 y 120 mg/kg) redujo el aumento inducido por MPH e inhibió la promoción inducida por MPH en la alteración de la actividad motora, la ansiedad y la depresión. El tratamiento previo de animales con KET, HAL, YOH y BIC inhibió el TPM, mejora la ansiedad y la depresión a través de la interacción con los receptores dopaminérgicos, GABAA, NMDA y ɑ2-adrenérgico.


Assuntos
Animais , Masculino , Ratos , Comportamento Animal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , /farmacologia , Transtornos Mentais/prevenção & controle , Metilfenidato/efeitos adversos , Ratos Wistar , Neurotransmissores/metabolismo , Transtornos Mentais/induzido quimicamente , Atividade Motora/efeitos dos fármacos
5.
Clin Drug Investig ; 39(11): 1067-1075, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31327127

RESUMO

BACKGROUND: Parkinson's disease is a disorder growing in prevalence, disability, and deaths. Healthcare databases provide a 'real-world' perspective for millions of individuals. We envisioned helping accelerate drug discovery by using these databases. OBJECTIVES: The objectives of this study were to assess the association of marketed medications with the risk of parkinsonism in four US claims databases and to evaluate the consistency of the association of ß-adrenoreceptor modulation with parkinsonism. METHODS: The study was conducted using a self-controlled cohort design in which subjects served as their own control. The time from treatment initiation until discontinuation or end of observation was the exposed period and a similar time preceding medication was the unexposed period. Medications were studied at ingredient and class level. The incidence rate ratio (IRR) and combined IRR were calculated. RESULTS: We assessed 2181 drugs and 117,015,066 people. Diphenhydramine, isradipine, methylphenidate, armodafinil, and modafinil were associated with reduced risk for parkinsonism in at least two databases. Armodafinil, modafinil, methylphenidate, and the ß-agonist albuterol were associated with a 56%, 54%, 39%, and 17% reduction in the risk of having parkinsonism, respectively. Isradipine results were heterogeneous and no significant association was found. Propranolol was associated with a 32% increased risk, the only ß-adrenoceptor antagonist (ß-blocker) associated with an increased risk. CONCLUSIONS: Armodafinil, modafinil, and methylphenidate were associated with a decreased risk of parkinsonism, as were ß-agonists. Of the ß-blockers, only propranolol was associated with increased risk. Healthcare database analyses that incorporate scientific rigor provide insight and direction for drug discovery efforts. These findings show association not causality; however, they offer considerable support to the association between ß-adrenergic receptor modulation and risk of Parkinson's disease.


Assuntos
Antiparkinsonianos/uso terapêutico , Descoberta de Drogas/métodos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/diagnóstico , Vigilância de Produtos Comercializados/métodos , Antagonistas Adrenérgicos beta/efeitos adversos , Adulto , Estudos de Coortes , Bases de Dados Factuais/normas , Feminino , Humanos , Masculino , Metilfenidato/efeitos adversos , Modafinila/efeitos adversos , Doença de Parkinson Secundária/prevenção & controle
6.
Pak J Pharm Sci ; 32(3): 899-903, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31278697

RESUMO

Methylphenidate (MPD), a psycho-stimulant is a prescription medicine for the treatment of Attention deficit hyperactivity disorder (ADHD). The drug is also being increasingly used by general population for enhancing cognition. Only few preclinical studies have been carried out on the effects of MPD on cognition and these studies show either an enhancement or impairment of memory following the administration of MPD. The present study was designed to evaluate the effects of different doses of methylphenidate on acquisition and retention of memory in Morris water-maze test. Twenty four male Albino Wistar rats (weighing 180-220gm) were randomly assigned to four groups: (1) Control (2) 0.5mg/kg (3) 2.5mg/kg (4) 5 mg/kg methylphenidate. Animals received drug or water orally before training phase. Memory acquisition was monitored 2hrs post drug administration while memory retention was determined next day. It was found that the clinically relevant doses of methylphenidate (0.5mg/kg and 2.5mg/kg) improved memory acquisition and its retention but higher dose (5mg/kg) impaired both. We suggest that MPD-induced increase of catecholamine neurotransmission may have a role in the improvement of water maze performance while agonist activity of the drug for 5HT-1A receptor in the impaired performance at high doses. Food intake and body weight changes were not affected by MPD administration due to short-term administration of the drug. Results may help in improving pharmaco-therapeutic use of MPD for ADHD.


Assuntos
Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Metilfenidato/administração & dosagem , Metilfenidato/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Masculino , Metilfenidato/efeitos adversos , Ratos Wistar
7.
Turk Neurosurg ; 29(5): 734-742, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31353439

RESUMO

AIM: To investigate the effects of methylphenidate (MPH), on intervertebral disc tissue (IVD) cell cultures and extracellular matrix structures. Changes in the expression of some important marker genes involved in anabolic and catabolic mechanisms of IVD extracellular matrix formation were also evaluated. MATERIAL AND METHODS: Primary cultures of nucleus pulposus cells (NPCs) and annulus fibrosus cells (AFCs) were isolated from tissues obtained from the operated patients. Cell viability and proliferation were tested, and the cell surface morphologies were evaluated by microscopy. The expressions of the chondroadherin (CHAD), cartilage oligomeric matrix protein (COMP), interleukin-1 beta (IL-1ß) and matrix metalloproteinase (MMP) -7 and MMP-19 genes were evaluated using the quantitative real-time polymerase chain reaction (qRT-PCR). A value of p < 0.05 was considered statistically significant. RESULTS: The viability and proliferation of intervertebral disc tissue cells decreased in response to MPH treatment and the expression of the investigated genes also changed. CONCLUSION: The data obtained from in-vitro studies may not directly adaptable to clinical applications. However, the fact that the central nervous system stimulant MPH can suppress proliferation of cells derived from IVD tissue should be considered carefully by clinicians.


Assuntos
Estimulantes do Sistema Nervoso Central/efeitos adversos , Disco Intervertebral/efeitos dos fármacos , Metilfenidato/efeitos adversos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos
8.
J Clin Psychopharmacol ; 39(4): 386-392, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205193

RESUMO

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) can be comorbid with frequent anxiety and mood disorders, as well as emotional symptoms (anxiety, irritability, mood lability). These may also be triggered by drugs and appear as adverse drug reactions (ADRs). METHODS: We mined data from the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database, focused on methylphenidate, atomoxetine, amphetamine, lisdexamfetamine, and their derivatives. We collected reports of ADRs connected with mood or emotional symptoms in pediatric patients, excluding drug abuse/accidents. Reporting odds ratios (RORs) were calculated and compared between drug classes and children/adolescents. RESULTS: We collected 6176 ADRs of interest of which 59% occurred in children. Atomoxetine accounted for 50.7% of reports, methylphenidate for 32.5%, lisdexamfetamine for 14.2%, and amphetamine for 2.6%. Irritability, anxiety, obsessive thoughts, depressed mood, and euphoria scored significant RORs for all drugs, overall with an increasing risk from methylphenidate to atomoxetine, lisdexamfetamine, and amphetamine. Apathy regarded mostly atomoxetine, and crying regarded all drugs except methylphenidate. Several age-based differences were found. Notably, affect lability hit only adolescents. All drugs scored significant self-injury RORs, except lisdexamfetamine in adolescents, with an increasing risk from methylphenidate to lisdexamfetamine, atomoxetine, and amphetamine. For suicidality, all drugs had significant RORs in children, and methylphenidate was better than atomoxetine and lisdexamfetamine. In adolescents, only methylphenidate and atomoxetine scored significant RORs. CONCLUSIONS: We conclude that real-world data from the US Food and Drug Administration Adverse Event Reporting System are consistent with previous evidence from meta-analyses. They support a hierarchy of drug safety for several ADRs (except self-injury/suicidality) with methylphenidate as safest, followed by atomoxetine, lisdexamfetamine, and amphetamine last. Self-injury and suicidality RORs were overall higher in children.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Adolescente , Inibidores da Captação Adrenérgica/efeitos adversos , Anfetamina , Cloridrato de Atomoxetina/efeitos adversos , Criança , Humanos , Dimesilato de Lisdexanfetamina/efeitos adversos , Metilfenidato/efeitos adversos , Estados Unidos , United States Food and Drug Administration
9.
Lancet Psychiatry ; 6(8): 651-658, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31221557

RESUMO

BACKGROUND: There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder. METHODS: In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12-30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis. FINDINGS: We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38·7%) individuals were assessed and 37 916 (61·3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2·0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1·04 (95% CI 0·80-1·34) in adolescents and young adults without a history of psychosis and 0·95 (0·69-1·30) among those with a history of psychosis. INTERPRETATION: Contrary to clinical concerns, we found no evidence that initiation of methylphenidate treatment increases the risk of psychotic events in adolescents and young adults, including in those individuals with a history of psychosis. Our study should reassure clinicians considering initiating methylphenidate treatment for ADHD in adolescents and young adults, and it challenges the widely held view in clinical practice that methylphenidate should be avoided, or its use restricted, in individuals with a history of psychosis. FUNDING: Swedish Research Council, National Institute of Mental Health, UK National Institute of Health Research Nottingham Biomedical Research Centre.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Metilfenidato/administração & dosagem , Psicoses Induzidas por Substâncias/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Metilfenidato/efeitos adversos , Farmacovigilância , Suécia/epidemiologia , Adulto Jovem
10.
Med Hypotheses ; 128: 6-10, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31203911

RESUMO

The underlining mechanism in neural mitochondrial dysfunction and consequences neurotoxicity, and cognitive behavior after methylphenidate (MPH) prolonged uses is unclear and proposing of therapeutic approaches for treatment of these types of neurotoxicity is one of the main goals of scientist in this manner. MPH-induced mitochondrial dysfunction in neural cells caused induction of oxidative stress, apoptosis, inflammation and cognition impairment, which leads to neurotoxicity, was reported previously but role of key neural cells proteins and involved signaling pathway in this manner remained indeterminate. Tau protein aggregation is a biomarker for mitochondrial dysfunction, neurodegenerative event and cognition impairment. Tau aggregation occur by stimulation effects of Glycogen synthase kinase-3(GSK3ß) and phosphatidylinositol 3-kinase (PI3K) which activates protein kinase B(Akt) and causes inhibition of phosphorylation(activation) of GSK3ß, thus Akt activation can cause inhibition of tau aggregation (hyper-phosphorylation). Management of mentioned MPH-induced mitochondrial dysfunction and consequences of neurotoxicity, and cognitive behavior through a new generation neuroprotective combination, based on modulation of disturbed in Akt function and inhibition of GSK3ß and tau hyper-phosphorylation can be a prefect therapeutic interventions. Therefore, finding, introduction and development of new neuroprotective properties and explanation of their effects with potential capacity for modulation of tau hyper-phosphorylation via PI3/Akt/GSK signaling pathway is necessitated. During recent years, using new neuroprotective compounds with therapeutic probability for treatment of psychostimulant-induced mitochondrial dysfunction, neurotoxicity and cognitive malicious effects have been amazingly increased. Many previous studies have reported the neuroprotective roles of minocycline (a broad-spectrum and long-acting antibiotic) in multiple neurodegenerative events and diseases in animal model. But the role of neuroprotective effects of this agent against MPH induced mitochondrial dysfunction, neurotoxicity and cognitive malicious and also role of tau hyper-phosphorylation by modulation of PI3/Akt/GSK signaling pathway in this manner remain unknown. Thus we suggested and theorized that by using minocycline in MPH addicted subject, it would provide neuroprotection against MPH-induced mitochondrial dysfunction, neurotoxicity and cognitive malicious. Also we hypothesized that minocycline, via modulation of PI3/Akt/GSK and inhibition of tau hyper-phosphorylation, can inhibit MPH-induced mitochondrial dysfunction, neurotoxicity and cognitive malicious. In this article, we tried to discuss our hypothesis regarding the possible role of minocycline, as a powerful neuroprotective agent, and also role of tau hyper-phosphorylation related to PI3/Akt/GSK signaling pathway in treatment of MPH-induced mitochondrial dysfunction, neurotoxicity and cognitive disturbance.


Assuntos
Metilfenidato/efeitos adversos , Minociclina/farmacologia , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais , Proteínas tau/química , Antibacterianos/farmacologia , Cognição , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Metilfenidato/farmacologia , Mitocôndrias/metabolismo , Modelos Biológicos , Doenças do Sistema Nervoso/terapia , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas tau/metabolismo
11.
Cornea ; 38(8): 1040-1042, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30950895

RESUMO

PURPOSE: To describe the development and resolution of corneal edema in 3 patients who were exposed to compounds that stimulate dopaminergic pathways. METHODS: We conducted a review of the literature on bilateral corneal edema secondary to amantadine use and report a case series of corneal edema seen in an outpatient ophthalmology specialty clinic, shortly after exposure to agents that enhance dopamine transmission. RESULTS: Cases 1 and 2 report a 25-year-old man with attention-deficit hyperactivity disorder and a 73-year-old man with Parkinson disease who were placed on dopaminergic medications to treat their conditions. The former was administered methylphenidate and the latter patient was administered ropinirole. Both patients developed corneal edema soon afterward. Case 3 is a 67-year-old man with a recent exposure to resin from Euphorbia resinifera, a cactus in his garden. After cessation of the offending medications and treatment for exposure to resiniferatoxin, the corneal edema progressively resolved and visual acuity returned to baseline in all 3 cases. CONCLUSIONS: Methylphenidate, ropinirole, and resiniferatoxin have different mechanisms of actions but have a common end point leading to increased dopamine. We believe that these agents are linked with the reversible corneal edema seen in our 3 patients. This strongly correlates with previous studies that have linked amantadine, a drug that blocks dopamine reuptake, to reversible corneal edema.


Assuntos
Edema da Córnea/induzido quimicamente , Dopaminérgicos/efeitos adversos , Adulto , Idoso , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Edema da Córnea/diagnóstico , Edema da Córnea/fisiopatologia , Diterpenos/efeitos adversos , Dopamina/metabolismo , Humanos , Indóis/efeitos adversos , Masculino , Metilfenidato/efeitos adversos , Neurotoxinas/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo
13.
N Engl J Med ; 380(12): 1128-1138, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30893533

RESUMO

BACKGROUND: The prescription use of the stimulants methylphenidate and amphetamine for the treatment of attention deficit-hyperactivity disorder (ADHD) has been increasing. In 2007, the Food and Drug Administration mandated changes to drug labels for stimulants on the basis of findings of new-onset psychosis. Whether the risk of psychosis in adolescents and young adults with ADHD differs among various stimulants has not been extensively studied. METHODS: We used data from two commercial insurance claims databases to assess patients 13 to 25 years of age who had received a diagnosis of ADHD and who started taking methylphenidate or amphetamine between January 1, 2004, and September 30, 2015. The outcome was a new diagnosis of psychosis for which an antipsychotic medication was prescribed during the first 60 days after the date of the onset of psychosis. To estimate hazard ratios for psychosis, we used propensity scores to match patients who received methylphenidate with patients who received amphetamine in each database, compared the incidence of psychosis between the two stimulant groups, and then pooled the results across the two databases. RESULTS: We assessed 337,919 adolescents and young adults who received a prescription for a stimulant for ADHD. The study population consisted of 221,846 patients with 143,286 person-years of follow up; 110,923 patients taking methylphenidate were matched with 110,923 patients taking amphetamines. There were 343 episodes of psychosis (with an episode defined as a new diagnosis code for psychosis and a prescription for an antipsychotic medication) in the matched populations (2.4 per 1000 person-years): 106 episodes (0.10%) in the methylphenidate group and 237 episodes (0.21%) in the amphetamine group (hazard ratio with amphetamine use, 1.65; 95% confidence interval, 1.31 to 2.09). CONCLUSIONS: Among adolescents and young adults with ADHD who were receiving prescription stimulants, new-onset psychosis occurred in approximately 1 in 660 patients. Amphetamine use was associated with a greater risk of psychosis than methylphenidate. (Funded by the National Institute of Mental Health and others.).


Assuntos
Anfetamina/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Metilfenidato/efeitos adversos , Psicoses Induzidas por Substâncias/epidemiologia , Adolescente , Adulto , Anfetamina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Incidência , Seguro Saúde , Masculino , Metilfenidato/uso terapêutico , Psicoses Induzidas por Substâncias/etiologia , Estados Unidos/epidemiologia , Adulto Jovem
17.
Int Clin Psychopharmacol ; 34(3): 138-142, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30640748

RESUMO

The aim of this study was to compare impulsivity levels, as assessed by a continuous performance test (CPT), and the correlations between baseline CPT performance and response to methylphenidate (MPH), as assessed by the conjunctive CPT (CCPT), in children with only Diagnostic and Statistical Manual of Mental Disorders, 5th ed. attention-deficit hyperactivity disorder with no oppositional defiant disorder (ADHD/noODD) or with comorbid ODD (ADHD/ODD). Fifty-three children and adolescents were included in the study (ADHD/noODD group, n = 25, 12 women/13 men and ADHD/ODD group, n = 28, eight females/20 males). Attention was assessed at baseline using CCPT. ADHD and ODD severities were assessed at baseline and following a 12-week MPH treatment using the ADHD-rating scale (ADHD-RS) completed by the parent and by a teacher and the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-ODD (K-SADS-ODD) completed by the treating psychiatrist. Higher baseline commission-errors rates (P = 0.0031) in ADHD-RS/parent-child, ADHD-RS/teacher, and K-SADS-ODD scores were detected in ADHD/ODD compared with the ADHD/noODD. Significant improvements in ADHD-RS/parent-child, ADHD-RS/teacher, and K-SADS-ODD scores were achieved following MPH treatment in both groups. Significant correlations were found between baseline CCPT commission-error rates and improvement in ADHD-RS-teacher in ADHD/noODD, but not in ADHD/ODD. Among the ADHD/ODD, but not the ADHD/noODD, a significant correlation was found between baseline CCPT commission-error rates and improvement in K-SADS-ODD. Baseline cognitive impulsivity (as measured by the CCPT) can predict response of ODD to MPH treatment in ADHD/ODD patients.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico , Cognição/efeitos dos fármacos , Comportamento Impulsivo/efeitos dos fármacos , Metilfenidato/efeitos adversos , Adolescente , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Comorbidade , Feminino , Humanos , Masculino , Metilfenidato/uso terapêutico
18.
Neurol Sci ; 40(4): 829-837, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30693423

RESUMO

Methylphenidate produces its effects via actions on cortical areas involved with attention and working memory, which have a direct role in time estimation judgment tasks. In particular, the prefrontal and parietal cortex has been the target of several studies to understand the effect of methylphenidate on executive functions and time interval perception. However, it has not yet been studied whether acute administration of methylphenidate influences performance in time estimation task and the changes in alpha band absolute power in the prefrontal and parietal cortex. The current study investigates the influence of the acute use of methylphenidate in both performance and judgment in the time estimation interpretation through the alpha band absolute power activity in the prefrontal and parietal cortex. This is a double-blind, crossover study with a sample of 32 subjects under control (placebo) and experimental (methylphenidate) conditions with absolute alpha band power analysis during a time estimation task. We observed that methylphenidate does not influence task performance (p > 0.05), but it increases the time interval underestimation by over 7 s (p < 0.001) with a concomitant decrease in absolute alpha band power in the ventrolateral prefrontal cortex and dorsolateral prefrontal cortex and parietal cortex (p < 0.001). Acute use of methylphenidate increases the time interval underestimation, consistent with reduced accuracy of the internal clock mechanisms. Furthermore, acute use of methylphenidate influences the absolute alpha band power over the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, and parietal cortex.


Assuntos
Ritmo alfa/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Julgamento/efeitos dos fármacos , Metilfenidato/farmacologia , Lobo Parietal/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos , Percepção do Tempo/efeitos dos fármacos , Adulto , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Humanos , Masculino , Metilfenidato/administração & dosagem , Metilfenidato/efeitos adversos , Adulto Jovem
19.
Brain Res Bull ; 144: 200-212, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30502401

RESUMO

There is growing concern that the psychostimulant Methylphenidate (MPD) is being abused for cognitive enhancement and recreation by healthy adults and adolescents seeking to improve their work or academic performance. This study concomitantly recorded the behavioral and prefrontal cortex (PFC) neuronal activity in freely behaving animals exposed to acute and chronic MPD doses (0.6, 2.5, and 10.0 mg/kg MPD) in order to compare MPD effects on adult and adolescent rats. The PFC is one of the primary brain areas affected by MPD and the drug of choice for treating ADHD. Moreover, the PFC is one of the last brain areas to complete development, suggesting that the behavioral and neurophysiological response to MPD may differ in adolescents and adults. In both adult and adolescent animals, it was observed that the same repetitive (chronic) dose of either 0.6, 2.5, or 10.0 mg/kg MPD elicited behavioral sensitization in some animals and tolerance in others, experimental biomarkers indicating drug of abuse symptoms, and the majority of PFC units recorded in animals expressing behavioral sensitization or tolerance to chronic MPD exposure responded by increasing and decreasing their neuronal firing rate, respectively. Further, it was shown that high doses of 10.0 mg/kg MPD significantly modified adolescent behavioral activity but did not impact adults suggesting that adolescents may be more receptive to chronic MPD exposure. These findings raise concerns regarding the use and abuse of MPD in normal, healthy individuals and support the notion that the adolescent PFC is more susceptible than the adult PFC to neuromodulation from chronic MPD use.


Assuntos
Metilfenidato/efeitos adversos , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Fatores Etários , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Tolerância a Medicamentos/fisiologia , Masculino , Metilfenidato/farmacologia , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
20.
Encephale ; 45(1): 74-81, 2019 Feb.
Artigo em Francês | MEDLINE | ID: mdl-30122296

RESUMO

OBJECTIVE: Off-label prescription is a common practice in psychiatry, raising health and economic concerns. Collegial consultation could allow a framed prescription of treatments that are not authorized in specific indications. Attention Deficit Hyperactivity in adult populations (ADHD) is a striking example of a pathology where off-label prescription is frequent. First considered to be a childhood disorder, the awareness of this condition in adults is increasing, leading to the development of new clinical practices and treatments. However, the adult ADHD diagnosis and its management are still emerging in France despite a high prevalence. Treatment of adult ADHD relies on methylphenidate prescription, but the initiation of this drug is not authorized in adult populations. Methylphenidate is a central nervous system stimulant that is structurally close to amphetamine and acts as a norepinephrine and dopamine reuptake inhibitor. Due to these pharmacological properties, neuropsychiatric and cardiovascular side-effects could occur. Furthermore, its addictive potential has led France to classify it as a psychoactive drug, dispensed via secured prescription. The first prescription and the one-year follow-up are restricted to neurologists, paediatrics, psychiatrists and sleep disorders specialists at hospital. The objective of this article is to propose a multidisciplinary framework for the off-label prescription of methylphenidate in adult ADHD. METHODS: The Multidisciplinary Advice Consultation for Exceptional Addiction Treatments (Consultation d'Avis Multidisciplinaire de Traitements d'Exception en Addictologie CAMTEA) was first set up in Lille for the prescription of baclofen in alcohol dependence and was then extended to topiramate in binge eating disorder. This procedure has been adapted to the particularities of ADHD in adult populations, the differential diagnosis (bipolar disorder, depressive disorder, anxious disorder, personality disorder, substance use disorder) and the co-morbidities requiring a full psychiatric and neuropsychological assessment. Moreover, a particular attention has been paid to the monitoring of neuropsychiatric, cardiovascular and misuse risk because of the potential side-effects of methylphenidate. RESULTS: The proposed prescription framework is structured into several specialized consultations. A first psychiatric evaluation aims to diagnose adult ADHD, using the French version of the Diagnostisch Interview Voor ADHD 2.0 questionnaire (DIVA 2.0), and to assess the quality of life impact with the Weiss Functional Inventory Rating Scale (WIFRS). It also searches for the presence of differential diagnosis or co-morbidities. The second appointment consists of a pharmacological evaluation that aims to search for contraindications and potential drug interaction. A neuropsychological evaluation based on standardized tests (Weschler Adulte Intelligence Scale [WAIS IV], Conner's Continuous Performance Test 3 [CPT] and the Minnesota Multiphasic Personnality Inventory [MMPI]) is also required to evaluate neurocognitive disabilities and personality features. Once the parameters of the different assessments have been collected, the synthesis is presented during a multidisciplinary meeting in order to assess the risk-benefit ratio for each patient. Several specialties are involved in this multidisciplinary meeting: psychiatry, addictology, general medicine, addictovigilance, pharmacovigilance and neuropsychology. One strategy among three possibilities can be decided: (1) contraindication to treatment with methylphenidate, (2) attention deficit disorder that does not require medication management, and (3) indication of treatment with methylphenidate with the choice of the pharmacological form (immediate or prolonged release). A biological check-up and an electrocardiogram are carried out systematically before any treatment. If the decision is made to initiate treatment, it is started at the lowest dosage and followed by a titration phase. A weekly follow-up is carried out during the titration phase in order to assess treatment efficacy and safety. After treatment stabilization, the general practitioner can carry out the renewal, and the patient will be reassessed within the framework of the multidisciplinary consultation every 3 months. CONCLUSION: When an off-label prescription is being considered, it must comply with the basic rules of good clinical practice, and the benefit/risk ratio should be constantly reassessed. The proposed multidisciplinary framework, adapted to the characteristics of adult ADHD and the pharmacological properties of methylphenidate, appears to be an interesting strategy to meet the requirements of the good clinical practice. The complementary assessments carried out and the collegial framework allow enhancing the patient's follow-up and minimize the drug risk, particularly in the psychiatric, addictive and cardiovascular adverse events. Finally, this framework could also help the monitoring of other off-label treatments for ADHD, such as atomoxetine or guanfacine.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/uso terapêutico , Uso Off-Label , Adulto , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Prescrições de Medicamentos , Eletrocardiografia , Feminino , França , Humanos , Masculino , Conduta do Tratamento Medicamentoso , Metilfenidato/administração & dosagem , Metilfenidato/efeitos adversos , Testes Neuropsicológicos , Equipe de Assistência ao Paciente , Escalas de Graduação Psiquiátrica , Encaminhamento e Consulta , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA