Assessing the Cardiovascular Effects of ADHD Medications

A recent systematic review and network meta-analysis assessed the cardiovascular effects of attention-deficit/hyperactivity disorder (ADHD) medications across children, adolescents, and adults with ADHD. The authors conclude that while changes in cardiovascular parameters were generally small, prescribers should routinely monitor patients during treatment.

Pharmacotherapy plays a key role in ADHD treatment, with both stimulants (eg, amphetamines, methylphenidate) and non-stimulants (eg, atomoxetine, clonidine, guanfacine, viloxazine) approved for use in the United States. Stimulants and some non-stimulants (atomoxetine and viloxazine) exert sympathomimetic noradrenergic effects, theoretically raising blood pressure and heart rate in some patients; conversely, the α2 agonists guanfacine and clonidine have sympatholytic effects, potentially leading to decreases in blood pressure and heart rate.¹ Viloxazine has exhibited fewer untoward cardiovascular effects,² but each of the aforementioned ADHD treatments carry warnings in their labels about potential increases or decreases in blood pressure or heart rate.^3-7 Stimulants and clonidine carry additional warnings for the potential risks in patients with serious cardiovascular disease.^3-5

Although observational studies and randomized controlled studies have raised concerns about the cardiovascular safety of ADHD medications, they have not established causality or quantified the extent of the risks.¹ One network meta-analysis examined cardiovascular effects, but only the effects on blood pressure.¹ To provide more comprehensive data on cardiovascular effects of ADHD medications, Farhat and colleagues (2025) performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) assessing the broader impact of ADHD medications on hemodynamic and electrocardiogram (ECG) parameters across children, adolescents, and adults with ADHD.¹ 

The investigators searched 12 electronic databases, including PubMed and Embase, and Cochrane CENTRAL for RCTs conducted through January 18, 2024.¹ Drugs studied included stimulants (amphetamines, lisdexamfetamine, methylphenidate), the selective norepinephrine inhibitor atomoxetine, the alpha-2 agonists clonidine and guanfacine, and the multimodal agent viloxazine. The primary outcomes were changes in systolic and diastolic blood pressure (mm Hg) and pulse (beats per minute) at 12, 26, and 52 weeks. Summary data were analyzed using random-effects network meta-analyses, with evidence certainty evaluated via the Confidence In Network Meta-Analysis (CINeMA) framework. A total of 102 randomized controlled trials with short-term follow-up (median 7 weeks) enrolling 13 315 children and adolescents and 9387 adults were included.¹

In short-term trials, stimulant and non-stimulant ADHD medications had varying effects on systolic blood pressure (SBP).¹ In children, atomoxetine, lisdexamfetamine, and methylphenidate increased SBP by a mean of 1.07 mm Hg, 1.76 mm Hg, and 1.81 mm Hg, respectively. In adults, methylphenidate, atomoxetine, and amphetamines increased SBP by a mean of 1.66 mm Hg, 2.25 mmHg, and 2.30 mm Hg, respectively. Guanfacine decreased SBP by a mean of 2.83 mm Hg in pediatric patients and a mean of 10.1 mm Hg in adults. No significant differences in SBP effects were found between medications within each age group. Certainty of evidence varied from moderate to very low, depending on the drug and population studied.¹

Several medications increased diastolic blood pressure (DBP).¹ In children, amphetamines, atomoxetine, lisdexamfetamine, methylphenidate, and viloxazine raised DBP by a mean of 1.93 to 2.42 mm Hg, while in adults, mean increases ranged from 1.6 mm Hg (methylphenidate) to 3.07 mm Hg (lisdexamfetamine). Guanfacine lowered DBP in both age groups, from a mean of –2.08 mm Hg in children to a mean of –7.73 mm Hg in adults. No significant differences were observed between medications within age groups. Evidence certainty ranged from high (eg, atomoxetine in children) to very low (eg, most adult findings).¹

Most ADHD medications increased pulse.¹ In children, mean increases ranged from 2.79 bpm (viloxazine) to 5.58 bpm (atomoxetine), while in adults, mean increases ranged from 2.95 bpm (bupropion) to 5.8 bpm (viloxazine). In children and adolescents, atomoxetine increased pulse by a mean of 1.7 bpm vs methamphetamine and by a mean of 2.79 bpm vs viloxazine in head-to-head trials. No other statistically significant differences between drugs were reported. Conversely, guanfacine reduced pulse in both age groups by a mean of 4.06 bpm in children and 6.83 bpm in adults. No other significant between-drug differences were found. Certainty of evidence ranged from high (eg, atomoxetine in children) to very low (adult estimates).¹

No ADHD medication significantly affected QTc in children.¹ In adults, atomoxetine modestly increased QTc (standardized mean difference of 0.27), though evidence was of very low certainty. Regarding other ECG parameters, several drugs increased heart rate across age groups—most notably amphetamines, atomoxetine, lisdexamfetamine, methylphenidate, and viloxazine. PR interval decreased with atomoxetine and viloxazine in both age groups and with amphetamines in children. QRS complex effects varied: lisdexamfetamine increased it in children, while methylphenidate increased it in adults; viloxazine and methylphenidate decreased QRS in children. Overall, these cardiac conduction effects were considered small but did vary by drug and age group.¹

The authors conclude that, on average, ADHD medications produced small short-term mean changes in cardiovascular parameters in children, adolescents, and adults. They note, however, that some individuals across age groups experience greater-than-average changes in blood pressure and pulse. Moreover, none of the studies included in the analysis were longer than 26 weeks in duration. The presence of individual outlier values and absence of long-term data on cardiovascular effects highlight the need for prescribers to adhere to guidelines and routinely monitor blood pressure and heart rate during treatment.¹ 

References:

1. Farhat LC, Lannes A, Del Giovane C, et al. Comparative cardiovascular safety of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: A systematic review and network meta-analysis. Lancet Psychiatry. 2025;12(5):355-365. doi:10.1016/S2215-0366(25)00062-8
2. Cutler AJ, Mattingly GW, Jain R, O'Neal W. Current and future nonstimulants in the treatment of pediatric ADHD: monoamine reuptake inhibitors, receptor modulators, and multimodal agents. CNS Spectr. 2022;27(2):199-207. doi:10.1017/S1092852920001984
3. Adderall XR. Package insert. Takeda Pharmaceuticals U.S.A.; 2023.
4. Ritalin. Package insert. Novartis Pharmaceuticals Corporation; 2019.
5. Catapres. Package insert. Boehringer Ingelheim International GmbH; 2023
6. Intuniv. Package insert. Shire US Inc; 2019.
7. Qelbree. Prescribing information. Supernus Pharmaceuticals; 2025.