Efficacy of atomoxetine in the treatment of attention-deficit hyperactivity disorder in patients with common comorbidities in children, adolescents and adults: a review.

Attention-deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed mental health disorders and is associated with higher incidence of comorbid oppositional or conduct, mood, anxiety, pervasive developmental, and substance-use disorders. Comorbid mental health conditions may alter the presence of symptoms and treatment of ADHD. Atomoxetine (ATX), a nonstimulant medication for the treatment of ADHD, may be prescribed for individuals with ADHD and comorbid conditions despite some risk for certain undesirable side effects and lower effectiveness for the treatment of ADHD than stimulants. In this paper, we review studies utilizing randomized, placebo-controlled trials (RCTs) as well as within-subject designs to determine the effectiveness of ATX in the treatment of children and adults with ADHD and comorbid conditions. The current review uses an expanded methodology beyond systematic review of randomized controlled trials in order to improve generalizability of results to real-world practice. A total of 24 articles published from 2007 to 2015 were reviewed, including 14 RCTs: n = 1348 ATX, and n = 832 placebo. The majority of studies show that ATX is effective in the treatment of ADHD symptoms for individuals with ADHD and comorbid disorders. Cohen's d effect sizes (ES) for improvement in ADHD symptoms and behaviors range from 0.47 to 2.21. The effectiveness of ATX to improve symptoms specific to comorbidity varied by type but appeared to be most effective for diminishing the presence of symptoms for those with comorbid anxiety, ES range of 0.40 to 1.51, and oppositional defiant disorder, ES range of 0.52 to 1.10. There are mixed or limited results for individuals with ADHD and comorbid substance-use disorders, autism spectrum disorders, dyslexia or reading disorder, depression, bipolar disorder, and Tourette syndrome. Results from this review suggest that ATX is effective in the treatment of some youth and adults with ADHD and comorbid disorders, and may be a treatment option in these patients.

Pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: clinical strategies.

Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder of childhood that can result in significant functional impairment, and if not adequately treated can lead to impaired quality of life. Pharmacotherapy is considered the first-line treatment for ADHD in children and adolescents. We review both recent literature and seminal studies regarding the pharmacological treatment of ADHD in children and adolescents. There is ample evidence for the efficacy and safety of both stimulants and non-stimulants in the treatment of ADHD. We review important aspects of evaluation and assessment and discuss first-line pharmacological treatments and as well as when to consider using alternative pharmacological agents. Treatment approaches to manage frequently seen comorbid disorders with ADHD are also covered.

Pharmacologic intervention for attention-deficit hyperactivity disorder in preschoolers : is it justified?

Pharmacologic intervention for attention-deficit hyperactivity disorder (ADHD) in preschool children is a controversial issue. Non-pharmacologic interventions (psychosocial and restricted dietary interventions) have been shown to benefit oppositional, non-compliant, aggressive and disruptive, as well as hyperactive and inattentive behaviors in preschoolers with ADHD and other disruptive behavior disorders. However, not all families have access to non-pharmacologic interventions or prefer them. The Preschool ADHD Treatment Study recently provided evidence of benefit with immediate-release methylphenidate; however, effect sizes were small to moderate and preschoolers had a high rate of adverse effects and a unique adverse effect profile. Furthermore, no information is available about long-term safety and effects of psychopharmacologic agents on the rapidly developing brains of preschoolers. Based on current evidence and guidelines, a careful trial with psychopharmacologic agents is indicated to treat ADHD in preschoolers if there is no improvement with behavior therapy and the preschoolers continue to exhibit significantly impaired hyperactive and inattentive symptoms. Preschoolers should be monitored closely for adverse effects and tried off medications after 6 months to assess the need for ongoing psychopharmacologic intervention. Further research is needed to identify predictors and moderators of response to guide individualized/optimal treatment options for ADHD in preschoolers.

Randomized, placebo-controlled, crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders.

OBJECTIVE: The aim of this study was to investigate the short-term efficacy and safety of methylphenidate (MPH) to treat attention-deficit/hyperactivity disorder (ADHD) symptoms in an understudied population of preschoolers with pervasive developmental disorder (PDD) or intellectual disability (ID). METHODS: Fourteen preschoolers with developmental disorders (DD, n = 14; PDD, n = 12; ID, n = 2) underwent MPH titration in a single-blind manner followed by a 4-week double-blind crossover phase. Each child was administered placebo for 2 weeks and "optimal dose" for 2 weeks. The primary outcome measure was the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) ADHD subscale of the Conners' Parent Rating Scale-Revised (CPRS-R-DSM-IV-ADHD). RESULTS: MPH improved parent-rated ADHD symptoms of the preschoolers; 50% were rated as responders. The CPRS-R-DSM-IV-ADHD subscale was significant for the PDD subgroup (p = 0.005, Cohen d = 0.97) and marginally significant for the entire DD sample (p = 0.08, Cohen d = 0.50). Half of the preschoolers experienced side effects with MPH, including reports of increased stereotypic behavior, upset stomach, sleep-related difficulties, and emotional lability. One child discontinued during titration due to side effects. CONCLUSION: The predominant direction of response in these preschoolers with both ADHD and PDD/ID favored MPH, even though the response was more subtle and variable than in older and typically developing children. Due to high rates of adverse effects, preschoolers should be monitored closely.

Prospective, naturalistic, pilot study of open-label atomoxetine treatment in preschool children with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of this study was to report preliminary data regarding effectiveness and tolerability of atomoxetine in 3- to 5-year-old preschool children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Nine boys and 3 girls (mean age = 5.0 +/- 0.72 years) diagnosed with ADHD were treated with atomoxetine in an open-label pilot study. Atomoxetine was gradually titrated to a maximum dose of 1.8 mg/kg per day. RESULTS: There was a significant effect of time from baseline to end point on the parent-rated hyperactivity/impulsivity Swanson Nolan and Pelham (SNAP-IV-HI) subscale ratings (F[9, 11] = 6.32, p < 0.0001). The mean difference between the baseline and end-point parent SNAP-IV-HI scores was 10.2 +/- 7.3 (p = 0.0005). The rate of positive response (defined as at least a 30% reduction in the end-point parent SNAP-IV-HI scores and a Clinical Global Impressions-Improvement [CGI-I] rating of Much Improved or Very Much Improved) was 75%. The Children's Global Assessment Scale scores improved significantly over time [F(9, 11) = 6.24 p < 0.001]. The mean end-point daily dose of atomoxetine was 1.59 +/- 0.3 mg/kg. A high proportion (66.7%) of the preschoolers experienced side effects with atomoxetine. Side effects of defiance, tantrums, aggression, and irritability were most disconcerting to parents, and gastrointestinal complaints were the most commonly reported adverse effects. One child was terminated from the study due to "chest ache." There were no changes in weight, height, or cardiovascular measures. CONCLUSION: This open-label pilot study provides preliminary evidence of effectiveness and tolerability of atomoxetine for treating ADHD in preschool children, although double-blind, randomized, placebo-controlled studies are needed to confirm this.