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1.
Expert Rev Neurother ; 24(5): 457-464, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38630024

RESUMO

INTRODUCTION: The dextroamphetamine transdermal system (d-ATS) is a stimulant patch recently approved by the United States (U.S.) Food and Drug Administration for the treatment of attention-deficit/hyperactivity disorder (ADHD). AREAS COVERED: The composition of the d-ATS, pharmacokinetics, and metabolism are presented along with data from dermal trials evaluating the tolerability of patch application at various skin sites. Efficacy and safety data from a laboratory classroom study in children and adolescents including effect sizes are assessed. Pharmacokinetic-pharmacodynamic modeling of variable wear times is also discussed. EXPERT OPINION: Although stimulants are recommended as first-line treatment for ADHD in the U.S. some patients may have difficulty swallowing intact tablets and capsules, or dislike the taste or texture of chewable, oral disintegrating, or liquid formulations. The d-ATS fills an unmet need for those with ADHD who are unable or prefer not to take medication orally. Varying wear time of the d-ATS also gives flexibility in length of stimulant effect which may be useful for patients with changing schedules. However, dermal discomfort must be considered in addition to the usual amphetamine side effects when prescribing the d-ATS. Patient and provider experience will determine how frequent the use of d-ATS becomes.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Adolescente , Adulto , Humanos , Criança , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Anfetamina/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dextroanfetamina/uso terapêutico
2.
Adv Pharmacol ; 99: 251-286, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467483

RESUMO

In this review, we critically evaluate the contribution of prodrugs to treating two related psychiatric disorders, attention-deficit hyperactivity disorder (ADHD) and binge-eating disorder (BED). ADHD is characterized by inattentiveness, distractibility, impulsiveness, and hyperactivity. BED is also an impulse-control disorder which leads to frequent, compulsive episodes of excessive eating (binges). Lisdexamfetamine (LDX; prodrug of d-amphetamine) is approved to treat both ADHD and BED. Serdexmethylphenidate (SDX; prodrug of d-threo-methylphenidate) is not clinically approved as monotherapy but, in a fixed-dose combination with immediate release d-threo-methylphenidate (Azstarys™), SDX is approved for managing ADHD in children/adolescents. The pharmacological actions of a stimulant mediate both its efficacy and side-effects. Therefore, daily management of ADHD or BED to maintain optimum efficacy and tolerability places highly restrictive requirements on the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of stimulant medications, especially prodrugs. Prodrugs must have good bioavailability and rapid metabolism to provide therapeutic efficacy soon after morning dosing combined with providing stimulant coverage throughout the day/evening. A wide selection of dosages and linear PK for the prodrug and its active metabolite are essential requirements for treatment of these conditions. The proposed neurobiological causes of ADHD and BED are described. The chemical, pharmacological and PK/PD properties responsible for the therapeutic actions of the prodrugs, LDX and SDX, are compared and contrasted. Finally, we critically assess their contribution as ADHD and BED medications, including advantages over their respective active metabolites, d-amphetamine and d-threo-methylphenidate, and also their potential for misuse and abuse.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno da Compulsão Alimentar , Estimulantes do Sistema Nervoso Central , Metilfenidato , Pró-Fármacos , Adolescente , Criança , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno da Compulsão Alimentar/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dextroanfetamina/uso terapêutico , Metilfenidato/uso terapêutico , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico
3.
Artigo em Espanhol | MEDLINE | ID: mdl-38412018

RESUMO

OBJECTIVE: To describe the presentation, management, and postmortem examination findings in a dog with confirmed lisdexamfetamine dimesylate (LDX) toxicosis. CASE SUMMARY: A 3-year-old female neutered mixed breed dog initially presented with neurological signs suspected to be secondary to LDX toxicosis. The dog was treated as typical for amphetamine toxicoses but developed severe respiratory and cardiovascular signs throughout their hospitalization. The progression of the cardiopulmonary signs led to cardiopulmonary arrest, for which CPR was unsuccessful. Postmortem examination exhibited severe hemorrhage throughout multiple organ systems. Toxicology testing confirmed the presence of unaltered LDX and its metabolite, amphetamine. NEW OR UNIQUE INFORMATION PROVIDED: This is the first case report documenting a severe progression of clinical signs and postmortem examination findings in a case of confirmed LDX toxicosis in a dog. Although the patient did not survive treatment, postmortem examination and microscopic evaluation of tissues allowed visualization of the extent of systemic pathophysiology. With prompt treatment, the prognosis of amphetamine toxicosis in dogs is generally considered good; however, this case report demonstrates a severe case in which even prompt and appropriate treatment did not prevent mortality. This suggests a need to establish negative prognostic indicators for which to monitor in cases of amphetamine toxicosis. Finally, this report is also unique in the fact that the LDX toxicosis was confirmed using a toxicological analysis technique not previously described clinically in dogs.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Humanos , Feminino , Cães , Animais , Dimesilato de Lisdexanfetamina/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dextroanfetamina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Resultado do Tratamento
4.
Toxicol Appl Pharmacol ; 484: 116867, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38378049

RESUMO

Lisdexamfetamine (LDX) is a d-amphetamine prodrug used to treat attention deficit and hyperactivity disorder, a common neurodevelopmental disorder in children and adolescents. Due to its action mediated by elevated levels of catecholamines, mainly dopamine and noradrenaline, which influence hormonal regulation and directly affect the gonads, this drug may potentially disrupt reproductive performance. This study evaluated the effects of exposure to LDX from the juvenile to peripubertal period (critical stages of development) on systemic and reproductive toxicity parameters in male rats. Male Wistar rats (23 days old) were treated with 0; 5.2; 8.6 or 12.1 mg/kg/day of LDX from post-natal day (PND) 23 to 53, by gavage. LDX treatment led to reduced daily food and water consumption, as well as a decrease in social behaviors. The day of preputial separation remained unaltered, although the treated animals exhibited reduced weight. At PND 54, the treated animals presented signs of systemic toxicity, evidenced by a reduction in body weight gain, increase in the relative weight of the liver, spleen, and seminal gland, reduction in erythrocyte and leukocyte counts, reduced total protein levels, and disruptions in oxidative parameters. In adulthood, there was an increase in immobile sperm, reduced sperm count, morphometric changes in the testis, and altered oxidative parameters, without compromising male sexual behavior and fertility. These findings showed that LDX-treatment during the juvenile and peripubertal periods induced immediate systemic toxicity and adversely influenced reproductive function in adult life, indicating that caution is necessary when prescribing this drug during the peripubertal phase.


Assuntos
Estimulantes do Sistema Nervoso Central , Dimesilato de Lisdexanfetamina , Humanos , Adulto , Criança , Adolescente , Masculino , Ratos , Animais , Dimesilato de Lisdexanfetamina/toxicidade , Estimulantes do Sistema Nervoso Central/toxicidade , Dextroanfetamina/toxicidade , Dextroanfetamina/uso terapêutico , Resultado do Tratamento , Ratos Wistar , Sêmen
5.
J Psychiatr Res ; 170: 19-26, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38101205

RESUMO

BACKGROUND: ADHD is often described as a disorder of altered reward sensitivity, yet few studies have examined the extent to which: (i) treatments for ADHD impact reward-related mechanisms; and (ii) changes in the reward system are associated with clinical improvement. This study addresses these issues - examining the extent to which clinical improvement following lisdexamfetamine (LDX) treatment is associated with changes in brain reward system activation. METHODS: Twenty adults (M = 11, 55%, F = 9, 45%), ages 19-52 (M = 33.9, SD = 10.0) with ADHD participated in a randomized cross-over study with lisdexamfetamine (LDX) and placebo (PB). Changes in brain activation were assessed during functional magnetic resonance (fMRI) scans: after receiving 3-5 weeks of treatment with LDX and 3-5 weeks of no drug/PB. fMRI contrasts were derived from the passive-avoidance (PA) learning task, which assessed reward-related learning using computational variables. We analyzed the following conditions: the Choice-Phase, modulated by the expected value (EV; i.e., object-choose and object-reject), and the Feedback-Phase, modulated by the prediction error (PE; i.e., reward and punish). Clinical symptom severity was assessed via interview with the ADHD-Rating Scale (ADHD-RS-IV). To address the primary objective, we performed group-level mass-univariate regression analyses between LDX and PB of percent change of the ADHD-RS total scores and the four contrast images under the Choice- and Feedback-conditions. Significance was set at a whole-brain voxel-wise threshold of p < 0.05 with family-wise error (FWE) correction and an extent (cluster) threshold of 50 contiguous voxels. RESULTS: Improvement in ADHD symptoms with LDX was accompanied by significantly increased activation in a series of brain regions previously implicated in reinforcement processing in the choice and feedback conditions (e.g., left caudate and putamen, right orbitofrontal cortex, left middle frontal, superior frontal, and precentral gyri). CONCLUSIONS: These findings, while preliminary, are the first to show that ADHD symptom improvement with stimulant treatment is associated with increased responsiveness of brain systems engaged in reward processing. Results support the hypothesis that LDX treatment may restore balance to dysfunction (e.g., hypoactivation) within the brain reward circuitry in adults with ADHD. Trial RegistrationClinicaltrials.gov Identifier: NCT01924429.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Adulto , Humanos , Dimesilato de Lisdexanfetamina/farmacologia , Dimesilato de Lisdexanfetamina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Dextroanfetamina/farmacologia , Dextroanfetamina/uso terapêutico , Resultado do Tratamento , Método Duplo-Cego , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Tomada de Decisões
7.
Drug Alcohol Depend ; 248: 109906, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37216808

RESUMO

BACKGROUND: Nicotine is commonly co-used with other psychostimulants. These high co-use rates have prompted much research on interactions between nicotine and psychostimulant drugs. These studies range from examination of illicitly used psychostimulants such as cocaine and methamphetamine to prescription psychostimulants used to treat attention deficit hyperactivity disorder (ADHD) such as methylphenidate (Ritalin™) and d-amphetamine (active ingredient of Adderall™). However, previous reviews largely focus on nicotine interactions with illicitly used psychostimulants with sparse mention of prescription psychostimulants. The currently available epidemiological and laboratory research, however, suggests high co-use between nicotine and prescription psychostimulants, and that these drugs interact to modulate use liability of either drug. The present review synthesizes epidemiological and experimental human and pre-clinical research assessing the behavioral and neuropharmacological interactions between nicotine and prescription psychostimulants that may contribute to high nicotine-prescription psychostimulant co-use. METHODS: We searched databases for literature investigating acute and chronic nicotine and prescription psychostimulant interactions. Inclusion criteria were that participants/subjects had to experience nicotine and a prescription psychostimulant compound at least once in the study, in addition to assessment of their interaction. RESULTS AND CONCLUSIONS: Nicotine clearly interacts with d-amphetamine and methylphenidate in a variety of behavioral tasks and neurochemical assays assessing co-use liability across preclinical, clinical, and epidemiological research. The currently available research suggests research gaps examining these interactions in women/female rodents, in consideration of ADHD symptoms, and how prescription psychostimulant exposure influences later nicotine-related outcomes. Nicotine has been less widely studied with alternative ADHD pharmacotherapy bupropion, but we also discuss this research.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Feminino , Humanos , Nicotina/farmacologia , Nicotina/uso terapêutico , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/farmacologia , Metilfenidato/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Dextroanfetamina/uso terapêutico , Prescrições
8.
CNS Neurol Disord Drug Targets ; 22(6): 857-874, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35549868

RESUMO

Stroke is a physiological disorder involving a prolonged local interruption of cerebral blood flow. It leads to massive neuronal death and causes short-term or long-lasting functional impairment. Most stroke victims regain some neural function weeks or months following a stroke, but this recovery can plateau six months or more after the injury. The goal of stroke therapy is the rehabilitation of functional capabilities, especially those affecting the patient's autonomy and quality of life. Recent clinical and animal studies combining acute dextro-amphetamine (d-AMPH) administration with rehabilitative training (RT) have revealed that this treatment has significant remedial effects. The review aims to examine the synergistic therapeutic effects of d-amphetamine coupled with RT, administered during the early or late subacute period, on neuronal activation, anatomic plasticity, and skilled motor function in a middle-aged rodent stroke model. The treatment will also include magnetic field stimulation. This review will help increase understanding of the mechanism of d-amphetamine coupled with RT and magnetic field stimulation and their converging therapeutic effects for stroke recovery.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Animais , Humanos , Qualidade de Vida , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/tratamento farmacológico , Encéfalo , Dextroanfetamina/farmacologia , Dextroanfetamina/uso terapêutico
9.
Cochrane Database Syst Rev ; 9: CD011376, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094728

RESUMO

BACKGROUND: Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016. OBJECTIVES: To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue. SEARCH METHODS: For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings. DATA COLLECTION AND ANALYSIS: Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes. MAIN RESULTS: The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.


Assuntos
Neoplasias Encefálicas , Glioma , Adulto , Neoplasias Encefálicas/complicações , Dextroanfetamina/uso terapêutico , Fadiga/etiologia , Fadiga/terapia , Humanos , Modafinila/uso terapêutico
10.
Front Endocrinol (Lausanne) ; 13: 845937, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355559

RESUMO

Introduction: Hypothalamic obesity (HO) in children has severe health consequences. Lifestyle interventions are mostly insufficient and currently no drug treatment is approved for children with HO. Amphetamines are known for their stimulant side-effect on resting energy expenditure (REE) and suppressing of appetite. Earlier case series have shown positive effects of amphetamines on weight in children with acquired HO. We present our experiences with dextroamphetamine treatment in the, up to now, largest cohort of children with HO. Methods: A retrospective cohort evaluation was performed of children with HO treated with dextroamphetamine at two academic endocrine pediatric clinics. Off-label use of dextroamphetamine was initiated in patients with progressive, therapy-resistant acquired or congenital HO. Anthropometrics, REE, self-reported (hyperphagic) behavior and energy level, and side effects were assessed at start and during treatment. Results: Nineteen patients with a mean age of 12.3 ± 4.0 years had been treated with dextroamphetamine. In two patients, ΔBMI SDS could not be evaluated due to short treatment duration or the simultaneous start of extensive lifestyle treatment. Mean treatment duration of the 17 evaluated patients was 23.7 ± 12.7 months. Fourteen patients (n = 10 with acquired HO, n = 4 with congenital HO) responded by BMI decline or BMI stabilization (mean ΔBMI SDS of -0.6 ± 0.8, after a mean period of 22.4 ± 10.5 months). In three patients, BMI SDS increased (mean ΔBMI SDS of +0.5 ± 0.1, after a mean period of 29.7 ± 22.6 months). In 11 responders, measured REE divided by predicted REE increased with +8.9%. Thirteen patients (68.4%) reported decreased hyperphagia, improvement of energy level and/or behavior during treatment. Two patients developed hypertension during treatment, which resulted in dosage adjustment or discontinuation of treatment. Twelve children continued treatment at last moment of follow-up. Conclusion: In addition to supportive lifestyle interventions, dextroamphetamine treatment may improve BMI in children with HO. Furthermore, dextroamphetamines have the potential to decrease hyperphagia and improve resting energy expenditure, behavior, and energy level. In patients with acquired HO, these effects seem to be more pronounced when compared to patients with congenital HO. Future studies are needed to support these results.


Assuntos
Doenças Hipotalâmicas , Obesidade , Adolescente , Criança , Dextroanfetamina/uso terapêutico , Metabolismo Energético , Humanos , Doenças Hipotalâmicas/tratamento farmacológico , Obesidade/complicações , Obesidade/tratamento farmacológico , Estudos Retrospectivos
11.
Subst Abuse Treat Prev Policy ; 16(1): 68, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530878

RESUMO

BACKGROUND: A high proportion of people receiving both oral and injectable opioid agonist treatment report concurrent use of stimulants (i.e. cocaine and or amphetamines), which has been associated with higher rates of continued illicit opioid use and treatment dropout. A recent randomized controlled trial demonstrated the effectiveness of dextroamphetamine (a prescribed stimulant) at reducing craving for and use of cocaine among patients receiving injectable opioid agonist treatment. Following this evidence, dextroamphetamine has been prescribed to patients with stimulant use disorder at a clinic in Vancouver. This study investigates perceptions of the effectiveness of dextroamphetamine from the perspective of these patients. METHODS: Data were collected using small focus groups and one-on-one interviews with patients who were currently or formerly receiving dextroamphetamine (n = 20). Thematic analysis was conducted using an iterative approach, moving between data collection and analysis to search for patterns in the data across transcripts. This process led to the defining and naming of three central themes responding to the research question. RESULTS: Participants reported a range of stimulant use types, including cocaine (n = 8), methamphetamine (n = 8), or both (n = 4). Three central themes were identified as relating to participants' perceptions of the effectiveness of the medication: 1) achieving a substitution effect (i.e. extent to which dextroamphetamine provided a substitution for the effect they received from use of illicit stimulants); 2) Reaching a preferred dose (i.e. speed of titration and effect of the dose received); and 3) Ease of medication access (i.e. preference for take home doses (i.e. carries) vs. medication integrated into care at the clinic). CONCLUSION: In the context of continued investigation of pharmacological treatments for stimulant use disorder, the present study has highlighted how the study of clinical outcomes could be extended to account for factors that contribute to perceptions of effectiveness from the perspective of patients. In practice, elements of treatment delivery (e.g. dosing and dispensation protocols) can be adjusted to allow for various scenarios (e.g. on site vs. take home dosing) by which dextroamphetamine and other pharmacological stimulants could be implemented to provide "effective" treatment for people with a wide range of treatment goals and needs.


Assuntos
Estimulantes do Sistema Nervoso Central , Metanfetamina , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dextroanfetamina/uso terapêutico , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
12.
CNS Drugs ; 35(10): 1035-1051, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34403134

RESUMO

Stimulants (methylphenidate or amphetamines) are the recommended first-line option for the pharmacological treatment of individuals with attention deficit hyperactivity disorder (ADHD). However, some patients with ADHD will not respond optimally to stimulants. Here, we discuss strategies to manage stimulant-refractory ADHD, based on the recommendations advanced in clinical guidelines, knowledge of expert practice in the field, and our own clinical recommendations, informed by a comprehensive literature search in PubMed, PsycInfo, EMBASE + EMBASE classic, OVID Medline, and Web of Science (up to 30 March 2021). We first highlight the importance of stimulant optimization as an effective strategy to increase response. We then discuss a series of factors that should be considered before using alternative pharmacological strategies for ADHD, including poor adherence, time action properties of stimulants (and wearing-off of effects), poor tolerability (that prevents the use of higher, more effective doses), excessive focus on or confounding from presence of comorbid non-ADHD symptoms, and tolerance. Finally, we consider the role of non-stimulants and combined pharmacological approaches. While the choice of medication for ADHD is still to a large extent based on a trial-and-error process, there are reasonably accepted data and guidelines to aid in clinical decision-making. It is hoped that advances in precision psychiatry in the years ahead will further guide prescribers to tailor medication choice to the specific characteristics of the patient.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Pesquisa Empírica , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Inibidores da Captação Adrenérgica/farmacologia , Inibidores da Captação Adrenérgica/uso terapêutico , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Cloridrato de Atomoxetina/farmacologia , Cloridrato de Atomoxetina/uso terapêutico , Estimulantes do Sistema Nervoso Central/farmacologia , Clonidina/farmacologia , Clonidina/uso terapêutico , Dextroanfetamina/farmacologia , Dextroanfetamina/uso terapêutico , Resistência a Medicamentos/fisiologia , Humanos , Metilfenidato/farmacologia , Metilfenidato/uso terapêutico
15.
JAMA Pediatr ; 175(9): 957-965, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34097007

RESUMO

Importance: Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms and common comorbidities. A better understanding of the medications used to manage comorbid conditions in this growing population is critical; however, most previous efforts have been limited in size, duration, and lack of broad representation. Objective: To use a nationally representative database to uncover trends in the prevalence of co-occurring conditions and medication use in the management of symptoms and comorbidities over time among US individuals with ASD. Design, Setting, and Participants: This retrospective, population-based cohort study mined a nationwide, managed health plan claims database containing more than 86 million unique members. Data from January 1, 2014, to December 31, 2019, were used to analyze prescription frequency and diagnoses of comorbidities. A total of 26 722 individuals with ASD who had been prescribed at least 1 of 24 medications most commonly prescribed to treat ASD symptoms or comorbidities during the 6-year study period were included in the analysis. Exposures: Diagnosis codes for ASD based on International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Main Outcomes and Measures: Quantitative estimates of prescription frequency for the 24 most commonly prescribed medications among the study cohort and the most common comorbidities associated with each medication in this population. Results: Among the 26 722 individuals with ASD included in the analysis (77.7% male; mean [SD] age, 14.45 [9.40] years), polypharmacy was common, ranging from 28.6% to 31.5%. Individuals' prescription regimens changed frequently within medication classes, rather than between classes. The prescription frequency of a specific medication varied considerably, depending on the coexisting diagnosis of a given comorbidity. Of the 24 medications assessed, 15 were associated with at least a 15% prevalence of a mood disorder, and 11 were associated with at least a 15% prevalence of attention-deficit/hyperactivity disorder. For patients taking antipsychotics, the 2 most common comorbidities were combined type attention-deficit/hyperactivity disorder (11.6%-17.8%) and anxiety disorder (13.1%-30.1%). Conclusions and Relevance: This study demonstrated considerable variability and transiency in the use of prescription medications by US clinicians to manage symptoms and comorbidities associated with ASD. These findings support the importance of early and ongoing surveillance of patients with ASD and co-occurring conditions and offer clinicians insight on the targeted therapies most commonly used to manage co-occurring conditions. Future research and policy efforts are critical to assess the extent to which pharmacological management of comorbidities affects quality of life and functioning in patients with ASD while continuing to optimize clinical guidelines, to ensure effective care for this growing population.


Assuntos
Transtorno do Espectro Autista/economia , Comorbidade , Acesso aos Serviços de Saúde/estatística & dados numéricos , Seguro/normas , Adolescente , Anfetaminas/administração & dosagem , Anfetaminas/uso terapêutico , Cloridrato de Atomoxetina/administração & dosagem , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Espectro Autista/epidemiologia , Bupropiona/administração & dosagem , Bupropiona/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Mineração de Dados/métodos , Mineração de Dados/estatística & dados numéricos , Transtorno Depressivo Maior/tratamento farmacológico , Cloridrato de Dexmetilfenidato/administração & dosagem , Cloridrato de Dexmetilfenidato/uso terapêutico , Dextroanfetamina/administração & dosagem , Dextroanfetamina/uso terapêutico , Feminino , Humanos , Seguro/estatística & dados numéricos , Dimesilato de Lisdexanfetamina/administração & dosagem , Dimesilato de Lisdexanfetamina/uso terapêutico , Masculino , Programas de Assistência Gerenciada/organização & administração , Programas de Assistência Gerenciada/estatística & dados numéricos , Prevalência , Estudos Retrospectivos
16.
Harm Reduct J ; 18(1): 57, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016137

RESUMO

BACKGROUND: For people with opioid use disorder who are not responding to oral opioid agonist treatment, evidence supports the effectiveness of injectable opioid agonist treatment with injectable hydromorphone (an opioid analgesic) and diacetylmorphine (pharmaceutical grade heroin). While this treatment is effective at reducing illicit opioid use, concurrent cocaine use is prevalent. Dextroamphetamine (a central nervous system stimulant) has been found to be a safe and effective treatment for cocaine dependence among people receiving injectable opioid agonist treatment in Europe. We present the first report of dextroamphetamine prescribing offered for the treatment of stimulant use disorder among a patient receiving iOAT outside of a clinical trial. This case report can be used to inform clinical practice in the treatment of cocaine use disorder, an area where interventions are currently lacking. CASE PRESENTATION: Dextroamphetamine was prescribed to a 51-year-old male who was diagnosed with concurrent opioid and stimulant use disorder in an injectable opioid agonist treatment clinic in Vancouver, Canada. He reported smoking crack cocaine daily for more than two decades and was experiencing health consequences associated with this use. He presented to his routine physician visit with the goal of reducing his cocaine use and was prescribed dextroamphetamine for the treatment of stimulant use disorder. After 4-weeks the patient was tolerating the medication with no observed adverse events and was achieving his therapeutic goal of reducing his cocaine use. CONCLUSIONS: Dextroamphetamine can be prescribed to support patients with stimulant use disorder to reduce or stop their use of cocaine. The case demonstrated that when dextroamphetamine was prescribed, a significant reduction in cocaine use was experienced among a patient that had been regularly using cocaine on a daily basis for many years. Daily contact with care for the opioid medication promoted adherence to the stimulant medication and allowed for monitoring of dose and tolerance. Settings where patients are in regular contact with care such as oral and injectable opioid agonist treatment clinics serve as a suitable location to integrate dextroamphetamine prescribing for patients that use illicit stimulants to reduce use and associated harms.


Assuntos
Estimulantes do Sistema Nervoso Central , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Canadá , Preparações de Ação Retardada/uso terapêutico , Dextroanfetamina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
17.
Exp Clin Psychopharmacol ; 29(4): 308-318, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32297783

RESUMO

There has been a lack of research on the third area of impairment noted in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-"occupational functioning." It is important to understand the impact of common treatments for attention-deficit/hyperactivity disorder (ADHD) in occupational settings. Twenty individuals with ADHD between ages 16 and 25 participated in a double-blind, placebo controlled evaluation of 40 mg lisdexamfetamine dimesylate in a setting designed to approximate a restaurant workplace with associated, simulated food delivery. Outcome measures included ratings of performance, as well as behavioral productivity. Results indicated that participants completed more workplace tasks when on medication, relative to placebo. Ratings of job application quality, job interview performance, and delivery outcomes were not significantly different on medication versus placebo. These results suggest positive effects of medication in a workplace environment, but also a need for study of additional interventions to support workplace-related behavior and functioning. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Dimesilato de Lisdexanfetamina , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dextroanfetamina/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Dimesilato de Lisdexanfetamina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
19.
Eur J Clin Pharmacol ; 77(1): 107-115, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32803292

RESUMO

PURPOSE: The aim of this study was to analyse whether the global trend in drug prescriptions for attention-deficit hyperactivity disorders (ADHD), as observed during the last years and often criticized as medicalization, have remained stable or shifted. METHODS: This observational study was based on a secondary analysis of data from a large German database including patients with an ADHD diagnosis between 2008 and 2018. Prescription data comprised all important ADHD drugs. RESULTS: A total of 620 practices delivered data from a total of 77,504 patients (31% of them females) with a diagnosis of AHDH. Nearly 38% (29,396/77,504) of all patients received, at least, one prescription for an ADHS medicine between 2008 and 2018. The number of patients receiving a drug steadily increased annually until 2012 and then slowly fell, but unevenly distributed across the age groups. While the number of younger patients ( ≤ 16 years) receiving a prescription fell by 24% and the defined daily doses (DDDs) remained stable, the number of patients between 17 and 24 years receiving a prescription increased by 113% and the DDDs by 150%. Respectively, the number of older adults (≥ 25 years) with a prescription increased by 355% and the DDDs by 515%. Nearly one-third of older adults received an ADHD medicine only once. CONCLUSION: The ever-increasing prescription of ADHD medicines stopped some years ago for children. ADHS and its pharmacological management are increasingly observed among older adolescents and adults, with a different pattern of drug persistence compared with children.


Assuntos
Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Padrões de Prática Médica/tendências , Adolescente , Adulto , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Pré-Escolar , Dextroanfetamina/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Alemanha , Guanfacina/uso terapêutico , Humanos , Masculino , Metilfenidato/uso terapêutico , Adulto Jovem
20.
PLoS One ; 15(11): e0241968, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33216781

RESUMO

INTRODUCTION AND AIMS: The non-medical use of prescription stimulants such as methylphenidate, dexamphetamine and modafinil is increasing in popularity within tertiary academic settings. There is a paucity of information on awareness, attitudes, and acceptability by professionals of use in this context. This study aimed to investigate professionals' knowledge of and attitudes towards the use of cognitive enhancers (CEs) in academic settings, and their willingness to use a hypothetical CE. DESIGN AND METHODS: A mail survey was sent to doctors, pharmacists, nurses, accountants and lawyers in New Zealand. These disciplines were chosen as they require professional registration to practice. The questionnaire comprised four sections: (1) demographics, (2) knowledge of CEs, (3) attitudes towards the use of CEs, and (4) willingness to use hypothetical CEs. RESULTS: The response rate was 34.5% (414/1200). Overall, participants strongly disagreed that it was fair to allow university students to use CEs for cognitive enhancement (Mdn = 1, IQR: 1,3), or that it is ethical for students without a prescription to use cognitive enhancers for any reason (Mdn = 1, IQR: 1,2). Professions differed in their attitudes towards whether it is ethical for students without a prescription to use CEs for any reason (p = 0.001, H 31.527). DISCUSSION AND CONCLUSION: Divergent views and lack of clear consensus within professions and between professionals on the use of CEs have the potential to influence both professionals and students as future professionals. These divergent views may stem from differences in the core values of self-identity as well as extrinsic factors of acceptability within the profession in balancing the elements of opportunity, fairness and authenticity in cognitive enhancement. Further research is required to inform the development of policy and guidelines that are congruent with all professions.


Assuntos
Cognição/efeitos dos fármacos , Pessoal de Saúde/psicologia , Medicamentos sob Prescrição/uso terapêutico , Adulto , Idoso , Atitude do Pessoal de Saúde , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dextroanfetamina/uso terapêutico , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Metilfenidato/uso terapêutico , Pessoa de Meia-Idade , Modafinila/uso terapêutico , Nova Zelândia , Estudantes/psicologia , Inquéritos e Questionários , Universidades , Adulto Jovem
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