Efficacy, Acceptability, and Tolerability of Lisdexamfetamine, Mixed Amphetamine Salts, Methylphenidate, and Modafinil in the Treatment of Attention-Deficit Hyperactivity Disorder in Adults: A Systematic Review and Meta-analysis

2018 ◽  
Vol 53 (2) ◽  
pp. 121-133 ◽  
Author(s):  
Matej Stuhec ◽  
Petar Lukić ◽  
Igor Locatelli
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Clinical Trials ◽  
Effect Size ◽  
Attention Deficit ◽  
Data Extraction ◽  
Meta Analysis ◽  
Sole Source ◽  
Adhd Symptoms ◽  
Double Blind ◽  
Hyperactivity Disorder

Objective: Psychostimulants are the first-line treatment in adults with attention-deficit hyperactivity disorder (ADHD). This meta-analysis aimed to evaluate the efficacy, acceptability, and tolerability of lisdexamfetamine (LDX), mixed amphetamine salts (MASs), modafinil (MDF), and methylphenidate (MPH) in comparison with placebo. Data Sources: We systematically searched PubMed/MEDLINE and Clinicaltrials.gov in May 2016, along with CENTRAL and EU Clinical Trials Register in February 2016, for the randomized, double-blind, placebo-controlled, parallel-group clinical trials conducted on adults diagnosed with ADHD. Study Selection and Data Extraction: Substantial comorbidity, substance abuse or dependence, and nonpharmacological interventions represented grounds for exclusion. Published reports were the sole source for data extraction. Improvement in ADHD symptoms was the primary outcome. Random-effects model meta-analysis was applied to calculate the standardized mean difference (SMD) with 95% CIs. Data Synthesis: The search retrieved 701 records, of which 20 studies were eligible for analysis. High effect size (expressed as SMD) in reducing ADHD symptoms was observed for LDX (−0.89; 95% CI = −1.09, −0.70), whereas MASs (−0.64; 95% CI = −0.83, −0.45) and MPH (−0.50; 95% CI = −0.58, −0.41) reduced symptoms moderately compared with placebo. No efficacy was shown for MDF (0.08; 95% CI; −0.18, 0.34). Relevance to Patient Care and Clinical Practice: In this meta-analysis, the efficacy, tolerability, and acceptability of psychostimulants were compared with that for placebo. Five of the included trials have not been evaluated in any of the previously published meta-analyses. Conclusions: The results suggest that LDX has the largest effect size and has a promising potential for treating adults with ADHD.

Atomoxetine versus Methylphenidate in Paediatric Outpatients with Attention Deficit Hyperactivity Disorder: A Randomized, Double-Blind Comparison Trial

2007 ◽  
Vol 41 (3) ◽  
pp. 222-230 ◽  
Author(s):  
Yufeng Wang ◽  
Yi Zheng ◽  
Yasong Du ◽  
Dong H. Song ◽  
Yee-Jin Shin ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Rating Scale ◽  
Response Rates ◽  
Double Blind Study ◽  
Adhd Symptoms ◽  
Double Blind ◽  
Hyperactivity Disorder ◽  
End Point ◽  
Blind Comparison

Objective: To (i) test whether atomoxetine is non-inferior to methylphenidate in treating symptoms of attention deficit hyperactivity disorder (ADHD) in paediatric patients; and (ii) determine the tolerability of the two drugs. Method: This double-blind study was conducted in 6- to 16-year-old outpatients with ADHD (DSM-IV) in China, Korea and Mexico (January–October 2004). Patients were randomly assigned to once-daily atomoxetine (0.8–1.8 mg kg−1 day−1; n = 164) or twice-daily methylphenidate (0.2–0.6 mg kg−1 day−1; n = 166) for ∼8 weeks. Primary efficacy assessment was the comparison of response rates (≥40% reduction from baseline to end point in total score) on the Attention Deficit Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and -Scored. Tolerability measures included, but were not limited to, the assessment of treatment-emergent adverse events (TEAEs) and weight. Results: Atomoxetine was non-inferior to methylphenidate in improving ADHD symptoms based on response rates (atomoxetine, 77.4%; methylphenidate, 81.5%; one-sided 95% lower confidence limit = −11.7%, p = 0.404). Treatment-emergent adverse effects experienced significantly more frequently in the atomoxetine group, compared with the methylphenidate group, included anorexia (37.2% vs. 25.3%; p = 0.024), nausea (20.1% vs. 10.2%; p = 0.014), somnolence (26.2% vs. 3.6%; p <0.001), dizziness (15.2% vs. 7.2%; p = 0.024) and vomiting (11.6% vs. 3.6%; p = 0.007), most of which were of mild or moderate severity. Atomoxetine-treated patients experienced a small but significantly greater mean weight loss from baseline to end point than methylphenidate-treated patients (−1.2 kg vs. −0.4 kg; p <0.001). Conclusions: This study suggests that atomoxetine is non-inferior to methylphenidate in the improvement of ADHD symptoms in paediatric outpatients. Although both of the drugs were well tolerated, atomoxetine was associated with a higher incidence of TEAEs than methylphenidate.

scholarly journals Effects of stimulants and atomoxetine on emotional lability in adults: A systematic review and meta-analysis

2017 ◽  
Vol 44 ◽  
pp. 198-207 ◽  
Author(s):  
T.R. Moukhtarian ◽  
R.E. Cooper ◽  
E. Vassos ◽  
P. Moran ◽  
P. Asherson
Keyword(s):  
Systematic Review ◽  
Effect Size ◽  
Meta Analysis ◽  
Emotional Lability ◽  
Adhd Symptoms ◽  
Double Blind ◽  
Hyperactivity Disorder ◽  
Ovid Medline ◽  
Weighted Effect ◽  
The Difference

AbstractBackground:Emotional lability (EL) is an associated feature of attention-deficit/hyperactivity disorder (ADHD) in adults, contributing to functional impairment. Yet the effect of pharmacological treatments for ADHD on EL symptoms is unknown. We conducted a systematic review and meta-analysis to examine the effects of stimulants and atomoxetine on symptoms of EL and compare these with the effects on core ADHD symptoms.Methods:A systematic search was conducted on the databases Embase, PsychInfo, and Ovid Medline®and the clinicaltrials.gov website. We included randomised, double-blind, placebo-controlled trials of stimulants and atomoxetine in adults aged 18–60 years, with any mental health diagnosis characterised by emotional or mood instability, with at least one outcome measure of EL. All identified trials were on adults with ADHD. A random-effects meta-analysis with standardised mean difference and 95% confidence intervals was used to investigate the effect size on EL and compare this to the effect on core ADHD symptoms.Results:Of the 3,864 publications identified, nine trials met the inclusion criteria for the meta-analysis. Stimulants and atomoxetine led to large mean weighted effect-sizes for on ADHD symptoms (n= 9, SMD = −0.8, 95% CI:−1.07 to −0.53). EL outcomes showed more moderate but definite effects (n= 9, SMD = −0.41, 95% CI:−0.57 to −0.25).Conclusions:In this meta-analysis, stimulants and atomoxetine were moderately effective for EL symptoms, while effect size on core ADHD symptoms was twice as large. Methodological issues may partially explain the difference in effect size. Reduced average effect size could also reflect heterogeneity of EL with ADHD pharmacotherapy responsive and non-responsive sub-types. Our findings indicate that EL may be less responsive than ADHD symptoms overall, perhaps indicating the need for adjunctive psychotherapy in some cases. To clarify these questions, our findings need replication in studies selecting subjects for high EL and targeting EL as the primary outcome.

scholarly journals Behavioural effects of methylphenidate in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis protocol

2018 ◽  
Vol 2 (1) ◽  
pp. e000001 ◽  
Author(s):  
Douglas Teixeira Leffa ◽  
Alana Castro Panzenhagen ◽  
Diego Luiz Rovaris ◽  
Claiton Henrique Dotto Bau ◽  
Luis Augusto Rohde ◽  
...  
Keyword(s):  
Systematic Review ◽  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Spontaneously Hypertensive Rat ◽  
Data Extraction ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Spontaneously Hypertensive ◽  
Hyperactivity Disorder ◽  
Behavioural Effects

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is a prevalent condition related to several negative outcomes, and its pathophysiology is still poorly understood. The spontaneously hypertensive rats (SHRs) are the most commonly used animal model of ADHD. How ever, its validity, and especially its predictive validity, has been questioned. Therefore, the current protocol discloses the background, aims and methods of a systematic review and meta-analysis of studies reporting the behavioural effects of methylphenidate (MPH), the most commonly prescribed treatment for ADHD, in the SHR.Search strategyStudies will be identified through a literature search using three different electronic databases: Medline, Embase and Web of Science. There will be no language restrictions. All s tudies that administered MPH to SHR and evaluated locomotion, attention, impulsivity or memory will be included.Screening and annotationStudies will be prescreened based on title and abstract, and a full-text review will be performed if necessary. Screening will be performed by two authors, and any disagreement will be discussed with a third author.Data management and reportingData extraction will be performed by two independent authors according to a standardised form. Studies will be grouped according to the behavioural outcomes reported, and a meta-analysis will be performed for each group. The influence of predefined covariates on the effects of MPH will be evaluated using meta-regression and sensitivity analyses. Data will be reported following PRISMA guidelines.

scholarly journals Shared Care Models in the Treatment of Pediatric Attention-Deficit/Hyperactivity Disorder (ADHD)

2018 ◽  
Vol 5 ◽  
pp. 233339281876288 ◽  
Author(s):  
Meshal A. Sultan ◽  
Carlos S. Pastrana ◽  
Kathleen A. Pajer
Keyword(s):  
Mental Health ◽  
Systematic Review ◽  
Attention Deficit Hyperactivity Disorder ◽  
Effect Size ◽  
Attention Deficit ◽  
Collaborative Care ◽  
Meta Analysis ◽  
Care Providers ◽  
Hyperactivity Disorder ◽  
Care Models

Objectives: The aim of this review is to evaluate the effectiveness of shared/collaborative care between mental health-care providers and primary care providers (PCPs) on the outcomes of children and adolescents with attention-deficit/hyperactivity disorder (ADHD). This evaluation will be very helpful in the allocation of ADHD resources for models with the strongest evidence. Methods: Using the Preferred Reporting Items for Systematic Review and Meta-analysis statement, we searched for randomized controlled trials, cohort, case–control, and cross-sectional studies on shared/collaborative care models in the treatment of ADHD. Using MEDLINE, PsycINFO, and CENTRAL databases from January 2000 to December 2016, we retrieved English language articles for review. The validation search identified 75 records. Five studies met the inclusion criteria and were analyzed in this systematic review. There were insufficient data for a meta-analysis. The included studies involved 655 children and adolescents who had a diagnosis of ADHD. The Cochrane Collaboration’s tool for assessing risk of bias was used to estimate bias. Results: Overall, the results show that the effects of shared/collaborative care models were small to moderate (effect size: 0.1-0.6, P = .04) on symptom rating scales, but all positively affected functional outcomes (effect size: 0.3-0.7, P = .04-.01). The data indicated that the models were associated with increased PCPs’ comfort levels, but the evidence for increased capacity for diagnosing and managing ADHD was weaker. Conclusions: This review concludes that the current studies do not show strong evidence for the outcome of collaboration between PCPs and mental health professionals on ADHD management. Future research should consider providing education to PCPs on management guidelines prior to conducting the trials, and more innovation is needed to discover methods of collaboration that affect the direct care of ADHD.

scholarly journals Effects of methylphenidate on executive functioning in attention-deficit/hyperactivity disorder across the lifespan: a meta-regression analysis

2016 ◽  
Vol 46 (9) ◽  
pp. 1791-1807 ◽  
Author(s):  
H. G. H. Tamminga ◽  
L. Reneman ◽  
H. M. Huizenga ◽  
H. M. Geurts
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Working Memory ◽  
Sustained Attention ◽  
Response Inhibition ◽  
Attention Deficit ◽  
Animal Studies ◽  
Meta Analysis ◽  
Double Blind ◽  
Hyperactivity Disorder ◽  
Age Related

Attention-deficit/hyperactivity disorder (ADHD) in childhood and adulthood is often treated with the psychostimulant methylphenidate (MPH). However, it is unknown whether cognitive effects of MPH depend on age in individuals with ADHD, while animal studies have suggested age-related effects. In this meta-analysis, we first determined the effects of MPH on response inhibition, working memory and sustained attention, but our main goal was to examine whether these effects are moderated by age. A systematic literature search using PubMed, PsycINFO, Web of Science and MEDLINE for double-blind, placebo-controlled studies with MPH resulted in 25 studies on response inhibition (n = 775), 13 studies on working memory (n = 559) and 29 studies on sustained attention (n = 956) (mean age range 4.8–50.1 years). The effects of MPH on response inhibition [effect size (ES) = 0.40, p < 0.0001, 95% confidence interval (CI) 0.22–0.58], working memory (ES = 0.24, p = 0.053, 95% CI 0.00–0.48) and sustained attention (ES = 0.42, p < 0.0001, 95% CI 26–0.59) were small to moderate. No linear or quadratic age-dependencies were observed, indicating that effects of MPH on executive functions are independent of age in children and adults with ADHD. However, adolescent studies are lacking and needed to conclude a lack of an age-dependency across the lifespan.

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