Efficacy, safety and variability in pharmacotherapy for adults with attention deficit hyperactivity disorder: a meta-analysis and meta-regression in over 9000 patients

Cunill, Ruth; Castells, Xavier; Tobías, Aurelio; Capellà, Dolors

doi:10.1007/s00213-015-4099-3

Cited by 74 publications

(52 citation statements)

References 47 publications

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“…Pharmacological treatments overall, compared with placebo in adults with ADHD, seem to be slightly less well accepted (OR 1.18, 95% CI 1.02 to 1.36) and less well tolerated (OR 2.29, 95% CI 1.97 to 2.66) 14. Mean adherence rate for all pharmacological treatments in adult ADHD in retrospective naturalistic studies ranged from 52% to 87% 30.…”

Section: Resultsmentioning

confidence: 97%

“…Overall, pharmacological treatments have been found to be efficacious, at least in the short term, for reducing ADHD symptoms in adults, when compared with placebo (standardised mean difference (SMD) 0.45, 95% CI 0.37 to 0.52) 14. Psychostimulants are the most commonly researched medications for ADHD in children and adolescents, and also in adults.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological and non-pharmacological treatment of adults with ADHD: a meta-review

Crescenzo

Cortese

Adamo

et al. 2016

Evid Based Mental Health

111

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Attention-deficit/hyperactivity disorder (ADHD) is characterised by a persistent and impairing pattern of inattention and/or hyperactivity/impulsivity and it is one of the most common neuropsychiatric conditions. Evidence about interventions of adults with ADHD is growing rapidly and clinicians need a reliable summary of all the best available information in order to better inform their daily practice. We searched MEDLINE, PubMed, PsycINFO and Cochrane databases until 31 May 2016 for systematic reviews about pharmacological and non-pharmacological treatments in adults with ADHD and carried out a meta-review to address clinically relevant questions. We identified a total of 40 papers. Psychostimulants-such as methylphenidate, dexamphetamine, mixed amphetamine salts and lisdexamfetamine-and non-psychostimulants-such as atomoxetine-were the most studied agents. Overall, pharmacological treatments were significantly more efficacious than placebo (standardised mean difference (SMD) 0.45, 95% CI 0.37 to 0.52), albeit less well accepted (OR 1.18, 95% CI 1.02 to 1.36) and tolerated (OR 2.29, 95% CI 1.97 to 2.66). The effects of pharmacological treatment for individuals with co-occurring ADHD and substance use disorder are still uncertain. The evidence for the efficacy and effectiveness of non-pharmacological treatments of ADHD in adults, as well as the combination of pharmacological and non-pharmacological strategies, is only preliminary. In conclusion, while available evidence addressed mainly the efficacy and tolerability of psychostimulants and nonpsychostimulants for ADHD core symptoms in the short term, we still need further empirical support for the non-pharmacological and multimodal treatments. A comprehensive evidence-informed hierarchy of ADHD drugs based on their efficacy and tolerability is not yet available but it should be the next research priority in the field. INTRODUCTIONAttention-deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric conditions, 1 with a pooled worldwide prevalence estimated at about 5% in school-aged children and persistence of impairing symptoms in adulthood in up to 65% of cases.1 The pooled estimated prevalence of ADHD (as categorical diagnosis) in adults is around 2.5%.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Pharmacological and non-pharmacological treatment of adults with ADHD: a meta-review

Crescenzo

Cortese

Adamo

et al. 2016

Evid Based Mental Health

111

View full text Add to dashboard Cite

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“…The stronger pre‐FU than pre‐post effects may reflect lasting effects of brain self‐regulation training on brain plasticity that may build up over time. The concept of a finite training providing longer‐term persistent changes is particularly attractive given that one of the key limitations of stimulant medication is that effects only last for 24 hours after administration and even with chronic administration longer‐term beneficial clinical effects beyond several years have not been demonstrated [Cunill et al, 2016; Molina et al, 2009], possibly due to evidence for brain dopaminergic adaptation to the medication [Fusar‐Poli et al, 2012; Wang et al, 2013]. …”

Section: Discussionmentioning

confidence: 99%

“…Psychostimulants improve ADHD symptoms in about 70% of patients with effect sizes of 0.6 for parent and up to 0.8 for teacher ratings [Stevens et al, 2013]. Although superior to behavioral treatments in the shortterm, longer-term efficacy has not been demonstrated [Cunill et al, 2016;Molina et al, 2009], which may be related to evidence from positron emission tomography studies for dopaminergic brain adaptation to psychostimulant medication [Fusar-Poli et al, 2012;Wang et al, 2013]. Moreover, because of their potential for abuse and diversion, adverse effects, and unknown longer-term brain effects, non-pharmacological treatments are preferred, but have limited efficacy [Sonuga- Barke et al, 2013].…”

Section: Introductionmentioning

confidence: 99%

Real‐time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder

Alegría

Wulff

Brinson

et al. 2017

Human Brain Mapping

117

103

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Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self‐control, underpinned by inferior fronto‐striatal deficits. Real‐time functional magnetic resonance neurofeedback (rtfMRI‐NF) allows participants to gain self‐control over dysregulated brain regions. Despite evidence for beneficial effects of electrophysiological‐NF on ADHD symptoms, no study has applied the spatially superior rtfMRI‐NF neurotherapy to ADHD. A randomized controlled trial tested the efficacy of rtfMRI‐NF of right inferior prefrontal cortex (rIFG), a key region that is compromised in ADHD and upregulated with psychostimulants, on improvement of ADHD symptoms, cognition, and inhibitory fMRI activation. To control for region‐specificity, an active control group received rtfMRI‐NF of the left parahippocampal gyrus (lPHG). Thirty‐one ADHD boys were randomly allocated and had to learn to upregulate their target brain region in an average of 11 rtfMRI‐NF runs over 2 weeks. Feedback was provided through a video‐clip of a rocket that had to be moved up into space. A transfer session without feedback tested learning retention as a proximal measure of transfer to everyday life. Both NF groups showed significant linear activation increases with increasing number of runs in their respective target regions and significant reduction in ADHD symptoms after neurotherapy and at 11‐month follow‐up. Only the group targeting rIFG, however, showed a transfer effect, which correlated with ADHD symptom reductions, improved at trend level in sustained attention, and showed increased IFG activation during an inhibitory fMRI task. This proof‐of‐concept study demonstrates for the first time feasibility, safety, and shorter‐ and longer‐term efficacy of rtfMRI‐NF of rIFG in adolescents with ADHD. Hum Brain Mapp 38:3190–3209, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

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“…Furthermore, the between-study variability on efficacy and safety was large, with some randomized placebo-controlled clinical trials (RPCCTs) showing substantial symptom improvement compared with placebo, while others found no evidence of efficacy on relevant clinical outcomes (Corey-Bloom et al, 1998; Rogers et al, 1998; Wilcock et al, 2000; AD2000 Collaborative Group, 2004). With the aim of determining the reasons behind such variability, we grouped the factors explaining between-study variability into 3 categories: (1) factors related to the design of the study, such as the existence of a lead-in phase (Cunill et al, 2016) or the number of study sites (Undurraga et al, 2012), (2) intervention-related factors such as dose (Castells et al, 2011) and treatment duration (Pérez-Mañá et al, 2013), and (3) patient-related factors such as age (Stone et al, 2009) and the severity of the disease (Schwartz et al, 2014). To achieve these goals, a systematic review with meta-analysis and meta-regression was carried out.…”

Section: Introductionmentioning

confidence: 99%

Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer’s Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients

Blanco-Silvente

Castells

Sáez

et al. 2017

International Journal of Neuropsychopharmacology

118

115

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Background:We investigated the effect of cholinesterase inhibitors on all-cause discontinuation, efficacy and safety, and the effects of study design-, intervention-, and patient-related covariates on the risk-benefit of cholinesterase inhibitors for Alzheimer’s disease.Methods:A systematic review and meta-analysis of randomized placebo-controlled clinical trials comparing cholinesterase inhibitors and placebo was performed. The effect of covariates on study outcomes was analysed by means of meta-regression using a Bayesian framework.Results:Forty-three randomized placebo-controlled clinical trials involving 16106 patients were included. All-cause discontinuation was higher with cholinesterase inhibitors (OR = 1.66), as was discontinuation due to adverse events (OR=1.75). Cholinesterase inhibitors improved cognitive function (standardized mean difference = 0.38), global symptomatology (standardized mean difference=0.28) and functional capacity (standardized mean difference=0.16) but not neuropsychiatric symptoms. Rivastigmine was associated with a poorer outcome on all-cause discontinuation (Diff OR = 1.66) and donepezil with a higher efficacy on global change (Diff standardized mean difference = 0.41). The proportion of patients with serious adverse events decreased with age (Diff OR = -0.09). Mortality was lower with cholinesterase inhibitors than with placebo (OR = 0.65).Conclusion:While cholinesterase inhibitors show a poor risk-benefit relationship as indicated by mild symptom improvement and a higher than placebo all-cause discontinuation, a reduction of mortality was suggested. Intervention- and patient-related factors modify the effect of cholinesterase inhibitors in patients with Alzheimer’s disease.

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Efficacy, safety and variability in pharmacotherapy for adults with attention deficit hyperactivity disorder: a meta-analysis and meta-regression in over 9000 patients

Cited by 74 publications

References 47 publications

Pharmacological and non-pharmacological treatment of adults with ADHD: a meta-review

Pharmacological and non-pharmacological treatment of adults with ADHD: a meta-review

Real‐time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder

Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer’s Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients

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