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Xenobiotica; the Fate of Foreign... Jul 2022The metabolism of most medications approved for the treatment of attention deficit/hyperactivity disorder (ADHD) is not fully understood. studies using cryopreserved,...
The metabolism of most medications approved for the treatment of attention deficit/hyperactivity disorder (ADHD) is not fully understood. studies using cryopreserved, plated human hepatocytes (cPHHs) and pooled human liver microsomes (HLMs) were performed to more thoroughly characterise the metabolism of several ADHD medications.The use of enzyme-specific chemical inhibitors indicated a role for CYP2D6 in atomoxetine (ATX) metabolism, and roles for CYP3A4/5 in guanfacine (GUA) metabolism.The 4-hydroxy-atomoxetine and N-desmethyl-atomoxetine pathways represented 98.4% and 1.5% of ATX metabolism in cPHHs, respectively. The 3-OH-guanfacine pathway represented at least 2.6% of GUA metabolism in cPHHs, and 71% in HLMs.The major metabolising enzyme for methylphenidate (MPH) and dexmethylphenidate (dMPH) could not be identified using these methods because these compounds were too unstable. Hydrolysis of these medications was spontaneous and did not require the presence of protein to occur.Clonidine (CLD), amphetamine (AMPH), and dextroamphetamine (dAMPH) did not deplete substantially in cPHHs nor HLMs, suggesting that these compounds may not undergo considerable hepatic metabolism. The major circulating metabolites of AMPH and dAMPH (benzoic acid and hippuric acid) were not observed in either system, and therefore could not be characterised. Additionally, inhibition experiments suggested a very minimal role for CYP2D6 in CLD and AMPH metabolism.
Topics: Humans; Attention Deficit Disorder with Hyperactivity
PubMed: 36317558
DOI: 10.1080/00498254.2022.2141151 -
Ochsner Journal 2021Both psychiatric disorders and diverse medications used to treat them have been associated with alopecia. The objective of our study was to investigate the existence of...
Both psychiatric disorders and diverse medications used to treat them have been associated with alopecia. The objective of our study was to investigate the existence of an association between attention-deficit/hyperactivity disorder (ADHD) stimulant medication (ASM) and various types of alopecia. We conducted a retrospective case-control medical record review of patients between the ages of 6 and 18 years seen in dermatology clinics during a 10-year period. Cases included patients diagnosed with alopecia areata (AA), alopecia totalis (AT), or alopecia universalis (AU). We matched 3 controls on age and sex to each case. We reviewed patients' medical records for the following medications: lisdexamfetamine, amphetamine/dextroamphetamine, dexmethylphenidate, and methylphenidate. We examined the association between medications used to treat ADHD and diagnoses of AA, AT, and/or AU by calculating a series of odds ratios and 95% CIs. We identified 124 cases (110 with AA, 11 with AT, and 3 with AU) and 372 controls. We found a strong association between AU and ASM use (<0.0071). No relationship between ASM use and other types of hair loss was found. Although the sample size of cases with AU was small, we found a significant association between AU and ASM. While further study is needed, practitioners may consider close monitoring of patients with AA who use ASM for the development of worsening disease and discontinue the medication if the patient experiences an increase in hair loss that appears to be progressing to AU.
PubMed: 34239372
DOI: 10.31486/toj.20.0025 -
The Medical Letter on Drugs and... Mar 2009
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Humans; Methylphenidate; Treatment Outcome
PubMed: 19305368
DOI: No ID Found -
The American Journal of Emergency... Apr 2023In parallel with the opioid epidemic, there has been a resurgence in abuse, medical complications, and deaths related to amphetamines. The opioid epidemic began with...
OBJECTIVES
In parallel with the opioid epidemic, there has been a resurgence in abuse, medical complications, and deaths related to amphetamines. The opioid epidemic began with increasing rates of prescription products that evolved overtime to include heroin and more recently, fentanyl analogues. Current trends in amphetamine prescriptions are less well described. We sought to determine if there has been a change in amphetamine prescriptions given at discharge in U.S. emergency departments (EDs) in recent years.
METHODS
We conducted a retrospective review of data provided by the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2012 to 2019. We computed total number of visits that were given amphetamine prescriptions (amphetamine salts, methylphenidate derivatives, and dexmethylphenidate) at discharge for each year. We computed the total number and rate of visits (of all ED visits) that had both amphetamines and opioids prescribed at discharge over the years. We computed data normality using Shapiro Wilke's test and used descriptive statistics such as mean to describe the data distribution as applicable. We used spearman's rho (SR) or pearson's correlation (PC) as applicable to describe trends in data. All p-values were one-tailed and were reported at a 0.05 significance level. All analyses were conducted in IBM SPSS version 28.
RESULTS/FINDINGS
From 2012 to 2019, there were an estimated 817,895 ED visits where an amphetamine prescription was given at discharge, with an overall strong increase in rate over time (SR = 0.71, p = 0.02). At the beginning of the study period (2012) there were 83,503 (0.06%) visits and in 2019 there were 186,539 (0.12%) visits (123% absolute increase). On average, there were 102,237 (SD: 52,725) visits with discharge amphetamine prescriptions per year. There was a strong, linear increase in number of visits that involved a discharge amphetamine salt prescription (PC = 0.92, p = 0.001). In 2012, there were a total of 23,676 visits and in 2019, a total of 124,773 visits (427% increase). There was no trend in visits where both an amphetamine and opioid were prescribed (PC: 0.61, p = 0.06).
CONCLUSION
There have been increases in discharge prescriptions for amphetamines in the ED over time. This was largely driven by prescriptions for amphetamine salts. Future research initiatives should continue to monitor this trend and in prescriptions and associated abuse in the setting of rising amphetamine abuse.
Topics: Humans; Amphetamine; Patient Discharge; Salts; Practice Patterns, Physicians'; Analgesics, Opioid; Prescriptions; Emergency Service, Hospital; Health Care Surveys; Drug Prescriptions
PubMed: 36738570
DOI: 10.1016/j.ajem.2023.01.042 -
Cureus Jun 2022Hippocampal ischemia is a rare complication of cocaine abuse that has been thought to arise from vasospasm, anoxic injury, and/or catecholaminergic excitotoxicity. We...
Hippocampal ischemia is a rare complication of cocaine abuse that has been thought to arise from vasospasm, anoxic injury, and/or catecholaminergic excitotoxicity. We present two cases of patients abusing cocaine, who presented with an acute onset anterograde amnesia due to bilateral hippocampal ischemia, and had different outcomes. Case 1 is a 49-year-old male with a history of IV heroin abuse who presented after being found down for an unknown period of time. He awoke with no memory of events leading up to hospitalization and was unable to retain new information. Urine toxicology was positive for cocaine and opiates. Traditional vascular risk factors included obesity, hypertension, and hyperlipidemia. His recovery was complicated by continued drug use and one episode of cardiac arrest. Despite cognitive rehabilitation, only minimal improvements in his anterograde memory were observed during his annual follow-up. Case 2 is a 23-year-old male with a history of attention deficit disorder treated with dexmethylphenidate and a history of consistent marijuana and cocaine abuse, who presented with nausea, vomiting, chest pain, shortness of breath, and acute-onset short-term memory loss. Urine toxicology was negative for cocaine and opiates and positive for marijuana. He had no known vascular risk factors. With cognitive rehabilitation and discontinuation of illicit drug use, he demonstrated a significant improvement in his memory function over the course of six months. Brain MRI in both patients showed symmetric bilateral hippocampal diffusion restriction without post-contrast enhancement with corresponding hyperintensities on fluid-attenuated inversion recovery sequences. In both patients, cerebrospinal fluid (CSF) studies were unremarkable for inflammation or infection, and electroencephalograms were normal in awake and drowsy states. Bilateral hippocampal ischemia should be considered as a potential cause of acute onset anterograde amnesia in patients with a history of cocaine abuse. Other substances such as heroin and dexmethylphenidate may potentially increase susceptibility for hippocampal ischemia in patients using cocaine. Discontinuation of illicit drug abuse can influence the degree of recovery from acute bilateral hippocampal ischemia.
PubMed: 35915690
DOI: 10.7759/cureus.26435 -
Journal of Child and Adolescent... Nov 2021To evaluate the efficacy and safety of once-daily serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) capsules (Azstarys) compared with placebo in children with... (Randomized Controlled Trial)
Randomized Controlled Trial
To evaluate the efficacy and safety of once-daily serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) capsules (Azstarys) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a randomized, double-blind, dose-optimized laboratory classroom study. Children ages 6-12 with ADHD were enrolled. During a 3-week, open-label, Dose Optimization Phase, subjects initiated treatment with 39.2 mg/7.8 mg/day of SDX/d-MPH and were titrated weekly to an optimal dose (maximum dose of 52.3/10.4 mg). During the double-blind Treatment Phase, subjects were randomized to receive their optimal dose of SDX/d-MPH or placebo for 7 days. On day 7, efficacy was assessed in the laboratory classroom using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP). To evaluate safety, adverse events (AEs), vital signs, and electrocardiograms were assessed, and suicide risk was assessed. A total of 149 subjects completed the study. In the primary efficacy analysis, the mean postdose change from baseline in SKAMP-Combined scores averaged over the laboratory classroom day was significantly improved with SDX/d-MPH versus placebo (least-squares mean treatment difference [95% confidence interval]: -5.41 [-7.10 to -3.71]; < 0.001). A significant treatment effect for SDX/d-MPH compared with placebo was observed from 1 to 10 hours postdose. A analysis more comparable with that conducted in similar studies indicated a 0.5- to 13-hour onset and duration of efficacy. Both average postdose PERMP-Attempted and PERMP-Correct score changes from baseline were significantly improved among those treated with SDX/d-MPH versus placebo ( < 0.001 for both). No serious AEs were reported. During the Dose Optimization Phase, two-thirds of subjects reported AEs; the most common being insomnia and decreased appetite. SDX/d-MPH showed significant improvement in ADHD symptoms compared with placebo in children 6-12 years of age, with a rapid onset and extended duration of treatment effect. SDX/d-MPH was safe, with AEs comparable with those observed with other stimulant treatments.
Topics: Attention Deficit Disorder with Hyperactivity; Capsules; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Laboratories; Methylphenidate; Treatment Outcome
PubMed: 34714120
DOI: 10.1089/cap.2021.0077 -
Mutation Research May 2003D-Methylphenidate (dexmethylphenidate; D-MPH) and its racemate D,L-methylphenidate (D,L-MPH) are currently prescribed for the chronic treatment of attention deficit...
D-Methylphenidate (dexmethylphenidate; D-MPH) and its racemate D,L-methylphenidate (D,L-MPH) are currently prescribed for the chronic treatment of attention deficit hyperactivity disorder (ADHD) in children. Studies have shown that D-MPH is the pharmacologically active enantiomer for ADHD and is therefore the preferred drug for the treatment of ADHD symptoms. Although studies on the mutagenicity of D,L-MPH have been conducted, similar data for D-MPH are lacking. Therefore, D-MPH was evaluated in the bacterial reverse mutation and mouse lymphoma assays with and without S9 and in a bone marrow micronucleus test in male and female CD-1 mice. As a comparison, the L-enantiomer and racemate were also included in the assessments. While MPH-associated toxicity was observed in the mammalian tests, none of the three compounds tested induced mutagenic or clastogenic effects. Our present results along with published epidemiological data from patient populations are consistent with the conclusion that D-MPH and D,L-MPH do not present a carcinogenic risk to humans.
Topics: Adrenergic Uptake Inhibitors; Animals; Cloning, Molecular; Dexmethylphenidate Hydrochloride; Dose-Response Relationship, Drug; Female; In Vitro Techniques; Lymphoma; Male; Methylphenidate; Mice; Micronucleus Tests; Models, Chemical; Mutagens; Mutation; Stereoisomerism; Time Factors
PubMed: 12742508
DOI: 10.1016/s1383-5718(03)00053-6 -
Journal of Child and Adolescent... Dec 2016This study examines cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB)... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVES
This study examines cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB) during acute and long-term treatment of youth with attention-deficit/hyperactivity disorder.
METHODS
Two hundred seven participants aged 7-14 years enrolled in an 8-week double-blind randomized trial of GUAN-IR (1-3 milligrams (mg)/day), DMPH (5-20 mg/day), or COMB with fixed-flexible dosing and titrated to optimal behavioral response. Heart rate, systolic blood pressure (BP), diastolic BP, and electrocardiograms were assessed at baseline, end of blinded optimization, and over a 1-year open-label maintenance phase.
RESULTS
During acute titration, GUAN-IR decreased heart rate, systolic BP, and diastolic BP; DMPH increased heart rate, systolic BP, diastolic BP, and corrected QT (QTc) interval; COMB increased diastolic BP, but had no effects on heart rate, systolic BP, or QTc. During maintenance, GUAN-IR-associated decreases in heart rate and DMPH-associated increases in systolic BP returned to baseline values. Other variables across the three groups remained unchanged from the end of blinded titration. There were no discontinuations due to CV adverse events.
CONCLUSION
GUAN-IR, DMPH, and COMB were well tolerated and safe. Expected changes in CV parameters during acute titration were seen in GUAN-IR and DMPH groups, with COMB values falling intermediately between the two other treatment groups. No serious CV events occurred in any participant. GUAN-IR- and DMPH-associated CV changes generally returned to baseline with sustained therapy. These data suggest that COMB treatment might attenuate long-term CV effects of GUAN-IR and stimulant monotherapy, possibly reducing risk of the small but statistically significant changes associated with either single treatment. Clinicaltrials.gov Identifier: NCT00429273.
Topics: Adolescent; Adrenergic alpha-2 Receptor Agonists; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Dexmethylphenidate Hydrochloride; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Female; Guanfacine; Heart Rate; Humans; Male; Time Factors
PubMed: 27483130
DOI: 10.1089/cap.2015.0264 -
Psychiatry (Edgmont (Pa. : Township)) Apr 2010In this article, we provide information on patient-reported side effects from a cross-section of real-world patients. Specifically, data on side effects were tabulated...
In this article, we provide information on patient-reported side effects from a cross-section of real-world patients. Specifically, data on side effects were tabulated for patients taking one of the following attention deficit hyperactivity disorder medications: amphetamine and dextroamphetamine; atomoxetine; dexmethylphenidate; isdexamfetamine; and methylphenidate. Forty-eight percent of the approximately 325 patients surveyed reported having experienced a side effect as a result of taking an attention deficit hyperactivity disorder medication. Most common side effects mentioned included loss of appetite, sleep problems, and mood disturbances. Only 21 percent of side effects were considered very bothersome or extremely bothersome. Regardless of how bothersome the side effects were, only 20 percent of patients mentioned the side effects to their prescribing physicians.
PubMed: 20508803
DOI: No ID Found -
JAMA Pediatrics Sep 2021Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms...
IMPORTANCE
Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms and common comorbidities. A better understanding of the medications used to manage comorbid conditions in this growing population is critical; however, most previous efforts have been limited in size, duration, and lack of broad representation.
OBJECTIVE
To use a nationally representative database to uncover trends in the prevalence of co-occurring conditions and medication use in the management of symptoms and comorbidities over time among US individuals with ASD.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, population-based cohort study mined a nationwide, managed health plan claims database containing more than 86 million unique members. Data from January 1, 2014, to December 31, 2019, were used to analyze prescription frequency and diagnoses of comorbidities. A total of 26 722 individuals with ASD who had been prescribed at least 1 of 24 medications most commonly prescribed to treat ASD symptoms or comorbidities during the 6-year study period were included in the analysis.
EXPOSURES
Diagnosis codes for ASD based on International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.
MAIN OUTCOMES AND MEASURES
Quantitative estimates of prescription frequency for the 24 most commonly prescribed medications among the study cohort and the most common comorbidities associated with each medication in this population.
RESULTS
Among the 26 722 individuals with ASD included in the analysis (77.7% male; mean [SD] age, 14.45 [9.40] years), polypharmacy was common, ranging from 28.6% to 31.5%. Individuals' prescription regimens changed frequently within medication classes, rather than between classes. The prescription frequency of a specific medication varied considerably, depending on the coexisting diagnosis of a given comorbidity. Of the 24 medications assessed, 15 were associated with at least a 15% prevalence of a mood disorder, and 11 were associated with at least a 15% prevalence of attention-deficit/hyperactivity disorder. For patients taking antipsychotics, the 2 most common comorbidities were combined type attention-deficit/hyperactivity disorder (11.6%-17.8%) and anxiety disorder (13.1%-30.1%).
CONCLUSIONS AND RELEVANCE
This study demonstrated considerable variability and transiency in the use of prescription medications by US clinicians to manage symptoms and comorbidities associated with ASD. These findings support the importance of early and ongoing surveillance of patients with ASD and co-occurring conditions and offer clinicians insight on the targeted therapies most commonly used to manage co-occurring conditions. Future research and policy efforts are critical to assess the extent to which pharmacological management of comorbidities affects quality of life and functioning in patients with ASD while continuing to optimize clinical guidelines, to ensure effective care for this growing population.
Topics: Adolescent; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Bupropion; Child; Child, Preschool; Cohort Studies; Comorbidity; Data Mining; Depressive Disorder, Major; Dexmethylphenidate Hydrochloride; Dextroamphetamine; Female; Health Services Accessibility; Humans; Insurance; Lisdexamfetamine Dimesylate; Male; Managed Care Programs; Prevalence; Retrospective Studies
PubMed: 34097007
DOI: 10.1001/jamapediatrics.2021.1329