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BMJ Mental Health Apr 2024Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent...
BACKGROUND
Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent studies suggest a potential association between use of psychostimulants and psychotic symptoms. The risk may not be the same between different psychostimulants.
OBJECTIVE
To assess whether amphetamine or atomoxetine use is associated with a higher risk of reporting symptoms of psychosis than methylphenidate use in adolescents and adults, particularly in patients with ADHD.
METHODS
Using VigiBase, the WHO's pharmacovigilance database, disproportionality of psychotic symptoms reporting was assessed among adverse drug reactions related to methylphenidate, atomoxetine and amphetamines, from January 2004 to December 2018, in patients aged 13-25 years. The association between psychotic symptoms and psychostimulants was estimated through the calculation of reporting OR (ROR).
FINDINGS
Among 13 863 reports with at least one drug of interest, we found 221 cases of psychosis with methylphenidate use, 115 with atomoxetine use and 169 with a prescription of an amphetamine drug. Compared with methylphenidate use, amphetamine use was associated with an increased risk of reporting psychotic symptoms (ROR 1.61 (95% CI 1.26 to 2.06)]. When we restricted the analysis to ADHD indication, we found a close estimate (ROR 1.94 (95% CI 1.43 to 2.64)). No association was found for atomoxetine.
CONCLUSION
Our study suggests that amphetamine use is associated with a higher reporting of psychotic symptoms, compared with methylphenidate use.
CLINICAL IMPLICATIONS
The prescription of psychostimulants should consider this potential adverse effect when assessing the benefit-risk balance.
Topics: Adult; Humans; Adolescent; Amphetamine; Methylphenidate; Atomoxetine Hydrochloride; Central Nervous System Stimulants; Psychotic Disorders; Drug-Related Side Effects and Adverse Reactions
PubMed: 38609318
DOI: 10.1136/bmjment-2023-300876 -
Respirology (Carlton, Vic.) Mar 2023
Topics: Humans; Atomoxetine Hydrochloride; Precision Medicine; Sleep Apnea, Obstructive; Sleep
PubMed: 36257913
DOI: 10.1111/resp.14395 -
Revista Paulista de Pediatria : Orgao... 2023The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD).
OBJECTIVE
The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD).
DATA SOURCE
A high-sensitivity electronic search was performed in the following databases: Cochrane Library, MEDLINE via PubMed, LILACS via the Regional Health Portal (BVS), Embase, Scopus, CINAHL, and Web of Science, as recommended by the Cochrane Handbook, and which has undergone peer review according to the PRESS Guide.
DATA SYNTHESIS
The studies contemplated the use of the drugs atomoxetine, guanfacine, methylphenidate, dasotraline, L-theanine, and lisdexamfetamine. They showed efficiency in reducing the symptoms of ADHD, although all, except atomoxetine, affected sleep quality, such as by reducing total rapid eye movement (REM), non-REM phase, slow-wave sleep time, and longer sleep-onset latency.
CONCLUSIONS
The drugs used in the treatment of ADHD seem to have negative repercussions on the sleep quality of children, with the drug atomoxetine showing lesser effects on this variable.
Topics: Child; Humans; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Central Nervous System Stimulants; Methylphenidate; Sleep
PubMed: 37255110
DOI: 10.1590/1984-0462/2023/41/2022065 -
The Journal of Clinical Psychiatry Jan 2023Most research on safety of attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy concerns central nervous system stimulants, while little is...
Most research on safety of attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy concerns central nervous system stimulants, while little is known about the safety of atomoxetine, a primary treatment alternative. We assessed the prevalence of major congenital malformations overall, and cardiac malformations and limb malformations specifically, after first-trimester exposure. In this cohort study, we included all approximately 2.4 million pregnancies ending in live births recorded in the population-based nationwide health registers of Denmark, Iceland, Norway, and Sweden (2003-2017) and approximately 1.8 million publicly insured pregnancies ending in live births recorded in the US Medicaid Analytic eXtract (MAX, 2001-2013) health care claims database. We compared the prevalence of major congenital malformations in the newborn among pregnancies exposed and unexposed to atomoxetine. For each country, we calculated prevalence ratios (PRs), crude and stratified by propensity scores (PSs). We pooled the country-specific PS strata to obtain a PR adjusted for potential confounding factors. We identified 368 pregnancies exposed to atomoxetine during the first trimester in the 4 Nordic countries and 622 in the US. The pooled crude PR for any major congenital malformation was 1.18 (95% CI, 0.88-1.60), and the adjusted PR was 0.99 (95% CI, 0.74-1.34). For cardiac malformations, the adjusted PR was 1.34 (95% CI, 0.86-2.09). For limb malformations, the adjusted PR was 0.90 (95% CI, 0.38-2.16). After atomoxetine exposure in early pregnancy, we observed no increase in major congenital malformations overall and, although with some uncertainty due to sample size, no statistically increased risk estimates for cardiac malformations and limb malformations.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Atomoxetine Hydrochloride; Cohort Studies; Prevalence; Abnormalities, Drug-Induced; Pregnancy Trimester, First; Heart Defects, Congenital
PubMed: 36652686
DOI: 10.4088/JCP.22m14430 -
Indian Pediatrics Jul 2006
Review
Topics: Administration, Oral; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Child; Humans; Methylphenidate; Propylamines
PubMed: 16891679
DOI: No ID Found -
Psychological Medicine Jan 2022There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This... (Meta-Analysis)
Meta-Analysis Review
There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63-2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06-1.56), guanfacine (OR = 1.43, 95% CI = 1.12-1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09-1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.
Topics: Child; Humans; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Guanfacine; Central Nervous System Stimulants; Methylphenidate; Drug-Related Side Effects and Adverse Reactions; Comorbidity; Headache; Randomized Controlled Trials as Topic
PubMed: 34635194
DOI: 10.1017/S0033291721004141 -
Biomolecules Oct 2022Changes in dopaminergic and noradrenergic transmission are considered to be the underlying cause of attention deficit and hyperactivity disorder (ADHD). Atomoxetine...
Changes in dopaminergic and noradrenergic transmission are considered to be the underlying cause of attention deficit and hyperactivity disorder (ADHD). Atomoxetine (ATX) is a selective norepinephrine transporter (NET) inhibitor that is currently used for ADHD treatment. In this study, we aimed to evaluate the effect of atomoxetine on the behavior and brain activity of dopamine transporter knockout (DAT-KO) rats, which are characterized by an ADHD-like behavioral phenotype. Prepulse inhibition (PPI) was assessed in DAT-KO and wild type rats after saline and ATX injections, as well as behavioral parameters in the Hebb-Williams maze and power spectra and coherence of electrophysiological activity. DAT-KO rats demonstrated a pronounced behavioral and electrophysiological phenotype, characterized by hyperactivity, increased number of errors in the maze, repetitive behaviors and disrupted PPI, changes in cortical and striatal power spectra and interareal coherence. Atomoxetine significantly improved PPI and decreased repetitive behaviors in DAT-KO rats and influenced behavior of wild-type rats. ATX also led to significant changes in power spectra and coherence of DAT-KO and wild type rats. Assessment of noradrenergic modulation effects in DAT-KO provides insight into the intricate interplay of monoaminergic systems, although further research is still required to fully understand the complexity of this interaction.
Topics: Rats; Animals; Atomoxetine Hydrochloride; Dopamine Plasma Membrane Transport Proteins; Norepinephrine Plasma Membrane Transport Proteins; Cognition; Norepinephrine; Corpus Striatum
PubMed: 36291693
DOI: 10.3390/biom12101484 -
Journal of Clinical Sleep Medicine :... Jun 2023Pharmacotherapy for obstructive sleep apnea (OSA) regained consideration after the discovery that atomoxetine and oxybutynin greatly reduced OSA severity. However,... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVES
Pharmacotherapy for obstructive sleep apnea (OSA) regained consideration after the discovery that atomoxetine and oxybutynin greatly reduced OSA severity. However, atomoxetine and oxybutynin reduced the arousal threshold and may therefore be poorly tolerated in patients with OSA and disturbed sleep. As a result, we tested the combination of atomoxetine plus 2 hypnotics in patients with OSA. The effects of atomoxetine plus: (1) trazodone (Ato-Trazo) and (2) lemborexant vs placebo on apnea-hypopnea index, hypoxic burden, arousal threshold, and total sleep time were assessed. Drug safety was also ascertained, together with the effect of the combinations on other OSA traits, self-reported sleep quality, and next-day alertness.
METHODS
Following a baseline study, 15 patients with mild-to-severe OSA with moderate upper airway collapsibility were administered Ato-Trazo, atomoxetine and lemborexant, and matching placebo according to a double-blind, randomized, crossover design. Apnea-hypopnea index and other objective outcomes were calculated from 3 clinical, in-laboratory polysomnograms.
RESULTS
Ato-Trazo significantly reduced apnea-hypopnea index from a median [interquartile range] of 18.2 [11.8 to 31.3] on placebo to 7.4 [5.4 to 16.1] events/h, = .024, and hypoxic burden from 46.3 [25.1 to 88.3] on placebo to 18.7 [14.9 to 43.5], = .003. This effect was likely driven by an increase in polysomnography-estimated pharyngeal muscle activity during the events ( = .029). Atomoxetine and lemborexant had smaller statistically insignificant effects. Contrary to atomoxetine and oxybutynin, Ato-Trazo and atomoxetine and lemborexant did not reduce the arousal threshold. Both combinations had no effect on total sleep time but worsened self-reported sleep quality.
CONCLUSIONS
Ato-Trazo has the potential to become a useful drug combination, however, longer trials are needed to determine the best dosage and the subgroup of patients who may benefit most from this combination.
CLINICAL TRIAL REGISTRATION
Registry: ClinicalTrials.gov; Name: Crossover Trial of AD182 and AD504 in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04645524; Identifier: NCT04645524.
CITATION
Corser B, Eves E, Warren-McCormick J, Rucosky G. Effects of atomoxetine plus a hypnotic on obstructive sleep apnea severity in patients with a moderately collapsible pharyngeal airway. . 2023;19(6):1035-1042.
Topics: Humans; Atomoxetine Hydrochloride; Hypnotics and Sedatives; Sleep Apnea, Obstructive; Pharynx
PubMed: 36734173
DOI: 10.5664/jcsm.10464 -
Biological Psychiatry Jun 2011The symptoms of attention-deficit/hyperactivity disorder (ADHD) involve impairments in prefrontal cortical top-down regulation of attention and behavior. All current... (Review)
Review
The symptoms of attention-deficit/hyperactivity disorder (ADHD) involve impairments in prefrontal cortical top-down regulation of attention and behavior. All current pharmacological treatments for ADHD facilitate catecholamine transmission, and basic research suggests that these compounds have prominent actions in the prefrontal cortex (PFC). The dorsolateral PFC is especially sensitive to levels of norepinephrine and dopamine, whereby either too little or too much markedly impairs PFC function. Recent physiological studies have shown that norepinephrine strengthens PFC network connectivity and maintains persistent firing during a working memory task through stimulation of postsynaptic α(2A)-adrenoceptors on PFC neurons. Conversely, dopamine acts at D1 receptors to narrow spatial tuning, sculpting network inputs to decrease noise (i.e., stabilization of the representation). The stimulant medications and atomoxetine appear to enhance PFC function by indirectly increasing these catecholamine actions through blockade of norepinephrine and/or dopamine transporters. In contrast, guanfacine mimics the enhancing effects of norepinephrine at postsynaptic α(2A)-receptors in the PFC, strengthening network connectivity. Stronger PFC regulation of attention, behavior, and emotion likely contributes to the therapeutic effects of these medications for the treatment of ADHD.
Topics: Adrenergic Uptake Inhibitors; Adrenergic alpha-Agonists; Animals; Arousal; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Catecholamines; Cognition; Guanfacine; Humans; Memory, Short-Term; Methylphenidate; Models, Neurological; Neural Pathways; Prefrontal Cortex; Propylamines; Synaptic Transmission
PubMed: 21489408
DOI: 10.1016/j.biopsych.2011.01.027 -
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