BACKGROUND Fatigue is common in multiple sclerosis (MS) and adversely affects function and quality of life. We examined clinical correlates of fatigue, its relationship with depression and sleepiness, and whether fatigue-related medications improve patient-reported outcomes. MATERIAL AND METHODS This single-center, longitudinal observational study retrospectively analyzed prospectively collected data from 203 veterans, categorized based on the presence or absence of fatigue. Primary outcomes were changes in the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), and Epworth Sleepiness Scale (ESS) from baseline to 12 months. Secondary outcomes included changes in the EuroQol 5-Dimension Questionnaire (EQ-5D), EQ visual analog scale (EQ-VAS), Total Functional Independence Measure (TFIM), Expanded Disability Status Scale (EDSS), 2-Minute Walk Test (2MWT), and Beck Depression Inventory (BDI). Medication exposure (amantadine, modafinil/armodafinil, methylphenidate/dextroamphetamine) was recorded. RESULTS Fatigue was present in 134 of 203 (66%) and associated with higher body mass index (30.1±5.5), hyperlipidemia (53.7%), diabetes (16.4%), higher BDI (4.58±4.36) and ESS (10.7±6.51), and worse EQ-5D VAS (all P<0.01). Strong positive correlations were observed among fatigue (FSS/MFIS), depression (BDI), sleepiness (ESS), and disability (EDSS) scales (P<0.05). Compared with no medication, fatigue-related medications did not improve FSS/MFIS or EQ-VAS scores; however, modest gains favored treated patients in TFIM change (P=0.04) and 2MWT distance (P=0.02). Post hoc comparisons across amantadine, modafinil/armodafinil, and amphetamine showed no between-drug differences in primary or secondary outcomes. CONCLUSIONS MS fatigue in veterans is highly prevalent and closely linked to metabolic comorbidities, depression, and sleep disturbance. Common fatigue medications provided no improvement in fatigue severity and quality of life.

Dextroamphetamine is a psychostimulant widely used in the treatment of attention-deficit/hyperactivity disorder and as a model compound in clinical toxicology and pharmacokinetic studies, and some studies report its use in cocaine dependence treatment. The present work describes the development and validation of a capillary electrophoresis (CE) method coupled with diode array (DAD) and capacitively coupled contactless conductivity (C4D) detectors for the simultaneous analysis of dextroamphetamine and its main urinary metabolites. Although phenylacetone is a key intermediate in the oxidative deamination pathway, this study focuses on the determination of 4-hydroxyamphetamine, norephedrine, hippuric acid, and benzoic acid in synthetic urine and spiked human samples. The method was optimized for background electrolyte composition, pH, and separation voltage, allowing efficient resolution and dual detection. Rapid separations were obtained, with migration times under 8 min. Linear responses were observed for all compounds within 1-200 μM (R2 ≥ 0.955), with LOD/LOQ ranging 0.32-32.2 μM and 1.07-97.6 μM, respectively. For dextroamphetamine, migration occurred at 3.64 min (DAD) and 3.41 min (C4D), with LOD/LOQ of 2.16/7.19 μM (DAD) and 8.58/28.60 μM (C4D). Intra- and inter-day repeatability tests demonstrated analytical precision with acceptable limits. The method was applied to spiked human urine samples using the standard addition technique for endogenous metabolites (hippuric acid and benzoic acid). This study demonstrates the feasibility of clinical and toxicological monitoring involving psychostimulant determination.

ADHD is a neurodevelopmental condition marked by persistent symptoms of inattention, hyperactivity, and impulsivity. The gold standard pharmacotherapy for the treatment of ADHD is CNS psychostimulants. However, a shortage of CNS psychostimulants used for the treatment of ADHD has persisted since 2022, and many patients have been forced to switch medications or have been unable to obtain medication at all, raising concerns about symptom management and quality of life. This case report describes a 30-year-old female who was unable to obtain lisdexamfetamine amid the shortage, found mixed amphetamine salts ineffective, but found success with immediate-release dextroamphetamine sulfate, a less frequently used amphetamine. This report serves to demonstrate that immediate-release dextroamphetamine sulfate may be a viable alternative stimulant to address the shortage; however, more research must be conducted to confirm these findings.

Stimulant medications are increasingly prescribed for attention-deficit/hyperactivity disorder (ADHD) in men of reproductive age, yet their impact on semen quality remains poorly characterized. We aimed to evaluate whether recent stimulant exposure would negatively affect semen parameters in reproductive-age men with ADHD. We performed a multi-center retrospective analysis of 2039 men aged 18-40 years with a diagnosis of ADHD and available semen volume data between 1995-2025. We excluded men with diagnoses or treatments known to affect spermatogenesis or ejaculatory function. Exposure was defined as an active outpatient prescription for methylphenidate, amphetamine, lisdexamfetamine, dextroamphetamine, or methamphetamine within 90 days prior to semen testing. Exposed patients were matched 2:1 by age (±4 years) to stimulant-unexposed controls with ADHD. The final cohort included 388 exposed and 776 matched controls, with median ages of 33 (IQR 30-37) and 33 (IQR 29-37) years, respectively. Stimulant exposure was associated with lower semen volume (median 2.70 mL [IQR 1.9-3.7] vs. 2.95 mL [IQR 2.0-4.1], p = 0.02). No significant differences were observed between groups in other semen parameters (p > 0.25). On univariable regression, stimulant exposure was associated with a 5.7% decrease in semen volume (p = 0.02). After adjustment in multivariable regression, stimulant exposure remained associated with an 8.4% lower semen volume (p = 0.01). Among reproductive-age men with ADHD, recent stimulant use was associated with a modest decrease in semen volume, while other semen parameters remained unchanged. Importantly, preserved sperm quality suggests that stimulant use during attempts at conception is unlikely to significantly impair fertility.

Nonmedical prescription stimulant use is prevalent among college students despite no evidence of meaningful neuropsychological improvement in students without attention-deficit/hyperactivity disorder (ADHD). The present study addresses methodological limitations of existing placebo-controlled stimulant administration research by including a within-subject design, baseline comparison, and self-report/subjective measures of neuropsychological functioning to better clarify evidence of cognitive enhancement among college students without ADHD. Participants (n = 21) completed a no-drug baseline session and two counterbalanced experimental sessions that involved ingesting a placebo capsule or an amphetamine-dextroamphetamine immediate release 10 mg capsule. For each session, participants completed objective and self-report/subjective neuropsychological measures. Results indicated no significant differences across sessions for self-report/subjective measures and most objective measures. Specifically, for two outcomes on an objective measure (i.e., continuous performance task-identical pairs), performance improved in either the stimulant and placebo conditions compared to baseline or only the placebo condition compared to baseline. Taken together, the results of this study provide further evidence that stimulant medication does not confer neuropsychological improvement in students without ADHD, and perceived improvements may be better attributed to placebo, rather than pharmacological effects of a stimulant medication for this group. This information can inform ongoing efforts to discourage nonmedical prescription stimulant among college students without ADHD. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Lisdexamfetamine dimesylate (LDX) is a psychostimulant, that has been widely recommended in recent years for the treatment of Attention-Deficit/Hyperactivity Disorder. The present study aims to evaluate the effects of LDX administration on the hepatic morphophysiology of pubertal Wistar rats, since the liver plays a central role in systemic metabolism. Male Wistar rats were randomly distributed into two experimental groups: LDX group (LDX) - received 11.3 mg/kg/day of LDX diluted in tap water; and the Control group (C) - received tap water only. Animals were treated by gavage during puberty, from postnatal day (PND) 25 to PND 65. The results showed that administration of LDX decreased white adipose tissue weight without altering overall body weight gain. Plasma biochemical analysis demonstrated an increase in plasma total cholesterol and in the concentration of hepatic transaminases in LDX rats. In addition, LDX animals exhibited an increase in N-acetyl-β-D-glucosaminidase activity, indirectly indicating macrophage recruitment to the liver. This study shows that daily exposure to LDX during puberty causes early liver inflammation and damage due, in part, to increased hepatic transaminases and associated with indirect signs of macrophage recruitment. This finding highlights the importance of monitoring the indiscriminate use of amphetamines and alerting patients to possible liver disorders.

Psychotropic medicines are known to impair cognitive function acutely, but the specific effects of individual substances remain underexplored. This study investigates the effects of dexamphetamine and zolpidem on cognitive performance to quantify the potential risk of intake and their pharmacokinetic and pharmacodynamic relationship. This randomized, double-blind, placebo-controlled trial (EudraCT 2021-005381 - 17) included 60 healthy men aged 26 ± 5 (mean ± SD) years. Participants received a single oral dose of 30-mg dexamphetamine, 5-mg zolpidem, or placebo (n = 20 per group). Cognitive performance was assessed at baseline and 3 and 8 h after dosing using the computerized Psytest system. Dexamphetamine and zolpidem improved sustained attention, with significant reduction of omissions at 8 h. Reaction time improved in both groups, but zolpidem impaired phasic alertness. Working memory remained unchanged. Plasma concentration of dexamphetamine and zolpidem was 70.8 ± 10.4 ng/mL and 39.0 ± 20.7 ng/mL at 3 h and 45.9 ± 7.9 ng/mL and 8.7 ± 6.6 ng/mL at 8 h, respectively. No correlation between drug plasma concentration and cognitive performance measures was demonstrable. Dexamphetamine caused the strongest subjective effects and highest liking ratings, whereas zolpidem elicited greater subjective dislike. Tolerability was best with placebo, followed by zolpidem and dexamphetamine. Single therapeutic doses of dexamphetamine and zolpidem modestly affected cognitive function 3 h after intake, with no relationship between cognitive performance and the study medicines' plasma concentration. Both medicines improve cognition after 8 h but differed in subjective emotional effects. Nevertheless, generalizability is limited by the inclusion of healthy men only. Trial Registration: EudraCT: Nr: 2021-005381-17.

Acquired hypothalamic obesity (aHO) is a disease characterized by rapid, clinically significant, and persistent weight gain resulting from damage to hypothalamic structures. aHO is associated with substantial morbidity, increased mortality, and marked impairment in quality of life. Etiologies include craniopharyngioma and other space-occupying lesions of the sellar/parasellar region, neurosurgical procedures, cranial irradiation, and traumatic brain injury. A multidisciplinary panel comprising ten specialists in neuroendocrinology, neurooncology, and neurosurgery from Germany, Austria, and Switzerland convened in Frankfurt am Main, Germany, on November 10, 2025, to discuss contemporary challenges and advances in this field. aHO should be conceptualized and treated within the broader clinical entity of hypothalamic syndrome, a complex disorder involving multiple neuroendocrine deficiencies, disturbances of circadian regulation, impaired control of hunger, satiety, and thirst, altered thermoregulation, and a range of cognitive, sleep-related, and psychosocial dysfunctions. Long-term outcomes for affected individuals are frequently unfavorable, largely due to increased risks of metabolic syndrome, cardiovascular disease, profound reductions in health-related quality of life, and elevated rates of premature mortality. The management of hypothalamic syndrome remains particularly challenging. Pharmacological strategies, including dextroamphetamine and glucagon-like peptide-1 receptor agonists, have demonstrated potential benefits for weight and hyperphagia-related outcomes. Recently, preliminary findings from a prospective, randomized, placebo-controlled clinical trial (TRANSCEND) provided encouraging evidence for the efficacy of setmelanotide, a melanocortin-4 receptor agonist. This perspectives report reviews clinical advances in epidemiology, diagnostics, treatment, and follow-up of patients with aHO and outlines key directions for future research aimed at improving outcomes in this vulnerable population.

Dexamfetamine (DEX) and lisdexamfetamine (LDX) are both prescribed to treat adult ADHD in the Netherlands. LDX is marketed as a long-acting prodrug of DEX requiring once-daily dosing, unlike DEX, which typically is administered two times daily. However, empirical evidence for this distinct dosing regimens remains sparse. This open-label, cross-over study compared the daytime effects of bioequivalent doses of DEX (twice daily) and LDX (once daily) in sixteen adults with ADHD. It was hypothesized that twice-daily DEX is associated with a faster onset and longer duration of clinical effect due to the second dose, compared to once-daily LDX. Dexamfetamine plasma concentrations, ADHD symptoms, subjective effects, and vital signs were assessed at multiple time points over 12 h post-dose. A significant treatment-by-time interaction was observed for plasma concentrations (F(5,165) = 12.21, p < 0.001), as well as for subjective effects related to wanting more drug (F(4,135) = 2.47, p = 0.047), and contentedness (F(4,135) = 2.50, p = 0.045). We further report a slope-dependent relationship between plasma levels and treatment effects, subjective effects fluctuations appeared more pronounced with DEX, potentially increasing the perceived need for repeated dosing and titration complexity. In contrast, the smoother pharmacokinetic profile of LDX provides objective support for current clinical guidelines that often prefer long-acting formulations for adult ADHD due to their potential for improved adherence and reduced burden of titration.

Lisdexamfetamine is a prodrug of dextroamphetamine. In dosages prescribed for medical indications, some evidence indicates that dextroamphetamine might not affect nursing infants adversely. The effect of dextroamphetamine in milk on the neurological development of the infant has not been well studied. It is possible that large dosages of dextroamphetamine might interfere with milk production, especially in women whose lactation is not well established. Although most manufacturers advise that mothers not breastfeed while taking amphetamine, some experts state that therapeutic dosages of amphetamine can be used during nursing with monitoring of the infant for irritability, insomnia, and feeding difficulty.[1] Breastfeeding is generally discouraged in mothers who are actively abusing amphetamines.[2-4]