Short- and Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended Release in Children

Findling, Robert L.; Biederman, Joseph; Wilens, Timothy E.; Spencer, Thomas; McGough, James J.; López, Frank A.; Tulloch, Simon

doi:10.1016/j.jpeds.2005.03.014

Cited by 73 publications

(46 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cardiovascular changes observed during combination therapy were consistent with increases in blood pressure documented in children with ADHD treated with stimulants (Findling et al 2005;Wilens et al 2005;Donner et al 2007) and ATMX (Michelson et al 2001;Wernicke et al 2003). In addition, there were no serious cardiovascular AEs during combination therapy, and no subject discontinued due to cardiovascular AEs.…”

Section: Hammerness Et Alsupporting

confidence: 74%

An Open Study of Adjunct OROS-Methylphenidate in Children Who Are Atomoxetine Partial Responders: II. Tolerability and Pharmacokinetics

Hammerness

Georgiopoulos

Doyle

et al. 2009

Journal of Child and Adolescent Psychopharmacology

Self Cite

View full text Add to dashboard Cite

Objective: The aim of this study was to evaluate the tolerability of adding OROS methylphenidate (MPH) to children who are partial responders to atomoxetine (ATMX) in the treatment of attention-deficit=hyperactivity disorder (ADHD). Methods: This was a two-phase, 7-week, open study in children aged 6-17 years. Phase 1 initiated ATMX for a minimum of 4 weeks. Phase 2 entered partial responders to ATMX and added OROS MPH to their regimen. Safety was assessed using blood pressure and heart rate measurements, electrocardiogram readings, AEs, laboratories, and ATMX levels. Results: Fifty subjects who were partial responders to ATMX received the combination therapy, with 41 subjects completing the entire protocol. As reported elsewhere , OROS MPH added to partial responders of ATMX was accompanied by a 40% reduction in the ADHD rating scale score and improvements in executive functioning. However, the combination of ATMX plus OROS MPH was associated with greater rates of insomnia, irritability, and loss of appetite compared to ATMX alone. A small significant increase in diastolic blood pressure was observed during adjunctive OROS MPH, with no clinically meaningful changes in electrocardiogram (ECG) parameters during the study. ATMX levels and liver function tests did not significantly change during the combination treatment. Conclusion: Adjunct OROS MPH in ATMX partial responders yielded an additive adverse effect burden in this short-term study. Further controlled research with larger samples of children is warranted.

show abstract

Section: Hammerness Et Alsupporting

confidence: 74%

An Open Study of Adjunct OROS-Methylphenidate in Children Who Are Atomoxetine Partial Responders: II. Tolerability and Pharmacokinetics

Hammerness

Georgiopoulos

Doyle

et al. 2009

Journal of Child and Adolescent Psychopharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, similar to previous research, trends for acute decreases in heart rate and BP were noted with GUAN (Biederman et al 2008;Connor et al 2010;Hirota et al 2014). Although prior reports of stimulant-associated increases in BP and QTc intervals have lacked clinical significance (Findling et al 2001(Findling et al , 2005Donner et al 2007), the relationship between QTc changes and GUAN-IR is less clear. While our study found a small (2 ms) decrease in QTC, another reported a small (5.3 ms) increase (Hirota et al 2014), while a third found no meaningful change .…”

Section: Discussionsupporting

confidence: 77%

Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder

Sayer¹,

McGough²,

Levitt³

et al. 2016

Journal of Child and Adolescent Psychopharmacology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…1 These agents can increase systolic and diastolic blood pressure (on average 1-4 mm Hg) and heart rate (on average 3-8 beats per minute). [2][3][4] Case reports of sudden death in children and adolescents receiving these agents have led to the concern that they might increase the risk of cardiovascular events, especially in those with structural cardiac abnormalities or other serious heart problems. To date, 3 studies [5][6][7] have tried to evaluate the association between exposure to ADHD medications in children and adolescents and cardiovascular events.…”

mentioning

confidence: 99%

Cardiovascular Events and Death in Children Exposed and Unexposed to ADHD Agents

et al. 2011

View full text Add to dashboard Cite

WHAT'S KNOWN ON THIS SUBJECT:Attention-deficit/ hyperactivity disorder agents increase systolic and diastolic blood pressure and heart rate. Case reports of sudden death in children and adolescents receiving these agents have led to the concern that they might increase the risk of cardiovascular events. WHAT THIS STUDY ADDS:Low rates of validated cardiovascular events and of all-cause death, nonsuicide, and non-accidental death were found in children and adolescents receiving attention-deficit/ hyperactivity disorder medications.abstract OBJECTIVE: The objective of this study was to compare the rate of severe cardiovascular events and death in children who use attentiondeficit/hyperactivity disorder (ADHD) medications versus nonusers. PATIENTS AND METHODS:We performed a large cohort study using data from 2 administrative databases. All children aged 3 to 17 years with a prescription for an amphetamine, atomoxetine, or methylphenidate were included and matched with up to 4 nonusers on the basis of data source, gender, state, and age. Cardiovascular events were validated using medical records. Proportional hazards regression was used to calculated hazard ratios. RESULTS: We identified 241 417 incident users (primary cohort) CONCLUSIONS:The rate of cardiovascular events in exposed children was very low and in general no higher than that in unexposed control subjects. Because of the low number of events, we have limited ability to rule out relative increases in rate.

show abstract

Short- and Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended Release in Children

Cited by 73 publications

References 20 publications

An Open Study of Adjunct OROS-Methylphenidate in Children Who Are Atomoxetine Partial Responders: II. Tolerability and Pharmacokinetics

An Open Study of Adjunct OROS-Methylphenidate in Children Who Are Atomoxetine Partial Responders: II. Tolerability and Pharmacokinetics

Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder

Cardiovascular Events and Death in Children Exposed and Unexposed to ADHD Agents

Contact Info

Product

Resources

About