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The Lancet. Psychiatry Sep 2018The benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.
BACKGROUND
The benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are preferred across different age groups. We aimed to estimate the comparative efficacy and tolerability of oral medications for ADHD in children, adolescents, and adults.
METHODS
We did a literature search for published and unpublished double-blind randomised controlled trials comparing amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo. We systematically contacted study authors and drug manufacturers for additional information. Primary outcomes were efficacy (change in severity of ADHD core symptoms based on teachers' and clinicians' ratings) and tolerability (proportion of patients who dropped out of studies because of side-effects) at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. We estimated summary odds ratios (ORs) and standardised mean differences (SMDs) using pairwise and network meta-analysis with random effects. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool and confidence of estimates with the Grading of Recommendations Assessment, Development, and Evaluation approach for network meta-analyses. This study is registered with PROSPERO, number CRD42014008976.
FINDINGS
133 double-blind randomised controlled trials (81 in children and adolescents, 51 in adults, and one in both) were included. The analysis of efficacy closest to 12 weeks was based on 10 068 children and adolescents and 8131 adults; the analysis of tolerability was based on 11 018 children and adolescents and 5362 adults. The confidence of estimates varied from high or moderate (for some comparisons) to low or very low (for most indirect comparisons). For ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (eg, SMD -1·02, 95% CI -1·19 to -0·85 for amphetamines, -0·78, -0·93 to -0·62 for methylphenidate, -0·56, -0·66 to -0·45 for atomoxetine). By contrast, for available comparisons based on teachers' ratings, only methylphenidate (SMD -0·82, 95% CI -1·16 to -0·48) and modafinil (-0·76, -1·15 to -0·37) were more efficacious than placebo. In adults (clinicians' ratings), amphetamines (SMD -0·79, 95% CI -0·99 to -0·58), methylphenidate (-0·49, -0·64 to -0·35), bupropion (-0·46, -0·85 to -0·07), and atomoxetine (-0·45, -0·58 to -0·32), but not modafinil (0·16, -0·28 to 0·59), were better than placebo. With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36-3·89) and adults (3·26, 1·54-6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20-5·81); and atomoxetine (2·33, 1·28-4·25), methylphenidate (2·39, 1·40-4·08), and modafinil (4·01, 1·42-11·33) were less well tolerated than placebo in adults only. In head-to-head comparisons, only differences in efficacy (clinicians' ratings) were found, favouring amphetamines over modafinil, atomoxetine, and methylphenidate in both children and adolescents (SMDs -0·46 to -0·24) and adults (-0·94 to -0·29). We did not find sufficient data for the 26-week and 52-week timepoints.
INTERPRETATION
Our findings represent the most comprehensive available evidence base to inform patients, families, clinicians, guideline developers, and policymakers on the choice of ADHD medications across age groups. Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD. New research should be funded urgently to assess long-term effects of these drugs.
FUNDING
Stichting Eunethydis (European Network for Hyperkinetic Disorders), and the UK National Institute for Health Research Oxford Health Biomedical Research Centre.
Topics: Adolescent; Adrenergic alpha-2 Receptor Agonists; Adult; Attention Deficit Disorder with Hyperactivity; Bupropion; Central Nervous System Stimulants; Child; Clonidine; Dose-Response Relationship, Drug; Humans; Methylphenidate; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 30097390
DOI: 10.1016/S2215-0366(18)30269-4 -
PloS One 2020Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD.
METHODS
We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework.
RESULTS
Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration.
CONCLUSIONS
Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs.
REGISTRATION
PROSPERO no. CRD 42015026049.
Topics: Adult; Amphetamine; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Bayes Theorem; Bupropion; Central Nervous System Stimulants; Dextroamphetamine; Drug-Related Side Effects and Adverse Reactions; Female; Guanfacine; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Modafinil; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 33085721
DOI: 10.1371/journal.pone.0240584 -
Neuroscience and Biobehavioral Reviews May 2021Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders worldwide, and in the majority of patients persists into... (Review)
Review
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders worldwide, and in the majority of patients persists into adulthood. However, it remains unclear how maternal ADHD could affect pregnancy and birth as well as early mother-(father)-child interaction. There are several studies investigating the effect of depressed or anxious parents on parent-child-interactions in early infancy, but data about the influence of parental ADHD is lacking although it is a common mental disorder in parents. Additionally, the prescription of stimulant and other ADHD medication for adult ADHD patients is rising due to improved diagnostic procedures and a greater awareness of this disorder in adulthood among psychiatrists and psychologists. However, this leads to increased numbers of treated ADHD women that wish to have children or experience unplanned pregnancies while taking stimulant medication. In our systematic review we aimed at analysing the current evidence for the association of maternal ADHD with pregnancy and birth outcomes, pregnancy risks and health behaviour in pregnancy, as well as the association of parental ADHD with early parent-child interaction and early child development in the first 3 years. Furthermore, we reviewed recent evidence on the risks of stimulant and non-stimulant treatment for ADHD in pregnancy and lactation.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Female; Humans; Methylphenidate; Parent-Child Relations; Parents; Postpartum Period; Pregnancy
PubMed: 33516734
DOI: 10.1016/j.neubiorev.2021.01.002 -
CNS Drugs Mar 2017Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine.
BACKGROUND
Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be associated with cardiovascular effects. It is important to identify whether mean group effects translate into clinically relevant increases for some individual patients, and/or increase the risk for serious cardiovascular adverse events such as stroke or sudden death.
OBJECTIVES
To evaluate potential cardiovascular effects of these treatments, we conducted a systematic review and meta-analysis of the effects of methylphenidate (MPH), amphetamines (AMP), and atomoxetine (ATX) on diastolic and systolic blood pressure (DBP, SBP) and heart rate (HR) in children and adolescents with ADHD.
METHODS
We conducted systematic searches in electronic databases (PsychINFO, EMBASE and Medline) to identify published trials which involved individuals who were (i) diagnosed with ADHD and were aged between 0-18 years; (ii) treated with MPH, AMP or ATX and (iii) had their DBP and SBP and/or HR measured at baseline (pre) and the endpoint (post) of the study treatment. Studies with an open-label design or a double-blind randomised control design of any duration were included. Statistical analysis involved calculating differences between pre- and post-treatment measurements for the various cardiovascular parameters divided by the pooled standard deviation. Further, we assessed the percentage of clinically relevant increased BP or HR, or documented arrhythmias.
RESULTS
Eighteen clinical trials met the inclusion criteria (10 for MPH, 5 for AMP, and 7 for ATX) with data from 5837 participants (80.7% boys) and average duration of 28.7 weeks (range 4-96 weeks). All three medications were associated with a small, but statistically significant pre-post increase of SBP (MPH: standard mean difference [SMD] 0.25, 95% confidence interval [CI] 0.08-0.42, p < 0.01; AMP: SMD 0.09, 95% CI 0.03-0.15, p < 0.01; ATX: SMD 0.16, 95% CI 0.04-0.27, p = 0.01). MPH did not have a pre-post effect on DBP and HR. AMP treatment was associated with a small but statistically significant pre-post increase of DBP (SMD 0.16, CI 0.03-0.29, p = 0.02), as was ATX treatment (SMD 0.22, CI 0.10-0.34, p < 0.01). AMP and ATX were associated with a small to medium statistically significant pre-post increase of HR (AMP: SMD 0.37, CI 0.13-0.60, p < 0.01; ATX: SMD 0.43, CI 0.26-0.60, p < 0.01). The head-to-head comparison of the three medications did not reveal significant differences. Sensitivity analyses revealed that AMP studies of <18 weeks reported higher effect sizes on DBP compared with longer duration studies (F(1) = 19.55, p = 0.05). Further, MPH studies published before 2007 reported higher effect sizes on SBP than studies after 2007 (F(1) = 5.346, p = 0.05). There was no effect of the following moderators: type of medication, doses, sample size, age, gender, type of ADHD, comorbidity or dropout rate. Participants on medication reported 737 (12.6%) other cardiovascular effects. Notably, 2% of patients discontinued their medication treatment due to any cardiovascular effect. However, in the majority of patients, the cardiovascular effects resolved spontaneously, medication doses were changed or the effects were not considered clinically relevant. There were no statistically significant differences between the medication treatments in terms of the severity of cardiovascular effects.
CONCLUSIONS
Statistically significant pre-post increases of SBP, DBP and HR were associated with AMP and ATX treatment in children and adolescents with ADHD, while MPH treatment had a statistically significant effect only on SBP in these patients. These increases may be clinically significant for a significant minority of individuals that experience larger increases. Since increased BP and HR in general are considered risk factors for cardiovascular morbidity and mortality during adult life, paediatric patients using ADHD medication should be monitored closely and regularly for HR and BP.
Topics: Adolescent; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Child; Child, Preschool; Clinical Trials as Topic; Heart Rate; Humans; Infant; Methylphenidate; Psychotropic Drugs
PubMed: 28236285
DOI: 10.1007/s40263-017-0410-7 -
Molecular Psychiatry Jul 2016The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies... (Meta-Analysis)
Meta-Analysis Review
The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug. Finally some peripheral biomarkers were identified in ADHD adult patients. We believe this work is the first systematic review and meta-analysis of candidate gene association studies, pharmacogenetic and biochemical (metabolomics) studies performed in adults with ADHD to identify potential genetic, predictive and peripheral markers linked specifically to ADHD in adults. After screening 5129 records, we selected 87 studies of which 61 were available for candidate gene association studies, 5 for pharmacogenetics and 21 for biochemical studies. Of these, 15 genetic, 2 pharmacogenetic and 6 biochemical studies were included in the meta-analyses. We obtained an association between adult ADHD and the gene BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), even after Bonferroni correction, with any heterogeneity in effect size and no publication bias. If we did not apply the Bonferroni correction, a trend was found for the carriers allele 9R of dopamine transporter SLC6A3 40 bp variable tandem repeat polymorphism (VNTR) and for 6/6 homozygotes of SLC6A3 30 bp VNTR. Negative results were obtained for the 9-6 haplotype, the dopamine receptor DRD4 48 bp VNTR, and the enzyme COMT SNP rs4680. Concerning pharmacogenetic studies, no association was found for the SLC6A3 40 bp and response to MPH with only two studies selected. For the metabolomics studies, no differences between ADHD adults and controls were found for salivary cortisol, whereas lower serum docosahexaenoic acid (DHA) levels were found in ADHD adults. This last association was significant even after Bonferroni correction and in absence of heterogeneity. Other polyunsaturated fatty acids (PUFAs) such as AA (arachidonic acid), EPA (eicosapentaenoic acid) and DyLA (dihomogammalinolenic acid) levels were not different between patients and controls. No publication biases were observed for these markers. Genes linked to dopaminergic, serotoninergic and noradrenergic signaling, metabolism (DBH, TPH1, TPH2, DDC, MAOA, MAOB, BCHE and TH), neurodevelopment (BDNF and others), the SNARE system and other forty genes/proteins related to different pathways were not meta-analyzed due to insufficient data. In conclusion, we found that there were not enough genetic, pharmacogenetic and biochemical studies of ADHD in adults and that more investigations are needed. Moreover we confirmed a significant role of BAIAP2 and DHA in the etiology of ADHD exclusively in adults. Future research should be focused on the replication of these findings and to assess their specificity for ADHD.
Topics: Adult; Alleles; Attention Deficit Disorder with Hyperactivity; Biomarkers; Docosahexaenoic Acids; Dopamine Plasma Membrane Transport Proteins; Female; Gene Frequency; Genetic Association Studies; Genotype; Humans; Male; Methylphenidate; Minisatellite Repeats; Nerve Tissue Proteins; Pharmacogenetics; Polymorphism, Genetic; Receptors, Dopamine D4
PubMed: 27217152
DOI: 10.1038/mp.2016.74 -
Neuroscience and Biobehavioral Reviews Jan 2021Methylphenidate (MPH) is an efficacious treatment for ADHD but concerns have been raised about potential adverse effects of extended treatment on growth. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Methylphenidate (MPH) is an efficacious treatment for ADHD but concerns have been raised about potential adverse effects of extended treatment on growth.
OBJECTIVES
To systematically review the literature, up to December 2018, conducting a meta-analysis of association of long-term (> six months) MPH exposure with height, weight and timing of puberty.
RESULTS
Eighteen studies (ADHD n = 4868) were included in the meta-analysis. MPH was associated with consistent statistically significant pre-post difference for both height (SMD = 0.27, 95% CI 0.16-0.38, p < 0.0001) and weight (SMD = 0.33, 95% CI 0.22-0.44, p < 0.0001) Z scores, with prominent impact on weight during the first 12 months and on height within the first 24-30 months. No significant effects of dose, formulation, age and drug-naïve condition as clinical moderators were found. Data on timing of puberty are currently limited.
CONCLUSIONS
Long-term treatment with MPH can result in reduction in height and weight. However, effect sizes are small with possible minimal clinical impact. Long-term prospective studies may help to clarify the underlying biological drivers and specific mediators and moderators.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Body Weight; Central Nervous System Stimulants; Child; Humans; Methylphenidate; Prospective Studies; Treatment Outcome
PubMed: 33080250
DOI: 10.1016/j.neubiorev.2020.09.031 -
Journal of the American College of... May 2021It is increasingly recognized that non-opioid analgesia is an important analgesia in the perioperative period. Specifically, NSAIDs (nonsteroidal anti-inflammatory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is increasingly recognized that non-opioid analgesia is an important analgesia in the perioperative period. Specifically, NSAIDs (nonsteroidal anti-inflammatory drugs) have been touted as an adjunct, or even replacement, for opioids. However, uptake of NSAIDs has been slow due to concern for side effects, including bleeding. We sought to understand the risk of bleeding caused by NSAIDs in the perioperative period.
STUDY DESIGN
A physician-librarian team performed a search of electronic databases (MEDLINE, EMBASE), using search terms covering the targeted intervention (use of NSAIDs) and outcomes of interest (surgical complications, bleeding), limited to English language articles of any date. We performed a systematic review and meta-analysis of the data.
RESULTS
A total of 2,521 articles were screened, and 229 were selected on the basis of title and abstract for detailed assessment. Including reference searching, 74 manuscripts met inclusion criteria spanning years 1987-2019. These studies included 151,031 patients. Studies included 12 types of NSAIDs, the most common being ketorolac, diclofenac, and ibuprofen, over a wide-range of procedures, from otorhinolaryngology (ENT), breast, abdomen, plastics, and more. More than half were randomized control trials. The meta-analyses for hematoma, return to the operating room for bleeding, and blood transfusions showed no difference in risk in any of 3 categories studied between the NSAID vs non-NSAID groups (p = 0.49, p = 0.79, and p = 0.49, respectively). Quality scoring found a wide range of quality, with scores ranging from lowest quality of 12 to highest quality of 25, out of a total of 27 (average = 16).
CONCLUSIONS
NSAIDs are unlikely to be the cause of postoperative bleeding complications. This literature covers a large number of patients and remains consistent across types of NSAIDs and operations.
Topics: Analgesia; Anti-Inflammatory Agents, Non-Steroidal; Blood Loss, Surgical; Blood Transfusion; Diclofenac; Humans; Ibuprofen; Ketorolac; Pain, Postoperative; Pain, Procedural; Perioperative Period; Postoperative Hemorrhage; Surgical Procedures, Operative; Treatment Outcome
PubMed: 33515678
DOI: 10.1016/j.jamcollsurg.2021.01.005 -
Expert Review of Neurotherapeutics 2016Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard... (Review)
Review
Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder.
Topics: Adrenergic alpha-Agonists; Adult; Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bupropion; Central Nervous System Stimulants; Desipramine; Dopamine Agents; Droxidopa; Drug Combinations; Duloxetine Hydrochloride; Guanfacine; Histamine Agents; Humans; Lisdexamfetamine Dimesylate; Lithium Compounds; Lobeline; Mecamylamine; Memantine; Modafinil; Morpholines; Nicotinic Agonists; Nicotinic Antagonists; Nomifensine; Paroxetine; Pyridines; Pyridoxine; Pyrrolidonecarboxylic Acid; Quinazolinones; Reboxetine; Venlafaxine Hydrochloride; Wakefulness-Promoting Agents
PubMed: 26693882
DOI: 10.1586/14737175.2016.1135735 -
Journal of Child Psychology and... Jun 2021Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The... (Meta-Analysis)
Meta-Analysis
Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis.
BACKGROUND
Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta-analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation.
METHODS
We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25 years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha-2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random-effects model.
RESULTS
Twenty-five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent-rated: standardized mean difference [SMD] = -.63, 95%CI = -.95,-.30; teacher-rated: SMD = -.81, 95%CI = -1.43,-.19) and inattention (parent-rated: SMD = -.36, 95%CI = -.64,-.07; teacher-rated: SMD = -.30, 95%CI = -.49,-.11). Atomoxetine reduced inattention (parent-rated: SMD = -.54, 95%CI = -.98,-.09; teacher/investigator-rated: SMD = -0.38, 95%CI = -0.75, -0.01) and parent-rated hyperactivity (parent-rated: SMD = -.49, 95%CI = -.76,-.23; teacher-rated: SMD = -.43, 95%CI = -.92, .06). Indirect evidence for significant reductions in hyperactivity with second-generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events.
CONCLUSIONS
Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long-term continuation is undertaken to help guide clinical decision-making regarding treatment of co-occurring ADHD symptoms in children and youth with ASD.
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Central Nervous System Stimulants; Child; Guanfacine; Humans; Methylphenidate
PubMed: 32845025
DOI: 10.1111/jcpp.13305 -
Journal of Child and Adolescent... Mar 2023Non-stimulant guanfacine is a common second-line medication for attention-deficit hyperactivity disorder (ADHD). Numerous randomized controlled trials (RCTs) have... (Meta-Analysis)
Meta-Analysis Review
Non-stimulant guanfacine is a common second-line medication for attention-deficit hyperactivity disorder (ADHD). Numerous randomized controlled trials (RCTs) have explored the efficacy of guanfacine in ADHD treatment. This meta-analysis combined data from selected RCTs to analyze the efficacy and safety of guanfacine in treating ADHD. RCTs were identified from published sources through searches in PubMed, Cochrane Library, Web of Science, and Embase (up to February 2022), defining the Clinical Global Impression of Improvement (CGI-I) treatment response score of ≤2 as the primary outcome. Subgroup analysis was performed with a bound treatment duration of 10 weeks. Safety was defined by treatment-emergent adverse events (TEAEs). Twelve out of 332 studies with 2653 participants were included. All studies compared guanfacine with placebos. Guanfacine was significantly more effective in treating ADHD (Risk Ratio [RR] 1.78, 95% CI: 1.59-2.01). In the <10 weeks subgroup, the efficacy in the guanfacine group compared with the placebo group was 58.5% versus 29.4%, respectively (RR 1.97, 95% CI: 1.71-2.26). In the >10 weeks subgroup, the efficacy in the guanfacine group compared with the placebo group was 63.6% versus 39.7%, respectively (RR 1.57, 95% CI: 1.37-1.79). Both subgroups lacked heterogeneity ( = 0), and a funnel plot showed a low publication bias risk. Around 80% of participants in the guanfacine group experienced at least one TEAE, compared with 66.5% in the placebo group (RR 1.23, 95% CI: 1.14-1.32), with low heterogeneity ( = 46, = 0.05). The most common TEAEs in the guanfacine group were somnolence (38.6%), headaches (20.5%), and fatigue (15.2%). Guanfacine is safe and effective for treating ADHD, with no serious adverse events. Guanfacine should be considered as an effective treatment option where effectiveness or tolerability of the central nervous system stimulant is of concern. There is stronger evidence of efficacy for children; more clinical studies are needed for adults.
Topics: Child; Adult; Humans; Guanfacine; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Treatment Outcome; Duration of Therapy
PubMed: 36944092
DOI: 10.1089/cap.2022.0038