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Innovations in Clinical Neuroscience 2024Stimulants are the first-line pharmacological treatment for attention deficit hyperactivity disorder (ADHD). We present the unique case of a patient who developed a...
Stimulants are the first-line pharmacological treatment for attention deficit hyperactivity disorder (ADHD). We present the unique case of a patient who developed a chewing compulsion when taking mixed amphetamine salts (MAS). A 32-year-old female patient with a past medical history of gastroesophageal reflux disease (GERD), gastroparesis, and migraines was seen for initial psychiatric assessment due to concerns for irritability. She was diagnosed with post-traumatic stress disorder (PTSD); generalized anxiety disorder; ADHD, inattentive type; and unspecified bipolar disorder. Lamotrigine was started and titrated to 25mg twice per day, with improved mood stability. MAS immediate-release (IR) was started at 2.5mg and titrated to 5mg daily for ADHD. She then experienced an uncontrollable urge to chew, finding relief when chewing on a child's teething necklace, which provided satisfaction and a reduction in anxiety. She denied jaw tightness or teeth grinding. The dose of MAS IR was reduced to 2.5mg daily with improvement in symptoms and later increased again to 5mg daily, which she was then able to tolerate. Stereotyped biting behaviors have been observed in rats with the use of amphetamines, and the onset of compulsive behavior has emerged in children with the use of dextroamphetamine. However, this is the first known case of compulsive chewing or biting movements reported in humans with MAS use. This case highlights the need to assess patients for adverse events, such as compulsive biting and chewing movements or other oral facial stereotypies, after commencement of stimulants, including MAS.
PubMed: 38938532
DOI: No ID Found -
Journal of Psychoactive Drugs Jun 2024Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the...
Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the combination of psilocybin mushrooms with a monoamine oxidase inhibitor (MAOI). A 42-year-old man with treatment-resistant major depressive disorder took 1 g of mushrooms, while prescribed tranylcypromine, extended-release dextroamphetamine-amphetamine, and other medications. Approximately half an hour later, he developed severe hypertension with chest pain, palpitations, and headache. Upon hospital presentation, the electrocardiogram demonstrated ST-elevation. The patient was diagnosed with a myocardial infarction and treated with lorazepam, nitroglycerin, and aspirin. He subsequently underwent emergency cardiac catheterization, which revealed no significant cardiac abnormalities. Following overnight hospitalization, he was discharged home with no lasting physical sequelae. Though data are few, past studies suggest that classic serotonergic psychedelics (5HT-2A receptor agonists) such as dimethyltryptamine (DMT), lysergic acid (LSD), and synthetic psilocybin should not produce hypertensive emergency when combined with MAOIs. We suspect phenylethylamine, found in and other species of psilocybin mushrooms, interacted with tranylcypromine and dextroamphetamine-amphetamine to produce this hypertensive emergency. Patients prescribed MAOIs should be warned of the potential for hypertensive emergency when consuming psilocybin mushrooms, particularly when also prescribed norepinephrine releasers such as dextroamphetamine-amphetamine.
PubMed: 38903003
DOI: 10.1080/02791072.2024.2368617 -
Journal of Managed Care & Specialty... Jun 2024Head-to-head trials comparing centanafadine, an investigational therapy for adults with attention-deficit/hyperactivity disorder (ADHD), with other treatment options are... (Comparative Study)
Comparative Study
Assessment of centanafadine in adults with attention-deficit/hyperactivity disorder: A matching-adjusted indirect comparison vs lisdexamfetamine dimesylate, atomoxetine hydrochloride, and viloxazine extended-release.
BACKGROUND
Head-to-head trials comparing centanafadine, an investigational therapy for adults with attention-deficit/hyperactivity disorder (ADHD), with other treatment options are lacking.
OBJECTIVE
To compare safety and efficacy outcomes of centanafadine sustained-release vs lisdexamfetamine dimesylate (lisdexamfetamine), atomoxetine hydrochloride (atomoxetine), and viloxazine extended-release (viloxazine ER), respectively, using matching-adjusted indirect comparison (MAIC).
METHODS
This MAIC included patient-level data pooled from 2 centanafadine trials (NCT03605680 and NCT03605836) and published aggregate data from comparable trials of 3 comparators-lisdexamfetamine (NCT00334880), atomoxetine (NCT00190736), and viloxazine ER (NCT04016779)-in adult patients with ADHD. Propensity score weighting was used to match characteristics of individual patients from the centanafadine trials to aggregate baseline characteristics from the respective comparator trials. Safety outcomes were rates of adverse events for which information was available in the centanafadine and respective comparator trials. Efficacy outcome was mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) score (ADHD Rating Scale [ADHD-RS] was used as proxy in the comparison with lisdexamfetamine). Anchored indirect comparisons were conducted across matched populations of the centanafadine and respective comparator trials.
RESULTS
After matching, baseline characteristics in the centanafadine trials were the same as those in the respective comparator trials. Compared with lisdexamfetamine, centanafadine was associated with a significantly lower risk of lack of appetite (risk difference [RD] in percentage points: 23.42), dry mouth (19.27), insomnia (15.35), anxiety (5.21), nausea (4.90), feeling jittery (3.70), and diarrhea (3.47) (all < 0.05) but a smaller reduction in the AISRS/ADHD-RS score (6.58-point difference; < 0.05). Compared with atomoxetine, centanafadine was associated with a significantly lower risk of nausea (RD in percentage points: 18.64), dry mouth (17.44), fatigue (9.21), erectile dysfunction (6.76), lack of appetite (6.71), and urinary hesitation (5.84) (all < 0.05) and no statistically significant difference in the change in AISRS score. Compared with viloxazine ER, centanafadine was associated with a significantly lower risk of fatigue (RD in percentage points: 11.07), insomnia (10.67), nausea (7.57), and constipation (4.63) (all < 0.05) and no statistically significant difference in the change in AISRS score.
CONCLUSIONS
In an anchored MAIC, centanafadine showed a significantly better short-term safety profile than lisdexamfetamine, atomoxetine, and viloxazine ER; efficacy was lower than with lisdexamfetamine and comparable (ie, nondifferent) with atomoxetine and viloxazine ER. This MAIC provides important insights on the relative safety and efficacy of common treatment options to help inform treatment decisions in adults with ADHD. Safety assessment was limited to rates of adverse events reported in both trials of a given comparison.
STUDY REGISTRATION NUMBERS
NCT03605680, NCT03605836, NCT00334880, NCT00190736, and NCT04016779.
Topics: Adolescent; Adult; Female; Humans; Male; Middle Aged; Young Adult; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Lisdexamfetamine Dimesylate; Treatment Outcome; Viloxazine; Clinical Trials, Phase III as Topic
PubMed: 38824626
DOI: 10.18553/jmcp.2024.30.6.528 -
Drug and Alcohol Dependence Jul 2024A return to cocaine use following abstinence frequently occurs in a social context, and the presence of other individuals using cocaine may contribute to the likelihood...
RATIONALE
A return to cocaine use following abstinence frequently occurs in a social context, and the presence of other individuals using cocaine may contribute to the likelihood of use. Previous studies have reported that chronic d-amphetamine treatment decreases cocaine self-administration in laboratory animals and reduces a return to cocaine use following abstinence in humans.
OBJECTIVE
The purpose of this study was to examine the effects of chronic d-amphetamine treatment on the reacquisition of cocaine use in rats self-administering cocaine in different social contexts.
METHODS
Male and female rats were implanted with intravenous catheters and trained to self-administer cocaine during daily 6-hr sessions. After 14 days, cocaine self-administration was extinguished by substituting saline for the cocaine stimulus. At this time, rats were randomized to receive chronic treatment with either d-amphetamine or saline. After 9 days of extinction, cocaine was again made available during daily 6-hr sessions. At this time, rats were further randomized into three social conditions: (1) rats continued self-administering cocaine in isolation, (2) rats self-administered cocaine in the presence of a same-sex partner that also self-administered cocaine, or (3) rats self-administered cocaine in the presence of a same-sex partner that did not have access to cocaine. Daily treatment with d-amphetamine or saline continued for the duration of reacquisition testing.
RESULTS
Chronic treatment with d-amphetamine decreased cocaine intake during reacquisition, but these effects were not influenced by the social context. No sex differences were observed.
CONCLUSION
These data support previous studies reporting that d-amphetamine decreases cocaine intake and demonstrate its efficacy across social contexts.
Topics: Animals; Male; Self Administration; Female; Rats; Cocaine; Dextroamphetamine; Central Nervous System Stimulants; Extinction, Psychological; Cocaine-Related Disorders; Rats, Sprague-Dawley; Social Behavior; Social Environment
PubMed: 38776581
DOI: 10.1016/j.drugalcdep.2024.111328 -
Expert Review of Neurotherapeutics May 2024The dextroamphetamine transdermal system (d-ATS) is a stimulant patch recently approved by the United States (U.S.) Food and Drug Administration for the treatment of... (Review)
Review
INTRODUCTION
The dextroamphetamine transdermal system (d-ATS) is a stimulant patch recently approved by the United States (U.S.) Food and Drug Administration for the treatment of attention-deficit/hyperactivity disorder (ADHD).
AREAS COVERED
The composition of the d-ATS, pharmacokinetics, and metabolism are presented along with data from dermal trials evaluating the tolerability of patch application at various skin sites. Efficacy and safety data from a laboratory classroom study in children and adolescents including effect sizes are assessed. Pharmacokinetic-pharmacodynamic modeling of variable wear times is also discussed.
EXPERT OPINION
Although stimulants are recommended as first-line treatment for ADHD in the U.S. some patients may have difficulty swallowing intact tablets and capsules, or dislike the taste or texture of chewable, oral disintegrating, or liquid formulations. The d-ATS fills an unmet need for those with ADHD who are unable or prefer not to take medication orally. Varying wear time of the d-ATS also gives flexibility in length of stimulant effect which may be useful for patients with changing schedules. However, dermal discomfort must be considered in addition to the usual amphetamine side effects when prescribing the d-ATS. Patient and provider experience will determine how frequent the use of d-ATS becomes.
Topics: Adolescent; Adult; Humans; Child; Attention Deficit Disorder with Hyperactivity; Amphetamine; Central Nervous System Stimulants; Dextroamphetamine
PubMed: 38630024
DOI: 10.1080/14737175.2024.2329306 -
Journal of Child and Adolescent... Apr 2024This study aimed to examine switch from first-line methylphenidate (MPH) to lisdexamfetamine (LDX) in school-aged children with attention-deficit/hyperactivity disorder... (Observational Study)
Observational Study
This study aimed to examine switch from first-line methylphenidate (MPH) to lisdexamfetamine (LDX) in school-aged children with attention-deficit/hyperactivity disorder (ADHD). This is a retrospective observational study based on systematic review of patient records of all children (7-13 years) diagnosed with ADHD and referred to a Danish specialized outpatient clinic. The study included 394 children switching from MPH to LDX as either second-line or third-line treatment (atomoxetine [ATX] as second-line treatment) during the study period from April 1, 2013, to November 5, 2019. One in five children switched from MPH to LDX at some point during the study period. The most frequent reasons for switching to LDX were adverse effects (AEs; 70.0% for MPH, 68.3% for ATX) and lack of efficiency (52.0% for MPH, 72.7% for ATX). Top five AEs of LDX were decreased appetite (62.4%), insomnia (28.7%), irritability/aggression (26.1%), weight decrease (21.1%), and mood swings (13.9%). MPH and LDX had similar AE profiles, yet most AEs were less frequent after switching to LDX. At the end of the study period, the majority were prescribed LDX as second-line rather than third-line treatment (86.1% in 2019). However, the likelihood of LDX as second-line treatment decreased with the number of psychiatric comorbidities, ADHD symptom severity as assessed by parents, and if AEs were a reason for MPH discontinuation. Among children observed for at least 1 year after initiation of LDX, 41.3% continued LDX treatment for a year or longer. LDX continuation was less likely if AEs were a reason for MPH discontinuation. Similarly to MPH and ATX, the most frequent reasons for LDX discontinuation were AEs (74.4%) and lack of efficiency (34.7%). The findings support LDX as an important option in the personalized treatment of children with ADHD and may support prescribers in the clinical decision-making on switching medication.
Topics: Child; Humans; Attention Deficit Disorder with Hyperactivity; Lisdexamfetamine Dimesylate; Cohort Studies; Methylphenidate; Atomoxetine Hydrochloride; Ambulatory Care Facilities; Denmark
PubMed: 38608011
DOI: 10.1089/cap.2023.0077 -
Drug Testing and Analysis Apr 2024This study evaluated an alternative routine for reporting urinary chiral amphetamine results in assessment of attention-deficit/hyperactivity disorder (ADHD) treatment...
This study evaluated an alternative routine for reporting urinary chiral amphetamine results in assessment of attention-deficit/hyperactivity disorder (ADHD) treatment with amphetamine medications and for detecting side-use of illicit racemic amphetamine. Currently in Sweden, only enantiopure d-amphetamine-based ADHD medications (lisdexamphetamine dimesylate and dexamphetamine sulfate) are approved. It is therefore unsuitable to express the chiral result as the l/d-ratio, as before, because l-amphetamine should not be present provided treatment compliance. A new routine for LC-MS/MS chiral amphetamine testing was therefore introduced in 2020, whereby the relative proportion (%) of l-amphetamine and the total amphetamine and creatinine concentrations are reported. Evaluation of the new routine on 24,354 results from 2013 to 2023 revealed that it was useful to distinguish ADHD medication adherence from illicit drug use as the source for a positive test. The l-amphetamine proportion also reflected the enantiomeric content of the medications used. Overall, most results confirmed adherence to ADHD medication, as the l-amphetamine percentage was <1% in 76% of samples (2023) which is the recommended cutoff with enantiopure d-amphetamine medications. However, in all years, illicit drug use was indicated (>40% l-amphetamine) in 8.3%-14.5% of cases. In conclusion, this study demonstrated the clinical value and utility of a new routine for reporting urinary chiral amphetamine results to differentiate adherence to ADHD medication from illicit drug use. Unlike the l/d-amphetamine ratio, it considers differences in total amphetamine concentration and urine dilution, factors that can affect the interpretation.
PubMed: 38600633
DOI: 10.1002/dta.3690 -
Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes.JAMA Network Open Mar 2024Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD...
IMPORTANCE
Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD medications are associated with overall treatment outcomes among these patients.
OBJECTIVE
To investigate the association of the use of specific ADHD medications with hospitalization outcomes and work disability among adolescents and adults with ADHD.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide register-based cohort study identified individuals (aged 16-65 years) with ADHD from Swedish nationwide registers of inpatient health care, specialized outpatient health care, sickness absence, and disability pension during the years 2006 to 2021. Data analysis was performed from November 2022 to August 2023.
EXPOSURE
Use of specific ADHD medications.
MAIN OUTCOMES AND MEASURES
The main outcome measure was psychiatric hospitalization, and secondary outcomes were suicide attempt and/or death by suicide, nonpsychiatric hospitalization, and work disability (ie, sickness absence or disability pension). The risk of outcomes between use vs nonuse periods of ADHD medications was compared in a within-individual design, where a person acts as their own control, and was analyzed with stratified Cox models.
RESULTS
A total of 221 714 persons with ADHD were included in the study cohort (mean [SD] age, 25.0 [11.2] years; 120 968 male individuals [54.6%]). Methylphenidate was the most commonly used ADHD medication (151 837 individuals [68.5%]), followed by lisdexamphetamine (78 106 individuals [35.2%]) during the follow-up (mean [SD], 7.0 [4.7] years). The following medications were associated with a decreased risk of psychiatric hospitalization: amphetamine (adjusted hazard ratio [aHR], 0.74; 95% CI, 0.61-0.90), lisdexamphetamine (aHR, 0.80; 95% CI, 0.78-0.82), ADHD drug polytherapy (aHR, 0.85; 95% CI, 0.82-0.88), dexamphetamine (aHR, 0.88; 95% CI, 0.83-0.94), and methylphenidate (aHR, 0.93; 95% CI, 0.92-0.95). No associations were found for modafinil, atomoxetine, clonidine, and guanfacine. Decreased risk of suicidal behavior was associated with the use of dexamphetamine (aHR, 0.69; 95% CI, 0.53-0.89), lisdexamphetamine (aHR, 0.76; 95% CI, 0.68-0.84), and methylphenidate (aHR, 0.92; 95% CI, 0.86-0.98). None of the medications was associated with increased risk of nonpsychiatric hospitalization; instead, use of amphetamine, lisdexamphetamine, polytherapy, dexamphetamine, methylphenidate, and atomoxetine were associated with decreased risk of nonpsychiatric hospitalization. The results regarding work disability were significant only for the use of atomoxetine (aHR, 0.89; 95% CI, 0.82-0.97), especially among adolescents and young adults aged 16 to 29 years, (aHR, 0.82; 95% CI, 0.73-0.92).
CONCLUSIONS AND RELEVANCE
In this nationwide cohort study of adolescents and adults with ADHD, the use of ADHD medication was associated with fewer hospitalizations for both psychiatric and nonpsychiatric morbidity and lower suicidal behavior.
Topics: Adolescent; Young Adult; Humans; Male; Adult; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Cohort Studies; Lisdexamfetamine Dimesylate; Methylphenidate; Amphetamine
PubMed: 38506810
DOI: 10.1001/jamanetworkopen.2024.2859 -
Behavioural Brain Research May 2024Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly...
Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it.
Topics: Rats; Animals; Lisdexamfetamine Dimesylate; Dextroamphetamine; Treatment Outcome; Attention Deficit Disorder with Hyperactivity; Amnesia; Central Nervous System Stimulants; Double-Blind Method
PubMed: 38499158
DOI: 10.1016/j.bbr.2024.114963 -
European Addiction Research 2024Sleep disturbance is common during methamphetamine (MA) use and withdrawal; however, the feasibility of combined subjective-objective measurement of sleep-wake has not...
INTRODUCTION
Sleep disturbance is common during methamphetamine (MA) use and withdrawal; however, the feasibility of combined subjective-objective measurement of sleep-wake has not been shown in this population. Actigraphy is a well-established, non-invasive measure of sleep-wake cycles with good concordance with polysomnography. This study aimed to investigate the feasibility and utility of using actigraphy and sleep diaries to investigate sleep during MA withdrawal.
METHODS
We conducted a feasibility and utility study of actigraphy and sleep diaries during a clinical trial of lisdexamfetamine for MA withdrawal. Participants were inpatients for 7 days, wore an actigraph (Philips Actiwatch 2) and completed a modified Consensus Sleep Diary each morning. Participants were interviewed between days 3-5.
RESULTS
Ten participants (mean age 37 years, 90% male) were enrolled. No participant removed the device prematurely. Participants interviewed (n = 8) reported that the actigraph was not difficult or distracting to wear or completion of daily sleep diary onerous. Actigraphic average daily sleep duration over 7 days was 568 min, sleep onset latency 22.4 min, wake after sleep onset (WASO) 75.2 min, and sleep efficiency 83.6%. Sleep diaries underreported daily sleep compared with actigraphy (sleep duration was 56 min (p = 0.008) and WASO 47 min (p < 0.001) less). Overall sleep quality was 4.4 on a nine-point Likert scale within the diary.
CONCLUSIONS
Continuous actigraphy is feasible to measure sleep-wake in people withdrawing from MA, with low participant burden. We found important differences in self-reported and actigraphic sleep, which need to be explored in more detail.
Topics: Humans; Male; Adult; Female; Feasibility Studies; Lisdexamfetamine Dimesylate; Sleep; Polysomnography; Actigraphy; Substance Withdrawal Syndrome
PubMed: 38498995
DOI: 10.1159/000536328