Acute and long-term cardiovascular effects of stimulant, guanfacine, and combination therapy for attention-deficit/hyperactivity disorder
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OBJECTIVES: This study examines cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB) during acute and long-term treatment of youth with attention-deficit/hyperactivity disorder. METHODS: Two hundred seven participants aged 7-14 years enrolled in an 8-week double-blind randomized trial of GUAN-IR (1-3 milligrams (mg)/day), DMPH (5-20 mg/day), or COMB with fixed-flexible dosing and titrated to optimal behavioral response. Heart rate, systolic blood pressure (BP), diastolic BP, and electrocardiograms were assessed at baseline, end of blinded optimization, and over a 1-year open-label maintenance phase. RESULTS: During acute titration, GUAN-IR decreased heart rate, systolic BP, and diastolic BP; DMPH increased heart rate, systolic BP, diastolic BP, and corrected QT (QTc) interval; COMB increased diastolic BP, but had no effects on heart rate, systolic BP, or QTc. During maintenance, GUAN-IR-associated decreases in heart rate and DMPH-associated increases in systolic BP returned to baseline values. Other variables across the three groups remained unchanged from the end of blinded titration. There were no discontinuations due to CV adverse events. CONCLUSION: GUAN-IR, DMPH, and COMB were well tolerated and safe. Expected changes in CV parameters during acute titration were seen in GUAN-IR and DMPH groups, with COMB values falling intermediately between the two other treatment groups. No serious CV events occurred in any participant. GUAN-IR- and DMPH-associated CV changes generally returned to baseline with sustained therapy. These data suggest that COMB treatment might attenuate long-term CV effects of GUAN-IR and stimulant monotherapy, possibly reducing risk of the small but statistically significant changes associated with either single treatment. Clinicaltrials.gov Identifier: NCT00429273.
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Non-stimulants, particularly clonidine and guanfacine, are likely to have an opposite effect on ANS functioning, i.e., reducing HR and blood pressure, compared with stimulants, but they have similar benefits on cognitive performance and ADHD symptoms.
“Non-stimulants, particularly clonidine and guanfacine, are likely to have an opposite effect on ANS functioning, i.e., reducing HR and blood pressure (see, for example, Sayer et al., 2016) compared with stimulants, but they have similar benefits on cognitive performance and ADHD symptoms.”
From Is autonomic nervous system function atypical in Attention Deficit Hyperactivity Disorder (ADHD)? A systematic review of the evidence (2020) · cites this paper as Sayer et al., 2016
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- Authors
- Sayer, G. R., McGough, J. J., Levitt, J., Cowen, J., Sturm, A., Castelo, E., & McCracken, J. T.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- Journal of Child and Adolescent Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2016-12
- Volume
- 26
- Issue
- 10
- Pages
- 882-888
- ISSN
- 1044-5463 (ISSN-L)
- 1557-8992
- PMC
- PMC5178010
- OpenAlex
- W2509336638
- Cited by
- 28
- References
- 45
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 1
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Child and Adolescent Psychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- attention deficit hyperactivity disorder, guanfacine, dexmethylphenidate, cardiovascular effects, heart rate, blood pressure, QTc interval, pediatric ADHD treatment, long-term maintenance therapy
- MeSH terms
- Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Blood Pressure, Child, Delayed-Action Preparations, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Electrocardiography, Female, Heart Rate, Humans, Male, Time Factors, Guanfacine, Adrenergic alpha-2 Receptor Agonists, Dexmethylphenidate Hydrochloride
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