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2.
S D Med ; 74(8): 372-375, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34461003

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a commonly encountered diagnosis in the child and adolescent populations, and stimulant medications are often prescribed for their treatment. There are numerous available options in this category, including immediate and extended release formulations. There have been many case reports in the literature involving purposeful overdose on immediate release stimulants, but a relative paucity involving extended release forms. Additionally, they often involve Caucasian and Asian populations. We treated a Native American adolescent who took an overdose of extended-release methylphenidate with the intention of suicide. He developed transient orofacial dyskinesia and upper extremity choreoathetosis as a result which did not abate during his time in the emergency department. Once transferred to our care, he was given a one-time benzodiazepine dose with some benefit. This case report describes objective sequelae of a long-acting methylphenidate overdose as well as treatment for the benefit of treating clinicians with similar patient populations and situations.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Discinesias , Metilfenidato , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Discinesias/tratamento farmacológico , Humanos , Masculino , Metilfenidato/efeitos adversos , Extremidade Superior
3.
Drug Alcohol Depend ; 226: 108841, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34271513

RESUMO

INTRODUCTION: Prescription stimulants and methamphetamine have similarities in chemical structure and impact on biological functioning. However, there is limited literature on prescription stimulant misuse among sexual and gender minorities as well as how prescription misuse may impact later methamphetamine use. METHODS: We used data collected from a HIV prevention cohort to describe (e.g., frequencies, percentages) prescription stimulant use/misuse and methamphetamine use at baseline and 12-month follow-up (n = 4857). We then used multivariable logistic regression models to determine the impact of baseline prescription stimulant misuse and methamphetamine use on 12-month prescription stimulant misuse and methamphetamine use. RESULTS: At baseline, 10.2 % of participants misused prescription stimulants and 12 % of participants used methamphetamine in the past 3 months, while at 12-month follow-up 11.6 % of participants misused prescription stimulants and 11.2 % of participants used methamphetamine in the past 3 months. Multivariable regression analyses indicated that participants who misused prescription stimulants (in the absence of methamphetamine) at baseline had 2.51 (95 % CI: 1.44-3.59, ref. no stimulant or methamphetamine use) times the odds of using methamphetamine at 12-month follow-up. DISCUSSION: Findings suggest that prescription stimulant use is a risk factor for continued meth use. Therefore, earlier and targeted public health interventions could reduce methamphetamine use by disrupting the progression from prescription stimulant misuse to methamphetamine use through early screening and interventions for prescription stimulant misuse.


Assuntos
Estimulantes do Sistema Nervoso Central , Infecções por HIV , Metanfetamina , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Estimulantes do Sistema Nervoso Central/efeitos adversos , Infecções por HIV/epidemiologia , Humanos , Masculino , Prescrições
4.
Am J Cardiol ; 154: 86-91, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34233837

RESUMO

Methamphetamine-associated cardiomyopathy (MACM) in an increasingly prevalent disease yet presenting clinical characteristics have not been well studied. We studied consecutive patients with MACM presenting between June 2018 and March 2020 who were interviewed for drug use and medical history. We retrospectively identified an age- and gender-matched cohort of Non-MACM (NMACM) patients and compared clinical characteristics. 140 patients (70 MACM and 70 NMACM) were studied. MACM patients were young (49.6 ± 10 years) and predominantly male (94%). Compared to NMACM, MACM patients were more likely to be Caucasian (21% vs 6%, p = 0.007) and homeless (47% vs 7%, p = 0.001). MACM was characterized by lower left ventricular ejection fraction (EF) (p <0.001) and greater LV end diastolic volume (LVEDV) (p = 0.024). Right ventricular (RV) dilation was present more often (p = s0.001) and was more often severe (p = 0.03). Among MACM cases, half of the cohort developed MACM within 5 years of starting MA (18% within 1 year). There was no apparent relationship between frequency or amount of MA used weekly with time until heart failure onset. Drug use patterns were not clearly related to the degree of LV structural change however there were more consistent, significant associations with RV and right atrial (RA) size parameters. In conclusion, patients with MACM have more severe myocardial impairment with lower EF, greater LVEDV and RV dilation. Drug use patterns do not clearly impact degree of LV structural changes by echocardiography however may be related to RV and RA size.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Cardiomiopatias/fisiopatologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Metanfetamina/efeitos adversos , Administração Intranasal , Adulto , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/epidemiologia , Cardiotoxicidade , Estudos de Casos e Controles , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar , Volume Sistólico , Disfunção Ventricular Esquerda
5.
J Affect Disord ; 292: 416-423, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34144366

RESUMO

BACKGROUND: Globally, depression impacts nearly 300 million people, and roughly half do not achieve remission with standard first-line therapies. For such individuals, augmentation strategies are often helpful at reducing the severity of depression. While there are many potential adjunctive medication choices, psychostimulants are among the more controversial options. OBJECTIVES: The present review sought to clarify the comparative efficacy and safety of different stimulant-like medications to treat depression. METHODS: We conducted a systematic review and network meta-analysis of randomized, controlled trials (RCTs) using psychostimulant medications to treat adults with depression. Outcomes were pooled using rate ratios (RRs) for dichotomous outcomes (e.g., response, adverse events) and standardized mean differences (SMDs) for continuous outcomes (e.g., change in depression scores). RESULTS: We identified 37 eligible studies (ranging from 1958 to 2016). We assessed nine psychostimulants: methylphenidate (n=14), dextroamphetamine (n=9), modafinil (n=6), lisdexamphetamine (n=3), methylamphetamine (n=3), pemoline (n=2), atomoxetine (n=1), desipramine (n=1), and imipramine (n=1). Overall, psychostimulants demonstrated efficacy for depression, reduced fatigue and sleepiness, and appeared well-tolerated. However, there was inconsistent evidence across particular psychostimulants. For example, the only psychostimulant which demonstrated efficacy for depression-in terms of both symptom severity and response rates-was methylphenidate. CONCLUSIONS: While our review suggests that some psychostimulants-particularly methylphenidate-appear well-tolerated and demonstrate some efficacy for depression, as well as fatigue and sleepiness, the strength of evidence in our estimates was low to very low for most agents given the small sample sizes, few RCTs, and imprecision in most estimates. A lack of consistent evidence precludes a definitive hierarchy of treatments and points to a need for additional, high-quality RCTs.


Assuntos
Estimulantes do Sistema Nervoso Central , Metilfenidato , Adulto , Estimulantes do Sistema Nervoso Central/efeitos adversos , Depressão , Fadiga , Humanos , Metilfenidato/efeitos adversos , Metanálise em Rede
6.
J Clin Psychiatry ; 82(4)2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34166587

RESUMO

Objective: Delayed-release and extended-release methylphenidate (DR/ER-MPH), the first stimulant predicted to be absorbed primarily in the colon, demonstrated significant improvements in attention-deficit/hyperactivity disorder (ADHD) symptoms and functional impairment from awakening until evening versus placebo in clinical trials. The clinical significance of these improvements was explored post hoc by examining response and remission thresholds as well as safety in the context of dose optimization.Methods: Data from the open-label, treatment-optimization phase of a phase 3 study of DR/ER-MPH in children (aged 6-12 years) with ADHD, as diagnosed by DSM-5 criteria and enrolled between July 2015 and March 2016, were analyzed. Thresholds for response (anchored to Clinical Global Impressions-Improvement scale [CGI-I] score of 1 or 2) and remission were applied to ADHD Rating Scale-IV (ADHD-RS-IV), Before School Functioning Questionnaire (BSFQ), and Parent Rating of Evening and Morning Behavior, Revised, Morning Subscale (PREMB-R AM) and Evening Subscale (PREMB-R PM) scores. Rates of response, remission, and treatment-emergent adverse events by starting dose were examined.Results: Mean DR/ER-MPH dose increased from 29.7 mg/d at baseline (51% on 20 mg/d; 49% on 40 mg/d) to 66.2 mg/d at week 6. At week 6, most participants achieved response/remission thresholds (response/remission: ADHD-RS-IV: 97%/89%; BSFQ: 98%/94%; PREMB-R AM: 94%/98%; PREMB-R PM: 91%/84%). More participants starting on a 40-mg versus 20-mg dose achieved thresholds at week 1 (P < .02). Weekly treatment-emergent adverse event rates over the open-label period were similar between starting doses.Conclusions: When DR/ER-MPH dosing was optimized for ADHD symptom control throughout the day, the majority of participants achieved thresholds indicating all-day control of ADHD symptoms and functional impairment to the level of their non-ADHD peers.Trial Registration: Data used in this post hoc analysis came from the study with ClinicalTrials.gov identifier: NCT02493777.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Metilfenidato/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Preparações de Ação Retardada/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Metilfenidato/efeitos adversos , Indução de Remissão , Resultado do Tratamento
7.
Am J Health Syst Pharm ; 78(10): 840-849, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33954419

RESUMO

PURPOSE: Current literature on the safety and efficacy of intermediate- and long-acting formulations of methylphenidate and dexmethylphenidate for attention-deficit/hyperactivity disorder (ADHD) is evaluated. SUMMARY: Methylphenidate has been an established treatment for ADHD, but due to its relatively short half-life, numerous intermediate- and long-acting products have been developed. While these extended-release products provide efficacy similar to that of immediate-acting products, the pharmacokinetics and adverse effects can vary. Intermediate-acting methylphenidate products have effects that can last as long as 8 hours, but clinically patients have still required twice-daily dosing. Long-acting products have helped to address these challenges, with recently developed products including controlled-release and bimodal-delivery systems and a patch formulation. Many of these products can be opened and sprinkled on applesauce for ease of administration. CONCLUSION: Knowledge of the various formulations of methylphenidate and dexmethylphenidate is crucial for appropriate medication selection for control of ADHD symptoms. Knowledge of differences between release mechanisms and the pharmacokinetic properties are essential for appropriate use of these products.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Cloridrato de Dexmetilfenidato , Metilfenidato , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Preparações de Ação Retardada , Cloridrato de Dexmetilfenidato/uso terapêutico , Meia-Vida , Humanos , Metilfenidato/efeitos adversos
8.
J Clin Hypertens (Greenwich) ; 23(6): 1264-1268, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33939242

RESUMO

Prescription stimulants are an important cause of secondary hypertension and their use is increasing in adult patients who are also at risk for essential hypertension. Although stimulants increase blood pressure, a systematic approach for assessing their impact in individual patients is lacking. We developed a protocol using ambulatory blood pressure monitoring for up to 36 h to compare blood pressure over two sequential days. Average blood pressure on the first day (without stimulant medication) was compared to average blood pressure on the second day (after re-starting stimulant medication). We describe the outcomes of this protocol for a case series of eleven adults. Patients demonstrated one of three outcomes: normal blood pressure on both days, hypertension on both days, or hypertension only on the day patients received their stimulant medications. This novel protocol provides valuable information on the blood pressure effects of stimulant medications and allows clinicians to make personalized decisions regarding treatment.


Assuntos
Estimulantes do Sistema Nervoso Central , Hipertensão , Adulto , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Estimulantes do Sistema Nervoso Central/efeitos adversos , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Prescrições
9.
J Clin Psychiatry ; 82(3)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-34000130

RESUMO

OBJECTIVE: The aim of this report was to evaluate the psychometric properties of the Pain Frequency, Intensity, and Burden Scale (P-FIBS), a brief measure of pain, as well as the association of pain with irritability and depression and how these symptoms relate to functional impairments. METHODS: Participants of 2 randomized controlled trials (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care [EMBARC; n = 251 with DSM-IV diagnosis of major depressive disorder; study duration: August 2011-December 2015] and STimulant Reduction Intervention Using Dosed Exercise [STRIDE; n = 302 with DSM-IV diagnosis of stimulant abuse or dependence; study-duration: July 2010-February 2013]) and treatment-seeking patients in primary care clinics from an ongoing quality-improvement project (VitalSign6; n = 4,370; project duration: August 2014-July 2019) were included. Psychometric properties of the P-FIBS were evaluated with confirmatory factor and item response theory analyses in EMBARC and VitalSign6. The approach of Baron and Kenny was used to assess whether irritability accounted for the effect of pain on depression. RESULTS: Cronbach α (0.84-0.89) and model fits for single-factor structure of P-FIBS were acceptable. Pain was positively correlated with irritability (r = 0.22-0.29) and depression (r = 0.10-0.33). Irritability accounted for 40.7%-65.5% of the effect of pain on depression. Higher irritability and depression were associated with poorer social functioning, quality of life, and productivity in work- and non-work-related activities. Pain was associated with non-work-related activity impairments even after controlling for irritability and depression. CONCLUSIONS: The P-FIBS is a brief and reliable measure of pain. Irritability is associated with pain and accounts for a large proportion of the effect of pain on depression. Symptoms of pain, irritability, and depression are associated with functional impairments. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT01407094 (EMBARC), NCT01141608 (STRIDE).


Assuntos
Depressão/fisiopatologia , Humor Irritável/fisiologia , Medição da Dor/normas , Dor/diagnóstico , Dor/fisiopatologia , Psicometria/normas , Funcionamento Psicossocial , Índice de Gravidade de Doença , Adulto , Antidepressivos/farmacologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estudos Transversais , Depressão/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Psicometria/instrumentação , Melhoria de Qualidade , Qualidade de Vida , Reprodutibilidade dos Testes , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto Jovem
10.
JAMA ; 325(20): 2067-2075, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-33946100

RESUMO

Importance: Attention-deficit/hyperactivity disorder (ADHD) is diagnosed in approximately 2.4% of preschool-age children. Stimulants are recommended as first-line medication treatment. However, up to 25% of preschool-age children with ADHD are treated with α2-adrenergic agonist medications, despite minimal evidence about their efficacy or adverse effects in this age range. Objective: To determine the frequency of reported improvement in ADHD symptoms and adverse effects associated with α2-adrenergic agonists and stimulant medication for initial ADHD medication treatment in preschool-age children. Design, Setting, and Participants: Retrospective electronic health record review. Data were obtained from health records of children seen at 7 outpatient developmental-behavioral pediatric practices in the Developmental Behavioral Pediatrics Research Network in the US. Data were abstracted for 497 consecutive children who were younger than 72 months when treatment with an α2-adrenergic agonist or stimulant medication was initiated by a developmental-behavioral pediatrician for ADHD and were treated between January 1, 2013, and July 1, 2017. Follow-up was complete on February 27, 2019. Exposures: α2-Adrenergic agonist vs stimulant medication as initial ADHD medication treatment. Main Outcomes and Measures: Reported improvement in ADHD symptoms and adverse effects. Results: Data were abstracted from electronic health records of 497 preschool-age children with ADHD receiving α2-adrenergic agonists or stimulants. Median child age was 62 months at ADHD medication initiation, and 409 children (82%) were males. For initial ADHD medication treatment, α2-adrenergic agonists were prescribed to 175 children (35%; median length of α2-adrenergic agonist use, 136 days) and stimulants were prescribed to 322 children (65%; median length of stimulant use, 133 days). Improvement was reported in 66% (95% CI, 57.5%-73.9%) of children who initiated α2-adrenergic agonists and 78% (95% CI, 72.4%-83.4%) of children who initiated stimulants. Only daytime sleepiness was more common for those receiving α2-adrenergic agonists vs stimulants (38% vs 3%); several adverse effects were reported more commonly for those receiving stimulants vs α2-adrenergic agonists, including moodiness/irritability (50% vs 29%), appetite suppression (38% vs 7%), and difficulty sleeping (21% vs 11%). Conclusions and Relevance: In this retrospective review of health records of preschool-age children with ADHD treated in developmental-behavioral pediatric practices, improvement was noted in the majority of children who received α2-adrenergic agonists or stimulants, with differing adverse effect profiles between medication classes. Further research, including from randomized clinical trials, is needed to assess comparative effectiveness of α2-adrenergic agonists vs stimulants.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Guanfacina/uso terapêutico , Metilfenidato/uso terapêutico , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Pré-Escolar , Distúrbios do Sono por Sonolência Excessiva/induzido quimicamente , Registros Eletrônicos de Saúde , Transtornos da Alimentação e da Ingestão de Alimentos/induzido quimicamente , Feminino , Guanfacina/efeitos adversos , Humanos , Humor Irritável , Masculino , Metilfenidato/efeitos adversos , Estudos Retrospectivos
12.
BMJ Open ; 11(5): e044696, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006547

RESUMO

OBJECTIVES: To examine the safety of an agonist-type treatment, lisdexamfetamine (LDX), at 250 mg/day among adults with methamphetamine (MA) dependence. DESIGN: A dose-escalating, phase-2, open-label, single-group study of oral LDX at two Australian drug treatment services. SETTING: The study was conducted at two Australian stimulant use disorder treatment clinics. PARTICIPANTS: There were 16 participants: at least 18 years old, MA dependent for at least the preceding 2 years using ICD-10 criteria, reporting use of MA on at least 14 of the preceding 28 days. INTERVENTIONS: Daily, supervised LDX of 100-250 mg, single-blinded to dose, ascending-descending regimen over 8 weeks (100-250 mg over 4 weeks; followed by 4-week dose reduction regimen, 250-100 mg). Participants were followed through to week 12. OUTCOMES: Primary outcomes were safety, drug tolerability and regimen completion at the end of week 4. Participants were followed to week 12. Secondary outcomes included: change in MA use; craving; withdrawal; severity of dependence; risk behaviour; change in other substance use; medication acceptability; potential for non-prescription use; adherence and neurocognitive functioning. RESULTS: Fourteen of 16 participants (87.5%) completed escalation to 250 mg/day. Two participants withdrew from the trial in the first week: one relocated away from the study site, the other self-withdrew due to a possible, known side effect of LDX (agitation). There was one serious adverse event of suicidal ideation which resolved. All other adverse events were mild or moderate in severity and known side effects of LDX. No participant was withdrawn due to adverse events. MA use decreased from a median of 21 days (IQR: 16-23) to 13 days (IQR: 11-17) over the 4-week escalation period (p=0.013). CONCLUSIONS: LDX at a dose of up to 250 mg/day was safe and well tolerated by study participants, warranting larger trials as a pharmacotherapy for MA dependence. TRIAL REGISTRATION NUMBER: ACTRN12615000391572.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Estimulantes do Sistema Nervoso Central , Metanfetamina , Adolescente , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Austrália , Estimulantes do Sistema Nervoso Central/efeitos adversos , Método Duplo-Cego , Humanos , Dimesilato de Lisdexanfetamina , Metanfetamina/efeitos adversos , Resultado do Tratamento
14.
Viruses ; 13(5)2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919273

RESUMO

Psychostimulant use is a major comorbidity in people living with HIV, which was initially explained by them adopting risky behaviors that facilitate HIV transmission. However, the effects of drug use on the immune system might also influence this phenomenon. Psychostimulants act on peripheral immune cells even before they reach the central nervous system (CNS) and their effects on immunity are likely to influence HIV infection. Beyond their canonical activities, classic neurotransmitters and neuromodulators are expressed by peripheral immune cells (e.g., dopamine and enkephalins), which display immunomodulatory properties and could be influenced by psychostimulants. Immune receptors, like Toll-like receptors (TLRs) on microglia, are modulated by cocaine and amphetamine exposure. Since peripheral immunocytes also express TLRs, they may be similarly affected by psychostimulants. In this review, we will summarize how psychostimulants are currently thought to influence peripheral immunity, mainly focusing on catecholamines, enkephalins and TLR4, and shed light on how these drugs might affect HIV infection. We will try to shift from the classic CNS perspective and adopt a more holistic view, addressing the potential impact of psychostimulants on the peripheral immune system and how their systemic effects could influence HIV infection.


Assuntos
Doenças Transmissíveis/etiologia , Suscetibilidade a Doenças , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Sistema Imunitário/efeitos dos fármacos , Animais , Biomarcadores , Estimulantes do Sistema Nervoso Central/efeitos adversos , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/metabolismo , Suscetibilidade a Doenças/imunologia , Infecções por HIV/etiologia , Infecções por HIV/metabolismo , Humanos , Imunidade/efeitos dos fármacos , Imunomodulação , Vigilância da População , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Receptores Toll-Like/metabolismo
15.
Genes (Basel) ; 12(4)2021 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-33920292

RESUMO

This study investigated whether four single nucleotide polymorphisms (SNPs) moderated caffeine effects on vigilance and performance in a double-blind and crossover total sleep deprivation (TSD) protocol in 37 subjects. In caffeine (2 × 2.5 mg/kg/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-α SNP A allele appear to be more sensitive than homozygote G/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-α, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882).


Assuntos
Cafeína/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Doenças do Sistema Nervoso/genética , Desempenho Psicomotor , Privação do Sono/complicações , Adulto , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Doenças do Sistema Nervoso/induzido quimicamente
16.
Acta Paediatr ; 110(10): 2825-2832, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33876865

RESUMO

AIM: Treatment of childhood obesity is often insufficient and may be aggravated by high co-occurrence of attention-deficit/hyperactivity disorder (ADHD). We aimed to investigate whether children with overweight or obesity normalised in weight when receiving stimulant treatment for ADHD. METHODS: Growth data of 118 children were obtained from medical records at outpatient paediatric and children's psychiatric services in the Gothenburg area, Sweden. The children were diagnosed with ADHD and were between 6 and 17 years at the start of stimulant treatment. The pre-treatment data act as an internal control where every child is their own control. RESULTS: At the start of treatment, 74 children had normal weight and 44 had either overweight or obesity. During the year with stimulants, the mean (SD) body mass index (BMI) in standard deviation score (SDS) decreased significantly: -0.72 (0.66) compared with 0.17 (0.43) during the year before treatment (p < 0.01). After one year with treatment, 43% of those with overweight or obesity had reached normal weight. CONCLUSIONS: Stimulant treatment for ADHD yields significant weight loss. In children with overweight or obesity and ADHD, this is an important finding showing additional benefit in terms of weight management.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Obesidade Pediátrica , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Índice de Massa Corporal , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Humanos , Sobrepeso/complicações , Obesidade Pediátrica/complicações
17.
Cochrane Database Syst Rev ; 4: CD008189, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33914901

RESUMO

BACKGROUND: Infertility is a prevalent problem that has significant consequences for individuals, families, and the community. Modifiable lifestyle factors may affect the chance of people with infertility having a baby. However, no guideline is available about what preconception advice should be offered. It is important to determine what preconception advice should be given to people with infertility and to evaluate whether this advice helps them make positive behavioural changes to improve their lifestyle and their chances of conceiving. OBJECTIVES: To assess the safety and effectiveness of preconception lifestyle advice on fertility outcomes and lifestyle behavioural changes for people with infertility. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, trial registers, Google Scholar, and Epistemonikos in January 2021; we checked references and contacted field experts to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), randomised cross-over studies, and cluster-randomised studies that compared at least one form of preconception lifestyle advice with routine care or attention control for people with infertility. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Primary effectiveness outcomes were live birth and ongoing pregnancy. Primary safety outcomes were adverse events and miscarriage. Secondary outcomes included reported behavioural changes in lifestyle, birth weight, gestational age, clinical pregnancy, time to pregnancy, quality of life, and male factor infertility outcomes. We assessed the overall quality of evidence using GRADE criteria. MAIN RESULTS: We included in the review seven RCTs involving 2130 participants. Only one RCT included male partners. Three studies compared preconception lifestyle advice on a combination of topics with routine care or attention control. Four studies compared preconception lifestyle advice on one topic (weight, alcohol intake, or smoking) with routine care for women with infertility and specific lifestyle characteristics. The evidence was of low to very low-quality. The main limitations of the included studies were serious risk of bias due to lack of blinding, serious imprecision, and poor reporting of outcome measures. Preconception lifestyle advice on a combination of topics versus routine care or attention control Preconception lifestyle advice on a combination of topics may result in little to no difference in the number of live births (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.79 to 1.10; 1 RCT, 626 participants), but the quality of evidence was low. No studies reported on adverse events or miscarriage. Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice on a combination of topics affects lifestyle behavioural changes: body mass index (BMI) (mean difference (MD) -1.06 kg/m², 95% CI -2.33 to 0.21; 1 RCT, 180 participants), vegetable intake (MD 12.50 grams/d, 95% CI -8.43 to 33.43; 1 RCT, 264 participants), alcohol abstinence in men (RR 1.08, 95% CI 0.74 to 1.58; 1 RCT, 210 participants), or smoking cessation in men (RR 1.01, 95% CI 0.91 to 1.12; 1 RCT, 212 participants). Preconception lifestyle advice on a combination of topics may result in little to no difference in the number of women with adequate folic acid supplement use (RR 0.98, 95% CI 0.95 to 1.01; 2 RCTs, 850 participants; I² = 4%), alcohol abstinence (RR 1.07, 95% CI 0.99 to 1.17; 1 RCT, 607 participants), and smoking cessation (RR 1.01, 95% CI 0.98 to 1.04; 1 RCT, 606 participants), on low quality evidence. No studies reported on other behavioural changes. Preconception lifestyle advice on weight versus routine care Studies on preconception lifestyle advice on weight were identified only in women with infertility and obesity. Compared to routine care, we are uncertain whether preconception lifestyle advice on weight affects the number of live births (RR 0.94, 95% CI 0.62 to 1.43; 2 RCTs, 707 participants; I² = 68%; very low-quality evidence), adverse events including gestational diabetes (RR 0.78, 95% CI 0.48 to 1.26; 1 RCT, 317 participants; very low-quality evidence), hypertension (RR 1.07, 95% CI 0.66 to 1.75; 1 RCT, 317 participants; very low-quality evidence), or miscarriage (RR 1.50, 95% CI 0.95 to 2.37; 1 RCT, 577 participants; very low-quality evidence). Regarding lifestyle behavioural changes for women with infertility and obesity, preconception lifestyle advice on weight may slightly reduce BMI (MD -1.30 kg/m², 95% CI -1.58 to -1.02; 1 RCT, 574 participants; low-quality evidence). Due to very low-quality evidence, we are uncertain whether preconception lifestyle advice affects the percentage of weight loss, vegetable and fruit intake, alcohol abstinence, or physical activity. No studies reported on other behavioural changes. Preconception lifestyle advice on alcohol intake versus routine care Studies on preconception lifestyle advice on alcohol intake were identified only in at-risk drinking women with infertility. We are uncertain whether preconception lifestyle advice on alcohol intake affects the number of live births (RR 1.15, 95% CI 0.53 to 2.50; 1 RCT, 37 participants; very low-quality evidence) or miscarriages (RR 1.31, 95% CI 0.21 to 8.34; 1 RCT, 37 participants; very low-quality evidence). One study reported on behavioural changes for alcohol consumption but not as defined in the review methods. No studies reported on adverse events or other behavioural changes. Preconception lifestyle advice on smoking versus routine care Studies on preconception lifestyle advice on smoking were identified only in smoking women with infertility. No studies reported on live birth, ongoing pregnancy, adverse events, or miscarriage. One study reported on behavioural changes for smoking but not as defined in the review methods. AUTHORS' CONCLUSIONS: Low-quality evidence suggests that preconception lifestyle advice on a combination of topics may result in little to no difference in the number of live births. Evidence was insufficient to allow conclusions on the effects of preconception lifestyle advice on adverse events and miscarriage and on safety, as no studies were found that looked at these outcomes, or the studies were of very low quality. This review does not provide clear guidance for clinical practice in this area. However, it does highlight the need for high-quality RCTs to investigate preconception lifestyle advice on a combination of topics and to assess relevant effectiveness and safety outcomes in men and women with infertility.


Assuntos
Infertilidade/terapia , Estilo de Vida , Nascido Vivo , Cuidado Pré-Concepcional/métodos , Abandono do Hábito de Fumar , Consumo de Bebidas Alcoólicas , Viés , Cafeína/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Aconselhamento/métodos , Dieta Saudável , Exercício Físico , Feminino , Ácido Fólico/administração & dosagem , Humanos , Infertilidade Feminina/terapia , Nascido Vivo/epidemiologia , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Sexuais , Complexo Vitamínico B/administração & dosagem , Perda de Peso
18.
Br J Pharmacol ; 178(13): 2551-2568, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33786822

RESUMO

The vast majority of illicit stimulants act at monoaminergic systems, causing both psychostimulant and adverse effects. Stimulants can interact as substrates or antagonists at the nerve terminal monoamine transporter that mediates the reuptake of monoamines across the nerve synaptic membrane and at the vesicular monoamine transporter (VMAT-2) that mediates storage of monoamines in vesicles. Stimulants can act directly at presynaptic or postsynaptic receptors for monoamines or have indirect monoamine-mimetic actions due to the release of monoamines. Cocaine and other stimulants can acutely increase the risk of sudden cardiac death. Stimulants, particularly MDMA, in hot conditions, such as that occurring at a "rave," have caused fatalities from the consequences of hyperthermia, often compounding cardiac adverse actions. This review examines the pharmacology of the cardiovascular and temperature adverse actions of stimulants.


Assuntos
Estimulantes do Sistema Nervoso Central , Cocaína , Transporte Biológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Cocaína/efeitos adversos , Temperatura , Proteínas Vesiculares de Transporte de Monoamina/metabolismo
19.
Psychiatry Res ; 300: 113861, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33780716

RESUMO

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders in children and although stimulant medications remain first line to treat the disorder, some families prefer nonstimulants. The goal is to analyze the adverse events (AE) associated with nonstimulant medications using post-marketing drug surveillance data. We aim to increase awareness and aide patient education. A retrospective study of adverse drug events with atomoxetine, clonidine, and guanfacine was performed using the Federal Drug Administration Adverse Event Reporting System (FAERS) Database. Results show that the most commonly reported AEs, as defined by FAERS, were ineffectiveness (9.91-14.15%) fatigue (8.93%), and somnolence (8.8-10.16%). Of those taking atomoxetine, suicidal and self-injurious ideation was reported to a similar degree amongst all age groups. Suicidal ideation was listed within the top 20 most reported AEs for all three medications. It is more likely that some patients will experience milder side effects. We suggest providing these data to patients to help overcome the stigma of starting medication, especially if they prefer nonstimulants. Serious AEs are still reported to a small degree, thus monitoring and consistent patient education remains important. We also recommend educating a wider demographic of patients about recognizing potential development of suicidal thoughts.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Preparações Farmacêuticas , Cloridrato de Atomoxetina/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Humanos , Estudos Retrospectivos , Estados Unidos , United States Food and Drug Administration
20.
J Glaucoma ; 30(5): e259-e261, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33675339

RESUMO

Attention-deficit/hyperactivity disorder is commonly treated with amphetamines as first line therapy. Rare case reports have shown amphetamines are associated with open angle glaucoma. We report a rare case of a 14-year-old male who presented with bilateral acute angle closure presumed to be related to his use of lisdexamfetamine dimesylate (Vyvanse). The patient's medication was discontinued which resulted in complete resolution of angle closure.


Assuntos
Estimulantes do Sistema Nervoso Central , Glaucoma de Ângulo Aberto , Adolescente , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Dextroanfetamina/efeitos adversos , Humanos , Pressão Intraocular , Dimesilato de Lisdexanfetamina/efeitos adversos , Masculino , Resultado do Tratamento
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