[Attention deficit hyperactivity disorder in adults]. / Sindrom defitsita vnimaniya s giperaktivnost'yu u vzroslykh.

The article presents a review of scientific publications devoted to the study of the characteristics of the clinical picture and the dynamics of the main symptoms in adult patients with attention deficit hyperactivity disorder (ADHD). The authors present current data on the prevalence of this disease, leading clinical manifestations and the most common comorbid pathology. Research data on the impact of ADHD in adulthood on educational and professional activities are presented, and the economic and criminological aspects of ADHD are considered. The main methods of psychotherapeutic correction and pharmacological therapy are presented.

The Dose-Response Relationship of Atomoxetine for the Treatment of Children With ADHD: A Systematic Review and Dose-Response Meta-Analysis of Double-Blind Randomized Placebo-Controlled Trials.

OBJECTIVES: The present study aimed to meta-analytically estimate the dose-response relationship of atomoxetine for treating children with ADHD. METHODS: We systematically searched double-blind randomized placebo-controlled trials that evaluated the effectiveness of atomoxetine for treating ADHD in children. The search was carried out in PubMed, Cochrane Library, CINHAL, and ClinicalTrials.gov databases, covering articles from their inception until January 20, 2023. In addition, a dose-response meta-analysis was conducted. RESULTS: In this dose-response meta-analysis, 12 double-blind randomized placebo-controlled trials involving 2,250 patients were included. The efficacy of atomoxetine increased up to a dosage of 1.4 mg/kg, after which it reached a plateau. CONCLUSIONS: The first dose-response meta-analysis of atomoxetine dosing for children with ADHD conducted here enhances the robustness of the Food and Drug Administration and the European Medicines Agency dose recommendations.

Prescribing patterns for attention deficit hyperactivity disorder among children and adolescents in Taiwan from 2004 to 2017.

This study documented the prescribing patterns of methylphenidate and atomoxetine among patients aged 3 to 18 in Taiwan diagnosed with attention deficit hyperactivity disorder (ADHD) between 2004 and 2017. Initial treatment for ADHD, the time between the first diagnosis and the first prescription, and medication-switching patterns were investigated. The final cohort consisted of 256,882 patients, and 147,210 (57.3%) of them received medication treatment. Most of the patients (98.2%) received methylphenidate. Atomoxetine use increased from 0.1% in 2007 to 5.5% in 2017. The median time between the ADHD diagnosis and the first prescription was 21 days (IQR: 0-212 days). In patients who initiated methylphenidate, 12,406 (8.4%) patients switched to atomoxetine; 850 (31.3%) of the children began with atomoxetine and switched to methylphenidate. In conclusion, methylphenidate was the predominant treatment for ADHD in 2004-2017. However, the prevalence of pharmacotherapy for ADHD was relatively low. Further investigation on the reasons behind this pattern is recommended.

[A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder: CYP2D6 genetic testing and therapeutic drug monitoring]. / æ‰˜èŽ«è¥¿æ±€åœ¨æ³¨æ„åŠ›ç¼ºé™·å¤šåŠ¨éšœç¢æ‚£å„¿ä¸­çš„ç²¾å‡†è¯å­¦ç ”ç©¶ï¼šCYP2D6åŸºå› æ£€æµ‹å’Œæ²»ç–—è¯ç‰©ç›‘æµ‹.

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.

Personalizing atomoxetine dosing in children with ADHD: what can we learn from current supporting evidence.

PURPOSE: There is marked heterogeneity in treatment response of atomoxetine in patients with attention deficit/hyperactivity disorder (ADHD), especially for the pediatric population. This review aims to evaluate current evidence to characterize the dose-exposure relationship, establish clinically relevant metrics for systemic exposure to atomoxetine, define a therapeutic exposure range, and to provide a dose-adaptation strategy before implementing personalized dosing for atomoxetine in children with ADHD. METHODS: A comprehensive search was performed across electronic databases (PubMed and Embase) covering the period of January 1, 1985 to July 10, 2022, to summarize recent advances in the pharmacokinetics, pharmacogenomics/pharmacogenetics (PGx), therapeutic drug monitoring (TDM), physiologically based pharmacokinetics (PBPK), and population pharmacokinetics (PPK) of atomoxetine in children with ADHD. RESULTS: Some factors affecting the pharmacokinetics of atomoxetine were summarized, including food, CYP2D6 and CYP2C19 phenotypes, and drug‒drug interactions (DDIs). The association between treatment response and genetic polymorphisms of genes encoding pharmacological targets, such as norepinephrine transporter (NET/SLC6A2) and dopamine ß hydroxylase (DBH), was also discussed. Based on well-developed and validated assays for monitoring plasma concentrations of atomoxetine, the therapeutic reference range in pediatric patients with ADHD proposed by several studies was summarized. However, supporting evidence on the relationship between systemic atomoxetine exposure levels and clinical response was far from sufficient. CONCLUSION: Personalizing atomoxetine dosage may be even more complex than anticipated thus far, but elucidating the best way to tailor the non-stimulant to a patient's individual need will be achieved by combining two strategies: detailed research in linking the pharmacokinetics and pharmacodynamics in pediatric patients, and better understanding in nature and causes of ADHD, as well as environmental stressors.

Meta-analysis on the efficacy of the norepinephrine reuptake inhibitors reboxetine and atomoxetine for the treatment of schizophrenia and attention deficit hyperactivity disorder.

BACKGROUND: Norepinephrine transporter inhibitors that can alter the level of neurotransmitter in the brain are used to treat neurological disorders. However, a number of studies have reported their limited significance as a result of their slow onset of action and moderate efficacy. OBJECTIVES: To determine the effects of norepinephrine reuptake inhibitors (NRIs), reboxetine and atomoxetine on schizophrenia and attention deficit hyperactivity disorder (ADHD). MATERIAL AND METHODS: Relevant articles published between 2000 and 2022 were searched in the MEDLINE, CINAHL (via Ebsco), Web of Science and Scopus databases. Among the various NRIs, studies concerning the 2 potent drugs - reboxetine and atomoxetine - were selected for analysis. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated, along with the exploration of heterogeneity and publication bias, using RevMan software. RESULTS: A total of 14 eligible studies with a combined sample size of 970 patients were included. Using a random effects model, an OR of 0.55 (0.32-0.94), a Tau2 value of 0.23, a ÷2 value of 12.31, 8 degrees of freedom (df), an I2 of 35%, a Z value of 2.19, and a p-value of 0.03 were recorded for reboxetine. Atomoxetine had an OR of 0.35 (0.13-0.97), a Tau2 value of 0.58, a ÷2 value of 7.31, 4 df, an I2 of 45%, a Z value of 1.53, and a p-value of 0.04. All results were statistically significant with a low risk of publication bias, as was evident from the p-values >0.05 derived from the Egger's test and the Begg's test. These drugs provided comparable changes to control drugs in Hamilton Depression Rating Scale (HAM-D) scores, Positive and Negative Syndrome Scale (PANSS) scores and ADHD ratings. This confirms the efficacy of reboxetine for the treatment of schizophrenia and atomoxetine for the treatment of ADHD. CONCLUSION: The present meta-analysis suggests that NRIs are efficacious and therefore they are potential candidate drugs for the treatment of schizophrenia and ADHD.

A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder: CYP2D6 genetic testing and therapeutic drug monitoring / 中国当代儿科杂志

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.

A systematic review of the use of atomoxetine for management of comorbid anxiety disorders in children and adolescents with attention-deficit hyperactivity disorder.

BACKGROUND: Anxiety disorders are among the most common comorbid mental disorders in children and adolescents with attention-deficit hyperactivity disorder (ADHD). While the role of atomoxetine, a non-stimulant medication, is well-established in the management of ADHD symptoms since two decades, there is a dearth of evidence regarding its efficacy in the management of anxiety disorders in children and adolescents with ADHD. AIMS: We aimed to provide insights into (1) the comparative efficacy of atomoxetine in children and adolescents with comorbid ADHD and anxiety disorders, (2) change in severity of anxiety symptoms based on patients', parents', and clinicians' ratings, (3) tolerability and side effects. METHODS: We searched PubMed, EMBASE, and PsycINFO for clinical trials that addressed the efficacy of atomoxetine for anxiety symptoms in children and adolescents with ADHD. All published literature was systematically reviewed. RESULTS: We included four studies, out of which two specifically addressed comorbid ADHD and anxiety disorder. The studies suggested that atomoxetine did not exacerbate and in fact reduced anxiety symptoms in young patients with comorbid ADHD. CONCLUSIONS AND IMPLICATIONS: Overall, atomoxetine demonstrates good efficacy in improving anxiety symptoms in children and adolescents with ADHD. Further studies are needed to shed light on atomoxetine's efficacy for anxiety subtypes in ADHD.

Shared and Unique Effects of Long-Term Administration of Methylphenidate and Atomoxetine on Degree Centrality in Medication-Naïve Children With Attention-Deficit/Hyperactive Disorder.

BACKGROUND: Although methylphenidate (MPH) and atomoxetine (ATX) can improve clinical symptoms and functional impairments in attention deficit/hyperactive disorder (ADHD), the underlying psychopharmacological mechanisms have not been clearly elucidated. Therefore, we aimed to explore the shared and unique neurologic basis of these 2 medications in alleviating the clinical symptoms and functional impairments observed in ADHD. METHODS: Sixty-seven ADHD and 44 age-matched children with typical development were included and underwent resting-state functional magnetic resonance imaging scans at baseline. Then patients were assigned to MPH, ATX, or untreated subgroups, based on the patients' and their parents' choice, for a 12-week follow-up and underwent a second functional magnetic resonance imaging scan. The treatment effect on degree centrality (DC) was identified and correlated with clinical symptoms and functional impairments in the ADHD group. RESULTS: Both MPH and ATX normalized the DC value in extensive brain regions mainly involving fronto-cingulo-parieto-cerebellum circuits. However, ATX showed limited significant effects on the cerebellum compared with ADHD at baseline. The improvements in clinical symptoms were correlated with increased DC in the right inferior temporal gyrus in both MPH and ATX subgroups but showed opposite effects. The alleviation of functional impairments in the school/learning domain negatively correlated with decreased DC in the bilateral cerebellum after MPH treatment, and the family functional domain positively correlated with decreased DC in the cerebellum and negatively correlated with decreased DC in the postcentral gyrus after ATX treatment. CONCLUSIONS: Both MPH and ATX can normalize abnormal brain functions that mainly involve the fronto-cingulo-parieto-cerebellum circuit in ADHD. Furthermore, the 2 medications showed shared and unique effects on brain functions to alleviate clinical symptoms and functional impairment.

Identification of factors associated with the efficacy of atomoxetine in adult attention-deficit/hyperactivity disorder.

AIM: Atomoxetine (ATX) is a non-central stimulant and a standard treatment for adult attention-deficit/hyperactivity disorder (ADHD). The long-term efficacy of Atomoxetine is about 40% at 6 months. The variability in efficacy between individuals is thought to be related to patient-specific factors, but no detailed research has been conducted. In this retrospective cohort study, we aimed to identify the factors associated with Atomoxetine efficacy. METHODS: A total of 147 patients with attention-deficit/hyperactivity disorder aged ≥18 years who were using Atomoxetine for the first time were included in this study. The outcome was treatment success (treatment maintained for at least 6 months and improvement in symptoms). Symptom assessment was based on the overall improvement in symptoms judged by an expert physician. RESULTS: Of the patient sample, 103 (70.1%) achieved the outcome. Logistic regression analysis identified "the maximum dose of ATX" and "gambling habit" as factors associated with efficacy ( P  < 0.05). In the process of Atomoxetine titration, the larger the maximum dose, the higher the efficacy was shown to be. Gambling habits may be indicative of impulsivity, which is among the core symptoms of attention-deficit/hyperactivity disorder. Thus, a gambling habit may be considered a surrogate marker for impulsivity. CONCLUSIONS: Knowledge of these factors will help healthcare professionals to predict the likely efficacy of Atomoxetine in a given patient before subscribing it, facilitating individualized pharmacotherapy for adult attention-deficit/hyperactivity disorder.

A view of response and resistance to atomoxetine treatment in children with ADHD: effects of CYP2C19 polymorphisms and BDNF levels.

OBJECTIVE: Although several genes have previously been studied about the treatment of Attention Deficit Hyperactivity Disorder (ADHD), the number of studies investigating the effects of genes on atomoxetine (ATX) treatment is very limited. In this study, we aimed to investigate the effect of CYP2C19 polymorphisms, which have a role in ATX biotransformation, on the treatment response and also to assess whether there is a relationship between BDNF and treatment response in children and adolescents with ADHD. METHODS: One hundred children with ADHD and 100 healthy controls (HCs) were included in this study. The treatment response was assessed 2 months after the start of the ATX treatment. DNA samples from peripheral venous blood were replicated using PCR and analyzed using the ILLUMINA next-generation sequencing method. The resulting fastqs were analyzed using Basespace's Variant Interpreter Program. Plasma BDNF levels were evaluated with ELISA kits. RESULTS: Treatment response was found to be lower in both heterozygous and homozygous carriers of the c.681G > A (CYP2C19*2) polymorphism. When the BDNF level was compared, it was found to be significantly higher in the ADHD group compared to HCs. Also, BDNF has a stronger predictive value for assessing resistance to ATX treatment. CONCLUSIONS: To our knowledge, this is the first study to assess the effects of CYP2C19 polymorphisms and BDNF levels together on ATX treatment in children. Further studies with an extensive population are needed to better understand the effects of CYP2C19 polymorphisms on treatment and side effects, as well as the effects of BDNF levels.

Therapeutic drug monitoring of atomoxetine in children and adolescents with attention-deficit/ hyperactivity disorder: a naturalistic study.

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.

Prefrontal Cortex Activation and Stopping Performance Underlie the Beneficial Effects of Atomoxetine on Response Inhibition in Healthy Volunteers and Those With Cocaine Use Disorder.

BACKGROUND: Impaired response inhibition in individuals with cocaine use disorder (CUD) is hypothesized to depend on deficient noradrenergic signaling in corticostriatal networks. Remediation of noradrenergic neurotransmission with selective norepinephrine reuptake inhibitors such as atomoxetine may therefore have clinical utility to improve response inhibitory control in CUD. METHODS: We carried out a randomized, double-blind, placebo-controlled, crossover study with 26 participants with CUD and 28 control volunteers investigating the neural substrates of stop-signal inhibitory control. The effects of a single dose of atomoxetine (40 mg) were compared with placebo on stop-signal reaction time performance and functional network connectivity using dynamic causal modeling. RESULTS: We found that atomoxetine speeded Go response times in both control participants and those with CUD. Improvements in stopping efficiency on atomoxetine were conditional on baseline (placebo) stopping performance and were directly associated with increased inferior frontal gyrus activation. Further, stopping performance, task-based brain activation, and effective connectivity were similar in the 2 groups. Dynamic causal modeling of effective connectivity of multiple prefrontal and basal ganglia regions replicated and extended previous models of network function underlying inhibitory control to CUD and control volunteers and showed subtle effects of atomoxetine on prefrontal-basal ganglia interactions. CONCLUSIONS: These findings demonstrate that atomoxetine improves response inhibition in a baseline-dependent manner in control participants and in those with CUD. Our results emphasize inferior frontal cortex function as a future treatment target owing to its key role in improving response inhibition in CUD.

Reboxetine Plus Oxybutynin for OSA Treatment: A 1-Week, Randomized, Placebo-Controlled, Double-Blind Crossover Trial.

BACKGROUND: The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced OSA severity has revitalized interest in pharmacologic therapies for OSA. RESEARCH QUESTION: Would 1 week of reboxetine plus oxybutynin (Reb-Oxy) be effective on OSA severity? STUDY DESIGN AND METHODS: A randomized, placebo-controlled, double-blind, crossover trial was performed comparing 4 mg reboxetine plus 5 mg oxybutynin (Reb-Oxy) vs placebo in patients with OSA. After a baseline in-laboratory polysomnogram (PSG), patients underwent PSGs after 7 nights of Reb-Oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI), which was the primary outcome. Response rate was based on the percentage of subjects with a ≥ 50% reduction in AHI from baseline. Secondary outcomes included Epworth Sleepiness Scale (ESS) score and psychomotor vigilance test (PVT) values. Home oximetry evaluated overnight oxygen desaturation index (ODI) throughout treatment. RESULTS: Sixteen subjects aged 57 [51-61] years (median [interquartile range]) with a BMI of 30 [26-36] kg/m2 completed the study. Reb-Oxy lowered AHI from 49 [35-57] events per hour at baseline to 18 [13-21] events per hour (59% median reduction) compared with 39 [29-48] events per hour (6% median reduction) with placebo (P < .001). Response rate for Reb-Oxy was 81% vs 13% for placebo (P < .001). Although ESS scores were not significantly lowered, PVT median reaction time decreased from 250 [239-312] ms at baseline to 223 [172-244] ms on Reb-Oxy vs 264 [217-284] ms on placebo (P < .001). Home oximetry illustrated acute and sustained improvement in the oxygen desaturation index on Reb-Oxy vs placebo. INTERPRETATION: The administration of Reb-Oxy greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacologic treatment of OSA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04449133; URL: www.clinicaltrials.gov.

A Practical, Evidence-informed Approach to Managing Stimulant-Refractory Attention Deficit Hyperactivity Disorder (ADHD).

Stimulants (methylphenidate or amphetamines) are the recommended first-line option for the pharmacological treatment of individuals with attention deficit hyperactivity disorder (ADHD). However, some patients with ADHD will not respond optimally to stimulants. Here, we discuss strategies to manage stimulant-refractory ADHD, based on the recommendations advanced in clinical guidelines, knowledge of expert practice in the field, and our own clinical recommendations, informed by a comprehensive literature search in PubMed, PsycInfo, EMBASE + EMBASE classic, OVID Medline, and Web of Science (up to 30 March 2021). We first highlight the importance of stimulant optimization as an effective strategy to increase response. We then discuss a series of factors that should be considered before using alternative pharmacological strategies for ADHD, including poor adherence, time action properties of stimulants (and wearing-off of effects), poor tolerability (that prevents the use of higher, more effective doses), excessive focus on or confounding from presence of comorbid non-ADHD symptoms, and tolerance. Finally, we consider the role of non-stimulants and combined pharmacological approaches. While the choice of medication for ADHD is still to a large extent based on a trial-and-error process, there are reasonably accepted data and guidelines to aid in clinical decision-making. It is hoped that advances in precision psychiatry in the years ahead will further guide prescribers to tailor medication choice to the specific characteristics of the patient.

Methylphenidate and atomoxetine treatment negatively affect physical growth indexes of school-age children and adolescents with attention-deficit/hyperactivity disorder.

AIM: To determine the effects of drug therapy on the physical growth of school-age children and adolescents with attention-deficit/hyperactivity disorder (ADHD). METHOD: The medical records of 86 participants (average age: 8.9 ± 2.2 years) with ADHD prescribed methylphenidate (MPH) or atomoxetine (ATX) for ≥24 weeks from the Children's Hospital of Chongqing Medical University were analysed. RESULTS: The Z-scores of height, weight and body mass index (BMI) of children with ADHD decreased significantly over the first six months of MPH treatment (P < 0.001). The slopes of the fitting lines after the first six months of MPH (-0.18, -0.58 and -0.69, respectively) returned over the entire treatment (the slopes changed to -0.027, -0.26 and -0.20, respectively). For ATX, the Z-scores of height of children decreased significantly over the first six months (P < 0.001), but the Z-scores of weight and BMI did not (P > 0.05). The slopes of the fitting lines after the first six months of ATX (-0.058, -0.032 and 0.0094, respectively) changed over the entire treatment (slopes were 0.16, 0.52 and 0.26, respectively). Children taking MPH were more likely to report decreased appetite (P < 0.05). The weight and BMI of the children receiving MPH were significantly correlated with decreased appetite (P < 0.01). CONCLUSION: The physical growth indexes (PGIs) of school-age children and adolescents with ADHD were negatively affected while taking MPH, and these effects were gradually mitigated with continued treatment. ATX hardly had negative effects on weight and BMI. Neither MPH nor ATX had a significant negative effect on the height of children in long-term ADHD treatment. It is necessary for clinicians to consider children's diet during treatment.

Atomoxetine in Attention-Deficit/Hyperactivity Disorder in Children With and Without Comorbid Mood Disorders.

Objectives: Mood disorders are commonly associated with attention-deficit/hyperactivity disorder (ADHD), adding to the clinical complexity. Some symptoms associated with ADHD are often associated with an increase in emotional disorders and depression. Hence, the management of comorbid mood symptoms in the context of ADHD represents a particularly difficult clinical challenge. Few studies in literature, and probably none in the Arab world, have investigated the impact of individual common comorbid disorders on the efficacy of atomoxetine (a nonstimulant norepinephrine reuptake inhibitor) as a monotherapy for the treatment of these comorbid mood symptoms. Therefore, our aim was to investigate the effect of atomoxetine in a sample of drug-naive Egyptian children with ADHD, with and without comorbid mood disorders. Methods: A prospective, naturalistic, open-label study. Results: Atomoxetine is an effective treatment for the symptoms of ADHD in the presence of comorbid mood disorder, but with a slower rate of improvement than if applied in the absence of mood disorder; in addition, our study showed improvement regarding the depressive symptoms in the mood group after 1 month. Conclusions: The study highlighted that atomoxetine is an effective treatment for ADHD in the presence of comorbid mood disorder, and improves depressive symptoms in the mood group. It also predicts mild resistance to the effects of atomoxetine on ADHD with slower improvement than those with ADHD only.

Prevalence and determinants of attention deficit/hyperactivity disorder (ADHD) medication use during pregnancy: Results from the Quebec Pregnancy/Children Cohort.

AIMS: The use of attention deficit/hyperactivity disorder (ADHD) medications has grown over the past decade among pregnant women, but these treatments are not without risk. Updated prevalence of ADHD medication use and whether prescribed dosages follow guidelines are needed. The aim of this study is to describe the prevalence of ADHD medication use among pregnant women-dosages and switches-and identify determinants of ADHD medication use. METHOD: A population-based longitudinal cohort study within the Quebec Pregnancy/Children Cohort (QPC). Women aged 15-45 years old covered by the RAMQ prescription drug plan for at least 12 months before and during pregnancy from 1998 to 2015. ADHD medication exposure was assessed before and during pregnancy. We estimated odds ratios (ORs) for determinants of ADHD medication use during pregnancy with generalized estimating equations. RESULTS: Among 428,505 included pregnant women, 1,130 (0.26%) used ADHD medication. A 14-fold increase in the prevalence of ADHD medication use in pregnant women was observed, from 1998 (0.08%) to 2015 (1.2%). Methylphenidate was the most prevalent medication at 70.1%. ADHD medication fillings were at optimal dosage 91.8% of the time based on guidelines and 18.1% of women switched to another ADHD medication class during gestation. Main determinants of ADHD medication use during pregnancy were psychiatric disorders (aOR 2.19; 95% confidence interval [CI] 1.57, 2.96), mood and anxiety disorders (aOR 1.74; 95% CI 1.32, 2.24), and calendar year. CONCLUSIONS: The number of pregnancies exposed to ADHD medications has increased similarly to the increase reported in other countries between 1998 and 2015. In addition to the current literature, the use of ADHD medications during pregnancy is consistent with Canadian guidelines recommendations on dosage.

Differential Treatment Effects of Methylphenidate and Atomoxetine on Executive Functions in Children with Attention-Deficit/Hyperactivity Disorder.

Objectives: This study aimed to compare the efficacy of methylphenidate and atomoxetine on improving executive functions among children with attention-deficit/hyperactivity disorder (ADHD). Methods: This was an open-label, head-to-head, 3-month, randomized clinical trial with two-arm parallel-treatment groups: osmotic-release oral system methylphenidate (OROS-MPH; n = 79) and atomoxetine once daily (n = 78). Three major domains of executive functions were assessed, including response selection/inhibition, flexibility, and planning/working memory. The neuropsychological measures included the Conners' continuous performance test and the Cambridge Neuropsychological Test Automated Battery. Results: We found that both treatment groups showed improvement in executive functions (p-value <0.05 for the major indices of each domain). In addition, OROS-MPH was associated with a greater magnitude of improvement in the response selection/inhibition; the slope for detectability improvement in the Conners' continuous performance test was 0.06 for atomoxetine and 0.15 for OROS-MPH (p-value <0.01); the slope in rapid visual information processing was 2.22 for atomoxetine and 3.45 for OROS-MPH (p-value <0.05). Conclusion: Both OROS-MPH and atomoxetine improved various domains of executive functions in children with ADHD. There is greater improvement in response selection/inhibition among patients treated with OROS-MPH than those with atomoxetine. This trial was registered with ClinicalTrials.gov (no. NCT00916786).