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Trastorno Depresivo Mayor , Inhibidores Selectivos de la Recaptación de Serotonina , Inhibidores de Captación de Serotonina y Norepinefrina , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Inhibidores de Captación de Serotonina y Norepinefrina/farmacología , Sustitución de Medicamentos , Antidepresivos/efectos adversos , Inhibidores de Captación Adrenérgica/efectos adversos , Inhibidores de Captación Adrenérgica/uso terapéutico , Inhibidores de Captación Adrenérgica/administración & dosificaciónRESUMEN
Aim: To compare long-term safety and efficacy outcomes of centanafadine versus lisdexamfetamine dimesylate (lisdexamfetamine), methylphenidate hydrochloride (methylphenidate) and atomoxetine hydrochloride (atomoxetine), respectively, in adults with attention-deficit/hyperactivity disorder (ADHD) using matching-adjusted indirect comparisons (MAICs). Patients & methods: Patient-level data from a centanafadine trial (NCT03605849) and published aggregate data from a lisdexamfetamine trial (NCT00337285), a methylphenidate trial (NCT00326300) and an atomoxetine trial (NCT00190736) were used. Patient characteristics were matched in each comparison using propensity score weighting. Study outcomes were assessed up to 52 weeks and included safety (rates of adverse events [AEs]) and efficacy (mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale [AISRS] or ADHD Rating Scale [ADHD-RS] score). Results: In all comparisons of matched populations, risks of AEs were statistically significantly lower with centanafadine or non-different between centanafadine and comparator; the largest differences in AE rates included upper respiratory tract infection (risk difference in percentage points: 18.75), insomnia (12.47) and dry mouth (12.33) versus lisdexamfetamine; decreased appetite (20.25), headache (18.53) and insomnia (12.65) versus methylphenidate; and nausea (26.18), dry mouth (25.07) and fatigue (13.95) versus atomoxetine (all p < 0.05). Centanafadine had a smaller reduction in the AISRS/ADHD-RS score versus lisdexamfetamine (6.15-point difference; p < 0.05) and no statistically significant difference in the change in AISRS score versus methylphenidate (1.75-point difference; p = 0.13) and versus atomoxetine (1.60-point difference; p = 0.21). Conclusion: At up to 52 weeks, centanafadine showed significantly lower incidence of several AEs than lisdexamfetamine, methylphenidate and atomoxetine; efficacy was lower than lisdexamfetamine and non-different from methylphenidate and atomoxetine.
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Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Dimesilato de Lisdexanfetamina , Metilfenidato , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Clorhidrato de Atomoxetina/uso terapéutico , Clorhidrato de Atomoxetina/efectos adversos , Femenino , Dimesilato de Lisdexanfetamina/uso terapéutico , Dimesilato de Lisdexanfetamina/efectos adversos , Masculino , Adulto , Metilfenidato/uso terapéutico , Metilfenidato/efectos adversos , Estimulantes del Sistema Nervioso Central/uso terapéutico , Estimulantes del Sistema Nervioso Central/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , Inhibidores de Captación Adrenérgica/uso terapéutico , Inhibidores de Captación Adrenérgica/efectos adversosAsunto(s)
Inhibidores de Captación Adrenérgica , Clorhidrato de Atomoxetina , Bupropión , Humanos , Clorhidrato de Atomoxetina/efectos adversos , Bupropión/efectos adversos , Masculino , Inhibidores de Captación Adrenérgica/efectos adversos , Adulto , Eyaculación/efectos de los fármacos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Dolor/tratamiento farmacológico , Dolor/inducido químicamenteRESUMEN
INTRODUCTION: Tardive dyskinesia (TD) and Huntington's disease (HD)-associated chorea are persistent and disabling hyperkinetic disorders that can be treated with vesicular monoamine transporter type 2 (VMAT2) inhibitors, including the recently approved once-daily (QD) formulation of deutetrabenazine (DTBZ ER). While its efficacy and safety profile have not been directly investigated, currently available data confirms bioequivalence and similar bioavailability to the twice-daily formulation (DTBZ BID). AREAS COVERED: The authors briefly review the pivotal trials establishing efficacy of DTBZ for TD and HD-associated chorea, the pharmacokinetic data for bioequivalence between QD and BID dosing of DTBZ, as well as dose proportionality evidence, titration recommendations, and safety profile for DTBZ ER. EXPERT OPINION: Long-term data show that DTBZ is efficacious and well tolerated for the treatment of TD and HD-associated chorea. DTBZ ER likely demonstrates therapeutic equivalence with no new safety signals. Due to the lack of comparative clinical trial data, no evidence-based recommendation about choice of VMAT2 inhibitor or switching between VMAT2 inhibitors can be made about best practice. Ultimately, QD dosing may offer the chance of improved medication adherence, an important consideration in patients with complex treatment regimens and/or patients with cognitive decline.
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Preparaciones de Acción Retardada , Enfermedad de Huntington , Discinesia Tardía , Tetrabenazina , Humanos , Enfermedad de Huntington/tratamiento farmacológico , Enfermedad de Huntington/complicaciones , Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/análogos & derivados , Tetrabenazina/uso terapéutico , Tetrabenazina/administración & dosificación , Tetrabenazina/farmacocinética , Tetrabenazina/efectos adversos , Corea/tratamiento farmacológico , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Inhibidores de Captación Adrenérgica/administración & dosificación , Inhibidores de Captación Adrenérgica/uso terapéutico , Inhibidores de Captación Adrenérgica/farmacocinética , Inhibidores de Captación Adrenérgica/efectos adversos , ComprimidosRESUMEN
PURPOSE: Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine. METHODS: Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale. RESULTS: The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles. CONCLUSIONS: The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Discinesia Tardía , Tetrabenazina , United States Food and Drug Administration , Valina , Humanos , Tetrabenazina/análogos & derivados , Tetrabenazina/efectos adversos , Estados Unidos , Masculino , Femenino , Persona de Mediana Edad , Discinesia Tardía/inducido químicamente , Adulto , Anciano , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Valina/análogos & derivados , Valina/efectos adversos , Farmacovigilancia , Vigilancia de Productos Comercializados/estadística & datos numéricos , Adulto Joven , Inhibidores de Captación Adrenérgica/efectos adversos , AdolescenteRESUMEN
INTRODUCTION: Adrenergic neurotransmitter reuptake inhibitors are gaining attention in treatment for attention-deficit hyperactivity disorder (ADHD). Due to their effects on norepinephrine, dopamine, and serotonin neurotransmission, they benefit both ADHD and comorbid disorders and have some other advantages including longer duration of action and fewer adverse effects compared to stimulants. There is continued interest in these agents with novel mechanisms of action in treatment of ADHD. AREAS COVERED: The authors conducted a PubMed literature search using the following key words: 'ADHD' AND 'adrenergic reuptake inhibitors' OR 'nonstimulants' OR 'atomoxetine' OR 'Viloxazine' OR 'Dasotraline' OR 'Centanafadine' OR 'PDC-1421' OR 'Reboxetine' OR 'Edivoxetine' OR 'Bupropion' OR 'Venlafaxine' OR 'Duloxetine.' They reviewed FDA fact sheets of available medications for safety/tolerability studies and reviewed published clinical studies of these medications for treatment of ADHD. EXPERT OPINION: Adrenergic neurotransmitter reuptake inhibitors fit the diverse needs of children and adolescents with ADHD with 1) poor tolerability to stimulants (e.g. due to growth suppression, insomnia, rebound irritability, co-morbid depression, anxiety and tic disorders, substance abuse or diversion concerns), 2) cardiac risks, and/or 3) need for extended duration of action. Their differences in receptor affinities and modulating effects support the unique benefits of individual agents.
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Trastorno por Déficit de Atención con Hiperactividad , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Niño , Adolescente , Inhibidores de Captación Adrenérgica/uso terapéutico , Inhibidores de Captación Adrenérgica/farmacología , Inhibidores de Captación Adrenérgica/efectos adversos , Estimulantes del Sistema Nervioso Central/uso terapéutico , Estimulantes del Sistema Nervioso Central/efectos adversos , Estimulantes del Sistema Nervioso Central/farmacología , Animales , Inhibidores de la Captación de Neurotransmisores/uso terapéutico , Inhibidores de la Captación de Neurotransmisores/farmacología , Inhibidores de la Captación de Neurotransmisores/efectos adversosAsunto(s)
Inhibidores de Captación Adrenérgica , Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad , Humanos , Clorhidrato de Atomoxetina/efectos adversos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Inhibidores de Captación Adrenérgica/efectos adversos , Adolescente , Masculino , Femenino , SíndromeRESUMEN
BACKGROUND: Head-to-head trials comparing centanafadine, an investigational therapy for adults with attention-deficit/hyperactivity disorder (ADHD), with other treatment options are lacking. OBJECTIVE: To compare safety and efficacy outcomes of centanafadine sustained-release vs lisdexamfetamine dimesylate (lisdexamfetamine), atomoxetine hydrochloride (atomoxetine), and viloxazine extended-release (viloxazine ER), respectively, using matching-adjusted indirect comparison (MAIC). METHODS: This MAIC included patient-level data pooled from 2 centanafadine trials (NCT03605680 and NCT03605836) and published aggregate data from comparable trials of 3 comparators-lisdexamfetamine (NCT00334880), atomoxetine (NCT00190736), and viloxazine ER (NCT04016779)-in adult patients with ADHD. Propensity score weighting was used to match characteristics of individual patients from the centanafadine trials to aggregate baseline characteristics from the respective comparator trials. Safety outcomes were rates of adverse events for which information was available in the centanafadine and respective comparator trials. Efficacy outcome was mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) score (ADHD Rating Scale [ADHD-RS] was used as proxy in the comparison with lisdexamfetamine). Anchored indirect comparisons were conducted across matched populations of the centanafadine and respective comparator trials. RESULTS: After matching, baseline characteristics in the centanafadine trials were the same as those in the respective comparator trials. Compared with lisdexamfetamine, centanafadine was associated with a significantly lower risk of lack of appetite (risk difference [RD] in percentage points: 23.42), dry mouth (19.27), insomnia (15.35), anxiety (5.21), nausea (4.90), feeling jittery (3.70), and diarrhea (3.47) (all P < 0.05) but a smaller reduction in the AISRS/ADHD-RS score (6.58-point difference; P < 0.05). Compared with atomoxetine, centanafadine was associated with a significantly lower risk of nausea (RD in percentage points: 18.64), dry mouth (17.44), fatigue (9.21), erectile dysfunction (6.76), lack of appetite (6.71), and urinary hesitation (5.84) (all P < 0.05) and no statistically significant difference in the change in AISRS score. Compared with viloxazine ER, centanafadine was associated with a significantly lower risk of fatigue (RD in percentage points: 11.07), insomnia (10.67), nausea (7.57), and constipation (4.63) (all P < 0.05) and no statistically significant difference in the change in AISRS score. CONCLUSIONS: In an anchored MAIC, centanafadine showed a significantly better short-term safety profile than lisdexamfetamine, atomoxetine, and viloxazine ER; efficacy was lower than with lisdexamfetamine and comparable (ie, nondifferent) with atomoxetine and viloxazine ER. This MAIC provides important insights on the relative safety and efficacy of common treatment options to help inform treatment decisions in adults with ADHD. Safety assessment was limited to rates of adverse events reported in both trials of a given comparison. STUDY REGISTRATION NUMBERS: NCT03605680, NCT03605836, NCT00334880, NCT00190736, and NCT04016779.
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Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad , Preparaciones de Acción Retardada , Dimesilato de Lisdexanfetamina , Viloxazina , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Inhibidores de Captación Adrenérgica/efectos adversos , Inhibidores de Captación Adrenérgica/uso terapéutico , Clorhidrato de Atomoxetina/efectos adversos , Clorhidrato de Atomoxetina/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/efectos adversos , Estimulantes del Sistema Nervioso Central/uso terapéutico , Dimesilato de Lisdexanfetamina/efectos adversos , Dimesilato de Lisdexanfetamina/uso terapéutico , Resultado del Tratamiento , Viloxazina/efectos adversos , Viloxazina/uso terapéutico , Ensayos Clínicos Fase III como AsuntoAsunto(s)
Trastorno del Espectro Autista , Distonía , Tetrabenazina , Humanos , Tetrabenazina/farmacología , Tetrabenazina/administración & dosificación , Femenino , Trastorno del Espectro Autista/tratamiento farmacológico , Distonía/inducido químicamente , Tics/inducido químicamente , Tics/tratamiento farmacológico , Inhibidores de Captación Adrenérgica/efectos adversos , Inhibidores de Captación Adrenérgica/administración & dosificación , Adulto , Adulto JovenRESUMEN
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) therapies including atomoxetine, methylphenidate, and amphetamines are some of the most prescribed medications in North America. Due to their sympathomimetic action, these drugs are contraindicated in patients with a history of angle closure glaucoma (ACG). This study aims to determine the risk of ACG and open angle glaucoma (OAG) among users of these treatments. METHODS: This is a retrospective cohort study with a case control analysis using the PharMetrics Plus Database (IQVIA, USA). We created a cohort of new users of atomoxetine, methylphenidate, and amphetamines and they were followed to the first diagnosis of (1) ACG or OAG; or (2) end of follow up. For each case, four age-matched controls were selected. A conditional logistic regression model was used to adjust for confounders and to calculate adjusted incidence-rate-ratios (aIRRs). RESULTS: A total of 240,257 new users of the ADHD medications were identified. The mean age was 45.0 ± 19.4 years and 55% of the cohort was female. Regular users of atomoxetine and amphetamines had a higher aIRR for developing ACG compared with non-users (aIRR = 2.55 95% CI [1.20-5.43] and 2.27 95% CI [1.42-3.63], respectively); while users of methylphenidate had a higher aIRR for developing OAG (aIRR = 1.23 95% CI [1.05-1.59]). CONCLUSIONS: Use of amphetamines and atomoxetine had a higher risk for ACG, while use of methylphenidate was associated with a higher risk for OAG. Given the prevalence of ADHD medication use (medically and recreationally), our current data on their associated risk of glaucoma have profound public health implications.
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Anfetaminas , Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Glaucoma de Ángulo Cerrado , Glaucoma de Ángulo Abierto , Metilfenidato , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Femenino , Masculino , Estudios Retrospectivos , Metilfenidato/efectos adversos , Metilfenidato/uso terapéutico , Clorhidrato de Atomoxetina/uso terapéutico , Clorhidrato de Atomoxetina/efectos adversos , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , Estimulantes del Sistema Nervioso Central/efectos adversos , Estimulantes del Sistema Nervioso Central/uso terapéutico , Anfetaminas/efectos adversos , Glaucoma de Ángulo Cerrado/inducido químicamente , Glaucoma de Ángulo Cerrado/epidemiología , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glaucoma de Ángulo Abierto/epidemiología , Glaucoma de Ángulo Abierto/inducido químicamente , Factores de Riesgo , Inhibidores de Captación Adrenérgica/efectos adversos , Inhibidores de Captación Adrenérgica/uso terapéutico , Incidencia , Anciano , Presión Intraocular/efectos de los fármacos , Presión Intraocular/fisiología , Adulto JovenRESUMEN
Integrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and <18, who visited the psychological and behavioral clinic of Children's Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023. The demographic information and laboratory examination data, including CYP2D6 genotype tests and routine TDM of atomoxetine were obtained from the hospital information system. We used univariate analysis, Mann-Whitney U nonparametric test, Kruskal-Wallis test, and the receiver operating characteristic (ROC) curve to investigate outcomes of interest. 515 plasma atomoxetine concentrations of 385 children (325 boys and 60 girls) with ADHD between 6 and 16 years of age were included for statistical analysis in this study. Based on genotyping results, >60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while <40% fell into the intermediate metabolizer (IM). CYP2D6 IMs exhibited higher dose-corrected plasma atomoxetine concentrations by 1.4-2.2 folds than those CYP2D6 EMs. Moreover, CYP2D6 IMs exhibited a higher response rate compare to EMs (93.55% vs 85.71%, P = 0.0132), with higher peak plasma atomoxetine concentrations by 1.67 times than those of EMs. Further ROC analysis revealed that individuals under once daily in the morning (q.m.) dosing regimen exhibited a more effective response to atomoxetine when their levels were ≥ 268 ng/mL (AUC = 0.710, P < 0.001). In addition, CYP2D6 IMs receiving q.m. dosing of atomoxetine were more likely to experience adverse reactions in the central nervous system and gastrointestinal system when plasma atomoxetine concentrations reach 465 and 509 ng/mL, respectively. The findings in this study provided promising treatment strategy for Chinese children with ADHD based on their CYP2D6 genotypes and plasma atomoxetine concentration monitoring. A peak plasma atomoxetine concentration higher than 268 ng/mL might be requisite for q.m. dosing. Assuredly, to validate and reinforce these initial findings, it is necessary to collect further data in controlled studies with a larger sample size.
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Trastorno por Déficit de Atención con Hiperactividad , Adolescente , Niño , Femenino , Humanos , Masculino , Inhibidores de Captación Adrenérgica/efectos adversos , Clorhidrato de Atomoxetina/efectos adversos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/genética , Citocromo P-450 CYP2D6/genética , Monitoreo de Drogas , Genotipo , Propilaminas/efectos adversos , Estudios Retrospectivos , Lactante , PreescolarRESUMEN
Huntington disease (HD) is a hereditary neurodegenerative disorder with a hallmark feature of chorea. While no disease-modifying therapies currently exist for HD, symptomatic treatment of HD-associated chorea includes US Food and Drug Administration-approved vesicular monoamine transporter type 2 inhibitors-tetrabenazine and deutetrabenazine. Deutetrabenazine was more recently approved (2017), and while structurally similar to tetrabenazine, deutetrabenazine has a unique pharmacokinetic profile that allows for a longer half-life, reduced plasma fluctuations, and less frequent dosing. In pivotal trials, deutetrabenazine seemed to have an improved safety and tolerability profile over tetrabenazine but real-world data to confirm this are lacking. Here, we evaluate our real-world clinical experience with deutetrabenazine for HD-associated chorea. We performed a retrospective chart review of all patients with HD who initiated treatment with deutetrabenazine from January 2017 to May 2019 at the University of Alabama at Birmingham. Total maximal chorea scores, patient-reported subjective efficacy, dosing information, and subjective reports of adverse events (AEs) were abstracted for each patient. Our review included 58 patients with a mean length of treatment of 476.4 days. In the reviewed time period, the mean treatment difference in total maximal chorea scores was 4.4. The combined total rate of occurrence of any AEs was relatively low, at 32.8%, and the most commonly reported AEs were sedation (15.5%), insomnia (6.9%), and diarrhea (3.4%). Our real-world data support current literature indicating that deutetrabenazine is an effective and well-tolerated treatment for HD-associated chorea. Further studies repeating this on a larger scale, across a greater geography and practice pattern, are needed.
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Corea , Enfermedad de Huntington , Humanos , Enfermedad de Huntington/tratamiento farmacológico , Corea/tratamiento farmacológico , Corea/inducido químicamente , Tetrabenazina/efectos adversos , Estudios Retrospectivos , Inhibidores de Captación Adrenérgica/efectos adversosRESUMEN
OBJECTIVE: To investigate the association between atomoxetine or methylphenidate use and arrhythmia, heart failure (HF), stroke, and myocardial infarction (MI) in attention-deficit/hyperactivity disorder (ADHD) patients mainly focused on the people of working age. METHODS: In a self-controlled case series study using a Japanese claims database, we identified events of arrhythmia, HF, stroke, and MI among 15,472 atomoxetine new users and 12,059 methylphenidate new users. Adjusted incidence rate ratios (aIRRs) of outcome events were estimated using multivariable conditional Poisson regression. RESULTS: An increased risk of arrhythmia was observed during the first 7 days after the initial atomoxetine exposure (aIRR 6.22, 95% CI [1.90, 20.35]) and in the subsequent exposure (3.23, [1.58, 6.64]). No association was found between methylphenidate exposure and arrhythmia, nor between atomoxetine or methylphenidate exposure and HF. The limited number of stroke and MI cases prevented thorough analysis. CONCLUSIONS: Clinicians should consider monitoring for arrhythmia after patients initiating or re-initiating atomoxetine.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Accidente Cerebrovascular , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/inducido químicamente , Metilfenidato/efectos adversos , Clorhidrato de Atomoxetina/efectos adversos , Japón/epidemiología , Estimulantes del Sistema Nervioso Central/efectos adversos , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/tratamiento farmacológico , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular/tratamiento farmacológico , Inhibidores de Captación Adrenérgica/efectos adversosRESUMEN
This study documented the prescribing patterns of methylphenidate and atomoxetine among patients aged 3 to 18 in Taiwan diagnosed with attention deficit hyperactivity disorder (ADHD) between 2004 and 2017. Initial treatment for ADHD, the time between the first diagnosis and the first prescription, and medication-switching patterns were investigated. The final cohort consisted of 256,882 patients, and 147,210 (57.3%) of them received medication treatment. Most of the patients (98.2%) received methylphenidate. Atomoxetine use increased from 0.1% in 2007 to 5.5% in 2017. The median time between the ADHD diagnosis and the first prescription was 21 days (IQR: 0-212 days). In patients who initiated methylphenidate, 12,406 (8.4%) patients switched to atomoxetine; 850 (31.3%) of the children began with atomoxetine and switched to methylphenidate. In conclusion, methylphenidate was the predominant treatment for ADHD in 2004-2017. However, the prevalence of pharmacotherapy for ADHD was relatively low. Further investigation on the reasons behind this pattern is recommended.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Humanos , Niño , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Clorhidrato de Atomoxetina/uso terapéutico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Taiwán , Metilfenidato/uso terapéutico , Inhibidores de Captación Adrenérgica/uso terapéutico , Inhibidores de Captación Adrenérgica/efectos adversosRESUMEN
BACKGROUND: Methylphenidate and atomoxetine are used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Our previous studies established the validity of the 6-hydroxydopamine (6-OHDA) mouse model of ADHD and demonstrated hypersensitivity to pain, in line with clinical reports in ADHD patients. Acute methylphenidate treatment reduces hyperactivity and increases attention, but does not affect pain behaviors in this mouse model. Whereas atomoxetine has been shown to be effective against some symptoms of ADHD, nothing is known about its possible action on comorbid pain hypersensitivity. The objectives of the present research are (1) to investigate the effects of acute and chronic treatment with atomoxetine on ADHD-like symptoms and nociceptive thresholds, and (2) to explore the catecholaminergic systems underlying these effects. METHODS: Sham and 6-OHDA cohorts of male mice were tested for hyperactivity (open field), attention and impulsivity (5-choice serial reaction time task test), and thermal (hot plate test) and mechanical (von Frey test) thresholds after acute or repeated treatment with vehicle or atomoxetine (1, 3 or 10 mg/kg). RESULTS: Acute administration of atomoxetine (10 mg/kg) reduced the hyperactivity and impulsivity displayed by 6-OHDA mice, without affecting attention or nociception. However, atomoxetine administered at 3 mg/kg/day for 7 days alleviated the ADHD-like core symptoms and attenuated the hyperalgesic responses. Furthermore, hyperlocomotion and anti-hyperalgesic activity were antagonized with phentolamine, propranolol, and sulpiride pre-treatments. CONCLUSION: These findings demonstrated that when administered chronically, atomoxetine has a significant effect on ADHD-associated pain hypersensitization, likely mediated by both α- and ß-adrenergic and D2/D3 dopaminergic receptors, and suggest new indications for atomoxetine that will need to be confirmed by well-designed clinical trials.
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Trastorno por Déficit de Atención con Hiperactividad , Metilfenidato , Masculino , Ratones , Animales , Clorhidrato de Atomoxetina/farmacología , Clorhidrato de Atomoxetina/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/inducido químicamente , Oxidopamina , Propilaminas/farmacología , Dolor/tratamiento farmacológico , Comorbilidad , Inhibidores de Captación Adrenérgica/efectos adversosRESUMEN
OBJECTIVES: Risperidone is an effective drug used for the treatment of irritability in children with autism spectrum disorder (ASD). Atomoxetine (ATX) is a well-tolerated drug used in first-line therapy in children with attention-deficit/hyperactivity disorder (ADHD). However, uncommon adverse effects of risperidone and ATX are a concern among mental health professionals. To our knowledge, this is the first case report of priapism after addition of ATX upon existing treatment with risperidone. METHODS: Written informed consent for publication was obtained from the patient and his parents, and their identities were concealed for ethical reasons. RESULTS: Here, we report a case of priapism as an adverse effect of ATX and risperidone treatment in a 7-year-old boy with ASD and comorbid ADHD. In this case, priapism was not observed with risperidone until ATX was added. CONCLUSIONS: Priapism is a condition viewed as a medical emergency. Although risperidone-induced priapism is a rare phenomenon, it is advised for clinicians to consider the drug interactions in treatment of ASD and ADHD in terms of early diagnosis and intervention.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Priapismo , Niño , Masculino , Humanos , Clorhidrato de Atomoxetina/efectos adversos , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/tratamiento farmacológico , Risperidona/efectos adversos , Inhibidores de Captación Adrenérgica/efectos adversos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Priapismo/inducido químicamenteRESUMEN
BACKGROUND: PTSD and ADHD often occur comorbidly. Research indicates that the cognitive deficits in PTSD may be related to the same disturbance of fronto-temporal systems as observed in ADHD, and ADHD has been shown to impact PTSD treatment outcomes. The presented study evaluated the safety and efficacy of atomoxetine in Veterans with comorbid ADHD/PTSD. METHODS: A double blind, randomized, placebo controlled, cross-over pilot and feasibility study was conducted. Atomoxetine was examined as an adjunctive treatment over this 10 weeks, two phase, crossover study which compared treatment with atomoxetine 80 mg daily to placebo daily. The primary outcome was improvement in ADHD symptoms as measured by the Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S), the Barkley Adult ADHD Rating Scale-IV (BAARS-IV), and the Adult ADHD Quality of Life-29 (AAQoL-29). Secondary outcomes included the Clinician Administered PTSD Scale (CAPS), Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and the response inhibition task Go/NoGo (GNG). RESULTS: Atomoxetine treated patients had greater reductions in ADHD symptoms as defined by total scores on the CAARS-S:S (F(1, 29) = 6.37, p = .017); both the BAARS-IV (F(1, 26) = 3.16, p = .087); and GNG overall errors test (F(1, 29) = 3.88, p = .06), reached a trend level of significance. No significant differences were noted in quality of life assessments, GNG latency periods, or CAPS scores. Atomoxetine was well-tolerated with no serious adverse events observed. CONCLUSIONS: In Veterans with ADHD comorbid with PTSD, atomoxetine demonstrated modest efficacy for ADHD symptoms; quality of life measures and PTSD symptoms were not affected.
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Trastorno por Déficit de Atención con Hiperactividad , Trastornos por Estrés Postraumático , Inhibidores de Captación Adrenérgica/efectos adversos , Adulto , Clorhidrato de Atomoxetina/uso terapéutico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Estudios Cruzados , Método Doble Ciego , Estudios de Factibilidad , Humanos , Propilaminas/efectos adversos , Calidad de Vida , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/epidemiología , Resultado del TratamientoRESUMEN
OBJECTIVES: To assess long-term safety and efficacy of deutetrabenazine in younger (<55 years) and older (≥55 years) adult participants with tardive dyskinesia (TD). DESIGN: Three-year, single-arm, open-label extension (OLE) study enrolling participants who completed the 12-week, pivotal ARM-TD or AIM-TD studies. SETTING: Seventy-six centers in the United States and Europe. PARTICIPANTS: A total of 337 participants with TD (119 younger and 218 older). INTERVENTION: Deutetrabenazine was initiated at 12 mg/day and titrated once weekly by 6 mg/day using a response-driven dosing regimen until adequate dyskinesia control was reached or a clinically significant adverse event occurred. MEASUREMENTS: This post hoc analysis assessed change and percent change from baseline in total motor Abnormal Involuntary Movement Scale (AIMS) score, response rates for ≥50% AIMS improvement, Clinical Global Impression of Change (CGIC), Patient Global Impression of Change (PGIC), and safety in younger and older participants with TD. RESULTS: After 3 years of open-label treatment, mean deutetrabenazine dose was â¼39.5 mg/day in both groups. Mean±SE changes from baseline in total motor AIMS score were -6.7 ± 0.62 and -6.5 ± 0.47 in younger and older participants, respectively (percent changes: -61.4% ± 4.10% and -54.6% ± 3.01%); 76% of younger and 62% of older participants achieved ≥50% AIMS response. Most younger and older participants achieved treatment success per CGIC (67% and 76%) and PGIC (64% and 63%). Deutetrabenazine was generally well tolerated in both groups. CONCLUSIONS: Deutetrabenazine treatment was associated with sustained improvements in total motor AIMS score, treatment success, and improved quality of life, and was well tolerated in younger and older adults with TD in this 3-year OLE study.
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Discinesia Tardía , Tetrabenazina , Inhibidores de Captación Adrenérgica/efectos adversos , Anciano , Humanos , Persona de Mediana Edad , Calidad de Vida , Discinesia Tardía/inducido químicamente , Discinesia Tardía/complicaciones , Discinesia Tardía/tratamiento farmacológico , Tetrabenazina/efectos adversos , Tetrabenazina/análogos & derivados , Resultado del TratamientoRESUMEN
OBJECTIVE: Atomoxetine (ATX), one of the most commonly used drugs after stimulants in attention deficit hyperactivity disorder (ADHD) treatment, is an inhibitor of the norepinephrine transporter (NET/SLC6A2), which is also associated with the etiology of ADHD. In this study, we aimed to investigate the effect of NET gene polymorphisms on response to ATX treatment and to find the answers to the questions about whether there is a relationship between the severity of the disorder and the observed side effects in children with ADHD. METHOD: About 100 children with ADHD and 80 healthy controls (HCs) were included in this study. The dose of ATX was started at 0.5 mg/kg/day and titrated at 1.2 mg/kg/day. Response to treatment of 78 patients was evaluated 2 months after the beginning of the treatment. After whole blood samples were obtained, DNAs were isolated, and samples were stored at -80°C. Two single-nucleotide polymorphisms (SNPs) (rs12708954 and rs3785143) were analyzed by real-time quantitative PCR (qRT-PCR). RESULTS: The patients with both rs12708954 and rs3785143 heterozygous genotype had better treatment response and more side effects than patients with wild type. There was not found any association between any of the investigated NET polymorphisms and ADHD severity. CONCLUSION: It was, however, found that the NET rs12708954 and rs3785143 genotypes affect the treatment response to ATX in our study; thus, further studies with a large population are needed to understand the effects of NET polymorphisms on treatment, side effects, and also the severity of ADHD.