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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 -
BMJ Clinical Evidence Feb 2011Prevalence estimates of attention deficit hyperactivity disorder (ADHD) vary according to the diagnostic criteria used and the population sampled. DSM-IV prevalence... (Review)
Review
INTRODUCTION
Prevalence estimates of attention deficit hyperactivity disorder (ADHD) vary according to the diagnostic criteria used and the population sampled. DSM-IV prevalence estimates among school children in the US are 3% to 5%, but other estimates vary from 1.7% to 16.0%. No objective test exists to confirm the diagnosis of ADHD, which remains a clinical diagnosis. Other conditions frequently co-exist with ADHD.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmacological treatments for ADHD in children and adolescents? What are the effects of psychological treatments for ADHD in children and adolescents? What are the effects of combination treatments for ADHD in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 70 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: atomoxetine, bupropion, clonidine, dexamfetamine sulphate, homeopathy, methylphenidate, modafinil, omega-3 polyunsaturated fatty acids, and psychological/behavioural treatment (either alone or in combination with a drug treatment).
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Attention Deficit and Disruptive Behavior Disorders; Child; Clonidine; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Humans; Methylphenidate; Schools
PubMed: 21718557
DOI: No ID Found -
Current Neuropharmacology 2019This brief review deals with the various issues that contributed to the creation of the new Diagnostic and Statistical Manual condition of hoarding disorder (HD) and... (Review)
Review
This brief review deals with the various issues that contributed to the creation of the new Diagnostic and Statistical Manual condition of hoarding disorder (HD) and attempts at reviewing its pharmacotherapy. It appears that after the newly founded diagnosis appeared in the literature as an autonomous entity, distinct from obsessive-compulsive disorder, drug trials are not being conducted and the disorder is left in the hands of psychotherapists, who on their part, report fair results in some core dimensions of HD. The few trials on HD specifically regard the serotonin-noradrenaline reuptake inhibitor venlafaxine, and, possibly due to the suggestion of a common biological background of HD with attention-deficit/hyperactivity disorder, the psychostimulant methylphenidate and the noradrenaline reuptake inhibitor atomoxetine. For all these drugs, positive results have been reported, but the evidence level of these studies is low, due to small samples and non-blind designs. Regretfully, there are currently no future studies aiming at seriously testing drugs in HD.
Topics: Atomoxetine Hydrochloride; Hoarding Disorder; Humans; Methylphenidate; Obsessive-Compulsive Disorder; Selective Serotonin Reuptake Inhibitors
PubMed: 30678629
DOI: 10.2174/1570159X17666190124153048 -
Journal of Child and Adolescent... Mar 2020The , fifth edition (DSM-5), classifies attention-deficit/hyperactivity disorder (ADHD) as a neurodevelopmental disorder, with symptoms becoming apparent as early as... (Review)
Review
The , fifth edition (DSM-5), classifies attention-deficit/hyperactivity disorder (ADHD) as a neurodevelopmental disorder, with symptoms becoming apparent as early as the preschool years. Early recognition can lead to interventions such as parent/teacher-administered behavior therapy, the recommended first-line treatment for preschool patients. There are few data, however, to inform the use of second-line, pharmacotherapy options in this population. In this review, we identified recent literature on the diagnosis and treatment of ADHD in preschool children. A PubMed and clinicaltrials.gov search was conducted for trials assessing efficacy or safety of ADHD medications in children aged <6 years. Diagnostic methods and criteria focusing on recognition of ADHD in preschool children were also surveyed. The DSM-5 describes different manifestations of ADHD in preschool versus school-aged children, but does not list separate criteria by age group. Importantly, behaviors indicative of ADHD in older children may be developmentally appropriate in preschool children. Several behavioral rating scales have been validated in children younger than 6 years of age for assessing ADHD. The Preschool ADHD Treatment Study (PATS) has provided the most extensive efficacy and safety data on methylphenidate (MPH) for ADHD in preschoolers to date, with significant improvement in ADHD symptoms observed with MPH compared with placebo, although adverse event-related discontinuation was higher in PATS compared with studies of MPH for ADHD in school-aged children. Since PATS was conducted, few studies designed to assess ADHD medication effectiveness in preschool children have been published. One article reported significant improvement in ADHD symptoms with MPH (immediate release) versus placebo, two studies showed no difference between MPH and risperidone or MPH plus risperidone in relief of ADHD symptoms, and one study demonstrated the efficacy of atomoxetine versus placebo for ADHD symptoms in preschoolers. Further research is needed on pharmacotherapy for preschool children with ADHD.
Topics: Age Factors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child, Preschool; Humans; Methylphenidate; Risperidone; Treatment Outcome
PubMed: 31967914
DOI: 10.1089/cap.2019.0116 -
Current Journal of Neurology Jul 2023Recent research shows that most of the patients with multiple sclerosis (MS) have cognitive-like disorders. Due to the beneficial effects of atomoxetine on improving...
Recent research shows that most of the patients with multiple sclerosis (MS) have cognitive-like disorders. Due to the beneficial effects of atomoxetine on improving cognition in limited animal and human surveys, the aim of the present study was to investigate the effect of the atomoxetine on improving cognitive disorders of MS. This study was a parallel, randomized clinical trial, designed to investigate the effect of atomoxetine drug on the improvement of cognitive impairment (CI) in MS, from April 2021 to March 2022. According to the inclusion and exclusion criteria, a total of 52 participants were involved in the study and then randomly divided in two groups of 26. Experimental group was treated with atomoxetine and the control group was treated with placebo. The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) test was performed for assessment at the beginning and after 3 months. The California Verbal Learning Test (CVLT), the CVLT-delay, the Brief Visuospatial Memory Test-Revised (BVMT-R), and the Symbol Digit Modalities Test (SDMT) were used to evaluate the CI and changes following medication. Finally, data were analyzed by SPSS software at significance level of 0.05. The mean age of patients in the experimental group was 37.7 ± 8.5 and in the placebo group was 37.8 ± 7.6 (P = 0.32). The results showed significant changes in cognitive levels before and after the use of atomoxetine and also in comparison to the placebo group (P < 0.05). This study showed that atomoxetine improved the cognitive domains after administration compared to placebo.
PubMed: 38011451
DOI: 10.18502/cjn.v22i3.13792 -
Journal of Neural Transmission (Vienna,... Jul 2022The selective norepinephrine reuptake inhibitor atomoxetine is potentially among the first-line pharmacotherapy options for ADHD. Therapeutic drug monitoring (TDM) with...
The selective norepinephrine reuptake inhibitor atomoxetine is potentially among the first-line pharmacotherapy options for ADHD. Therapeutic drug monitoring (TDM) with the quantification and interpretation of atomoxetine serum concentrations is used to determine an individual dose followed by an optimal effectiveness and minimal side effects. The aim of this retrospective pharmacokinetic-pharmacodynamic analysis was to derive age-appropriate recommendations for the implementation of TDM to improve the efficacy and tolerability of atomoxetine in children and adolescents. Using the analytical method of high-performance liquid chromatography with UV detection, 94 serum concentrations of 74 patients between 6 and 21 years of age were determined. Therapeutic effectiveness and side effects were evaluated according to the categories "low", "moderate", and "significant". As part of TDM, a time interval with maximum concentrations of 1-3 h after the administration of atomoxetine was determined for blood sampling. In this time interval, a significant correlation between the weight-normalized dose and the serum concentrations was found. The efficacy as well as the tolerability proved to be mainly moderate or significant. A preliminary therapeutic reference range was between 100 and 400 ng/ml. Naturalistic studies have limitations. Therefore, and due to a limited study population, the results have to be regarded as preliminary observations that must be confirmed in further studies. The preliminary therapeutic reference range for children and adolescents proved to be narrower than the reference range for adult patients. However, due to good efficacy and tolerability an exact reference range remained difficult to determine.
Topics: Adolescent; Adrenergic Uptake Inhibitors; Adult; Atomoxetine Hydrochloride; Attention; Attention Deficit Disorder with Hyperactivity; Child; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Humans; Propylamines; Retrospective Studies; Treatment Outcome
PubMed: 35391568
DOI: 10.1007/s00702-022-02483-8 -
Annals of Clinical and Translational... Jan 2020The efficacy and safety of 1-month atomoxetine and midodrine therapies were compared. Three-month atomoxetine and combination therapies were investigated for additional... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
The efficacy and safety of 1-month atomoxetine and midodrine therapies were compared. Three-month atomoxetine and combination therapies were investigated for additional benefits.
METHODS
This prospective open-label randomized trial included 50 patients with symptomatic neurogenic orthostatic hypotension (nOH). The patients received either atomoxetine 18 mg daily or midodrine 5 mg twice daily and were evaluated 1 and 3 months later. Those who still met the criteria for nOH at 1 month received both midodrine and atomoxetine for an additional 2 months, and if not, they continued their initial medication. The primary outcome was an improvement in orthostatic blood pressure (BP) drop (maximum BP change from supine to 3 min after standing) at 1 month. The secondary endpoints were symptom scores, percentage of patients with nOH at 1 and 3 months.
RESULTS
Patients with midodrine or atomoxetine treatment showed comparative improvement in the orthostatic BP drop, and overall only 26.2% of the patients had nOH at 1 month, which was similar between the treatment groups. Only atomoxetine resulted in significant symptomatic improvements at 1 month. For those without nOH at 1 month, there was additional symptomatic improvement at 3 months with their initial medication. For those with nOH at 1 month, the combination treatment resulted in no additional improvement. Mild-to-moderate adverse events were reported by 11.6% of the patients.
INTERPRETATION
One-month atomoxetine treatment was effective and safe in nOH patients. Atomoxetine improved orthostatic BP changes as much as midodrine and was better in terms of ameliorating nOH symptoms.
Topics: Adrenergic Uptake Inhibitors; Adrenergic alpha-1 Receptor Agonists; Aged; Atomoxetine Hydrochloride; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Midodrine; Outcome Assessment, Health Care; Prospective Studies
PubMed: 31856425
DOI: 10.1002/acn3.50968 -
Journal of Child and Adolescent... Apr 2013The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients... (Review)
Review
A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability.
OBJECTIVE
The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability.
METHODS
Literature databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms.
RESULTS
Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events.
CONCLUSIONS
Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success.
Topics: Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Drug Therapy, Combination; Humans; Propylamines; Treatment Outcome
PubMed: 23560600
DOI: 10.1089/cap.2012.0093 -
Molecular Psychiatry Jan 2024The stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) are frequently used for the treatment of attention-deficit/hyperactivity disorder (ADHD);...
The stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) are frequently used for the treatment of attention-deficit/hyperactivity disorder (ADHD); however, the function of these drugs in different types of brain cells and their effects on related genes remain largely unknown. To address these questions, we built a pipeline for the simultaneous examination of the activity behavior and transcriptional responses of Drosophila melanogaster at single-cell resolution following drug treatment. We selected the Drosophila with significantly increased locomotor activities (hyperactivity-like behavior) following the administration of each drug in comparison with the control (same food as the drug-treated groups with 5% sucrose, yeast, and blue food dye solution) using EasyFlyTracker. Subsequently, single cell RNA sequencing (scRNASEQ) was used to capture the transcriptome of 82,917 cells, unsupervised clustering analysis of which yielded 28 primary cell clusters representing the major cell types in adult Drosophila brain. Indeed, both neuronal and glial cells responded to MPH and ATX. Further analysis of differentially expressed genes (DEGs) revealed distinct transcriptional changes associated with these two drugs, such as two well-studied dopamine receptor genes (Dop2R and DopEcR) were responsive to MPH but not to ATX at their optimal doses, in addition to genes involved in dopamine metabolism pathways such as Syt1, Sytalpha, Syt7, and Ih in different cell types. More importantly, MPH also suppressed the expression of genes encoding other neurotransmitter receptors and synaptic signaling molecules in many cell types, especially those for Glu and GABA, while the responsive effects of ATX were much weaker. In addition to monoaminergic neuronal transmitters, other neurotransmitters have also shown a similar pattern with respect to a stronger effect associated with MPH than with ATX. Moreover, we identified four distinct glial cell subtypes responsive to the two drugs and detected a greater number of differentially expressed genes associated with ensheathing and astrocyte-like glia. Furthermore, our study provides a rich resource of candidate target genes, supported by drug set enrichment analysis (P = 2.10E-4; hypergeometric test), for the further exploration of drug repurposing. The whole list of candidates can be found at ADHDrug ( http://adhdrug.cibr.ac.cn/ ). In conclusion, we propose a fast and cost-efficient pipeline to explore the underlying molecular mechanisms of ADHD drug treatment in Drosophila brain at single-cell resolution, which may further facilitate drug repurposing applications.
Topics: Animals; Atomoxetine Hydrochloride; Methylphenidate; Drosophila melanogaster; Drug Repositioning; Brain; Attention Deficit Disorder with Hyperactivity; Single-Cell Analysis; Neurons; Transcriptome; Drosophila; Central Nervous System Stimulants; Male; Neuroglia; Locomotion; Disease Models, Animal
PubMed: 37957291
DOI: 10.1038/s41380-023-02314-6 -
Pharmacology, Biochemistry, and Behavior Aug 2017No pharmacotherapies are approved for the treatment of cocaine use disorders (CUD). Behavioral treatments for CUD are efficacious for some individuals, but recovery... (Randomized Controlled Trial)
Randomized Controlled Trial
No pharmacotherapies are approved for the treatment of cocaine use disorders (CUD). Behavioral treatments for CUD are efficacious for some individuals, but recovery rates from CUD remain low. Cognitive impairments in CUD have been linked with poorer clinical outcomes. Cognitive enhancing pharmacotherapies have been proposed as promising treatments for CUD. Atomoxetine, a norepinephrine transporter inhibitor, shows potential as a treatment for CUD based on its efficacy as a cognitive enhancer in other clinical populations and impact on addictive processes in preclinical and human laboratory studies. In this randomized, double-blind, crossover study, abstinent individuals with CUD (N=39) received placebo, 40 and 80mg atomoxetine, over three sessions. Measures of attention, response inhibition and working memory; subjective medication effects and mood; and cardiovascular effects were collected. Analyses assessed acute, dose-dependent effects of atomoxetine. In addition, preliminary analyses investigating the modulation of atomoxetine dose effects by sex were performed. Atomoxetine increased heart rate and blood pressure, was rated as having positive and negative subjective drug effects, and had only modest effects on mood and cognitive enhancement.
Topics: Adrenergic Uptake Inhibitors; Adult; Affect; Atomoxetine Hydrochloride; Attention; Cocaine-Related Disorders; Cognition; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hemodynamics; Humans; Inhibition, Psychological; Male; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Sex Characteristics
PubMed: 28716656
DOI: 10.1016/j.pbb.2017.07.002