Atomoxetine increases salivary cortisol in healthy volunteers

It has been proposed that acute hypothalamo-pituitary-adrenal (HPA) axis challenge using noradrenergic drugs may be of utility in assessing the functional integrity of central noradrenaline pathways. Atomoxetine (formerly tomoxetine) is a highly selective noradrenaline reuptake inhibitor, which has recently been licensed for the treatment of attention deficit hyperactivity disorder (ADHD).The aim of this study was to assess the effects of acute atomoxetine on salivary cortisol levels for the first time.A total of 60 healthy male volunteers received 60 mg atomoxetine, 30 mg citalopram, or placebo per os in a double-blind parallel groups design (n = 20 per group). Salivary cortisol, blood pressure and pulse rates were recorded at baseline and at +1.0, +1.5, +2.5 and +3.5 hours after capsule administration.60 mg atomoxetine led to highly significant increases in salivary cortisol and a moderate increase in pulse rate, in the absence of significant effects on blood pressure. 30 mg citalopram had no significant effects on cortisol or cardiovascular parameters.These data support the utility of atomoxetine neuroendocrine challenge for evaluating central noradrenaline pathways, which may be of future use in neuropsychiatric patient studies. Furthermore, the effects of atomoxetine on HPA axis function may have clinical implications given the use of this agent in the treatment of ADHD.     

Atomoxetine: the first nonstimulant for the management of attention-deficit/hyperactivity disorder.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety, drug interactions, dosage and administration, and place in therapy of atomoxetine in the treatment of attention-deficit/hyperactivity disorder (ADHD) are reviewed. SUMMARY: Atomoxetine is a methylphenoxy-benzenepropanamine derivative with antidepressant activity and is thought to enhance noradrenergic function via selective inhibition of the presynaptic norepinephrine transporter. Atomoxetine is rapidly absorbed from the gastrointestinal tract, reaching peak levels in 1.83 hours in pediatric patients and 1-1.5 hours in adults. The clinical efficacy of atomoxetine in the treatment of ADHD has been evaluated in six published clinical trials of children and adolescents and two studies enrolling only adults. Clinical trial data indicate that atomoxetine is safe and well tolerated for the treatment of ADHD; however, safety data about long-term use (greater than one year) are unavailable. Adverse events reported in clinical trials were mainly mild to moderate and transient in nature. Recommended dosing of atomoxetine is weight based, and dosages should be adjusted to a target dosage of 1.2 mg/kg/day in children and adolescents weighing 70 kg or less and to 80 mg/day in children and adolescents weighing over 70 kg and adults. While current guidelines from the American Academy of Pediatrics recommend stimulants and behavior modification as first-line therapy for the management of ADHD, atomoxetine offers those patients who do not respond to or cannot tolerate one or more stimulants an alternative treatment option. CONCLUSION: Atomoxetine, the first non-stimulant approved for the management of ADHD in children, adolescents, and adults, provides patients who have not responded to or cannot tolerate one or more stimulants an alternative treatment option.     

Atomoxetine

Atomoxetine, formerly tomoxetine, is a selective norepinephrine reuptake inhibitor and a new, nonstimulant treatment for attention deficit hyperactivity disorder (ADHD). In vitro, ex vivo and in vivo studies have shown that atomoxetine is a highly selective antagonist of the presynaptic norepinephrine transporter with little or no affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors. In four randomized, placebo-controlled clinical trials conducted over 6-9 weeks in children and adolescents with ADHD, atomoxetine (total daily dose 1-1.8 mg/kg administered in one or two doses daily) reduced symptoms (hyperactivity, impulsiveness and inattention) as determined by the reduction in ADHD total score (34-38% with atomoxetine versus 13-15.7% with placebo [p < 0.05]). Atomoxetine also significantly improved ADHD subscale rating scores (p < 0.05 and p < 0.001), psychosocial well-being (p < 0.05) and ADHD-related problem behavior according to parent and teacher ratings (p < 0.05). Atomoxetine was well tolerated in clinical trials and discontinuation rates due to adverse events were low (<5%). The most common treatment-related adverse event was decreased appetite. Atomoxetine shows no abuse potential and is not a controlled substance in the US.     

Atomoxetine, a novel treatment for attention-deficit-hyperactivity disorder

Atomoxetine is the first nonstimulant drug approved by the United States Food and Drug Administration (FDA) for the treatment of attention-deficit-hyperactivity disorder (ADHD), and the only agent approved by the FDA for the treatment of ADHD in adults. Atomoxetine is a norepinephrine transport inhibitor that acts almost exclusively on the noradrenergic pathway. Its mechanism of action in the control and maintenance of ADHD symptoms is thought to be through the highly specific presynaptic inhibition of norepinephrine. Clinical trials to evaluate the short-term effects of atomoxetine in children and adults have shown that atomoxetine is effective in maintaining control of ADHD. Likewise, long-term trials have determined that atomoxetine is effective in preventing relapse of ADHD symptoms without an increase in adverse effects. A comparative trial of atomoxetine with methylphenidate in school-aged children indicated similar safety and efficacy without the abuse liability associated with some psychostimulants. The most commonly reported adverse effects in children and adolescents are dyspepsia, nausea, vomiting, decreased appetite, and weight loss. The rates of adverse events in the trials were similar for both the once- and twice-daily dosing regimens. The discontinuation rate was 3.5% in patients treated with atomoxetine versus 1.4% for placebo and appeared to be dose dependent, wit a higher percentage of discontinuation at dosages greater than 1.5 mg/kg/day. In clinical trials involving adults, the emergence of clinically significant or intolerable adverse events was low. The most common adverse events in adults were dry mouth, insomnia, nausea, decreased appetite, constipation, urinary retention or difficulties with micturition, erectile disturbance, dysmenorrhea, dizziness, and decreased libido. Sexual dysfunction occurred in approximately 2% of patients treated with atomoxetine. Atomoxetine should be used with caution in patients who have hypertension or any significant cardiovascular disorder. Overall, atomoxetine therapy in patient with ADHD appears to be effective in controlling symptoms and maintaining remission, with the advantages being comparable efficacy with that of methylphenidate, a favorable safety profile, and non-controlled substance status. Additional long-term studies are needed to determine its continued efficacy for those who require lifelong treatment, and comparative trials against other stimulant and nonstimulant agents.     

Switching from neurostimulant therapy to atomoxetine in children and adolescents with attention-deficit hyperactivity disorder : clinical approaches and review of current available evidence

This review provides practical information on and clinical reasons for switching children and young people with attention-deficit hyperactivity disorder (ADHD) from neurostimulants to atomoxetine, detailing currently available evidence, and switching options. The issue is of particular relevance following recent guidance from the National Institute for Health and Clinical Excellence and European ADHD guidelines endorsing the use of atomoxetine, along with the stimulants methylphenidate and dexamphetamine, in the management of ADHD in children and adolescents in the UK. The selective norepinephrine (noradrenaline) reuptake inhibitor, atomoxetine, is a non-stimulant drug licensed for the treatment of ADHD in children and adolescents, and in adults who have shown a response in childhood. Following the once-daily morning dose, its therapeutic effects extend through the waking hours, into late evening, and in some patients, through to early the next morning. Atomoxetine may be considered for patients who are unresponsive or incompletely responsive to stimulant treatment, have co-morbid conditions (e.g. tics, anxiety, depression), and have sleep disturbances or eating problems, for patients in whom stimulants are poorly tolerated, and for situations where there is potential for drug abuse or diversion. Atomoxetine has been shown to be effective in relapse prevention and there is suggestion that atomoxetine may have a positive effect on global functioning; specifically health-related quality of life, self-esteem, and social and family functioning. According to one study, approximately 50% of non-responders to methylphenidate will respond to atomoxetine therapy and approximately 75% of responders to methylphenidate will also respond to atomoxetine. Atomoxetine may be initiated by a schedule of dose increases and cross-tapering with methylphenidate. A slow titration schedule with divided doses minimizes the impact of adverse events within the first several weeks of treatment. Atomoxetine may be co-administered with methylphenidate during the switching period without undue concern for adverse events, such as cardiovascular effects (although monitoring of blood pressure and heart rate is necessary). Atomoxetine may be discontinued abruptly and patients may miss the occasional dose without rebound effects or discontinuation syndrome. A trial period of at least 6-8 weeks, perhaps longer, is recommended before evaluation of the overall tolerability and efficacy of atomoxetine. We conclude that patients with ADHD can be switched from neurostimulants, specifically methylphenidate, to atomoxetine, and may benefit from symptom improvement.     

Efficacy and safety of atomoxetine for attention-deficit/hyperactivity disorder in children and adolescents—meta-analysis and meta-regression analysis

OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of atomoxetine in children and adolescents. MATERIALS AND METHODS: We searched for studies published between 1985 and 2006 through Medline, PubMed, PsychInfo and Cochrane Central Register of Controlled Trials (CENTRAL 2006 Issue 3) using keywords related to atomoxetine and attention-deficit/hyperactivity disorder (ADHD) and scanned though reference lists. We included nine randomized placebo-controlled trials (atomoxetine:placebo = 1,150:678). RESULTS: Atomoxetine was superior (p < 0.01) to placebo in reducing ADHD symptoms across different scales (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Conners' Parent and Teacher Rating Scales-Revised:Short Form, Clinical Global Impression-Severity) rated by different raters (parent, teacher, clinician). The number-needed-to-treat (NNTs) for treatment response and relapse prevention were 3.43 (95% CI, 2.79-4.45) and 10.30 (95% CI, 5.89-40.62), respectively. High baseline ADHD symptoms (p = 0.02) was associated with greater reduction in ADHD symptoms, whereas male gender (p = 0.02), comorbid oppositional defiant disorder (ODD) status (p = 0.01) and ADHD hyperactive/impulsive subtype (p = 0.01) were associated with smaller reductions. The commonest adverse events were gastrointestinal [appetite decrease, number-needed-to-harm (NNH) = 8.81; abdominal pain, NNH = 22.48; vomiting, NNH = 29.96; dyspepsia, NNH = 49.38] and sleep related (somnolence, NNH = 19.41). Young age (p = 0.03) and high baseline hyperactive/impulsive symptoms (p < 0.01) were associated with more adverse events, whereas ADHD inattentive subtype (p = 0.04) was associated with less adverse events. Quality of life using Child Health Questionnaire (CHQ) improved (p < 0.01) with atomoxetine treatment. Both ADHD and ODD symptoms (p < 0.01) were reduced in comorbid ADHD+ODD, and ODD status was not associated with more adverse events. Efficacy and side effects were not altered by comorbid general anxiety disorder or major depression. CONCLUSIONS: Atomoxetine is efficacious in reducing ADHD symptoms. It may have a role in treating comorbid ODD or depression, and probably in comorbid anxiety.     

Abuse liability assessment of atomoxetine in a drug-abusing population

BACKGROUND: Atomoxetine is a non-amphetamine medication approved to treat ADHD in children, adolescents, and adults. Previous studies demonstrated low abuse potential for atomoxetine in recreational drug users. This study assessed the abuse potential of atomoxetine in stimulant-preferring drug abusers compared to methylphenidate and phentermine as positive controls and desipramine and placebo as negative controls. METHODS: Forty male and female, 32-53 years old stimulant-preferring drug abusers completed this balanced Latin-square designed study. Subjects received acute, double-blind doses of placebo, desipramine (100 and 200 mg), methylphenidate (90 mg), phentermine (60 mg), and atomoxetine (45, 90, and 180 mg). Subjective and physiological effects were collected for 24 h following each drug treatment. RESULTS: Methylphenidate and phentermine were liked significantly more than placebo, atomoxetine, or desipramine. No atomoxetine dose was liked significantly more than placebo and liking scores for atomoxetine were similar to, or significantly lower than, desipramine, as assessed by the Drug Rating Questionnaire-Subject. While atomoxetine 45 and 180 mg did not significantly change any Addiction Research Center Inventory (ARCI) scores, atomoxetine 90 mg significantly increased A and BG stimulant scores of the ARCI and both methylphenidate and phentermine produced greater A and BG increases than any atomoxetine dose and also increased MBG (euphoria) scores relative to placebo. CONCLUSIONS: Atomoxetine has significantly less abuse liability than methylphenidate or phentermine and no greater abuse liability than desipramine.     

Atomoxetine blocks motor hyperactivity in neonatal 6-hydroxydopamine-lesioned rats: implications for treatment of attention-deficit hyperactivity disorder

We recently reported that selective inhibitors of neuronal transport of norepinephrine (NE), desipramine and nisoxetine, reversed motor hyperactivity in an animal model of attention-deficit hyperactivity disorder (ADHD). In this study, we examined behavioural effects of atomoxetine, a potent new NE reuptake blocker, in juvenile male rats with neonatal 6-hydroxydopamine (6-OHDA) lesions of dopamine projections to the forebrain. 6-OHDA (100 microg) was administered intracisternally on postnatal day (PD) 5 following desipramine (25 mg/kg s.c.) pretreatment to protect noradrenergic neurons. Atomoxetine (1 mg/kg) was given intraperitoneally before recording motor activity for 90 min at PD 23-26 in a novel environment. Atomoxetine greatly reduced motor hyperactivity in 6-OHDA-lesioned rats while exhibiting transient sedative effects in sham controls. The observed effects in this animal model for ADHD are consistent with the emerging clinical use of atomoxetine as a novel, non-stimulant treatment for ADHD.     

Atomoxetine: a selective noradrenaline reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder

Atomoxetine (Strattera^?, Eli Lilly & Co.) is a selective noradrenaline reuptake inhibitor that has been studied for use in the treatment of attention-deficit/hyperactivity disorder (ADHD). So far, two open-label and seven randomised, double-blind, placebo-controlled, clinical trials have been published, six in youths and three in adults. Each of these trials has shown a positive response as measured by the primary efficacy measures, the ADHD-IV Rating Scale (ADHD RS) or the Conners Adult ADHD Rating Scale (CAARS). Atomoxetine has generally been well tolerated. In November of 2002 the FDA approved atomoxetine for use in the US for the treatment of ADHD in children, adolescents and adults. Atomoxetine is the first nonstimulant approved by the FDA for the treatment of ADHD and the first medication approved for the treatment of adult ADHD.     

Atomoxetine: a selective noradrenaline reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder

Atomoxetine (Strattera, Eli Lilly & Co.) is a selective noradrenaline reuptake inhibitor that has been studied for use in the treatment of attention-deficit/hyperactivity disorder (ADHD). So far, two open-label and seven randomised, double-blind, placebo-controlled, clinical trials have been published, six in youths and three in adults. Each of these trials has shown a positive response as measured by the primary efficacy measures, the ADHD-IV Rating Scale (ADHD RS) or the Conners Adult ADHD Rating Scale (CAARS). Atomoxetine has generally been well tolerated. In November of 2002 the FDA approved atomoxetine for use in the US for the treatment of ADHD in children, adolescents and adults. Atomoxetine is the first nonstimulant approved by the FDA for the treatment of ADHD and the first medication approved for the treatment of adult ADHD.     

Changes in symptoms and adverse events after discontinuation of atomoxetine in children and adults with attention deficit/hyperactivity disorder: a prospective, placebo-controlled assessment

Drugs that affect neurotransmitter release can induce changes in neuroregulation during chronic administration. Thus, in addition to recurrence of symptoms of the illness, discontinuation of treatment can be associated with clinical signs and symptoms related to these changes. Atomoxetine, a new drug approved in the United States for treatment of attention deficit/hyperactivity disorder (ADHD), is associated with blockade of the presynaptic norepinephrine transporter. Because treatment of ADHD typically involves chronic treatment, the potential for production of a discontinuation syndrome as well as recurrence of symptoms upon drug discontinuation were assessed as part of the clinical development process. The effects of discontinuation of atomoxetine were assessed in children and adults with ADHD following 9 to 10 weeks of continuous therapy in 4 large studies. Symptoms of ADHD worsened following drug discontinuation but did not return to pretreatment levels. The incidence of discontinuation-emergent adverse events was low and there were no statistically significant differences between the patients abruptly discontinuing from atomoxetine and those continuing on placebo. Discontinuation of atomoxetine did not result in the development of an acute discontinuation syndrome and was well tolerated. It appears that atomoxetine may be discontinued without risk for symptom rebound or discontinuation-emergent adverse effects. Tapering of doses is not necessary when atomoxetine is discontinued.     

Update on atomoxetine in the treatment of attention-deficit/hyperactivity disorder

Background: Atomoxetine, an inhibitor of, the presynaptic transporter of norepinephrine, was approved for the treatment of attention-deficit/ hyperactivity disorder (ADHD) in children aged 6 years and older, adolescents and adults in the USA in 2002, and in Europe, first in the UK and then by mutual recognition in several countries during 2003 and 2004. Since that time, the use of atomoxetine has spread globally and extensive additional research has been conducted evaluating its efficacy and safety. Objective: The objective of this review is to provide a summary of the available data on atomoxetine, with an emphasis on postmarketing clinical research, which is helping to clarify the role of this agent in ADHD pharmacotherapy. Methods: Recent as well as long-term safety and efficacy data are reviewed, with an emphasis on comparison with long-acting psychostimulants, ADHD in special populations and in patients with psychiatric comorbidities. Results/conclusion: Atomoxetine is an effective acute and long-term pharmacotherapy for ADHD, and may play a particular role in the treatment of patients with comorbid disorders and those who have failed or are unable to tolerate stimulants.     

Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders

OBJECTIVE: Adults with attention-deficit/hyperactivity disorder (ADHD) have higher rates of alcohol and drug use disorders than adults without ADHD. The study aim was to determine if atomoxetine was superior to placebo in improving ADHD and alcohol use in recently abstinent adults with ADHD and comorbid alcohol use disorder. METHODS: Adults with DSM-IV diagnoses of ADHD and alcohol abuse and/or dependence were abstinent from alcohol at least 4 days (maximum 30 days) before study randomization. Participants received atomoxetine (25-100mg daily) or placebo for 12 weeks. ADHD symptoms were assessed using ADHD Investigator Symptom Rating Scale (AISRS) total score. Time-to-relapse to heavy alcohol use was analyzed using a 2-sided log-rank test based on Kaplan-Meier estimates and cumulative heavy drinking events over time were evaluated post hoc with recurrent-event analysis. RESULTS: Subjects received atomoxetine (n=72) or placebo (n=75) and 80 subjects completed the 12-week double-blind period (n=32 and 48, respectively). ADHD symptoms were significantly improved in the atomoxetine cohort compared to placebo (AISRS total score mean [S.D.], atomoxetine: -13.63 [11.35], P<.001; placebo: -8.31 [11.44], P<.001, difference: P=.007; effect size=0.48). No significant differences between treatment groups occurred in time-to-relapse of heavy drinking (P=.93). However, cumulative heavy drinking days were reduced 26% in atomoxetine-treated subjects versus placebo (event ratio=0.74, P=.023). There were no serious adverse events or specific drug-drug reactions related to current alcohol use. CONCLUSIONS: This 3-month, double-blind, placebo-controlled study of atomoxetine in adults with ADHD and comorbid alcohol use disorder demonstrates clinically significant ADHD improvement, and inconsistent effects on drinking behavior.     

Effects of atomoxetine on subjective and neurocognitive symptoms of nicotine abstinence

Nicotine dependence has been linked to attention-deficit hyperactivity disorder (ADHD) symptoms in both clinical and general populations. This behavioural pharmacology study used a within-subject, double-blind, crossover design to test the effects of atomoxetine, a medication for ADHD, on nicotine abstinence symptoms. Fifty non treatment-seeking smokers (>/=15 cigarettes/day) completed a baseline session when they were smoking as usual and then two laboratory testing sessions after overnight abstinence and treatment with 7 days of either atomoxetine (1.2 mg/kg) or placebo. During each laboratory session, participants completed subjective measures of abstinence symptoms and performed neurocognitive tasks. In mixed effects models, atomoxetine, compared with placebo, was found to be associated with a reduction in abstinence-induced subjective withdrawal symptoms. Atomoxetine was also associated with significant reductions in self-reported smoking urges amongst smokers who scored high on a baseline measure of smoking for stimulation. However, atomoxetine had no effect on any of the cognitive tasks employed in the study. Thus, atomoxetine may reduce cravings to smoke among smokers who use nicotine to increase arousal.     

Quality of life assessment in adult patients with attention-deficit/hyperactivity disorder treated with atomoxetine

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has its onset during childhood and is estimated to affect 3% to 7% of school-aged children. Unfortunately, the disorder frequently persists into adult life. The burden of this disorder is considerable and is often characterized by academic (or occupational) impairment and dysfunction within the family and society. Despite the existence of research demonstrating the effects of ADHD on certain aspects of life, the clinical trials of treatments for this disorder have focused primarily on efficacy and safety. METHODS: Atomoxetine was approved in the United States in November 2002 for the treatment of ADHD in children, adolescents, and adults. The present study uses data from a clinical trial of atomoxetine in adult patients with ADHD that incorporated a measure of health-related quality of life (the Medical Outcomes Study 36-item short-form health survey [SF-36]) as part of the overall assessment of the success of this relatively new treatment. The primary outcome measure for ADHD symptoms was the Conners Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS) ADHD total symptom score. RESULTS: In agreement with previous studies, adult patients with ADHD treated with atomoxetine at typical doses showed significant amelioration of ADHD symptoms, as measured on the CAARS. At baseline, the measures of overall mental health (one aspect of quality of life) of adult patients with ADHD were below the average level, as measured on the SF-36. Treatment with atomoxetine significantly improved the measures of mental health and ameliorated the ADHD symptoms. In addition, the 2 measures were correlated. CONCLUSIONS: These data suggest that pharmacological intervention with atomoxetine not only ameliorates ADHD symptoms in adult patients but also improves their perceived quality of life.     

Atomoxetine pharmacokinetics in healthy Chinese subjects and effect of the CYP2D6*10 allele

AIMS: To characterize atomoxetine pharmacokinetics, explore the effect of the homozygous CYP2D6*10 genotype on atomoxetine pharmacokinetics and evaluate the tolerability of atomoxetine, in healthy Chinese subjects. METHODS: Twenty-four subjects, all CYP2D6 extensive metabolizers (EM), were randomized to receive atomoxetine (40 mg qd for 3 days, then 80 mg qd for 7 days) or matching placebo (2 : 1 ratio) in a double-blind fashion. Atomoxetine serum concentrations were measured following single (40 mg) and multiple (80 mg) doses. Adverse events, clinical safety laboratory data and vital signs were assessed during the study. RESULTS: Atomoxetine was rapidly absorbed with median time to maximum serum concentrations of approximately 1.5 h after single and multiple doses. Atomoxetine concentrations appeared to decrease monoexponentially with a mean apparent terminal half-life (t(1/2)) of approximately 4 h. The apparent clearance, apparent volume of distribution and t(1/2) following single and multiple doses were similar, suggesting linear pharmacokinetics with respect to time. Homozygous CYP2D6*10 subjects had 50% lower clearances compared with other EM subjects, resulting in twofold higher mean exposures. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. CONCLUSIONS: The pharmacokinetics of atomoxetine in healthy Chinese subjects appears comparable to other ethnic populations. Multiple dosing of 80 mg qd atomoxetine was well tolerated in this study.     

Effect of comorbid symptoms of oppositional defiant disorder on responses to atomoxetine in children with ADHD: a meta-analysis of controlled clinical trial data

Rationale Up to 60% of children with attention-deficit/hyperactivity disorder (ADHD) suffer from comorbid affective or behavioral impairments, the most common condition being oppositional defiant disorder (ODD), which occurs in 40–60% of children with ADHD.Objectives This post hoc meta-analysis was performed to determine the effect of the presence of comorbid ODD symptoms on clinical outcomes among pediatric and adolescent subjects being treated for ADHD.Methods Acute-phase data were analyzed from three randomized, double-blind, placebo-controlled studies in outpatients aged 6–16 and meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for ADHD. Subjects received placebo or atomoxetine (max 1.8 mg/kg/day, daily) for 6–8 weeks. Patients were diagnosed with comorbid ODD on structured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-aged Children—Present and Lifetime Versions).Results Of the 512 subjects studied, 158 were diagnosed with comorbid ODD. Relative to placebo, atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects irrespective of the comorbidity with ODD. ADHD subjects also showed significant improvements from baseline on most of the psychosocial measures of the child health questionnaire irrespective of the comorbidity with ODD. Reduction in ODD symptoms was highly related to the magnitude of ADHD response.Conclusions Atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects to similar extents, indicating that the presence of comorbid symptoms of oppositionality does not affect clinical outcomes of treatment of ADHD with atomoxetine.     

A multi-centre,randomised, open-label study of atomoxetine compared with standard current therapy in UK children and adolescents with attention-deficit/hyperactivity disorder (ADHD)*

ABSTRACT

Objective: To assess the broader efficacy (i.e., improve­ments in quality of life/functional outcomes) of atomoxetine compared with standard current therapy (SCT) in UK paediatric patients with ADHD and to explore clinician/parent/child perceptions of ADHD.

Research design and methods: A total of 201 patients with ADHD were randomised into this multi-centre, open-label study to receive atomoxetine (n = 104) or SCT (n = 97) for 10 weeks. Broader efficacy was assessed using the parent-rated Child Health and Illness Profile-Child Edition (CHIP?CE) total (global) t-score. Secondary outcome measures included the five CHIP?CE domains; parent-rated Family Burden of Illness Module (FBIM); investigator-rated ADHD?Rating Scale; investigator-rated Clinical Global Impression (CGI)-Severity/Improvement scales; and child-rated Harter Self-Perception Profile (HSPP).

Results: Quality of life of children/adolescents with ADHD was extremely compromised at baseline (CHIP?CE total t-scores: atomoxetine, 23.2 ± 12.2; SCT, 23.9 ± 11.0), and improved during the 10-week study for both groups; the CHIP?CE score was statistically significantly higher for patients treated with atomoxetine (38.4 ± 1.3) compared with SCT (30.8 ± 1.3) at week 10 (?p < 0.001). ADHD?RS, CGI-Severity, and CGI-Improvement scores were significantly different between the groups in favour of atomoxetine (?p < 0.001). There was a statistically significant difference between the groups in the HSPP Social Acceptance domain in favour of atomoxetine, but not in the five other HSPP domains or FBIM total score. Atomoxetine was well-tolerated.

Conclusions: Results from this open-label trial show that atomoxetine is superior to SCT in addressing broader efficacy and functional outcomes in UK children/adoles­cents with ADHD. This study contributes to the under­standing of broader efficacy in children with ADHD, and is timely in light of recent NICE guidance.