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Importance: Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose escalation beyond US Food and Drug Administration recommendations is associated with positive risk benefits is unclear. Objective: To investigate the impact, based on averages, of stimulant doses on treatment outcomes in adults with ADHD and to determine, based on averages, whether unlicensed doses are associated with positive risk benefits compared with licensed doses. Data Sources: Twelve databases, including published (PubMed, Cochrane Library, Embase, Web of Sciences) and unpublished (ClinicalTrials.gov) literature, up to February 22, 2023, without language restrictions. Study Selection: Two researchers independently screened records to identify double-blinded randomized clinical trials of stimulants against placebo in adults (18 years and older) with ADHD. Data Extraction and Synthesis: Aggregate data were extracted and synthesized in random-effects dose-response meta-analyses and network meta-analyses. Main Outcome Measures: Change in ADHD symptoms and discontinuations due to adverse events. Results: A total of 47 randomized clinical trials (7714 participants; mean age, 35 (SD, 11) years; 4204 male [56%]) were included. For methylphenidate, dose-response curves indicated additional reductions of symptoms with increments in doses, but the gains were progressively smaller and accompanied by continued additional risk of adverse events dropouts. Network meta-analyses showed that unlicensed doses were associated with greater reductions of symptoms compared with licensed doses (standardized mean difference [SMD], -0.23; 95% CI, -0.44 to -0.02; very low certainty of evidence), but the additional gain was small and accompanied by increased risk of adverse event dropouts (odds ratio, 2.02; 95% CI, 1.19-3.43; moderate certainty of evidence). For amphetamines, the dose-response curve approached a plateau and increments in doses did not indicate additional reductions of symptoms, but there were continued increments in the risk of adverse event dropouts. Network meta-analysis did not identify differences between unlicensed and licensed doses for reductions of symptoms (SMD, -0.08; 95% CI, -0.24 to 0.08; very low certainty of evidence). Conclusions and Relevance: Based on group averages, unlicensed doses of stimulants may not have positive risk benefits compared with licensed doses for adults with ADHD. In general, practitioners should consider unlicensed doses cautiously. Practitioners may trial unlicensed doses if needed and tolerated but should be aware that there may not be large gains in the response to the medication with those further increments in dose. However, the findings are averages and will not generalize to every patient.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Adulto , Masculino , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/efectos adversos , Metilfenidato/uso terapéutico , Anfetaminas/uso terapéutico , Resultado del TratamientoRESUMEN
This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.
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3,4-Metilenodioxianfetamina , Estimulantes del Sistema Nervioso Central , Metanfetamina , N-Metil-3,4-metilenodioxianfetamina , Humanos , Anfetamina/efectos adversos , N-Metil-3,4-metilenodioxianfetamina/farmacología , Estimulantes del Sistema Nervioso Central/efectos adversos , Metanfetamina/efectos adversosAsunto(s)
Estimulantes del Sistema Nervioso Central , Enfermedades del Recién Nacido , Enfermedades del Prematuro , Recién Nacido , Humanos , Cafeína/uso terapéutico , Apnea/tratamiento farmacológico , Recien Nacido Prematuro , Estimulantes del Sistema Nervioso Central/efectos adversos , Enfermedades del Prematuro/tratamiento farmacológicoRESUMEN
OBJECTIVES: To characterize and compare the type and frequency of a range of common and uncommon adverse effects (AEs) associated with α-2 adrenergic agonist (A2A) and stimulant treatment of attention-deficit/hyperactivity disorder at preschool-age as well as to evaluate the impact of age on common AEs. STUDY DESIGN: This was a retrospective electronic medical record review of children <72 months of age (n = 497) evaluated at outpatient developmental-behavioral pediatric practices at 7 US academic medical centers within the Developmental-Behavioral Pediatrics Research Network. Data on AEs were abstracted for children who had treatment initiated by a developmental-behavioral pediatrician with an A2A or stimulant medication between January 2013 and July 2017; follow-up was complete by February 2019. RESULTS: A2A and stimulants had distinctive AE profiles. A2A compared with stimulants had a greater proportion with daytime sleepiness and headaches; stimulants had significantly greater proportions for most other AE, including moodiness/irritability, difficulty with sleep, appetite suppression, stomachaches, skin picking/repetitive behaviors, withdrawn behavior, and weight loss. Younger age was associated with disruptive behavior and difficulty with sleep. CONCLUSIONS: Stimulants had a greater rate of most AEs compared with A2A. AE profiles, together with efficacy, should inform clinical decision-making. Prospective randomized clinical trials are needed to fully compare efficacy and AE profiles of A2A and stimulants.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Pediatría , Niño , Preescolar , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estudios Retrospectivos , Estudios Prospectivos , Estimulantes del Sistema Nervioso Central/efectos adversos , Agonistas Adrenérgicos/uso terapéuticoRESUMEN
O consumo de psicoestimulantes tem crescido exponencialmente, sobretudo entre estudantes de medicina, na busca por aumentar o rendimento acadêmico. Atualmente, a extensa carga horária de aulas e estudos, exigências de produtividade e altos níveis de estresse podem desencadear o uso. Objetivo: Analisar o uso de psicoestimulantes por estudantes do curso de Medicina de um Centro Universitário privado em Minas Gerais. Métodos: Foi realizado um estudo descritivo, quantitativo, com delineamento transversal entre os discentes do 1° ao 5° ano do curso de Medicina no 2° semestre de 2021. Os participantes responderam ao questionário semi-estruturado elaborado pelos autores. Os dados obtidos foram tabulados no software Statistical Product and Service Solutions. Resultados: Dos 244 entrevistados, cerca de 57.4% faziam uso de algum psicoestimulante. Houve maior uso entre os estudantes do 2° ano e as principais substâncias utilizadas foram: cafeína (85%), energético (65%) e metilfenidato (60%). A melhora na concentração (97%) foi o efeito mais percebido pelos usuários, seguido de redução do sono (83%) e melhora de raciocínio (80%). Muitos consideraram que os estimulantes cerebrais têm o potencial de melhorar o rendimento acadêmico, mas pode reduzir a qualidade do sono e consequentemente torná-los susceptíveis a outras enfermidades. Conclusão: É notável que existe uso abusivo de estimulantes cerebrais, sendo fundamental o trabalho em conjunto entre instituição de ensino e familiares, em prol da prevenção e do controle de danos causados por esse hábito
The consumption of psychostimulants has grown exponentially, especially among medical students, in the quest to increase academic performance. Currently, the extensive workload of classes and studies, productivity demands and high levels of stress can trigger use. Objective: To analyze the use of psychostimulants by medical students at a private University Center in Minas Gerais. Methods: A descriptive, quantitative, cross-sectional study was carried out among students from the 1st to the 5th year of the medicine course in the 2nd semester of 2021. The participants answered the semi-structured questionnaire prepared by the authors. The data obtained were tabulated in the Statistical Product and Service Solutions software. Results: Of the 244 respondents, about 57.4% used some psychostimulant. There was greater use among 2nd year students and the main substances used were: caffeine (85%), energy drink (65%) and methylphenidate (60%). Improved concentration (97%) was the effect most perceived by users, followed by reduced sleep (83%) and improved thinking (80%). Many considered that brain stimulants have the potential to improve academic performance, but can reduce sleep quality and consequently make them susceptible to other illnesses. Conclusion: It is notable that there is abusive use of brain stimulants, and it is essential to work together between educational institutions and family members in order to prevent and control the damage caused by this habit
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Humanos , Masculino , Femenino , Adulto , Adulto Joven , Estudiantes de Medicina , Rendimiento Académico , Estimulantes del Sistema Nervioso Central/efectos adversos , Atención/efectos de los fármacos , Cafeína/efectos adversos , Consumo de Bebidas Alcohólicas , Paullinia/efectos adversos , Bebidas Energéticas/efectos adversos , Anfetaminas/efectos adversos , Metilfenidato/efectos adversosRESUMEN
BACKGROUND: There is insufficient evidence to support treatment recommendations for preschool children aged 3-5 years with attention-deficit hyperactivity disorder (ADHD). We aimed to investigate the efficacy and safety of methylphenidate and behavioural parent training in reducing the frequency and severity of symptoms and improving global functioning in preschool children with ADHD. METHODS: We did an 8-week, randomised, double-blind, placebo-controlled and sham behavioural parent training-controlled clinical trial (the MAPPA Study) in children aged 3-5 years with moderate-to-severe ADHD. The trial was conducted at the Institute of Psychiatry, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil. Participants were randomly assigned (1:1:1) to receive immediate-release methylphenidate plus educational intervention (sham behavioural parent training), placebo medication plus behavioural parent training, or placebo medication plus educational intervention. Randomisation was done by an independent research manager by use of a permuted block randomisation procedure. Parents, teachers, study staff, and evaluators remained masked to group allocation. Methylphenidate and placebo were titrated to a maximum dose of 1·25 mg/kg per day administered orally twice daily, and behavioural parent training and the educational intervention were delivered weekly through 90 min sessions with both the child and parent, conducted by two psychologists or learning therapists. The primary outcomes were parents' and teachers' composite scores of the Swanson, Nolan, and Pelham-IV scale (SNAP-IV-P/T), the Clinical Global Impressions Severity (CGI-S) scale, and the Children's Global Assessment Scale (CGAS). This trial is registered with ClinicalTrials.gov, NCT02807870, and is now complete. All participants were invited to participate in an open observational follow-up, which is ongoing. FINDINGS: Between Aug 21, 2016, and Oct 21, 2019, 153 children were randomly assigned to receive methylphenidate plus the educational intervention (n=51), placebo plus behavioural parent training (n=51), or placebo plus the educational intervention (n=51). Nine (6%) children discontinued treatment. All participants were included in the intention-to-treat analysis. Children in the methylphenidate plus educational intervention group showed greater reductions in the SNAP-IV-P/T (endpoint mean difference -3·93 [95% CI -7·14 to -0·73], p=0·049; effect size -0·55 [95% CI -0·99 to -0·10]) and CGI-S scores (endpoint mean difference -0·49 [-0·82 to -0·17], p=0·0088; effect size -0·70 [-1·16 to -0·24]) and a greater increase in CGAS scores (endpoint mean difference 5·25 [95% CI 2·09 to 8·40], p=0·0036; effect size 0·80 [95% CI 0·32 to 1·28]) than children in the placebo plus educational intervention group. Children in the placebo plus behavioural parent training group did not have significantly different SNAP-IV-P/T scores (endpoint mean difference -3·18 [95% CI -6·38 to 0·02], p=0·077; effect size -0·44 [95% CI -0·89 to 0·003]) or CGI-S scores (endpoint mean difference -0·35 [-0·68 to -0·03], p=0·052; effect size -0·50 [-0·96 to -0·04]) compared to children in the placebo plus educational intervention group, but they had a greater increase in CGAS scores compared to the placebo plus educational intervention group (endpoint mean difference 3·69 [0·53 to 6·85], p=0·033; effect size 0·56 [0·08 to 1·04]). Children in the methylphenidate plus educational intervention versus placebo plus behavioural parent training group did not have statistically or clinically significant differences in primary outcomes. Children in the methylphenidate plus educational intervention group had more mild adverse events than the other two groups, and there were no between-group differences for moderate or severe adverse events. INTERPRETATION: Methylphenidate was effective in reducing ADHD symptoms and improving functionality, and behavioural parent training was effective in improving functionality for preschool children with ADHD after 8 weeks of treatment. FUNDING: São Paulo Research Foundation and Brazilian National Council for Scientific and Technological Development.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Preescolar , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Brasil , Estimulantes del Sistema Nervioso Central/uso terapéutico , Estimulantes del Sistema Nervioso Central/efectos adversos , Metilfenidato/uso terapéutico , Metilfenidato/efectos adversos , Nucleotidiltransferasas/uso terapéutico , Padres/educaciónRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) symptoms usually impairs academic achievement and can trigger the onset of medication. Methylphenidate is a drug widely prescribed to treat ADHD. However, systematic reviews of randomized clinical trials suggest that it does not lead to great improvements in academic performance. Thus, we aimed to evaluate the evidence on the "real-world" effectiveness of methylphenidate in improving the academic achievement of ADHD students. METHODS: We conducted a systematic review of observational studies retrieved from five electronic databases, besides a manual search and search in grey literature. Studies evaluating treatment with methylphenidate compared to no treatment or other pharmacological/non-pharmacological alternatives used in ADHD were included. The risk of bias of the selected studies was assessed using adapted versions of the Newcastle-Ottawa Scale. RESULTS AND DISCUSSION: Nine studies (from ten reports) were included in the review: four cohorts, two before-and-after designs and three cross-sectional studies. They involved 12,269 children and adolescents aged 6-18 years. The doses of methylphenidate ranged from 10 to 72 mg/day, and the duration of the treatment from 2.6 months to 4.25 years. Five of these studies concluded that methylphenidate improves academic performance. However, three of the four lowest-bias risk studies concluded that the drug is ineffective. Five studies assessed the long-term use of methylphenidate, and four of them concluded that it does not result in better outcomes in the school setting. Most included studies had considerable limitations and significant heterogeneity regarding methodological design and academic performance measurement criteria. WHAT IS NEW AND CONCLUSION: Although some studies indicate that the short-term use of methylphenidate may improve outcomes in the school environment, the available evidence does not support the establishment of adequate conclusions about the real benefits of methylphenidate in the academic improvement of ADHD students.
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Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Metilfenidato/uso terapéutico , Estudiantes , Éxito Académico , Adolescente , Estimulantes del Sistema Nervioso Central/efectos adversos , Niño , Estudios Transversales , Humanos , Metilfenidato/efectos adversos , Estudios Observacionales como AsuntoRESUMEN
OBJECTIVE: To evaluate perspectives of youth regarding diverted stimulant use among a contemporary sample of adolescents and young adults. STUDY DESIGN: This study used MyVoice, a longitudinal national text message survey of American youth. In February 2019, 1228 MyVoice youth were asked 4 open-ended questions to elicit their perspectives on diverted stimulant use. Responses were assessed using thematic analysis, and quantitative results were summarized using descriptive statistics. RESULTS: Of 1228 youth, 906 responded to at least one survey question (relative risk, 74%). Respondents' ages ranged from 14 to 24 years with a mean age of 18.8 ± 2.9 years, 57% were female, and 66% identified as White. Peer pressure and coping were commonly perceived reasons for diversion, and respondents believed that many youth misuse stimulants. Many were aware of health risks of misuse, but few mentioned potential legal consequences. Youth thought stimulants could be obtained from peers, people with a prescription, dealers, and family, and some mentioned access through unnecessary prescriptions. CONCLUSIONS: The perspectives of a national sample of youth suggest that stimulant diversion continues to be a significant problem among American youth, with many noting that diverted stimulants are easy to obtain and are used to self-treat mental health issues. Standardized interventions at schools and in healthcare settings, as well as universal screening for diversion and mental health conditions, may combat this public health concern.
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Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/administración & dosificación , Conocimientos, Actitudes y Práctica en Salud , Mal Uso de Medicamentos de Venta con Receta/psicología , Adolescente , Adulto , Estimulantes del Sistema Nervioso Central/efectos adversos , Femenino , Humanos , Estudios Longitudinales , Masculino , Influencia de los Compañeros , Mal Uso de Medicamentos de Venta con Receta/estadística & datos numéricos , Medición de Riesgo , Encuestas y Cuestionarios , Envío de Mensajes de Texto , Estados Unidos , Adulto JovenRESUMEN
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.
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Enfermedades Transmisibles/etiología , Susceptibilidad a Enfermedades , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/inmunología , Sistema Inmunológico/efectos de los fármacos , Animales , Biomarcadores , Estimulantes del Sistema Nervioso Central/efectos adversos , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/metabolismo , Susceptibilidad a Enfermedades/inmunología , Infecciones por VIH/etiología , Infecciones por VIH/metabolismo , Humanos , Inmunidad/efectos de los fármacos , Inmunomodulación , Vigilancia de la Población , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Receptores Toll-Like/metabolismoRESUMEN
OBJECTIVE: To describe the clinical and psychosocial characteristics, and their hypothesized interrelations, as it pertains to risk for stimulant diversion (sharing, selling, or trading) for adolescents in pediatric primary care treatment for attention-deficit/hyperactivity disorder. METHODS: Baseline data for 341 adolescents in a cluster-randomized controlled trial of stimulant diversion prevention in pediatric primary care (NCT_03080259) were used to (1) characterize diversion and newly measured risk factors, (2) examine their associations with age and sex, and (3) test whether associations among risk factors were consistent with model-implied predictions. Data were collected through multi-informant electronic surveys from adolescents and parents. RESULTS: Diversion was rare (1%) in this sample (Mage = 15, SD = 1.5, 74% male participants). Older age was associated with being approached to divert (r = 0.25, p < 0.001) and higher risk on variables pertinent to stimulant treatment, such as treatment disclosure (r = 0.12, p < 0.05), tolerance for stimulant misuse and diversion (r = 0.17, p < 0.05), and peer norms favorable to stimulant misuse and diversion (r values = 0.15-0.34, p < 0.001). Sex differences were minimal. Variables from our conceptual model and specific to stimulants (e.g., perceived likelihood of negative consequences from diversion and schoolmate stimulant misuse/diversion) were related in multivariable regressions to hypothesized immediate precursors of diversion (e.g., diversion intentions). CONCLUSION: Although diversion was rare for these primary care-treated adolescents, risk levels appear to be higher for older adolescents. Prevention may be most effective by capitalizing on current psychosocial strengths and discussing stimulant-specific attitudes, behaviors, and social norms before vulnerability to diversion increases in the final years of high school and into college.
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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Adolescente , Anciano , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/efectos adversos , Niño , Femenino , Humanos , Masculino , Desvío de Medicamentos bajo Prescripción , Atención Primaria de Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children, adolescents, and adults. In some countries, methylphenidate is the first option to treat adults with moderate or severe ADHD. However, evidence on the efficacy and adverse events of immediate-release (IR) methylphenidate in the treatment of ADHD in adults is limited and controversial. OBJECTIVES: To evaluate the efficacy and harms (adverse events) of IR methylphenidate for treating ADHD in adults. SEARCH METHODS: In January 2020, we searched CENTRAL, MEDLINE, Embase, eight additional databases and three trial registers. We also searched internal reports on the European Medicines Agency and the US Food and Drug Administration websites. We checked citations of included trials to identify additional trials not captured by the electronic searches. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing IR methylphenidate, at any dose, with placebo or other pharmacological interventions (including extended-release formulations of methylphenidate) for ADHD in adults. Primary outcomes comprised changes in the symptoms of ADHD (efficacy) and harms. Secondary outcomes included changes in the clinical impression of severity and improvement, level of functioning, depression, anxiety and quality of life. Outcomes could have been rated by investigators or participants. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently on the characteristics of the trials, participants, interventions; outcomes and financial conflict of interests. We resolved disagreements by discussion or consulting a third review author. We obtained additional, unpublished information from the authors of one included trial that had reported efficacy data in a graph. We calculated mean differences (MDs) or standardized MDs (SMDs) with 95% confidence intervals (CIs) for continuous data reported on the same or different scales, respectively. We summarized dichotomous variables as risk ratios (RRs) with 95% CI. MAIN RESULTS: We included 10 trials published between 2001 and 2016 involving 497 adults with ADHD. Three trials were conducted in Europe and one in Argentina; the remaining trials did not report their location. The RCTs compared IR methylphenidate with placebo, an osmotic-release oral system (OROS) of methylphenidate (an extended-release formulation), an extended-release formulation of bupropion, lithium, and Pycnogenol® (maritime pine bark extract). Participants comprised outpatients, inpatients in addiction treatment, and adults willing to attend an intensive outpatient program for cocaine dependence. The duration of the follow-up ranged from 6 to 18 weeks. IR methylphenidate versus placebo We found very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce symptoms of ADHD when measured with investigator-rated scales (MD -20.70, 95% CI -23.97 to -17.43; 1 trial, 146 participants; end scores; Adult ADHD Investigator Symptom Report Scale (AISRS), scored from 0 to 54), but the evidence is uncertain. The effect of IR methylphenidate on ADHD symptoms when measured with participant-rated scales was moderate, but the certainty of the evidence is very low (SMD -0.59, 95% CI -1.25 to 0.06; I2 = 69%; 2 trials, 138 participants; end scores). There is very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce the clinical impression of the severity of ADHD symptoms (MD -0.57, 95% CI -0.85 to -0.28; 2 trials, 139 participants; I2 = 0%; change and end scores; Clinical Global Impression (CGI)-Severity scale (scored from 1 (very much improved) to 7 (very much worse))). There is low-certainty evidence that, compared with placebo, IR methylphenidate may slightly impact the clinical impression of an improvement in symptoms of ADHD (MD -0.94, 95% CI -1.37 to -0.51; 1 trial, 49 participants; end scores; CGI-Improvement scale (scored from 1 (very much improved) to 7 (very much worse))). There is no clear evidence of an effect on anxiety (MD -0.20, 95% CI -4.84 to 4.44; 1 trial, 19 participants; change scores; Hamilton Anxiety Scale (HAM-A; scored from 0 to 56); very low-certainty evidence) or depression (MD 2.80, 95% CI -0.09 to 5.69; 1 trial, 19 participants; change scores; Hamilton Depression Scale (HAM-D; scored from 0 to 52); very low-certainty evidence) in analyses comparing IR methylphenidate with placebo. IR methylphenidate versus lithium Compared with lithium, it is uncertain whether IR methylphenidate increases or decreases symptoms of ADHD (MD 0.60, 95% CI -3.11 to 4.31; 1 trial, 46 participants; end scores; Conners' Adult ADHD Rating Scale (scored from 0 to 198); very low-certainty evidence); anxiety (MD -0.80, 95% CI -4.49 to 2.89; 1 trial, 46 participants; end scores; HAM-A; very low-certainty evidence); or depression (MD -1.20, 95% CI -3.81 to 1.41, 1 trial, 46 participants; end scores; HAM-D scale; very low-certainty evidence). None of the included trials assessed participant-rated changes in symptoms of ADHD, or clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium. Adverse events were poorly assessed and reported. We rated all trials at high risk of bias due to selective outcome reporting of harms and masking of outcome assessors (failure to blind outcome assessor to measure adverse events). Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate in these trials increased the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96). Cardiovascular adverse events were reported inconsistently, preventing a comprehensive analysis. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively. We considered four trials to have notable concerns of vested interests influencing the evidence, and authors from two trials omitted information related to the sources of funding and conflicts of interest. AUTHORS' CONCLUSIONS: We found no certain evidence that IR methylphenidate compared with placebo or lithium can reduce symptoms of ADHD in adults (low- and very low-certainty evidence). Adults treated with IR methylphenidate are at increased risk of gastrointestinal and metabolic-related harms compared with placebo. Clinicians should consider whether it is appropriate to prescribe IR methylphenidate, given its limited efficacy and increased risk of harms. Future RCTs should explore the long-term efficacy and risks of IR methylphenidate, and the influence of conflicts of interest on reported effects.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/administración & dosificación , Metilfenidato/administración & dosificación , Adulto , Antidepresivos de Segunda Generación/administración & dosificación , Ansiedad/tratamiento farmacológico , Sesgo , Bupropión/administración & dosificación , Estimulantes del Sistema Nervioso Central/efectos adversos , Depresión/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Femenino , Flavonoides/administración & dosificación , Humanos , Compuestos de Litio/administración & dosificación , Masculino , Metilfenidato/efectos adversos , Persona de Mediana Edad , Placebos/administración & dosificación , Extractos Vegetales/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Adulto JovenRESUMEN
RATIONALE: The abuse of psychostimulants has adverse consequences on the physiology of the central nervous system. In Argentina, and other South American countries, coca paste or "PACO" (cocaine and caffeine are its major components) is massively consumed with deleterious clinical consequences for the health and well-being of the general population. A scant number of studies have addressed the consequences of stimulant combination of cocaine and caffeine on the physiology of the somatosensory thalamocortical (ThCo) system. OBJECTIVES: Our aim was to study ion conductances that have important implications regulating sleep-wake states 24-h after an acute or chronic binge-like administration of a cocaine and caffeine mixture following previously analyzed pasta base samples ("PACO"-like binge") using mice. METHODS: We randomly injected (i.p.) male C57BL/6JFcen mice with a binge-like psychostimulants regimen during either 1 day (acute) or 1 day on/1 day off during 13 days for a total of 7 binges (chronic). Single-cell patch-clamp recordings of VB neurons were performed in thalamocortical slices 24 h after the last psychostimulant injection. We also recorded EEG/EMG from mice 24 h after being systemically treated with chronic administration of cocaine + caffeine versus saline, vehicle. RESULTS: Our results showed notorious changes in the intrinsic properties of the VB nucleus neurons that persist after 24-h of either acute or chronic binge administrations of combined cocaine and caffeine ("PACO"-like binge). Functional dysregulation of HCN (hyperpolarization-activated cyclic nucleotide-gated) and T-type VGC (voltage-gated calcium) channels was described 24-h after acute/chronic "PACO"-like administrations. Furthermore, intracellular basal [Ca2+] disturbances resulted a key factor that modulated the availability and the activation of T-type channels, altering T-type "window currents." As a result, all these changes ultimately shaped the low-threshold spikes (LTS)-associated Ca2+ transients, regulated the membrane excitability, and altered sleep-wake transitions. CONCLUSION: Our results suggest that deleterious consequences of stimulants cocaine and caffeine combination on the thalamocortical physiology as a whole might be related to potential neurotoxic effects of soaring intracellular [Ca2+].
Asunto(s)
Cafeína/efectos adversos , Canales de Calcio Tipo T/metabolismo , Estimulantes del Sistema Nervioso Central/efectos adversos , Cocaína/efectos adversos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Neuronas/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Cafeína/administración & dosificación , Estimulantes del Sistema Nervioso Central/administración & dosificación , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Cocaína/administración & dosificación , Sinergismo Farmacológico , Masculino , Ratones , Ratones Endogámicos C57BL , Técnicas de Placa-Clamp , Distribución Aleatoria , Trastornos de la Transición Sueño-Vigilia/inducido químicamente , América del Sur , Tálamo/efectos de los fármacos , Tálamo/metabolismoRESUMEN
Caffeine is the most consumed psychostimulant worldwide. Its use among children is controversial. Although it produces an increase in brain activity, it could hamper growth and development in young consumers. Therefore, the aim of this review was to recognize changes produced by caffeine in children under 12 years of age and to identify the relevant alterations and the conditions of their occurrence. A systematic review of the literature was carried out using PRISMA. Initially, 5468 articles were found from the EBSCO, ScienceDirect, PubMed, and Clarivate Analytics databases. In this review, were retained 24 published articles that met the inclusion criteria. The results obtained showed that caffeine consumption hampers children's growth and development. In contrast, it supports the activation of the central nervous system and brain energy management.
Asunto(s)
Encéfalo , Cafeína , Estimulantes del Sistema Nervioso Central , Encéfalo/efectos de los fármacos , Cafeína/efectos adversos , Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/efectos adversos , Estimulantes del Sistema Nervioso Central/farmacología , Niño , Desarrollo Infantil , HumanosRESUMEN
Los fármacos estimulantes se usan, habitualmente, en la población pediátrica para tratar el trastorno por déficit de atención e hiperactividad, y sus efectos secundarios están bien descritos. Sin embargo, la tricotilomanía no aparece como uno de ellos. En la literatura, hay algunos casos publicados de tricotilomanía en relación con la administración de metilfenidato y dextroanfetamina. Se presentan dos casos de tricotilomanía de nueva aparición en niños en seguimiento en nuestro Centro por déficit de atención e hiperactividad y en tratamiento con fármacos psicoestimulantes (metilfenidato y lisdexanfetamina), como probable efecto adverso de estos.
Stimulant drugs are commonly used in pediatric population in the treatment of attention deficit hyperactivity disorder, and their side effects are well described, however trichotillomania does not appear as one of them. In the literature we found some published cases of trichotillomania in relation to methylphenidate and dextroamphetamine. We present two cases of new-onset trichotillomania in children followed up in our center by attention deficit hyperactivity disorder and treated with psychostimulant drugs (methylphenidate and lisdexamfetamine), as a probable adverse effect of this treatment
Asunto(s)
Humanos , Masculino , Niño , Tricotilomanía/inducido químicamente , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/efectos adversosRESUMEN
Stimulant drugs are commonly used in pediatric population in the treatment of attention deficit hyperactivity disorder, and their side effects are well described, however trichotillomania does not appear as one of them. In the literature we found some published cases of trichotillomania in relation to methylphenidate and dextroamphetamine. We present two cases of new-onset trichotillomania in children followed up in our center by attention deficit hyperactivity disorder and treated with psychostimulant drugs (methylphenidate and lisdexamfetamine), as a probable adverse effect of this treatment.
Los fármacos estimulantes se usan, habitualmente, en la población pediátrica para tratar el trastorno por déficit de atención e hiperactividad, y sus efectos secundarios están bien descritos. Sin embargo, la tricotilomanía no aparece como uno de ellos. En la literatura, hay algunos casos publicados de tricotilomanía en relación con la administración de metilfenidato y dextroanfetamina. Se presentan dos casos de tricotilomanía de nueva aparición en niños en seguimiento en nuestro Centro por déficit de atención e hiperactividad y en tratamiento con fármacos psicoestimulantes (metilfenidato y lisdexanfetamina), como probable efecto adverso de estos.
Asunto(s)
Estimulantes del Sistema Nervioso Central/efectos adversos , Dimesilato de Lisdexanfetamina/efectos adversos , Metilfenidato/efectos adversos , Tricotilomanía/inducido químicamente , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Humanos , Dimesilato de Lisdexanfetamina/uso terapéutico , Masculino , Metilfenidato/uso terapéuticoRESUMEN
BACKGROUND: Little is known about recent nonmedical prescription tranquilizer and stimulant use trends in Latin America. We tested whether recent trends among students in three South American countries differed by sex over time. METHODS: Three countries independently collected National School Students Survey on Drugs. Students in 8th, 10th, and 12th grades were sampled in Argentina (2007-2014, Nâ¯=â¯328,202), Chile (2007-2015, Nâ¯=â¯136,379), and Uruguay (2007-2016, Nâ¯=â¯32,371). Weighted linear regression models predicted the prevalences and trends over time of past-year nonmedical tranquilizer and stimulant use by country, and tested whether trends differed by sex, adjusting for school type and grade. RESULTS: In Argentina from 2007 to 2014, past-year nonmedical prescription tranquilizer (girls: 2.8 to 2.6%, boys: 2.5 to 2.3%) and stimulant (girls: 1.7 to 1.3%, boys: 1.9 to 1.5%) use trends did not differ by sex. In Chile from 2007 to 2015, nonmedical prescription tranquilizer use trends significantly differed comparing girls (3.9 to 10%) with boys (3.2 to 6.9%); stimulant use trends did not differ comparing girls (1.6 to 2.0%) with boys (2.0 to 1.3%). In Uruguay from 2007 to 2014 and 2014-2016, past-year nonmedical prescription tranquilizer (girls: 5.1 to 6.6%; boys: 2.8 to 4.2%) and stimulant (girls: 1.8 to 0.7%; boys: 1.8 to 0.7%) use trends did not differ by sex. CONCLUSIONS: Trends of nonmedical prescription tranquilizer use recently increased in Chile and Uruguay, widening by sex over time in Chile only. The drivers of increasing tranquilizer use among girls in Chile and Uruguay merit further investigation.
Asunto(s)
Estimulantes del Sistema Nervioso Central/efectos adversos , Instituciones Académicas/tendencias , Estudiantes/psicología , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/psicología , Tranquilizantes/efectos adversos , Adolescente , Argentina/epidemiología , Niño , Chile/epidemiología , Estudios Transversales , Femenino , Humanos , Hipnóticos y Sedantes/efectos adversos , Masculino , Autoinforme , Factores Sexuales , Trastornos Relacionados con Sustancias/diagnóstico , Uruguay/epidemiología , Adulto JovenRESUMEN
Methylphenidate produces its effects via actions on cortical areas involved with attention and working memory, which have a direct role in time estimation judgment tasks. In particular, the prefrontal and parietal cortex has been the target of several studies to understand the effect of methylphenidate on executive functions and time interval perception. However, it has not yet been studied whether acute administration of methylphenidate influences performance in time estimation task and the changes in alpha band absolute power in the prefrontal and parietal cortex. The current study investigates the influence of the acute use of methylphenidate in both performance and judgment in the time estimation interpretation through the alpha band absolute power activity in the prefrontal and parietal cortex. This is a double-blind, crossover study with a sample of 32 subjects under control (placebo) and experimental (methylphenidate) conditions with absolute alpha band power analysis during a time estimation task. We observed that methylphenidate does not influence task performance (p > 0.05), but it increases the time interval underestimation by over 7 s (p < 0.001) with a concomitant decrease in absolute alpha band power in the ventrolateral prefrontal cortex and dorsolateral prefrontal cortex and parietal cortex (p < 0.001). Acute use of methylphenidate increases the time interval underestimation, consistent with reduced accuracy of the internal clock mechanisms. Furthermore, acute use of methylphenidate influences the absolute alpha band power over the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, and parietal cortex.
Asunto(s)
Ritmo alfa/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Juicio/efectos de los fármacos , Metilfenidato/farmacología , Lóbulo Parietal/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Desempeño Psicomotor/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Percepción del Tiempo/efectos de los fármacos , Adulto , Estimulantes del Sistema Nervioso Central/administración & dosificación , Estimulantes del Sistema Nervioso Central/efectos adversos , Estudios Cruzados , Método Doble Ciego , Humanos , Masculino , Metilfenidato/administración & dosificación , Metilfenidato/efectos adversos , Adulto JovenRESUMEN
OBJECTIVE: The aim of the study was to analyze evidence comparing the profile of drugs used to treat ADHD in adult patients. METHOD: Systematic searches were conducted in electronic databases. Randomized, double-blind, parallel controlled trials that evaluated the safety of drugs in ADHD were included. The statistical analyses were conducted by pairwise meta-analyses and mixed treatment comparison (MTC). RESULTS: Ten ( n = 3006) trials were included in the analyses. We observed statistical differences for the following outcomes: decreased appetite between atomoxetine and placebo (odds ratio [OR] = 0.15, 95% credibility interval [CrI] = [0.05, 0.38]) and extended-release mixed amphetamine salts and placebo (OR = 0.06, 95% CrI = [0.00, 0.51]); insomnia between atomoxetine and placebo (OR = 0.48, 95% CrI = [0.27, 0.88]) and extended-release mixed amphetamine salts and placebo (OR = 0.23, 95% CrI = [0.06, 0.76]); sleepiness between atomoxetine and methylphenidate OROS (OR = 0.24, 95% CrI = [0.06, 0.97]); and decreased libido between atomoxetine and placebo (OR = 0.28, 95% CrI = [0.08, 0.90]). CONCLUSION: It was possible to generate evidence about the safety profile of different ADHD drugs.