ADHD drugs and cardiovascular effects: new data

New systematic reviews and network meta-analyses showed little difference between the cardiovascular (CV) effects of stimulants and noradrenaline reuptake inhibitors used to treat attention deficit/hyperactivity disorder (ADHD).

Short-term use of amphetamines, atomoxetine, lisdexamphetamine, methylphenidate, and biloxazine was associated with slight increases in blood pressure (BP), pulse, or both in children, adolescents, and adults.

Furthermore, the effects of stimulants, including amphetamines, lisdexamphetamine, or methylphenidic acid, were not significantly different from the effects of atomoxetine or biloxazine in the research group.

In contrast, the alpha-2A agonist guanfacin reduced BP and pulses in both groups compared to placebo.

“Our findings highlight the need to follow current recommendations for measuring blood pressure and pulse at baseline and follow-up,” said Professor MD, MD, MD, MD, MD, PhD, Professor of Child and Adolescent Psychiatry at the University of Southampton, University of Southampton, UK. Medscape Medical News. “They also show that the overall cardiovascular effect is small for the majority of patients.”

“In addition to evidence from other trials and observational studies, this suggests that the ratio of profit risk supports the benefits of ADHD medications in the majority of patients,” he added.

The research was It's published online April 6th Lancet Psychiatry.

Wide range of CV parameters

Previous systematic reviews and meta-analyses of randomized controlled trials (RCTs) link stimulants and atomoxetine to increased BP and pulse.

These studies generally focused on a single drug or a limited number of CV outcomes, Cortese noted. “Our one is the first to provide comparative evidence regarding the effects of ADHD drugs on a wide range of cardiovascular parameters.”

The network meta-analysis included 102 RCTs of at least 12 weeks of follow-up (median, 7 weeks) including 13,315 children and adolescents (mean age, 11 years, 73% male) and 9,387 adults (mean age, 35 years, 57% male). Lisdexamphetamine, methylphenidate, modafinil, or biloxazine. Three-quarters of all participants were white.

Compared to placebo, the mean increase in systolic BP was 1.07 mm Hg with atomoxetine in pediatric patients (95% CI, 0.36-1.79) and 2.25 mm Hg (95% CI, 0.84-3.67). Increased with methylphenidate averaged 1.81 mm Hg (95% CI, 1.05-2.57) and 1.66 mm Hg (95% CI, 0.38-2.93) respectively.

In adults, systolic BP was on average increased with bupropion (95% CI, 0.05-7.4) at 2.3 mm Hg (95% CI, 0.66-3.94) and 3.72 mm Hg, but the certainty of the evidence was very low. Lisdexamphetamine increased systolic BP in children and adolescents by only 1.76 (95% CI, 0.68-2.83).

The average increase in diastolic BP (MM Hg) in pediatric and adult patients

• Amphetamines: 1.93 (95% CI, 0.74-3.11) and 1.91 (95% CI, 0.17-3.65)
• Atomoxetine: 2.2 (95% CI, 1.55-2.85) and 1.83 (95% CI, 0.26-3.4)
• Lisdexamfetamine: 2.29 (95% CI, 1.25-3.34) and 3.07 (95% CI, 0.69-5.45)
• Methylphenidate: 2.42 (95% CI, 1.69-3.15) and 1.6 (95% CI, 0.29-2.91)

Viloxazine also increased short-term diastolic BP in children and adolescents with an average of 2.15 mm Hg (95% CI, 0.92-3.39).

There were no statistically significant pairwise differences between drugs regarding increased systolic or diastolic BP in either age group.

Compared to placebo, guanfacine reduced systolic BP of 2.83 mm Hg (95% CI, -3.8 to -1.85) in pediatric patients and 10.10 mm Hg (-13.76 to -6.44) in adults. and diastolic BP x 2.08 mm Hg (95% CI, -3 to -1.17) and 7.73 mm Hg (-11.88 to -3.58).

Pulse and ECG survey results

A significant increase in pulse was observed in placebo in children and adult patients taking atomoxetine (mean, 5.58 and 5.44), lisdexamphetamine (mean, 4.17 and 5.07), methylphenidate (mean, 3.88 and 4.37), and biloxazine (mean, 2.79 and 5.8).

Furthermore, amphetamines and bupropion increased the pulse in adults compared to placebo, while atomoxetine increased the pulse in children and adolescents compared to both methylphenidate and biloxazine.

Guan Facin reduced the pulses at a mean of 4.06 beats/min for pediatric patients and 6.83 beats/min for adults compared to placebo.

Less data was available for ECG parameters, but showed that amphetamines were associated with reduced PR intervals in children and adolescents. Atomoxetine reduced the PR interval in both age groups. Lisdexamfetamine increased the QRS complex in children and adolescents. Methylphenidate reduced QRS complexes in children and adolescents and increased QR in adults. Viloxazine reduced the PR interval in both age groups and reduced QRS complexes in children and adolescents.

The findings are inconclusive and the authors stated that more consistent reporting of ECG parameters in ADHD RCT should be sought.

The RCT data are group averages and “thus, it provides overall indications of cardiovascular effects, but is not applicable to individual patients,” Cortese said.

Next steps required

in An accompanying editStephen R. Prisca, professor and chair of the Department of Psychiatry at the University of Texas Health Center in San Antonio, said the changes in BP and pulse were small, in line with other studies showing average increases of 5 mm Hg and average increases of 5 beats/min in pulses.

“In general, such increases do not place patients outside of their healthy range,” he writes.

He also noted that changes represent average effects and that BP or pulse in some patients can spike at the borderline to abnormal levels. “Such patients need to transition to another ADHD medication,” he added.

Pliszka noted that slight changes in PR and QRS intervals should not raise concerns and that ECG before ADHD treatment should only be performed if the patient has a specific CV risk factor. Current Guidelines.

Pliszka and investigators said the meta-analysis could not shed light on long-term outcomes and called for further research, such as machine learning analyses in large databases, to predict whether ADHD patients are at the highest risk of CV disease.

“In summary, clinicians should be wary of side effects when using ADHD medications, but do not avoid using them,” says Pliszka.

The limited number of RCTS race/ethnic minorities, women and seniors is a significant limitation of the meta-analysis, Cortez said. Medscape Medical News. Certainly, a Previous analysis By group, over 40% of ADHD medications showed that published reports did not contain racial/ethnic data, despite improved reports over time.

Furthermore, greater representation of women in ADHD exams is also important for a more comprehensive understanding, as CV outcomes and risks generally differ between men and women throughout their lifetimes. Medscape Medical News.

This study was funded by the National Institute of Health and Therapy (NIHR). Cortese was funded by the NIHR for the project and reported additional NIHR grants and grants from the European Research Enforcement Agency. Farhatt was supported by the São Paulo Research Foundation. Pliszka does not report any related financial disclosures.