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2.
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
3.
Aerosp Med Hum Perform ; 90(5): 480-483, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31023409

RESUMO

INTRODUCTION: Modafinil is a wakefulness-promoting stimulant that has been approved by the Republic of Singapore Air Force (RSAF) as a fatigue countermeasure medication since 2011. Each RSAF aircrew member must undergo a ground test to exclude operationally relevant adverse drug effects prior to consuming the medication for operational reasons. This study describes the RSAF's modafinil ground testing outcomes over a 7-yr period.METHODS: This is a retrospective case series of 243 RSAF aircrew members who underwent modafinil 100-mg test dosing over the 7-yr period from September 2011 to September 2018.RESULTS: The median age was 31 yr (range, 21-53 yr) and mean age was 31.7 yr ± 6.19 yr. Of the aircrew members, 234 (96.3%) were men and all were of Asian ethnicity. Of the subjects, 237 (97.5%) were medically cleared for the operational use of modafinil. Among the six (2.47%) who failed modafinil ground testing, headache (cumulative incidence, 1.65%), anxiety (cumulative incidence, 0.41%), diarrhea (cumulative incidence, 0.41%), and insomnia (cumulative incidence, 0.41%) were reported as the side effects experienced. None of the aircrew members experienced major adverse drug events.DISCUSSION: Our findings suggest a low occurrence of adverse drug effects among military aircrew members who undergo modafinil test dosing prior to using the drug operationally. To our knowledge, this is the single largest published case series of modafinil ground testing outcomes among Asian military aviators.Ooi T, Wong SH, See B. Modafinil as a stimulant for military aviators. Aerosp Med Hum Perform. 2019; 90(5):480-483.


Assuntos
Medicina Aeroespacial/métodos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Militares , Modafinila/efeitos adversos , Pilotos , Acidentes Aeronáuticos/prevenção & controle , Adulto , Ansiedade/induzido quimicamente , Ansiedade/epidemiologia , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Relação Dose-Resposta a Droga , Fadiga/prevenção & controle , Feminino , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modafinila/administração & dosagem , Estudos Retrospectivos , Singapura , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Vigília/efeitos dos fármacos , Adulto Jovem
4.
J Clin Neurosci ; 63: 27-31, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30837110

RESUMO

Narcolepsy is a life-long neurological disorder characterized by excessive daytime sleepiness (EDS) and cataplexy. At present, Sodium oxybate, modafinil, methylphenidate and other stimulants are recommended first-line therapies for narcolepsy but are difficult to obtain in China. One hundred forty-eight patients with narcolepsy were treated with antidepressants and administered the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT) before and after treatment from August 2012 to August 2017. The subjects were followed for 1-6 years after treatment. Improvement in sleepiness, cataplexy, cataplexy-like episodes, and antidepressant side effects were assessed. There were significant differences in the mean sleep latency (MSL) and sleep onset rapid eye movement periods (SOREMPs) in MWT and ESS scores, cataplexy and cataplexy-like episodes before and after treatment (p < 0.01). Venlafaxine demonstrated significantly greater improvements in MSL in the MWT (p < 0.01). Early awakenings and dry mouth were the most common adverse effects.


Assuntos
Antidepressivos/uso terapêutico , Modafinila/uso terapêutico , Narcolepsia/tratamento farmacológico , Cloridrato de Venlafaxina/uso terapêutico , Adulto , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila/administração & dosagem , Modafinila/efeitos adversos , Estudos Prospectivos , Cloridrato de Venlafaxina/administração & dosagem , Cloridrato de Venlafaxina/efeitos adversos
7.
Int J Clin Pract ; 73(2): e13295, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30444561

RESUMO

INTRODUCTION: Stroke is a major cause of death and disability worldwide. The use of modafinil, a wakefulness-promoting agent, is hypothesised to benefit stroke patients. METHODS: We performed a systematic review in accordance with the Cochrane Handbook for Systematic Reviews of Interventions recommendations to assess the efficacy and safety of modafinil in poststroke patients. We prospectively registered the review protocol in PROSPERO (CRD42017078465) and reported the systematic review following the PRISMA statement. RESULTS: Two published studies (77 participants) and one ongoing randomised controlled trial, with limited methodological quality, assessed the effects of modafinil (200 mg or 400 mg) for adults from 14 days poststroke up to 3 months poststroke and fulfilled our inclusion criteria. The clinical and methodological variability between studies precluded meta-analyses. Overall, these studies showed some benefit of modafinil for fatigue, but no benefit for disability, cognition, and for subscores of stroke-specific quality of life. Data for adverse events were scarce and mortality was not considered by studies. Due to very low quality related to the evidence, we are uncertain about the effects of modafinil for all outcomes assessed by our systematic review. CONCLUSION: Based on two small randomised controlled trial, which provided very low quality evidence, the effects (benefits and harms) of modafinil for stroke patients are unclear and do not support its routinely use in clinical practice for this clinical situation. Number of Protocol registration in PROSPERO database: CRD42017078465 (available from http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017078465).


Assuntos
Modafinila/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Promotores da Vigília/uso terapêutico , Cognição , Fadiga/tratamento farmacológico , Fadiga/etiologia , Humanos , Modafinila/efeitos adversos , Qualidade de Vida , Acidente Vascular Cerebral/complicações , Promotores da Vigília/efeitos adversos
8.
Psychiatr Danub ; 30(3): 356-366, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30267529

RESUMO

BACKGROUND: Modafinil is a psychostimulant drug prescribed mainly for treatment of narcolepsy but is used as a "smart drug" by wide populations to increase wakefulness, concentration and overall mental performance. The aim of this study was to assess potential developmental toxicity of modafinil. MATERIALS AND METHODS: Pregnant female mice were given either saline or modafinil (50 mg/kg orally) from gestational day (GD) 3 to GD 10 and then a challenge dose on the GD 17. The male offspring were treated analogously at the age of 10 weeks. Changes in the spontaneous locomotor/exploratory behaviour and anxiogenic profile in the open-field test were assessed in naive animals, after an acute and 8th modafinil dose and the challenge dose following a 7-day wash-out period. One month after completion of the behavioural study, the leukocyte phagocytosis was examined by zymosan induced and luminol-aided chemiluminiscence assay in vitro. RESULTS: The most important finding of this study was the immunosuppressing effect on leukocyte activity, hypolocomotion and increased behavioural response to modafinil-induced psychostimulation caused by prenatal exposure to the same drug. We did not detect significantly altered anxiety-related behaviour in any group disregarding the pre- and postnatal treatments. CONCLUSION: This is the first evidence of developmental toxicity of modafinil which needs to be taken into account as a potential risk factor when modafinil is administered to women who may become or are pregnant.


Assuntos
Modelos Animais de Doenças , Leucócitos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Modafinila/efeitos adversos , Fagocitose/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Animais , Feminino , Idade Gestacional , Medições Luminescentes , Luminol , Masculino , Camundongos , Camundongos Endogâmicos ICR , Gravidez
9.
Pharmacoepidemiol Drug Saf ; 27(11): 1182-1190, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30106194

RESUMO

PURPOSE: This study examined the potential risk of cardiovascular (CV) events associated with modafinil and the consistency of the risk estimates across databases. METHODS: A retrospective, inception cohort design of patients who initiated treatment with modafinil between 2006 and 2008 was used in three US health care claims databases. Modafinil users were matched with nonusers. Patients were further divided into two cohorts of obstructive sleep apnea (OSA) and non-OSA (NOSA) cohorts. Endpoints of interest, including myocardial infarction (MI), stroke, CV hospitalizations, and all-cause death, were assessed using incidence rates and Cox proportional hazard ratios (HRs), adjusted for potential confounding factors. RESULTS: The cohorts included a total of 175 524 patients in MarketScan CM; 77 266-in IMS LifeLink; and 8174-in MarketScan Medicaid. No increased risk for MI in the OSA and NOSA cohorts was observed across all three databases. The risks of CV hospitalization in the OSA and NOSA cohorts were not different between the modafinil users and nonusers, except for IMS LifeLink database where the HR was lower than one in the modafinil users compared with the nonusers (HR, 0.69; 95% confidence interval [CI], 0.54 to 0.87). For OSA patients with prior stroke, an adjusted HR of 1.96 (95% CI, 1.02 to 3.76) was observed for stroke among modafinil users compared with nonusers. Among the NOSA, the HRs for all-cause death in the OSA were inconsistent across databases. CONCLUSIONS: Except for few CV outcomes, applying one common protocol generated consistent risk estimates of CV events following modafinil use across cohorts and databases.


Assuntos
Modafinila/efeitos adversos , Infarto do Miocárdio/epidemiologia , Síndromes da Apneia do Sono/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Promotores da Vigília/efeitos adversos , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Causas de Morte , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila/administração & dosagem , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/terapia , Farmacoepidemiologia/métodos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/terapia , Estados Unidos/epidemiologia , Promotores da Vigília/administração & dosagem , Adulto Jovem
10.
J Neurol Sci ; 393: 1-3, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30077942

RESUMO

Concurrent use of modafinil or armodafinil with monoamine oxidase inhibitors (MAOIs) is contraindicated due to a theoretical risk of drug synergism and acute hypertensive episodes. However, few data are available to substantiate that risk, and several case studies have suggested that the combination is safe. To our knowledge, we present the first case of a patient treated concurrently with armodafinil and tranylcypromine. The patient developed an acute hypertensive crisis with severe headache, nausea, blurry vision, and neck stiffness. Her symptoms corresponded with the predicted pharmacokinetic and pharmacodynamic response. She was also taking brexpiprazole, which could have contributed to her underlying symptoms. However, limited data suggest that the single combination of brexpiprazole with armodafinil or MAOIs would be safe. Upon review of the literature, two out of seven patients, including our own, treated concurrently with modafinil or armodafinil and an MAOI developed an adverse reaction. Physicians should exercise caution if using these classes of drugs together.


Assuntos
Cefaleia/etiologia , Hipertensão/etiologia , Modafinila/efeitos adversos , Inibidores da Monoaminoxidase/efeitos adversos , Tranilcipromina/efeitos adversos , Promotores da Vigília/efeitos adversos , Adulto , Sinergismo Farmacológico , Quimioterapia Combinada/efeitos adversos , Feminino , Cefaleia/terapia , Humanos , Hipertensão/terapia , Modafinila/farmacocinética , Modafinila/uso terapêutico , Inibidores da Monoaminoxidase/farmacocinética , Inibidores da Monoaminoxidase/uso terapêutico , Tranilcipromina/farmacocinética , Tranilcipromina/uso terapêutico , Promotores da Vigília/farmacocinética , Promotores da Vigília/uso terapêutico
12.
J Clin Sleep Med ; 14(5): 885-887, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29734973

RESUMO

ABSTRACT: We present the case of a 21-year-old woman in whom Stevens-Johnson syndrome (SJS) developed after initiation of armodafinil. Although this rare and life-threatening reaction is listed on armodafinil's label, no cases have been reported in the literature. This case, in addition to an update of the drug's label after post-marketing research, both support the link between armodafinil and SJS. Providers should maintain a high clinical suspicion for SJS when starting therapy to minimize associated morbidity and mortality by discontinuing armodafinil at the onset of first symptoms.


Assuntos
Modafinila/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Promotores da Vigília/efeitos adversos , Feminino , Humanos , Modafinila/uso terapêutico , Pele/patologia , Síndrome de Stevens-Johnson/patologia , Promotores da Vigília/uso terapêutico , Adulto Jovem
13.
Pediatrics ; 141(6)2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29784754

RESUMO

: media-1vid110.1542/5754332180001PEDS-VA_2017-3872Video Abstract OBJECTIVES: To describe the characteristics and trends of exposures to attention-deficit/hyperactivity disorder (ADHD) medications among individuals 0 to 19 years old reported to US poison control centers. METHODS: National Poison Data System data from 2000 through 2014 were retrospectively analyzed to examine pediatric ADHD medication exposures. RESULTS: From 2000 through 2014, there were 156 365 exposures reported to US poison control centers related to ADHD medications. The overall rate of reported exposures increased 71.2% from 2000 to 2011, followed by a 6.2% decrease from 2011 to 2014. Three-fourths (76.0%) of exposures involved children ≤12 years old. Methylphenidate and amphetamine medications accounted for 46.2% and 44.5% of exposures, respectively. The most common reason for exposure was therapeutic error (41.6%). Intentional medication exposures (including suspected suicide and medication abuse and/or misuse) were reported most often among adolescents (13-19 years old), accounting for 50.2% of exposures in this age group. Overall, the majority of exposed individuals (60.4%) did not receive health care facility treatment; however, 6.2% were admitted to a hospital for medical treatment, and there were 3 deaths. The increasing number and rate of reported ADHD medication exposures during the study period is consistent with increasing trends in ADHD diagnosis and medication prescribing. Exposures associated with suspected suicide or medication abuse and/or misuse among adolescents are of particular concern. CONCLUSIONS: Unintentional and intentional pediatric exposures to ADHD medications are an increasing problem in the United States, affecting children of all ages.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Centros de Controle de Intoxicações , Adolescente , Distribuição por Idade , Anfetamina/administração & dosagem , Anfetamina/efeitos adversos , Cloridrato de Atomoxetina/administração & dosagem , Cloridrato de Atomoxetina/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Criança , Pré-Escolar , Uso Indevido de Medicamentos/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Erros de Medicação/estatística & dados numéricos , Metilfenidato/administração & dosagem , Metilfenidato/efeitos adversos , Modafinila/administração & dosagem , Modafinila/efeitos adversos , Admissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Tentativa de Suicídio/estatística & dados numéricos , Estados Unidos/epidemiologia , Adulto Jovem
14.
J Sleep Res ; 27(4): e12627, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29047171

RESUMO

Effectiveness and side-effect profile data on pharmacotherapy for daytime sleepiness in central hypersomnias are based largely upon randomized controlled trials. Evidence regarding the use of combination therapy is scant. The aim of this study was to examine the effectiveness and occurrence of drug-related side effects of these drugs in routine clinical practice. Adult patients diagnosed with a central hypersomnia during a 54-month period at a tertiary sleep disorders centre were identified retrospectively. Side effects were recorded at every follow-up visit. A total of 126 patients, with 3275 patient-months of drug exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used as a first-line treatment (93%) and in combination therapy (70%). Thirty-nine per cent of the patients demonstrated a complete, 25% partial and 36% a poor response to treatment. Combination treatment improved daytime sleepiness in 55% of the patients with residual symptoms despite monotherapy. Sixty per cent of patients reported side effects, and 30% reported treatment-limiting side effects. Drugs had similar side-effect incidence (P = 0.363) and their side-effect profile met those reported in the literature. Twenty-seven per cent of the patients received combination treatment and had fewer side effects compared to monotherapy (29.4% versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory symptom control in most patients with central hypersomnia, but significant side effects are common. Combination therapy appears to be a useful and safe option in patients with refractory symptoms.


Assuntos
Estimulantes do Sistema Nervoso Central/administração & dosagem , /tratamento farmacológico , Modafinila/administração & dosagem , Narcolepsia/diagnóstico , Narcolepsia/tratamento farmacológico , Adulto , Estimulantes do Sistema Nervoso Central/efeitos adversos , Quimioterapia Combinada , Feminino , Seguimentos , Cefaleia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila/efeitos adversos , Transtornos do Humor/induzido quimicamente , Narcolepsia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
16.
Int J Neuropsychopharmacol ; 21(4): 345-354, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29206921

RESUMO

Background: Stimulants such as methylphenidate and modafinil are frequently used as cognitive enhancers in healthy people, whereas 3,4-methylenedioxymethamphetamine (ecstasy) is proposed to enhance mood and empathy in healthy subjects. However, comparative data on the effects of methylphenidate and modafinil on negative emotions in healthy subjects have been partially missing. The aim of this study was to compare the acute effects of methylphenidate and modafinil on the neural correlates of fearful face processing using 3,4-methylenedioxymethamphetamine as a positive control. Methods: Using a double-blind, within-subject, placebo-controlled, cross-over design, 60 mg methylphenidate, 600 mg modafinil, and 125 mg 3,4-methylenedioxymethamphetamine were administrated to 22 healthy subjects while performing an event-related fMRI task to assess brain activation in response to fearful faces. Negative mood states were assessed with the State-Trait Anxiety Inventory and subjective ratings. Results: Relative to placebo, modafinil, but not methylphenidate or 3,4-methylenedioxymethamphetamine, increased brain activation within a limbic-cortical-striatal-pallidal-thalamic circuit during fearful face processing. Modafinil but not methylphenidate also increased amygdala responses to fearful faces compared with 3,4-methylenedioxymethamphetamine. Furthermore, activation in the middle and inferior frontal gyrus in response to fearful faces correlated positively with subjective feelings of fearfulness and depressiveness after modafinil administration. Conclusions: Despite the cognitive enhancement effects of 600 mg modafinil in healthy people, potential adverse effects on emotion processing should be considered.


Assuntos
Encéfalo , Estimulantes do Sistema Nervoso Central/farmacologia , Expressão Facial , Reconhecimento Facial/efeitos dos fármacos , Medo/efeitos dos fármacos , Neuroimagem Funcional/métodos , Metilfenidato/farmacologia , Modafinila/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Neurotransmissores/farmacologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Metilfenidato/administração & dosagem , Metilfenidato/efeitos adversos , Modafinila/administração & dosagem , Modafinila/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Neurotransmissores/administração & dosagem , Neurotransmissores/efeitos adversos , Adulto Jovem
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