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PloS One 2023Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are no studies that have used spatial span tasks (SSTs) to assess the SWM effect of amphetamine and caffeine, although some studies have used digit span tasks (DST) to assess VWM. Previous reports also showed that increasing dopamine increases psychosis-like experiences (PLE, or schizotypy) scores which are in turn negatively associated with WM performance in people with high schizotypy and people with schizophrenia. Therefore, the present study aimed to examine the influence of d-amphetamine (0.45 mg/kg, PO), a dopamine releasing stimulant, on SST, DST, and on PLE in healthy volunteers. In a separate study, we examined the effect of caffeine, a nonspecific adenosine receptor antagonist with stimulant properties, on similar tasks.
METHODS
Healthy participants (N = 40) took part in two randomized, double-blind, counter-balanced placebo-controlled cross-over pilot studies: The first group (N = 20) with d-amphetamine (0.45 mg/kg, PO) and the second group (N = 20) with caffeine (200 mg, PO). Spatial span and digit span were examined under four delay conditions (0, 2, 4, 8 s). PLE were assessed using several scales measuring various aspects of psychosis and schizotypy.
RESULTS
We failed to find an effect of d-amphetamine or caffeine on SWM or VWM, relative to placebo. However, d-amphetamine increased a composite score of psychosis-like experiences (p = 0.0005), specifically: Scores on Brief Psychiatric Rating Scale, Perceptual Aberrations Scale, and Magical Ideation Scale were increased following d-amphetamine. The degree of change in PLE following d-amphetamine negatively and significantly correlated with changes in SWM, mainly at the longest delay condition of 8 s (r = -0.58, p = 0.006).
CONCLUSION
The present results showed that moderate-high dose of d-amphetamine and moderate dose of caffeine do not directly affect performances on DST or SST. However, the results indicate that d-amphetamine indirectly influences SWM, through its effect on psychosis-like experiences.
CLINICAL TRIAL REGISTRATION NUMBER
CT-2018-CTN-02561 (Therapeutic Goods Administration Clinical Trial Registry) and ACTRN12618001292268 (The Australian New Zealand Clinical Trials Registry) for caffeine study, and ACTRN12608000610336 for d-amphetamine study.
Topics: Humans; Dextroamphetamine; Caffeine; Healthy Volunteers; Dopamine; Australia; Amphetamine; Double-Blind Method
PubMed: 37440493
DOI: 10.1371/journal.pone.0287538 -
Lakartidningen Jan 2016Amphetamine dependence is relatively common in Sweden and it is the most frequently used substance among patients with intravenous drug abuse. Current treatment options... (Review)
Review
Amphetamine dependence is relatively common in Sweden and it is the most frequently used substance among patients with intravenous drug abuse. Current treatment options are limited but recently substitution therapy with psychostimulant medication has been evaluated in several clinical trials. Such treatment is controversial in Sweden, perhaps due to the failure of experimental prescription of psychostimulants in the 1960s. Recent clinical trials however indicate that structured treatment programs with psychostimulants might have positive effects, although the results are inconsistent and the evidence base is still limited. Future research is needed in order to determine the potential role of substitution therapy for amphetamine dependence in clinical practice.
Topics: Amphetamine-Related Disorders; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; History, 20th Century; Humans; Legislation, Drug; Methylphenidate; Sweden
PubMed: 26756343
DOI: No ID Found -
Children (Basel, Switzerland) Jan 2022The objectives of this study are to: (1) quantify the difference in the annual number of prescription medications (total and unique) between children and adolescents...
The objectives of this study are to: (1) quantify the difference in the annual number of prescription medications (total and unique) between children and adolescents with ADHD and those without ADHD; and (2) identify the most prescribed medication classes and unique medications among children and adolescents with ADHD. A retrospective cross-sectional study design was employed using data from the 2015 and 2017 Medical Expenditure Panel Survey. The study sample comprised children and adolescents (5-17 years). In the 5-12-year age group, those with ADHD were 2.4%, 17%, and 15% significantly more likely to have one, 2-4, and ≥5 prescription medications, respectively. Similarly, those in the 13-17-year age group were more likely to have one prescription medication (3%), 2-4 prescription medications (15%), and ≥5 prescription medications (12%) than those without ADHD. The most prescribed medications among children and adolescents with ADHD were methylphenidate and amphetamine-dextroamphetamine. ADHD was associated with both higher annual total and unique prescription medications. Additionally, concurrent use of prescription medications was more prevalent among children and adolescents with ADHD. High-quality randomized clinical trials on the safety and efficacy of combinations of multiple psychotherapeutics and stimulants' agents are required to guide the evidence-based practices.
PubMed: 35204892
DOI: 10.3390/children9020171 -
Frontiers in Endocrinology 2023Children with acquired hypothalamic obesity, e.g. following treatment for pediatric craniopharyngioma are at great risk for metabolic syndrome, cardiovascular health... (Randomized Controlled Trial)
Randomized Controlled Trial
Children with acquired hypothalamic obesity, e.g. following treatment for pediatric craniopharyngioma are at great risk for metabolic syndrome, cardiovascular health problems and premature mortality. Treatment for acquired hypothalamic obesity has thus far been disappointing. Several interventions were reported to be partially successful, including dextro-amphetamine and GLP-1R agonists, although results in acquired hypothalamic obesity are conflicting. Disruption of signaling through the melanocortin-4 receptor (MC4R) pathway results in hyperphagia and severe early-onset hypothalamic obesity. Recently, the MC4R agonist setmelanotide has shown promising results in children with genetic forms of hypothalamic obesity; POMC, PCSK1 and LEPR. Patient quotes such as "we have our family life back" illustrate the magnitude of the effect. Targeted hormone replacement therapy with a MC4R agonist for acquired hypothalamic obesity could be a game-changer. Preliminary results of setmelanotide treatment in 14, mostly pediatric, patients with acquired hypothalamic obesity are promising. The FDA has recommended that a prospective, randomized, blinded trial be conducted over a 12 months treatment period, comparable to pivotal trials for other obesity drugs. It may be discussed whether setmelanotide should be regarded as an obesity drug or whether it may be envisioned as an agent for hypothalamic substitution therapy. In this commentary we discuss the trial that is currently recruiting patients with acquired hypothalamic obesity.
Topics: Humans; Child; Prospective Studies; Obesity; alpha-MSH; Obesity, Morbid; Hypothalamic Diseases
PubMed: 38239988
DOI: 10.3389/fendo.2023.1307889 -
Journal of Child and Adolescent... Jun 2023Amphetamines are a preferred treatment for attention-deficit/hyperactivity disorder (ADHD), with the dextroamphetamine transdermal system (d-ATS) providing an... (Randomized Controlled Trial)
Randomized Controlled Trial
d-Amphetamine Transdermal System in Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: Secondary Endpoint Results and Effect Size Analyses from a Pivotal Trial.
Amphetamines are a preferred treatment for attention-deficit/hyperactivity disorder (ADHD), with the dextroamphetamine transdermal system (d-ATS) providing an alternative to oral formulations. A pivotal trial of d-ATS in children and adolescents with ADHD met primary and key secondary endpoints. This analysis reports additional endpoints and safety findings from the pivotal trial and evaluates effect size and number needed to treat (NNT) for d-ATS. In this study, a 5-week, open-label dose-optimization period (DOP) preceded a 2-week, randomized, crossover double-blind treatment period (DBP). Eligible patients received d-ATS 5 mg during the DOP, with weekly evaluations for increase to 10, 15, and 20 mg (equivalent to labeled doses of 4.5, 9, 13.5, and 18 mg/9 hours, respectively) until reaching and maintaining the optimal dose, which was utilized for the DBP. Secondary endpoints included assessment of Attention-Deficit/Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV), Conners' Parent Rating Scale Revised Short Form (CPRS-R:S), and Clinical Global Impression (CGI) scores. NNT was calculated for ADHD-RS-IV and CGI-Improvement (CGI-I). Safety assessments included treatment-emergent adverse events (TEAEs) and dermal safety. In total, 110 patients entered the DOP, with 106 patients randomized (DBP). During the DBP, the least-squares mean (95% confidence interval) difference for d-ATS versus placebo in ADHD-RS-IV total score was -13.1 (-16.2 to -10.0; < 0.001), with effect size of 1.1 and NNT of 3 for ADHD-RS-IV remission, ≥30% improvement, and ≥50% improvement. Significant differences between placebo and d-ATS were also observed for CPRS-R:S and CGI-I scales ( < 0.001), with NNT of 2 for CGI-I response. Most TEAEs were mild or moderate, with three leading to study discontinuation in the DOP and none in the DBP. No patients discontinued due to dermal reactions. d-ATS was effective in treating ADHD in children and adolescents, meeting all secondary endpoints, with a large effect size and NNT of 2-3 to achieve a clinically meaningful response. d-ATS was safe and well tolerated, with minimal dermal reactions. NCT01711021.
Topics: Humans; Adolescent; Child; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Treatment Outcome; Dose-Response Relationship, Drug; Dextroamphetamine
PubMed: 37339441
DOI: 10.1089/cap.2023.0005 -
Journal of Child and Adolescent... Mar 2022To assess efficacy and safety of the new Dextroamphetamine Transdermal System (d-ATS) to treat children and adolescents (aged 6-17 years) with... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Dextroamphetamine Transdermal System for the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: Results from a Pivotal Phase 2 Study.
To assess efficacy and safety of the new Dextroamphetamine Transdermal System (d-ATS) to treat children and adolescents (aged 6-17 years) with attention-deficit/hyperactivity disorder (ADHD). In this phase 2, randomized, placebo-controlled study, 4 d-ATS patches of differing doses (5, 10, 15, and 20 mg) were evaluated. Patients began a 5-week, open-label, stepwise dose-optimization period in which they received a 5-mg d-ATS patch (applied to hip) for 9 hours. During weekly visits, patients were evaluated for possible adjustments to the next dose level based on efficacy and safety. Once at the optimal dose, that dose was maintained during a 2-week, crossover double-blind treatment period. Primary endpoint was to assess efficacy of d-ATS versus placebo as measured by Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP) total score; key secondary endpoints included assessing onset and duration of efficacy by SKAMP total score, and additional secondary endpoints included Permanent Product Measure of Performance (PERMP) scores. Safety was assessed throughout. d-ATS treatment resulted in significant improvements versus placebo in ADHD symptoms as measured by SKAMP total score, with overall least-squares mean difference (95% confidence interval) versus placebo of -5.87 (6.76, -4.97; < 0.001) over the 12-hour assessment period. Onset of efficacy was observed at 2 hours postdose ( < 0.001), and duration of effect continued through 12 hours (patch removed at 9 hours), with significant differences between d-ATS and placebo at all time points from 2 hours onward (all ≤ 0.003). Significant improvements versus placebo in PERMP-A and PERMP-C scores were also observed from 2 to 12 hours postdose with d-ATS treatment. d-ATS was safe and well-tolerated, with a systemic safety profile similar to that observed with oral amphetamines. This study demonstrates that d-ATS is an effective and well-tolerated treatment for children and adolescents with ADHD. These data indicate that d-ATS can deliver sustained levels of efficacy along with the advantages of transdermal drug delivery, making it a beneficial new treatment option. NCT01711021.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Treatment Outcome
PubMed: 35020462
DOI: 10.1089/cap.2021.0107 -
Journal of Attention Disorders May 2023To evaluate the real-world efficacy, safety, and functional outcomes of PRC-063 (multilayer-release methylphenidate) versus lisdexamfetamine (LDX) in ADHD subjects in a...
Real-World Efficacy and Safety of Extended-Release Methylphenidate (PRC-063) in the Treatment of ADHD in Pediatric and Adult Subjects: Results of a Phase IV Multicenter Comparison With Lisdexamfetamine Dimesylate.
OBJECTIVE
To evaluate the real-world efficacy, safety, and functional outcomes of PRC-063 (multilayer-release methylphenidate) versus lisdexamfetamine (LDX) in ADHD subjects in a phase IV, open-label study.
METHOD
The primary endpoint was the change in the ADHD-DSM-5 Rating Scale (ADHD-5-RS) total score from baseline to Month 4. Secondary endpoints included a non-inferiority comparison between PRC-063 and LDX and measures of functioning and evening behavior.
RESULTS
One hundred forty-three pediatric and 112 adult subjects were enrolled. Mean ADHD-5-RS scores (standard deviation) were reduced in pediatric (-16.6 [10.4]) and adult (-14.8 [10.6]) subjects treated with PRC-063 ( < .001). PRC-063 was non-inferior to LDX in the pediatric population but not in the adult population. Significant improvements were demonstrated in quality of life and functionality. Both medications were well-tolerated; more adverse events led to study discontinuation in pediatric subjects treated with LDX versus PRC-063.
CONCLUSION
PRC-063 and LDX significantly improved ADHD symptomatology and functioning and were well-tolerated.
Topics: Humans; Adult; Child; Lisdexamfetamine Dimesylate; Attention Deficit Disorder with Hyperactivity; Methylphenidate; Central Nervous System Stimulants; Dextroamphetamine; Quality of Life; Treatment Outcome; Double-Blind Method; Dose-Response Relationship, Drug
PubMed: 37144295
DOI: 10.1177/10870547231172767 -
Journal of Child and Adolescent... Apr 2020Describe the safety and tolerability of lisdexamfetamine dimesylate (LDX) and provide data on clinical effects for efficacy-related endpoints and pharmacokinetics in...
Describe the safety and tolerability of lisdexamfetamine dimesylate (LDX) and provide data on clinical effects for efficacy-related endpoints and pharmacokinetics in preschool-aged children with attention-deficit/hyperactivity disorder (ADHD). This phase 2, multicenter, open-label, dose-optimization study (ClinicalTrials.gov registry: NCT02402166) was conducted at seven U.S. sites between April 15, 2015, and June 30, 2016. Children (4-5 years of age) meeting criteria for ADHD and having ADHD Rating Scale-IV Preschool version (ADHD-RS-IV-PS) total scores ≥28 (boys) or ≥24 (girls) were eligible. Open-label LDX (8-week duration) was initiated at 5 mg and titrated to 30 mg until achieving an optimal dose. Assessments included treatment-emergent adverse events (TEAEs), vital sign changes, ADHD-RS-IV-PS total score changes, and pharmacokinetic evaluations. Among 24 participants, the most frequently reported TEAE was decreased appetite (8/24; 33%). At week 8/early termination, mean (standard deviation) systolic and diastolic blood pressure and pulse changes from baseline were -1.1 (7.31) and 1.5 (6.93) mmHg and -0.8 (12.75) bpm, respectively. The mean (95% confidence interval) change from baseline ADHD-RS-IV-PS total score at the final on-treatment assessment was -26.1 (-32.2 to -20.0). Pharmacokinetic parameters of amphetamine, a major active metabolite of LDX, were characterized: -amphetamine exposure increased with LDX dose; mean and , respectively, ranged from 4.00 to 4.23 hours and 7.18 to 8.46 hours. In preschool-aged children with ADHD, LDX was generally well tolerated and reduced ADHD symptoms, consistent with observations in children 6-17 years of age. Based on these findings, a starting LDX dose as low as 5 mg in phase 3 studies in preschool-aged children is supported.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child, Preschool; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Treatment Outcome
PubMed: 32233956
DOI: 10.1089/cap.2019.0117 -
Drug Design, Development and Therapy 2015Several studies have shown that lisdexamfetamine (LDX) is efficacious in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Several studies have shown that lisdexamfetamine (LDX) is efficacious in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
OBJECTIVES
Aims of this study were to systematically review the efficacy, acceptability, and tolerability of LDX in child and adolescent ADHD. Any randomized controlled trials (RCTs) of LDX versus placebo carried out in children and adolescents with ADHD were included.
DATA SOURCES
The searches of the SCOPUS, MEDLINE, CINAHL and Cochrane Controlled Trials Register were performed in September 2014. Additional searches in the ClinicalTrials. gov and EU Clinical Trials Register database were conducted.
STUDY ELIGIBILITY CRITERIA PARTICIPANTS AND INTERVENTIONS
This review included all RCTs of LDX versus placebo which were carried out in children and adolescents up to 18 years old. Additionally, the included studies must have reported the final outcomes of: i) severity of ADHD symptoms with standardized scales, ii) rates of improvement, iii) rates of discontinuation. To be more thorough, the languages of such RCTs were not limited.
STUDY APPRAISAL AND SYNTHESIS METHODS
The abstracts from databases were inspected and the full text versions of relevant trials were examined and extracted for important outcomes. The efficacious measurements included either the pooled mean end-point or changed scores of ADHD rating scales, and the rate of improvement. Acceptability and tolerability were measured by the pooled overall discontinuation rate and the pooled discontinuation rate due to adverse events, respectively. A random effect model technique was utilized to synthesize the mean differences (either standardized mean differences or weighted mean differences) and relative risks (RRs) with 95% confidence intervals (CIs).
RESULTS
A total of 1,016 children and adolescents with ADHD were included. The dosage of LDX was 30 to 70 mg/day. The pooled mean change scores of LDX-treated group was significantly greater than that of the placebo (weighted mean difference [95% CI] of -15.20 [-19.95, -10.46], I (2)=94%). The pooled improvement rate of the LDX-treated group was also significantly higher than that of the placebo (RR [95% CI] of 0.34 [0.24, 0.47], I (2)=80%). The pooled overall discontinuation rate between the two groups was not significantly different (RR [95% CI] of 0.78 [0.46, 1.31], I (2)=63%). Similarly, the pooled discontinuation rate due to adverse events between the two groups showed no significant difference (RR [95% CI] of 1.99 [0.70, 5.64], I (2)=0%).
LIMITATIONS
The number of included studies was limited (five RCTs).
CONCLUSION
According to the present review, LDX was effective and well-tolerated in the treatment of child and adolescent ADHD. Unfortunately, the acceptability of LDX was not better than the placebo. Since the number of included studies was limited, the outcome from this review should be carefully interpreted and considered as preliminary. Further studies, therefore, should be conducted to confirm these findings.
IMPLICATION OF KEY FINDINGS
Lisdexamfetamine is an efficacious stimulant for treating child and adolescent ADHD.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Drug Tolerance; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic
PubMed: 25897203
DOI: 10.2147/DDDT.S79071 -
Cureus Apr 2021Attention-deficit hyperactivity disorder (ADHD) is a commonly diagnosed disorder that is managed with stimulant medications, which function by increasing the levels of...
Attention-deficit hyperactivity disorder (ADHD) is a commonly diagnosed disorder that is managed with stimulant medications, which function by increasing the levels of dopamine in the brain. Excess dopamine has been known to affect several body systems, including the endocrine system. This case presents male factor infertility caused by a negative interaction between excess dopamine and the endocrine system, inducing pituitary failure, which led to azoospermia. The patient and her partner presented to the fertility clinic for evaluation after one year of failing to conceive. The patient's partner had been treated throughout the conception of their first three pregnancies for ADHD with methylphenidate (Ritalin) for many years; however, eight months prior to presentation at the clinic, the partner had been switched to amphetamine-dextroamphetamine (Adderall) for treatment of ADHD. A fertility evaluation revealed azoospermia which was confirmed via two separate semen analyses two weeks apart. In addition, the patient's total testosterone, prolactin, luteinizing hormone, and follicle-stimulating hormone were below normal limits. A normal semen analysis was obtained after a five-month withdrawal of amphetamine-dextroamphetamine, which was followed by a naturally conceived pregnancy. The possibility of pre-testicular azoospermia caused by medication-induced pituitary failure should be considered in males prescribed stimulant medication who are seeking to reproduce.
PubMed: 33959450
DOI: 10.7759/cureus.14269