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Background: Recent epidemiological data has shown a sharp increase in stimulant use among older adults, which is notable as older adults may be especially vulnerable to their cardiovascular effects. Results of recent studies have shown an increase in cardiovascular events among older adults using stimulants; however, little data exists comparing cardiovascular safety of these agents head-to-head. Objective: To determine if the incidence of serious cardiovascular events, including myocardial infarction (MI), stroke/transient ischemic attack (TIA), or arrhythmia, are different in patients taking amphetamine/dextroamphetamine compared with patients taking methylphenidate. Methods: Retrospective chart review of veterans 50 years and older at the Veterans Affairs North Texas Health Care System (VANTHCS) who were first prescribed a stimulant between 2015 and 2021. The primary outcome was the difference in composite cardiovascular events between amphetamine/dextroamphetamine and methylphenidate. Secondary outcomes were the composite cardiovascular endpoints compared individually (MI, stroke/TIA, or arrhythmia). Hazard ratios were calculated based off of a time-to-event analysis displayed using a Kaplan-Meier curve for primary and secondary outcomes. Results: 466 veterans were screened for inclusion, 30 were excluded, and 436 were included. There was no difference found in composite cardiovascular events between the 241 veterans in the amphetamine/dextroamphetamine group and the 195 veterans in the methylphenidate group with 12 (5%) vs 8 (4.1%) events respectively (P =.6635). There was also no difference in time-to-event analysis (P =.4966). Conclusion: In elderly veterans, there was no difference found in incidence of major cardiovascular events with the use of amphetamine/dextroamphetamine compared with methylphenidate. [ABSTRACT FROM AUTHOR]

Purpose: Attention-deficit hyperactivity disorder (ADHD) is becoming more commonly diagnosed in women, consequently, more women of reproductive age are taking ADHD medication, such as dexamphetamine. However, the safety associated with continuing or ceasing dexamphetamine during pregnancy is unclear. This study investigates outcomes associated with the continuation of dexamphetamine during pregnancy compared to those who ceased or were unexposed. Methods: A population-based retrospective cohort of women from Western Australia who had been dispensed dexamphetamine during pregnancy and gave birth between 2003 and 2018. Women had either continued to take dexamphetamine throughout pregnancy (continuers, n = 547) or ceased dexamphetamine before the end of the second trimester (ceasers, n = 297). Additionally, a matched (1:1) comparison group of women who were dispensed an ADHD medication prior to pregnancy but not during pregnancy (unexposed) was included in the study (n = 844). Multivariable generalised linear models were used to compare maternal and neonatal health outcomes. Results: Compared to continuers, ceasers had greater odds of threatened abortion (OR: 2.28; 95%CI: 1.00, 5.15; p = 0.049). The unexposed had some benefits compared to the continuers, which included lower risk of preeclampsia (OR: 0.58; 95%CI: 0.35, 0.97; p = 0.037), hypertension (OR: 0.32; 95%CI: 0.11, 0.93; p = 0.036), postpartum haemorrhage (OR: 0.57; 95%CI: 0.41, 0.80; p = 0.001), neonatal special care unit admittance (OR: 0.16; 95%CI: 0.12, 0.20; p < 0.001) and fetal distress (OR: 0.73; 95%CI: 0.54, 0.99; p = 0.042). Conclusion: Continuing dexamphetamine throughout pregnancy was not associated with an increase in adverse neonatal and maternal health outcomes compared to ceasing. Ceasing dexamphetamine during pregnancy was associated with increased odds of threatened abortion compared with continuing dexamphetamine. However, this is something that requires further investigation due to the small sample size, difficulties examining timing, and the inability to examine spontaneous abortions. The unexposed showed some benefits compared to the continuers, suggesting that where possible the cessation of dexamphetamine prior to pregnancy may be advisable. [ABSTRACT FROM AUTHOR]

Background and Objectives: The risk of serotonin syndrome (SS), especially when linezolid is used concomitantly with methadone, buprenorphine, and/or dextroamphetamine, remains widely unstudied and may limit the options for antimicrobial therapy in these patient populations. Methods: We reviewed all adult encounters on linezolid with concomitant methadone, buprenorphine, and/or dextroamphetamine from April 2016 to June 2022. The primary outcomes included characterizing prescribing preferences and prevalence of confirmed and possible serotonin syndrome using ICD-10 diagnosis codes, cyproheptadine administration, and electronic medical record chart review using the Hunter Serotonin Toxicity Criteria. Results: Overall, 194 encounters were evaluated. 16.5%, 17.8%, and 7.1% were on high dose methadone, buprenorphine, and dextroamphetamine, respectively. Mean duration of overlap with linezolid was 4.6, 3.3, and 7 days respectively. One confirmed and two possible cases of serotonin syndrome were identified. Conclusion: Linezolid may be considered in patients who are concomitantly on methadone, buprenorphine, and/or dextroamphetamine. In our analysis of 194 encounters, one definitive case and two possible cases of SS were identified. Additional real-world studies are necessary to identify if exposure and/or duration may be correlated with an increased risk of serotonin syndrome. [ABSTRACT FROM AUTHOR]

Amphetamine preparations are one of the two categories of stimulant medications approved for the treatment of attention deficit hyperactivity disorder (ADHD). Optimal treatment of ADHD aims to reduce core symptoms for as much of the waking hours as possible, leading to longer-acting delivery formats. In addition, the pediatric population commonly has difficulty swallowing pills and manufacturers have developed a variety of options to facilitate this concern. These include chewable tablets, capsules that may be sprinkled on soft food, liquids and transdermal patches. This article reviews the once-daily extended-release preparations currently available for amphetamine compounds, their pharmacodynamics, and common adverse effects. There is an extensive evidence base supporting use of amphetamine preparations in the treatment of ADHD. Rapid onset of action and a favorable side effect profile make these widely used. The availability of once-daily extended-release chewable tablets, capsules that can be opened and sprinkled, and liquid formulations provides clinicians with multiple options to meet the specific needs of patients with difficulty swallowing whole pills. [ABSTRACT FROM AUTHOR]

Translation of drug targets from preclinical studies to clinical trials has been aided by cross-species behavioral tasks, but evidence for brain-based engagement during task performance is still required. Cross-species progressive ratio breakpoint tasks (PRBTs) measure motivation-related behavior and are pharmacologically and clinically sensitive. We recently advanced elevated parietal alpha power as a cross-species electroencephalographic (EEG) biomarker of PRBT engagement. Given that amphetamine increases breakpoint in mice, we tested its effects on breakpoint and parietal alpha power in both humans and mice. Twenty-three healthy participants performed the PRBT with EEG after amphetamine or placebo in a double-blind design. C57BL/6J mice were trained on PRBT with EEG (n = 24) and were treated with amphetamine or vehicle. A second cohort of mice was trained on PRBT without EEG (n = 40) and was treated with amphetamine or vehicle. In humans, amphetamine increased breakpoint. In mice, during concomitant EEG, 1 mg/kg of amphetamine significantly decreased breakpoint. In cohort 2, however, 0.3 mg/kg of amphetamine increased breakpoint consistent with human findings. Increased alpha power was observed in both species as they reached breakpoint, replicating previous findings. Amphetamine did not affect alpha power in either species. Amphetamine increased effort in humans and mice. Consistent with previous reports, elevated parietal alpha power was observed in humans and mice as they performed the PRBT. Amphetamine did not affect this EEG biomarker of effort. Hence, these findings support the pharmacological predictive validity of the PRBT to measure effort in humans and mice and suggest that this EEG biomarker is not directly reflective of amphetamine-induced changes in effort. [ABSTRACT FROM AUTHOR]

Longer duration of medication use for attention‐deficit hyperactivity disorder (ADHD) was associated with an increased risk of hypertension and arterial disease, a case‐control study has found. Over a 14‐year period, risk of cardiovascular diseases had the steepest increases during the first 3 years of cumulative use, the investigators reported. Study results were published online Nov. 22, 2023, in JAMA Psychiatry. [ABSTRACT FROM AUTHOR]

Background and Aims: There is currently no standard of care for pharmacological treatment of amphetamine‐type stimulant (ATS) use disorder (ATSUD). This systematic review with meta‐analysis (PROSPERO CRD42022354492) aimed to pool results from randomized placebo‐controlled trials (RCTs) to evaluate efficacy and safety of prescription psychostimulants (PPs) for ATSUD. Methods: Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random‐effect meta‐analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random‐effect meta‐analysis of continuous variables. Results: Ten RCTs (n = 561 participants) were included in the meta‐analysis. Trials studied methylphenidate (n = 7), with daily doses of 54–180 mg, and dextroamphetamine (n = 3), with daily doses of 60–110 mg, for 2–24 weeks. PPs significantly decreased end‐point craving [SMD −0.29; 95% confidence interval (CI) = −0.55, −0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85–1.01). No effect was observed for self‐reported ATS use, retention in treatment, dropout following adverse events, early‐stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79–0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention. Conclusions: Among individuals with amphetamine‐type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications. [ABSTRACT FROM AUTHOR]

Background: Lisdexamfetamine (LDX) and Methylphenidate (MPH) are stimulant agents that have been shown to provide significant benefits in the management of attention-deficit/hyperactivity disorder (ADHD) in patients. Aim: This study aimed to assess the cost-effectiveness and the budget impact of LDX compared to MPH as the first-line treatment for ADHD. Methods: A one-year cost-effectiveness analysis (CEA) was conducted to compare the effects of LDX and MPH in reducing disease symptoms and patient costs and improving quality of life (QoL) from a social perspective. Clinical data were obtained using the EQ-5D questionnaire. In contrast, economic data were sourced from the official website of the Iranian Food and Drug Association (FDA), the national book of tariffs, and specific questionnaires designed to evaluate patients' direct and indirect costs. 197 patients were included in the study, including individuals who sought psychiatric evaluation at a hospital in Mashhad and those who obtained ADHD medications from governmental pharmacies. The cost-effectiveness of the study medicine was assessed using the decision tree method, and the results were presented as the Incremental Cost-Effectiveness Ratio (ICER). Deterministic Sensitivity Analysis (DSA) and Probabilistic Sensitivity Analysis (PSA) were performed to assess the robustness of the findings. Additionally, a Budget Impact Analysis (BIA) was conducted over five years, considering three different scenarios, to evaluate the financial implications of incorporating LDX into the national pharmaceutical system. Results: The ICER for LDX therapy compared to MPH was estimated at USD 264.28 (with an incremental cost of USD 54.9, incremental effectiveness of 0.208, and Quality-Adjusted Life Years (QALYs) gained of 0.765). The PSA indicated a 0.994% probability of LDX being cost-effective, considering a threshold of USD 2450 per QALY. Furthermore, the DSA revealed that the acquisition cost of LDX influenced the model's sensitivity. The BIA demonstrated that incorporating LDX into Iran's healthcare system would result in a financial burden of approximately $368,566 in the first year, representing an additional cost of $11,154 compared to the non-availability of this medicine and the use of previous medications. It is projected that by 2027, the financial burden of treating ADHD with LDX will reach approximately USD 443,879 over five years, amounting to an increase of $71,154 compared to the absence of this medicine. Conclusion: From a social perspective, the inclusion of LDX in the treatment regimen for ADHD is associated with higher costs and an increased financial burden. However, based on our analysis, LDX appears to be a cost-effective choice for managing ADHD in Iran when compared to MPH. [ABSTRACT FROM AUTHOR]

Introduction: Methadone is a mu-opioid agonist with a delayed time to peak concentration that requires an extended period of monitoring following an overdose. Available data suggests that the combination of psychostimulants with methadone may augment antinociception and tolerance to opioids. Case Report: A 26-year-old male (83.9 kg) presented to the ED approximately 1 hour after unintentionally ingesting 200-250 mg of liquid methadone and an energy drink, along with 20 mg of dextroamphetamine/amphetamine prior to the event. Vital signs were: blood pressure (BP), 143/91 mmHg; heart rate (HR), 74; respirations (RR), 16; oxygen saturation 95% on room air. His urine drug screen was positive for amphetamines and methadone. Patient was monitored for 4 hours with no change in status and was discharged home. Approximately 26 hours later patient was found cyanotic and apneic. Patient was given 2 mg of naloxone and awoke with normal mental status. On presentation the patient's vital signs were: BP, 114/70 mmHg; HR, 114; RR 16; oxygen saturation 94% on 3 liters nasal cannula. During his ED stay, he required 2 doses of naloxone secondary to oxygen desaturation and was admitted to the hospital. His repeat urine drug screen was positive for amphetamines and methadone. The patient was discharged the following day. Discussion: This case illustrates an unintentional methadone overdose combined with the intentional ingestion of an energy drink and dextroamphetamine/amphetamine that possibly masked the toxicity for over 24 hrs. Monitoring parameters for methadone overdoses may need re-evaluation in the setting of the co-ingestion of a stimulant. [ABSTRACT FROM AUTHOR]

Background: Hypersomnias of central origin (HOCO) are diverse in origin and symptomatology and remain poorly described in an Australian population. We hypothesised that the rate of human leukocyte antigen (HLA) DQB1*0602 positivity in the Australian cohort would be comparable to international registries. Aims: The current study aims to evaluate epidemiological and clinical characteristics of Australian patients with HOCO, including prevalence of HLA DQB1*0602 positivity, the most specific HLA marker associated with narcolepsy. Methods: This is a retrospective study. Patients ≥ 16 years of age presenting with symptoms of hypersomnolence who attended one of two Australian sleep centres (New South Wales and Queensland) in the preceding 24 months and had undergone both HLA serology and multiple sleep latency tests (MSLTs) were included. Main outcome measures included demographics, HLA DQB1*0602 positivity, MSLT, and clinical parameters (presence of auxiliary narcolepsy symptoms, laboratory tests, relevant prescribed medications). Results: Eighty‐eight patients were included. HLA DQB1*0602 positivity was highest in those with type 1 narcolepsy (NT1) (95.7%) and lowest in those without a classifiable disorder (9.1%). Mean sleep latency was lowest and number of sleep‐onset rapid eye movement periods (SOREMPs) highest in the NT1 group. Comorbid disorders, particularly depression and overweight/obesity, were prevalent in all cohorts. Across all diagnostic groups, dexamphetamine was the most commonly prescribed agent for excessive daytime sleepiness. Conclusions: Patients with HOCO assessed in two specialised Australian clinics demonstrate comparable clinical characteristics to other published cohorts internationally; however, available pharmacological agents in Australia do not reflect international standards of care. [ABSTRACT FROM AUTHOR]

The global rise in methamphetamine use and its negative effects warrants the need for research exploring harm reduction and treatment interventions for individuals with methamphetamine use disorder. Agonist medications have been utilized for years for the treatment of heroin and opioid addiction, but have yet to be incorporated into mainstream Canadian practice for methamphetamine dependence. This review aims to provide an overview of the current trends of prescription psychostimulant usage for individuals with methamphetamine use disorder from a Canadian perspective, identifies the barriers to accessing prescription psychostimulants for methamphetamine use disorder and highlights the nursing clinical practice implications in caring for individuals with the disorder. Discourse on the sustained abstinence and harm reduction debate is presented from the perspective of methamphetamine abuse is provided along with the neuropsychiatric complications of chronic methamphetamine use. The impacts of specific prescription psychostimulants on cognition are discussed as is the use of neuroimaging techniques to assess neuronal damage in methamphetamine users. Sign of toxicity, overdose and the contraindications for use of these prescription psychostimulants is also presented. The implications to nursing clinical practice in caring for this population is provided, touching on the clinical presentation of methamphetamine use, completing thorough assessment and screening and patient education. The findings of this review indicate the need for further research in this area exploring the benefits of prescription psychostimulants as a harm reduction and treatment intervention for the global problem of methamphetamine dependence. [ABSTRACT FROM AUTHOR]

The objective of the study was to compare the use of attention deficit hyperactivity disorder (ADHD) medication among children and adolescents in Scandinavia 2010–2020. Using aggregated prescription data for individuals aged 5–19 years, we calculated annual prevalence proportions of ADHD medication (users/1000 inhabitants) for each country, overall and stratified by age and sex. Overall, use of ADHD medication increased during 2010–2020 in all countries. The increase was pronounced in Sweden reaching 35 users/1000 inhabitants in 2020 (119% increase), whereas it reached 22/1000 in Denmark and Norway (equivalent to a 38% and 16% increase, respectively). Methylphenidate was the most frequently used drug and Sweden had the highest use reaching 25/1000 in 2020 compared to 16/1000 and 18/1000 in Denmark and Norway, respectively. Lisdexamfetamine use increased steadily and was also highest in Sweden (13/1000 in 2020). In 2020, atomoxetine use was higher in Sweden (4.6/1000) and Denmark (4.5/1000) compared to Norway (2.2/1000). From 2015, use of guanfacine increased in Sweden reaching 4.4/1000 in 2020 but remained low in Denmark (0.4/1000) and Norway (0.7/1000). Use of dexamphetamine was low (ranging from 0.47 to 0.75/1000 in 2020) in the three countries. ADHD medication use was highest in Sweden across all age groups. In all countries, the prevalence was higher in males compared to females. In conclusion, use of ADHD medication among children and adolescents in Scandinavia is increasing. The prevalence of use is higher in Sweden for all drug groups compared to Norway and Denmark. [ABSTRACT FROM AUTHOR]

Pediatric attention-deficit disorder (ADHD) impacts a significant percentage of the population world-wide. Pharmacologic treatments have been shown to be safe and effective for managing symptoms. Various medication formulations exist, and new medication agents are continually approved each year. This article offers an overview of ADHD, an overview of both stimulant and non-stimulant medication options as well as an overview of stimulant misuse. It explores the medication mechanisms of action and side effect profiles, as well as offering an in-depth summary of the novel agents recently approved and soon-to-be approved for use in youth. PubMed and Medline were utilized. Search terms included children, adolescents, ADHD, and medication. FDA package inserts were reviewed for all medications. New formulations of medications include an evening administered, extended, and delayed-release form of methylphenidate (DR/ER MPH), a methylphenidate pro-drug (serdexmethylphenidate) and an amphetamine patch. The availability of a new SNRI (selective norepinephrine reuptake inhibitor), viloxazine extended-release (VER), and the pending approval of a triple reuptake inhibitor (centanafadine) provides welcome additions to the prescriber's toolbox. This article is a review of pharmacological treatment options for pediatric attention-deficit disorder (ADHD). It provides an overview of ADHD, an overview of the current stimulant and non-stimulant medication options as well as detailed information on the newer psychopharmacological options to assist in the education of the wide array of medication options for treatment. As ADHD is a heterogeneous illness, a wide array of medication options is helpful in the clinician's toolbox. Learning the mechanisms of action along with the side effect profile for newer medication options is the focus of this review. There are new options for patches and new combinations for long-acting and delayed-release formulations as well as new non-stimulant options which target different receptors. [ABSTRACT FROM AUTHOR]

Background: Methylphenidate, atomoxetine, and Amphetamine are the three most commonly used medications approved by the United States Food and Drug Administration (FDA) for the treatment of attention deficit/hyperactivity disorder (ADHD). However, a comprehensive analysis of their safety profiles across various age groups and genders in real-world contexts has yet to be conducted. In this study, a pharmacovigilance analysis was performed using the FDA Adverse Event Reporting System (FAERS) database to examine differences in adverse events between methylphenidate, atomoxetine, and Amphetamine. Methods: From January 2014 to September 2022, FAERS reports listing “Methylphenidate,” “Dexmethylphenidate,” “Atomoxetine,” “Amphetamine,” “Lisdexamfetamine,” “Dextroamphetamine,” and “Methamphetamine” as primary suspects were analyzed after removing duplicate reports. We used the standardized Medical Dictionary for Regulatory Activities (MedDRA) query generalized search for adverse events at the preferred term level based on case reports. After filtering duplicate reports, disproportionality analysis was used to detect safety signals according to the proportional reporting ratio (PRR). In order to delve into potential safety concerns, we undertook a twostep analysis of the data. Initially, the data was segmented based on age cohorts: 0–5 years, 6–12 years, 13–18 years, and individuals aged ≥19 years. Following this, after partitioning the data into males and females within the 0–18 years age group, and similarly for those aged ≥19 years, further analysis was conducted. Results: The pharmacovigilance analysis uncovered substantial safety signals in the standardized MedDRA queries. Methylphenidate was associated with dyskinesia (PRR = 21.15), myocardial infarction (PRR = 12.32), and hypertension (PRR = 8.95) in children aged 0–5, 6–12, and 13–18 years, respectively, as well as neonatal exposures via breast milk (PRR = 14.10) in adults aged ≥19 years. Atomoxetine was linked to hostility/aggression (PRR = 15.77), taste and smell disorders (PRR = 6.75), and hostility/aggression (PRR = 6.74) in children aged 0–5, 6–12, and 13–18 years, respectively, as well as hostility/aggression (PRR = 14.00) in adults aged ≥19 years. Amphetamine was associated with psychosis and psychotic disorders (PRR = 16.78), hostility/aggression (PRR = 4.39), and Other ischaemic heart disease (PRR = 10.77) in children aged 0–5 years, 6–12 years, and 13–18 years, respectively, and hostility/aggression in adults aged ≥19 years (PRR = 9.16). Significant and noteworthy adverse event signals were also identified at the preferred term level. Specifically, methylphenidate was associated with myocardial infarction, acute myocardial infarction, coronary artery dissection, electrocardiogram QT prolonged, growth retardation, self-destructive behavior, suicidal ideation, and completed suicide. Atomoxetine was linked to electrocardiogram QT prolonged, growth retardation, and tic. Amphetamine was recorded for coronary artery dissection, suicidal ideation, and completed suicide. It was observed that male patients, including both children and adults, showed a more significant and frequent occurrence of adverse events compared to females, particularly in terms of cardiac disorders. The intensity and quantity of adverse event signals were distinctly different between the two genders, with males having a higher number of signals. All detected safety signals were confirmed using signals obtained from the disproportionality analysis. Conclusion: This pharmacovigilance analysis demonstrated significant variations in the safety profiles of methylphenidate, atomoxetine, and Amphetamine across different age groups and between different genders. Following an in-depth analysis of the FAERS database, we discerned prominent safety signals. Notably, the strength of the signals associated with coronary artery dissection induced by methylphenidate and amphetamine, as well as those related to suicide, demand particular attention. Consequently, it remains imperative to persist in monitoring these medications, assessing the associated risks, and carrying out comparative studies particularly geared towards ADHD drugs. [ABSTRACT FROM AUTHOR]

The article focuses on the expanded access to publicly subsidized lisdexamfetamine treatment for adults with attention-deficit/hyperactivity disorder (ADHD) in Australia. The topics discussed include the prevalence and incidence of ADHD medicine use among adults in 2021, the impact of the subsidy changes on the dispensing of lisdexamfetamine and other ADHD medicines, and the potential factors driving these changes.

For the first time in 15 years the American Academy of Pediatrics (AAP) has issued comprehensive guidance on overweight and obesity, and recommends "immediate, intensive treatment for children and teens who are at or above the 85th percentile of body mass index (BMI) for their age and sex." [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of psychosis is complex, but a better understanding of stimulus binding windows (BWs) could help to improve our knowledge base. Previous studies have shown that dopamine release is associated with psychosis and widened BWs. We can probe BW mechanisms using drugs of specific interest to psychosis. Therefore, we were interested in understanding how manipulation of the dopamine or catecholamine systems affect psychosis and BWs. We aimed to investigate the effect of dexamphetamine, as a dopamine-releasing stimulant, on the BWs in a unimodal illusion: the tactile funneling illusion (TFI). Methods: We conducted a randomized, double-blind, counterbalanced placebo-controlled crossover study to investigate funnelling and errors of localization. We administered dexamphetamine (0.45 mg/kg) to 46 participants. We manipulated 5 spatial (5–1 cm) and 3 temporal (0, 500 and 750 ms) conditions in the TFI. Results: We found that dexamphetamine increased funnelling illusion (p = 0.009) and increased the error of localization in a delay-dependent manner (p = 0.03). We also found that dexamphetamine significantly increased the error of localization at 500 ms temporal separation and 4 cm spatial separation (p interaction = 0.009; p 500ms|4cm v. baseline = 0.01). Limitations: Although amphetamine-induced models of psychosis are a useful approach to understanding the physiology of psychosis related to dopamine hyperactivity, dexamphetamine is equally effective at releasing noradrenaline and dopamine, and, therefore, we were unable to tease apart the effects of the 2 systems on BWs in our study. Conclusion: We found that dexamphetamine increases illusory perception on the unimodal TFI in healthy participants, which suggests that dopamine or other catecholamines have a role in increasing tactile spatial and temporal BWs. [ABSTRACT FROM AUTHOR]

Background: Psychostimulants are frequently used to treat attention‐deficit/hyperactivity disorder (ADHD), but side effects are common leading to many patients discontinuing treatment. Identifying neural mechanisms by which psychostimulants attenuate symptoms may guide the development of more refined and tolerable therapeutics. Methods: We conducted a 12‐week, randomized, placebo‐controlled trial (RCT) of a long‐acting amphetamine, lisdexamfetamine (LDEX), in patients with ADHD, ages 6–25 years old. Of the 58 participants who participated in the RCT, 49 completed pre‐ and post‐RCT magnetic resonance imaging scanning with adequate data quality. Healthy controls (HCs; n = 46) were included for comparison. Treatment effects on striatal and thalamic functional connectivity (FC) were identified using static (time‐averaged) and dynamic (time‐varying) measures and then correlated with symptom improvement. Analyses were repeated in independent samples from the Adolescent Brain Cognitive Development study (n = 103) and the ADHD‐200 Consortium (n = 213). Results: In 49 participants (25 LDEX; 24 Placebo), LDEX increased static and decreased dynamic FC (DFC). However, only DFC was associated with the therapeutic effects of LDEX. Additionally, at baseline, DFC was elevated in unmedicated‐ADHD participants relative to HCs. Independent samples yielded similar findings – ADHD was associated with increased DFC, and psychostimulants with reduced DFC. Static FC findings were inconsistent across samples. Conclusions: Changes in dynamic, but not static, FC were associated with the therapeutic effects of psychostimulants. While prior research has focused on static FC, DFC may offer a more reliable target for new ADHD interventions aimed at stabilizing network dynamics, though this needs confirmation with subsequent investigations. [ABSTRACT FROM AUTHOR]

Impulsive-compulsive behaviours manifest in a substantial proportion of subjects with Parkinson's disease. Reduced ventral striatum dopamine receptor availability, and increased dopamine release is noted in patients with these symptoms. Prior studies of impulsivity suggest that midbrain D2 autoreceptors regulate striatal dopamine release in a feedback inhibitory manner, and in healthy populations, greater impulsivity is linked to poor proficiency of this inhibition. This has not been assessed in a Parkinson's disease population. Here, we applied 18F-fallypride PET studies to assess striatal and extrastriatal D2-like receptor uptake in a placebo-controlled oral dextroamphetamine sequence. We hypothesized that Parkinson's disease patients with impulsive-compulsive behaviours would have greater ventral striatal dopaminergic response to dextroamphetamine, and that an inability to attenuate ventral striatal dopamine release via midbrain D2 autoreceptors would underlie this response. Twenty patients with Parkinson's disease (mean age = 64.1 ± 5.8 years) both with (n = 10) and without (n = 10) impulsive-compulsive behaviours, participated in a single-blind dextroamphetamine challenge (oral; 0.43 mg/kg) in an OFF dopamine state. All completed PET imaging with 18F-fallypride, a high-affinity D2-like receptor ligand, in the placebo and dextroamphetamine state. Both voxelwise and region of interest analyses revealed dextroamphetamine-induced endogenous dopamine release localized to the ventral striatum, and the caudal-medial orbitofrontal cortex. The endogenous dopamine release observed in the ventral striatum correlated positively with patient-reported participation in reward-based behaviours, as quantified by the self-reported Questionnaire for Impulsivity in Parkinson's disease Rating Scale. In participants without impulsive-compulsive behaviours, baseline midbrain D2 receptor availability negatively correlated with ventral striatal dopamine release; however, this relationship was absent in those with impulsive-compulsive behaviours. These findings emphasize that reward-based behaviours in Parkinson's disease are regulated by ventral striatal dopamine release, and suggest that loss of inhibitory feedback from midbrain autoreceptors may underlie the manifestation of impulsive-compulsive behaviours. [ABSTRACT FROM AUTHOR]

Writing is an important and complex task that typically develops in early childhood. Dysgraphia is a learning disorder in which the individual's writing skills are below the level expected for his or her age and cognitive level. There are a variety of mechanisms by which dysgraphia may occur. It can present in isolation or with other learning or psychiatric disorders, and can often go undiagnosed. Although the diagnosis and management of dysgraphia usually occurs in an educational setting, the primary physician plays an important role in guidance and advocacy, as well as in the surveillance and evaluation of potential co-morbid conditions. [ABSTRACT FROM AUTHOR]

Aim: To test (1) if there was a change in self‐reported lifetime prevalence of meth/amphetamine use by birth cohort and (2) if the extent of under‐reporting of meth/amphetamine use was associated with the proportion of the population who nominated meth/amphetamine as a drug problem. Design Observational study using seven waves of repeated cross‐sectional nationally representative household surveys between 2001 and 2019. Setting: Australia. Participants: Participants were from three birth cohorts: 1951–60 (age 68–77 at the 2019 survey; n = 29 458; 55% female), 1961–1970 (age 58–67; n = 29 859; 57% female) and 1971–1980 (age 48–57; n = 28 758; 59% female). Data were weighted to align the sample to the Australian population. Measurements Past year meth/amphetamine use; under‐reporting of lifetime meth/amphetamine use in each birth cohort, year and survey stratum (operationalised as the difference between self‐reported lifetime prevalence in 2001 and that of each subsequent year); proportion of the population who nominated meth/amphetamine as a drug problem in each birth cohort, year and survey stratum. Under‐reporting was regressed on the proportion of people holding negative attitude towards meth/amphetamine. Survey year and birth cohort were adjusted for. Findings Between 2001 and 2019, the lifetime prevalence of meth/amphetamine decreased from 6.1% (95% CI = 5.3–6.9) to 1.7% (95% CI = 1.2–2.2) in the 1951–1960 birth cohort (p < 0.001), from 13.0% (95% CI = 12.0–14.1) to 4.4% (95% CI = 3.7–5.2) in the 1961–1970 birth cohort (p < 0.001) and from 21.4% (95% CI = 19.9–22.9) to 11.2% (95% CI = 10.0–12.4) in the 1971–1980 birth cohort (p < 0.001). The proportion who nominated meth/amphetamine as a 'drug problem' increased significantly in all three cohorts (all p < 0.001) and the degree of under‐reporting of meth/amphetamine use was significantly associated with proportion of people who nominated meth/amphetamine as the 'drug problem' (b = 0.09, SE = 0.01, p < 0.001). Conclusion: In Australia, the actual prevalence of lifetime meth/amphetamine use may be two‐ to fourfold higher than that estimated in the most recent national household surveys (2019). The level of under‐reporting is strongly associated with increasing negative attitudes towards methylamphetamine and d‐amphetamine use over the same period. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rationale: Misuse of dextroamphetamine occurs in work and recreational contexts. While acute drug effects broadly predict abuse liability, few studies have considered the relationship between acute effects and context. Objectives: This study examined how individual differences in acute effects of dextroamphetamine relate to desire to take dextroamphetamine again in different contexts. Methods: This secondary analysis used data from healthy adults with no history of moderate-to-severe substance use disorder, who received oral doses of placebo and dextroamphetamine (10 and 20 mg) over 3 sessions under double-blind, randomized conditions. Subjects rated subjective effects and completed reward-related behavioral tasks. Subjects rated their desire to take dextroamphetamine again in hypothetical work and recreational contexts. Multilevel models examined within-subjects change scores (10 mg-placebo; 20 mg-placebo) to determine how subjective effects and behavioral outcomes predicted desire to take dextroamphetamine again for work versus recreation. Results: Subjects reported more desire to take 20 mg dextroamphetamine again for work than for recreation. At 20 mg, there was an interaction between context and liking/wanting, such that liking/wanting predicted desire to use dextroamphetamine for work only. There was also an interaction at 20 mg between context and psychomotor speed, such that psychomotor speed predicted interest in using dextroamphetamine for recreation only. Conclusions: We found that positive subjective effects predicted desire to use dextroamphetamine again for work, while increased motor effects predicted desire to use dextroamphetamine recreationally. Hedonic effects may be perceived as advantageous when working, while increased physical energy may be preferred during recreation, suggesting that context of intended use is important when examining abuse liability. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article focuses on a recent study indicating that mothers using stimulant medications for ADHD during pregnancy didn't increase the risk of neurodevelopmental disorders in their children, based on a cohort study analyzing health care data of pregnant individuals.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression. As the left prefrontal cortex activity is linked to depression, rTMS induces blood flow in the left dorsolateral prefrontal cortex. We used rTMS in a middle-aged male patient with depression who had discontinued psychostimulant medication over a 12-month period. He had been consistently taking dextroamphetamine-amphetamine extended release 30 mg once daily prior to the onset of rTMS treatment. The patient achieved depression remission through 39 sessions of high-frequency left dorsolateral prefrontal cortex rTMS treatments. We assessed disease progression using the Quick Inventory of Depressive Symptomatology, and we measured blood pressure before each session of rTMS. After tapering the dextroamphetamine-amphetamine extended release from 30 mg to 10 mg, the patient's score on the Quick Inventory of Depressive Symptomatology increased slightly to 7 and then dropped to 0. The results indicate that interval rTMS can lower blood pressure and may be an alternative to adjunctive psychostimulants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: This study examined the feasibility, safety, and potential efficacy of lisdexamfetamine (LDX) as a treatment for adults with bulimia nervosa (BN). Method: An open‐label 8‐week feasibility study was conducted in participants with BN. Enrollment rate, dropout rate, safety outcomes, and eating disorder symptom change were examined. Results: Eighteen of 23 participants completed the study per protocol. There was no participant‐initiated dropout due to adverse drug reactions and no severe and unexpected adverse drug reactions. An average increase in heart rate of 12.1 beats/min was observed. There was a mean weight reduction of 2.1 kg and one participant was withdrawn for clinically significant weight loss. In the intent‐to‐treat sample, there were reductions in objective binge episodes and compensatory behaviors from Baseline to Post/End‐of‐Treatment (mean difference = −29.83, 95% confidence interval: −43.38 to −16.27; and mean difference = −33.78, 95% confidence interval: −48.74 to −18.82, respectively). Discussion: Results of this study indicate that a randomized controlled trial would be feasible with close monitoring of certain safety parameters (especially over a longer time period as long‐term safety is unknown). However, the results should not be used as evidence for clinicians to prescribe LDX to individuals with BN before its efficacy and safety are properly tested. Trial Registration Number: NCT03397446. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Fatigue is a common problem in aviation. The identification of efficacious fatigue countermeasures is crucial for sustaining flight performance during fatigue-inducing operations. Stimulants are not recommended for consistent use, but are often implemented during flight operations with a high risk of fatigue. As such, it is important to evaluate the efficacy of approved stimulants for sustaining flight performance, alertness, and mood. METHODS: Four electronic databases (PubMed, PsycInfo, SPORTDiscus, Web of Science) were systematically searched to identify research on the effects of caffeine, dextroamphetamine, and modafinil during simulated or in-flight operations. RESULTS: There were 12 studies identified that assessed the effects of at least 1 stimulant. Overall, dextroamphetamine and modafinil were effective for sustaining flight performance and pilot mood during extended wakefulness. Results with caffeine were inconsistent. DISCUSSION: Dextroamphetamine and modafinil appear to sustain flight performance and mood during extended wakefulness. However, most studies have used flight simulators and short operation durations. Additional research is needed in realistic settings and during longer duration operations. Caffeine's effects were inconsistent across studies, possibly due to differences in study methodology or individual caffeine responses. Despite fatigue being a common problem in civilian aviation as well, only one study in this review included civil aviators. More research should be conducted on the effects of caffeine during civil operations. CONCLUSION: Dextroamphetamine and modafinil appear to be effective fatigue countermeasures but should be further evaluated in more ecologically valid settings. The effects of caffeine are unclear at this time and should continue to be evaluated. [ABSTRACT FROM AUTHOR]

The article discusses research by E. Bowman et al, published in the journal "Science Advances," which determined whether use of methylphenidate, modafinil, or dextroamphetamine improved performance on a difficult task resembling everyday challenges.

Cortical neurons oscillate synchronously between the Up and Down state during slow-wave sleep and general anesthesia. Using local-field-potential recording in the rat prefrontal cortex (PFC), we have shown that systemic administration of methylphenidate promotes PFC Up states and reduces PFC slow oscillation, suggesting a depolarizing effect of the drug on PFC neurons. Here, we report that systemic injection of d-amphetamine produced similar effects. Our evidence further suggests that norepinephrine (NE) plays a major role in the effects of d-amphetamine since they were mimicked by the NE reuptake inhibitors tomoxetine and nisoxetine and completely blocked by the α1 receptor antagonist prazosin. The effects of d-amphetamine persisted, however, in the presence of α2 or β receptor blockade. Experiments with α1 subtype-selective antagonists further suggest that d-amphetamine's effects depend on activation of central, but not peripheral, α1A receptors. Unexpectedly, the putative α1 receptor agonist cirazoline failed to mimic the effects of d-amphetamine. Previous studies suggest that cirazoline is also an antagonist at α2 receptors. Furthermore, it is a partial, not full, agonist at α1B and α1D receptors. Whether or not these properties of cirazoline contribute to its failure to mimic d-amphetamine's effects remains to be determined. Methylphenidate and d-amphetamine are two most common medications for attention-deficit/hyperactivity disorder (ADHD). Both, however, are associated with adverse effects including abuse potential and psychotomimetic effects. Further understanding of their mechanisms of action will help develop safer treatments for ADHD and offer new insights into drug addiction and psychosis. [ABSTRACT FROM AUTHOR]

Background: Glutamate transmission is implicated in drug-induced behavioural sensitization and the associated long-lasting increases in mesolimbic output. Metabotropic glutamate type 5 (mGlu5) receptors might be particularly important, but most details are poorly understood. Methods: We first assessed in mice (n = 51, all male) the effects of repeated dextroamphetamine administration (2.0 mg/kg, i.p.) on locomotor activity and binding of the mGlu5 ligand [³H]ABP688. In a parallel study, in 19 stimulant-drug-naïve healthy human volunteers (14 female) we administered 3 doses of dextroamphetamine (0.3 mg/kg, p.o.) or placebo, followed by a fourth dose 2 weeks later. We measured [11C]ABP688 binding using positron emission tomography before and after the induction phase. We assessed psychomotor and behavioural sensitization using speech rate, eye blink rate and self-report. We measured the localization of mGlu5 relative to synaptic markers in mouse striatum using immunofluorescence. Results: We observed amphetamine-induced psychomotor sensitization in mice and humans. We did not see group differences in mGlu5 availability following 3 pre-challenge amphetamine doses, but group differences did develop in mice administered 5 doses. In mice and humans, individual differences in mGlu5 binding after repeated amphetamine administration were negatively correlated with the extent of behavioural sensitization. In drug-naïve mice, mGlu5 was expressed at 67% of excitatory synapses on dendrites of striatal medium spiny neurons. Limitations: Correlational results should be interpreted as suggestive because of the limited sample size. We did not assess sex differences. Conclusion: Together, these results suggest that changes in mGlu5 availability are not part of the earliest neural adaptations in stimulant-induced behavioural sensitization, but low mGlu5 binding might identify a higher propensity for sensitization. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness of stimulants in patients with depression, by using naturalistic outcome measures, such as psychiatric admissions, psychiatric bed-days and incidents of intentional self-harm or suicide attempts. Methods: Via linkage of the Danish nationwide health registers, we identified all patients with a diagnosis of depression initiating stimulants, including methylphenidate, modafinil, amphetamine, dexamphetamine or lisdexamphetamine, from 1995 to 2012. We used a mirror-image model to test whether redemption of a stimulant prescription was associated with a reduction in psychiatric admissions, inpatient days and incidents of intentional self-harm or suicide attempts. Specifically, the number of these outcomes in the 2 years leading up to redemption of a stimulant prescription was compared to the two subsequent years. Similar outcomes were used in a reverse mirror-image model to investigate the effect of stimulant termination. Results: A total of 3354, 935 and 105 patients diagnosed with depression redeemed prescriptions for methylphenidate, modafinil or amphetamine/dexamphetamine/lisdexamphetamine, respectively. Initiation of methylphenidate was not associated with a significant change in psychiatric admissions (mean: −0.02 admissions, p = 0.11) or inpatient days (mean: 0.13 days, p = 0.74). Similar findings were made for modafinil and the amphetamines. In addition, no clinically relevant change in psychiatric admissions or inpatient days was found after termination of a stimulant. After initiation of methylphenidate, the incidents of self-harm or suicide attempts were reduced by 54%, from 68 to 31 events (p = 0.004). No significant change in incidents of self-harm or suicide attempts were found for modafinil or the amphetamines. Conclusion: This nationwide study, using naturalistic outcomes, does not support the use of stimulants in patients with depression. However, the use of methylphenidate was associated with a 54% reduction in incidents of self-harm or suicide attempts, indicating that methylphenidate may potentially be useful in patients with depression with suicidal- or self-harming behaviour. However, further studies are needed, before any firm conclusions can be made. [ABSTRACT FROM AUTHOR]

Adult attention deficit/hyperactivity disorder (ADHD) is a significant and prevalent disorder. ADHD can impair adults' quality of life, so clinicians in multiple specialties should be able to recognize and treat the disorder. Much of the current literature has focused on childhood ADHD. However, adult ADHD is a common comorbidity in patients with mental illness, and it is essential that patients diagnosed with the disorder are treated appropriately, which can significantly improve outcomes. Adults with untreated ADHD are more likely to have substance dependence, job instability, and an overall poorer quality of life. This article reviews the screening and assessment for adult ADHD along with pharmacologic and nonpharmacologic recommendations for the management of the disorder. [ABSTRACT FROM AUTHOR]

c-Jun N-terminal kinase (JNK) signaling contributes to functional plasticity in the brain and cognition. Accumulating evidence implicates a role for MAP kinase kinase 7 (MAP2K7), a JNK activator encoded by the Map2k7 gene, and other JNK pathway components in schizophrenia (ScZ). Mice haploinsufficient for Map2k7 (Map2k7 +/− mice) display ScZ-relevant cognitive deficits, although the mechanisms are unclear. Here we show that Map2k7 +/− mice display translationally relevant alterations in brain function, including hippocampal and mesolimbic system hypermetabolism with a contrasting prefrontal cortex (PFC) hypometabolism, reminiscent of patients with ScZ. In addition Map2k7 +/− mice show alterations in functional brain network connectivity paralleling those reported in early ScZ, including PFC and hippocampal hyperconnectivity and compromised mesolimbic system functional connectivity. We also show that although the cerebral metabolic response to ketamine is preserved, the response to dextroamphetamine (d - amphetamine) is significantly attenuated in Map2k7 +/− mice, supporting monoamine neurotransmitter system dysfunction but not glutamate/NMDA receptor (NMDA-R) dysfunction as a consequence of Map2k7 haploinsufficiency. These effects are mirrored behaviorally with an attenuated impact of d - amphetamine on sensorimotor gating and locomotion, whereas similar deficits produced by ketamine are preserved, in Map2k7 +/− mice. In addition, Map2k7 +/− mice show a basal hyperactivity and sensorimotor gating deficit. Overall, these data suggest that Map2k7 modifies brain and monoamine neurotransmitter system function in a manner relevant to the positive and cognitive symptoms of ScZ. [ABSTRACT FROM AUTHOR]

Background: Recent decades have seen both an increased number of shift workers in order to deliver services 24/7, and increased potential for social interactions at all hours of the day. People have sought to engage in strategies, which either promote vigilance or facilitate sleep, with the use of sleep- and wake-promoting drugs representing one strategy. Methods: We investigated use of sleep- and wake-promoting drugs in participants (n = 377) who completed a survey investigating the type and source of sleep- and wake-promoting drugs, and their impact on sleep and performance outcomes. Results: The most commonly reported wake-promoting drugs were amphetamine and dextroamphetamin salts, modafinil, and illicit substances including methamphetamine and cocaine, while the most commonly reported sleep-promoting drugs were benzodiazepines and antihistamines. Use of a sleep-promoting drug in the past month was associated with higher odds of having poorer sleep quality (OR = 3.15) and moderate-high insomnia (OR = 3.30), while use of a wake-promoting drug was associated with poor sleep quality (OR = 3.76), or making a fatigue-related error (OR = 2.65). Conclusions: These findings represent novel data on the use and source of sleep- and wake-promoting- drugs, and suggest that despite their use, poor sleep and performance outcomes persist, likely representing individuals struggling to keep up with the 24/7 world. [ABSTRACT FROM AUTHOR]

Drug studies are powerful models to investigate the neuropharmacological mechanisms underlying temporal processing in humans. This study administered dexamphetamine to 24 healthy volunteers to investigate time perception at different time scales, along with contributions from working memory. Healthy volunteers were administered 0.45 mg/kg dexamphetamine or placebo in a double‐blind, crossover, placebo‐controlled design. Time perception was assessed using three experimental tasks: a time‐discrimination task, which asked participants to determine whether a comparison interval (1200 ± 0, 50, 100, 150, 200 ms) was shorter or longer than a standard interval (1200 ms); a retrospective time estimation task, which required participants to verbally estimate time intervals (10, 30, 60, 90 and 120 s) retrospectively; and a prospective time‐production task, where participants were required to prospectively monitor the passing of time (10, 30, 60, 90 and 120 s). Working memory was assessed with the backwards digit span. On the discrimination task, there was a change in the proportion of long‐to‐short responses and reaction times in the dexamphetamine condition (but no association with working memory), consistent with an increase in the speed of an internal pacemaker, and an overestimation of durations in the timing of shorter intervals. There was an interaction between dexamphetamine, working memory, and performance on the estimation and production tasks, whereby increasing digit span scores were associated with decreasing interval estimates and increased produced intervals in the placebo condition, but were associated with increased interval estimates and decreased produced intervals after dexamphetamine administration. These findings indicate that the dexamphetamine‐induced increase in the speed of the internal pacemaker was modulated by the basal working memory capacity of each participant. These findings in healthy humans have important implications for the role of dopamine, and its contributions to timing deficits, in models of psychiatric disorders. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder defined by impairing levels of inattention, disorganization, and/or hyperactivity-impulsivity. ADHD often persists into adulthood, with resultant impairments of social, academic and occupational functioning. ADHD is a very common disease during childhood and, the pooled overall prevalence of ADHD was found to be 5.29%. When screening for ADHD, clinicians should try to develop rapport with patients and their caregivers to increase the likelihood that they will follow the diagnostic process and treatment. The current drugs that have received Food and Drug Administration-approval for ADHD include stimulants (methylphenidate and dextroamphetamine) and non-stimulants (atomoxetine, guanfacine, and clonidine). Stimulants improve inattention, hyperactivity, and impulsivity in addition to decreasing disruptive behaviors and promoting academic achievement and the maintenance of appropriate friendships. In order to enhance drug compliance, the use of long-acting stimulants is increasing. Atomoxetine is a selective norepinephrine reuptake blocker, the effects of which may take 2 to 6 weeks to be noticeable. Furthermore, α2 agonists may help to improve behavioral side effects, tics, and sleep problems during stimulant or atomoxetine use. Common side effects of stimulants and atomoxetine include headache, stomachache, and loss of appetite. Routine electorcardiography before medication is not recommended unless there is a specific indication. Methylphenidate and atomoxetine are safe as first line therapies, and their side effects are well tolerated. [ABSTRACT FROM AUTHOR]

Background: A limited number of published case reports suggest a positive effect of dextroamphetamine, an adrenergic agonist affecting both the central nervous system (CNS) and peripheral nervous system, on physical activity and weight in patients with hypothalamic obesity (intractable obesity following CNS insult). Here, we present our clinical experience with dextroamphetamine treatment for hypothalamic obesity. Methods: The clinical course of all patients started on dextroamphetamine treatment for severe hypothalamic obesity at our institution between 2010 and 2013 is reported. Dextroamphetamine administration was initiated at a single dose of 5 mg per day and titrated to effect up to a dose of 20 mg/day. BMI z-score velocity was calculated as change in BMI z-score over standardized intervals of 12 months. Parameters of treatment success and adverse events were assessed in a standardized fashion. Results: Seven patients (2 males; mean age 17.6 years [range 12.9–24.5]) underwent individual treatment attempts with dextroamphetamine between 2010 and 2013. The primary diagnoses were craniopharyngioma (n = 4), ganglioglioma WHO I (n = 1), astrocytoma (n = 1), and neonatal meningitis (n = 1). Time from initial CNS insult to initiation of dextroamphetamine treatment averaged 5.2 years (range 2.4 months to 16.5 years). All patients demonstrated a steady increase in BMI z-score from the time of initial diagnosis until initiation of dextroamphetamine treatment. Mean baseline BMI z-score was +3.17 ± 0.93 (+1.9 to +4.4). Mean BMI z-score velocity decelerated to –0.18 ± 0.12 per year during the first year of treatment and stabilized at +0.05 ± 0.32 per year during the second year of treatment. No significant adverse events were reported. Conclusion: Dextroamphetamine treatment led to stabilization or reduction of BMI z-score in a cohort of 7 patients with hypothalamic obesity, with no adverse effects. Considering the projected increase in BMI z-score according to the natural course of the disease, these findings are promising and warrant further study. [ABSTRACT FROM AUTHOR]

In March, NICE updated its guidance on the diagnosis and management of attention deficit hyperactivity disorder (ADHD) for the first time in 10 years. This article provides a summary of the new guideline's main recommendations. [ABSTRACT FROM AUTHOR]