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Journal of Psychopharmacology (Oxford,... Dec 2016±3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that enhances sociability and feelings of closeness with others. These "prosocial" effects... (Review)
Review
±3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that enhances sociability and feelings of closeness with others. These "prosocial" effects appear to motivate the recreational use of MDMA and may also form the basis of its potential as an adjunct to psychotherapy. However, the extent to which MDMA differs from prototypic stimulant drugs, such as dextroamphetamine, methamphetamine, and methylphenidate, in either its behavioral effects or mechanisms of action, is not fully known. The purpose of this review is to evaluate human laboratory findings of the social effects of MDMA compared to other stimulants, ranging from simple subjective ratings of sociability to more complex elements of social processing and behavior. We also review the neurochemical mechanisms by which these drugs may impact sociability. Together, the findings reviewed here lay the groundwork for better understanding the socially enhancing effects of MDMA that distinguish it from other stimulant drugs, especially as these effects relate to the reinforcing and potentially therapeutic effects of the drug.
Topics: Central Nervous System Stimulants; Emotions; Hallucinogens; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Social Behavior
PubMed: 27562198
DOI: 10.1177/0269881116663120 -
American Journal of Obstetrics and... Jul 2024Attention-deficit/hyperactivity disorder is a childhood-onset neurodevelopmental disorder that frequently persists into adulthood with 3% of adult women having a... (Review)
Review
Attention-deficit/hyperactivity disorder is a childhood-onset neurodevelopmental disorder that frequently persists into adulthood with 3% of adult women having a diagnosis of attention-deficit/hyperactivity disorder. Many women are diagnosed and treated during their reproductive years, which leads to management implications during pregnancy and the postpartum period. We know from clinical practice that attention-deficit/hyperactivity disorder symptoms frequently become challenging to manage during the perinatal period and require additional support and attention. There is often uncertainty among healthcare providers about the management of attention-deficit/hyperactivity disorder in the perinatal period, particularly the safety of pharmacotherapy for the developing fetus. This guideline is focused on best practices in managing attention-deficit/hyperactivity disorder in the perinatal period. We recommend (1) mitigating the risks associated with attention-deficit/hyperactivity disorder that worsen during the perinatal period via individualized treatment planning; (2) providing psychoeducation, self-management strategies or coaching, and psychotherapies; and, for those with moderate or severe attention-deficit/hyperactivity disorder, (3) considering pharmacotherapy for attention-deficit/hyperactivity disorder, which largely has reassuring safety data. Specifically, providers should work collaboratively with patients and their support networks to balance the risks of perinatal attention-deficit/hyperactivity disorder medication with the risks of inadequately treated attention-deficit/hyperactivity disorder during pregnancy. The risks and impacts of attention-deficit/hyperactivity disorder in pregnancy can be successfully managed through preconception counselling and appropriate perinatal planning, management, and support.
Topics: Humans; Female; Attention Deficit Disorder with Hyperactivity; Pregnancy; Pregnancy Complications; Postpartum Period; Central Nervous System Stimulants; Methylphenidate; Psychotherapy; Atomoxetine Hydrochloride
PubMed: 38432409
DOI: 10.1016/j.ajog.2024.02.297 -
The Cochrane Database of Systematic... Sep 2022Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of... (Review)
Review
BACKGROUND
Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016.
OBJECTIVES
To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue.
SEARCH METHODS
For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings.
DATA COLLECTION AND ANALYSIS
Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes.
MAIN RESULTS
The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.
Topics: Adult; Brain Neoplasms; Dextroamphetamine; Fatigue; Glioma; Humans; Modafinil
PubMed: 36094728
DOI: 10.1002/14651858.CD011376.pub3 -
The Journal of Neuroscience : the... Oct 2023Prevailing frameworks propose that a key feature of attention-deficit/hyperactivity disorder (ADHD) is lower motivation. An important component of motivation is the...
Prevailing frameworks propose that a key feature of attention-deficit/hyperactivity disorder (ADHD) is lower motivation. An important component of motivation is the willingness to engage in cognitively or physically effortful behavior. However, the degree to which effort sensitivity is impaired in ADHD has rarely been tested, and the efficacy of stimulant medication in ameliorating any such impairments is unclear. Here, we tested 20 individuals with ADHD (11 males, 9 females) who were managed with amphetamine-based medication (dexamfetamine, lisdexamfetamine), and 24 controls (8 males, 16 females). Individuals with ADHD were tested over two counterbalanced sessions, ON and OFF their usual amphetamine-based medication. In each session, participants performed an effort-based decision-making task, in which they were required to choose how much cognitive or physical effort they were willing to engage in return for reward. Our results revealed three main findings. First, individuals with ADHD had lower motivation relative to controls to invest effort in both the cognitive and physical domains. Second, amphetamine increased motivation uniformly across both domains. Finally, the net effect of amphetamine treatment was to mostly restore motivation across both domains of effort relative to healthy controls. These data provide clear evidence for a heightened sensitivity to both cognitive and physical effort in ADHD, and reveal the efficacy of amphetamine-based drugs in restoring effort sensitivity to levels similar to controls. These findings confirm the existence of reduced motivational drive in ADHD, and more broadly provide direct causal evidence for a domain-general role of catecholamines in motivating effortful behavior. A core feature of attention-deficit/hyperactivity disorder (ADHD) is thought to be a heightened aversion to effort. Surprisingly, however, the degree to which effort sensitivity is impaired in ADHD has rarely been tested. More broadly, the relative efficacy of catecholamines in motivating the investment of cognitive and physical effort is unclear. We tested 20 individuals with ADHD ON and OFF amphetamines, and compared their behavior on an effort-based decision-making task to 24 controls. When tested OFF medication, the ADHD group was less cognitively and physically motivated than controls. However, amphetamines led to a comparable increase in motivation across both domains. This demonstrates the efficacy of catecholamines in facilitating domain-general effort, and highlights the broader potential of such drugs to treat disorders of motivation.
Topics: Male; Female; Humans; Attention Deficit Disorder with Hyperactivity; Motivation; Amphetamines; Lisdexamfetamine Dimesylate; Catecholamines; Central Nervous System Stimulants
PubMed: 37666665
DOI: 10.1523/JNEUROSCI.0982-23.2023 -
Clinical Drug Investigation May 2016Lisdexamfetamine dimesylate (LDX) is a long-acting d-amphetamine prodrug used to treat attention-deficit/hyperactivity disorder (ADHD) in children, adolescents and... (Review)
Review
Lisdexamfetamine dimesylate (LDX) is a long-acting d-amphetamine prodrug used to treat attention-deficit/hyperactivity disorder (ADHD) in children, adolescents and adults. LDX is hydrolysed in the blood to yield d-amphetamine, and the pharmacokinetic profile of d-amphetamine following oral administration of LDX has a lower maximum plasma concentration (Cmax), extended time to Cmax (Tmax) and lower inter- and intra-individual variability in exposure compared with the pharmacokinetic profile of an equivalent dose of immediate-release (IR) d-amphetamine. The therapeutic action of LDX extends to at least 13 h post-dose in children and 14 h post-dose in adults, longer than that reported for any other long-acting formulation. Drug-liking scores for LDX are lower than for an equivalent dose of IR d-amphetamine, which may result from the reduced euphorigenic potential associated with its pharmacokinetic profile. These pharmacokinetic and pharmacodynamic characteristics of LDX may be beneficial in the management of symptoms in children, adolescents and adults with ADHD.
Topics: Administration, Oral; Adolescent; Adult; Amphetamine; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Drug Delivery Systems; Humans; Lisdexamfetamine Dimesylate; Male; Prodrugs; Treatment Outcome
PubMed: 27021968
DOI: 10.1007/s40261-015-0354-y -
Frontiers in Endocrinology 2022Hypothalamic obesity (HO) in children has severe health consequences. Lifestyle interventions are mostly insufficient and currently no drug treatment is approved for...
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 ( = 10 with acquired HO, = 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.
Topics: Adolescent; Child; Dextroamphetamine; Energy Metabolism; Humans; Hypothalamic Diseases; Obesity; Retrospective Studies
PubMed: 35355559
DOI: 10.3389/fendo.2022.845937 -
Mayo Clinic Proceedings Aug 2021A 45-year-old woman presented to our clinic in July 2019 for evaluation of intermittent fever, rigors, diaphoresis, malaise, and urinary symptoms of frequency and...
A 45-year-old woman presented to our clinic in July 2019 for evaluation of intermittent fever, rigors, diaphoresis, malaise, and urinary symptoms of frequency and urgency of 5 days’ duration. Her history was notable for Graves disease after total thyroidectomy 8 months previously after failed medical management, with no neck swelling or pain at present; an incidentally discovered and resected papillary thyroid microcarcinoma; and hypertension. A reconciled medication list included levothyroxine (125 μg/d), sertraline (100 mg/d), amphetamine-dextroamphetamine (20 mg/d), propranolol (40 mg twice daily), selenium (200 μg/d), and biotin (10 mg/d). She reported no relevant family history or sick contacts, but she may have had tick exposure. Physical examination revealed a temperature of 39.4 °C, heart rate of 64 beats/min, blood pressure of 98/56 mm Hg, weight of 85 kg, exophthalmos and lagophthalmos, and healed Kocher incision with no neck masses or tenderness. Abdominal examination revealed mild suprapubic tenderness. The differential diagnosis included infection (urinary tract infection [UTI], viral syndrome, tick-borne illness) and hyperthyroidism in the setting of ongoing levothyroxine therapy and her history of Graves disease. Subsequent laboratory studies revealed the following (reference ranges provided parenthetically): hemoglobin, 10.7 g/dL (11.6 to 15.0 g/dL); white blood cell count, 16.7 × 10/L (3.4 to 9.6 × 10/L); creatinine, 0.91 mg/dL (0.59 to 1.04 mg/dL); 2 sets of blood cultures with negative results; urine culture growing , greater than 100,000 colony-forming units per milliliter; and negative results on a tick-borne pathogen panel including Lyme disease serology. Chest radiography revealed no abnormalities. Thyroid function testing (TFT) revealed the following: thyrotropin, 0.01 mIU/L (0.3 to 4.2 mIU/L); free thyroxine (fT4), 1.3 ng/dL (0.9 to 1.7 ng/dL); and free triiodothyronine (fT3) 2.4 pg/mL (2.8 to 4.4 pg/mL). Antimicrobial therapy was initiated for a UTI.
Topics: Biomarkers; Diagnosis, Differential; Female; Fever; Humans; Middle Aged; Thyroid Diseases; Thyrotropin
PubMed: 34226032
DOI: 10.1016/j.mayocp.2020.11.038 -
Cureus Jul 2022Rhabdomyolysis ranges from being asymptomatic with elevated creatine kinase (CK) to a potentially life-threatening condition involving multiple organ systems. Muscular...
Rhabdomyolysis ranges from being asymptomatic with elevated creatine kinase (CK) to a potentially life-threatening condition involving multiple organ systems. Muscular trauma is the most common cause, followed by enzyme deficiencies, electrolyte abnormalities, drugs, toxins, and endocrinopathies. While these risk factors are delineated, it is not clear if mild exposure to a combination of risk factors could lead to the development of rhabdomyolysis. In this case report, a 22-year-old male of Pakistani/Caucasian ethnicity presented to the emergency room with myalgias and tea-colored urine after starting a new exercise program. His serum CK level and liver function tests were significantly elevated. He was successfully treated for acute rhabdomyolysis with aggressive hydration. However, the etiology of his condition was not clear given that his exercise was not considered vigorous. The only plausible explanation for his symptoms included the use of prescribed dextroamphetamine, which may have exacerbated the physiologic responses induced by exercise. This report describes a novel case in which a patient may have developed recurrent episodes of rhabdomyolysis due to low-dose dextroamphetamine use. The combination of exercise and dextroamphetamine use may predispose patients to develop rhabdomyolysis.
PubMed: 36046308
DOI: 10.7759/cureus.27357 -
Expert Opinion on Drug Safety Jan 2018Eating disorders represent a set of psychiatric illnesses with lifelong complications and high relapse rates. Individuals with eating disorders are often stigmatized and... (Review)
Review
INTRODUCTION
Eating disorders represent a set of psychiatric illnesses with lifelong complications and high relapse rates. Individuals with eating disorders are often stigmatized and clinicians have a limited set of treatments options. Pharmacotherapy has the potential to improve long term compliance and patient commitment to treatment for eating disorders.
AREAS COVERED
This review will examine the efficacy and safety profile of the FDA-approved medications for the treatment of bulimia nervosa (BN) and binge eating disorder (BED). This will include the evaluation of fluoxetine for BN, and lisdexamfetamine for BED. Safety information will be review from randomized control trials (RCT), open label trials, and case reports.
EXPERT OPINION
Fluoxetine for BN and lisdexamfetamine for BED are relatively safe and well-tolerated. Despite these properties, these two medications represent a limited arsenal for the pharmacological treatment of eating disorders. Thus, more research-based strategies are needed to develop safe, effective, and more targeted therapies for eating disorders.
Topics: Binge-Eating Disorder; Bulimia Nervosa; Fluoxetine; Humans; Lisdexamfetamine Dimesylate; Medication Adherence; Randomized Controlled Trials as Topic
PubMed: 29053927
DOI: 10.1080/14740338.2018.1395854 -
British Journal of Pharmacology Sep 2022Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by... (Review)
Review
Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by the psychostimulant d-amphetamine. Exaggerated 50-kHz USV emission evoked by d-amphetamine is modulated by dopamine, noradrenaline and 5-hydroxytyrptamine receptor ligands and inhibited by the mood stabilizer lithium, the gold standard anti-manic drug for treating bipolar disorder. This indicates that exaggerated 50-kHz USV emission can serve as a reliable and valid measure for assessing mania-like elevated mood in rats with sufficient translational power for gaining a better understanding of relevant pathophysiological mechanisms and the identification of new therapeutic targets. The improved capacity to study the effects of anti-manic pharmacological interventions on a broader range of behaviours by including exaggerated 50-kHz USV emission as preclinical outcome measure complementary to locomotor hyperactivity will refine rodent models for mania. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.
Topics: Amphetamine; Animals; Antimanic Agents; Dextroamphetamine; Mania; Rats; Ultrasonics; Vocalization, Animal
PubMed: 33830495
DOI: 10.1111/bph.15487