Which type of stimulant is associated with less tachycardia (rapid heart rate)?

From the Guidelines

Among stimulant medications, non-amphetamine stimulants like methylphenidate generally cause less tachycardia than amphetamine-based stimulants such as Adderall or Vyvanse, as evidenced by the most recent study in 2022 1. This is because methylphenidate works primarily by blocking dopamine reuptake, while amphetamines both block reuptake and increase dopamine release, resulting in more potent cardiovascular effects. The difference in heart rate effects is typically modest but clinically relevant, especially for patients with pre-existing cardiovascular concerns. When initiating stimulant therapy, starting with a low dose of methylphenidate and gradually titrating upward can minimize tachycardia. Regular monitoring of heart rate and blood pressure is recommended regardless of which stimulant is chosen, as stimulant medications are associated with statistically significant increases in blood pressure and heart rate, although these effects are small on the group level, they may be clinically relevant for a small subgroup of patients, especially those with preexisting cardiovascular diseases 1. Individual responses vary significantly, and some patients may experience minimal heart rate changes even with amphetamine-based medications, while others might be sensitive to even small doses of methylphenidate. Key points to consider when choosing a stimulant medication include:

• The mechanism of action, with methylphenidate having a more targeted effect on dopamine reuptake
• The potential for cardiovascular side effects, with amphetamine-based stimulants having a higher risk of increased heart rate and blood pressure
• The importance of regular monitoring of heart rate and blood pressure, regardless of which stimulant is chosen
• The need for individualized treatment, taking into account the patient's unique response to the medication and any pre-existing medical conditions.

From the FDA Drug Label

Atomoxetine hydrochloride should be used with caution in patients whose underlying medical conditions could be worsened by increases in blood pressure or heart rate such as certain patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease In placebo-controlled registration studies involving pediatric patients, tachycardia was identified as an adverse event for 0. 3% (5/1,597) of these atomoxetine hydrochloride patients compared with 0% (0/934) of placebo patients. The mean heart rate increase in extensive metabolizer (EM) patients was 5 beats/minute, and in poor metabolizer (PM) patients 9. 4 beats/minute. In adult clinical trials where EM/PM status was available, the mean heart rate increase in PM patients was significantly higher than in EM patients (11 beats/minute versus 7. 5 beats/minute).

The stimulant type with less tachycardia is not directly stated in the provided drug label. However, based on the information provided, atomoxetine appears to have a lower incidence of tachycardia compared to other stimulants, with 0.3% of pediatric patients and 1.5% of adult patients experiencing tachycardia as an adverse event. Additionally, the mean heart rate increase was lower in extensive metabolizer (EM) patients (5 beats/minute in pediatric patients and 7.5 beats/minute in adult patients) compared to poor metabolizer (PM) patients (9.4 beats/minute in pediatric patients and 11 beats/minute in adult patients) 2.

From the Research

Stimulant Types and Tachycardia

• The relationship between stimulant types and tachycardia is complex, with various studies examining the effects of different stimulants on heart rate and blood pressure 3, 4, 5, 6, 7.
• Modafinil, a central nervous system stimulant, has been shown to have a lower risk of tachycardia compared to other stimulants such as amphetamines and methylphenidate 3, 4.
• A study published in 2017 found that modafinil did not cause a clinically significant increase in heart rate, systolic blood pressure, and diastolic blood pressure in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) 4.
• In contrast, amphetamines and methylphenidate have been reported to cause minor increases in heart rate and blood pressure, although the clinical significance of these effects is unclear 5, 7.
• The mechanisms underlying the therapeutic efficacy of modafinil, including its effects on dopamine, GABA, glutamate, serotonin, and norepinephrine, may contribute to its unique pharmacology and lower risk of tachycardia 6.

Comparison of Stimulant Types

• Modafinil: lower risk of tachycardia, minimal increases in heart rate and blood pressure 3, 4.
• Amphetamines: minor increases in heart rate and blood pressure, potential for cumulative effects over time 5, 7.
• Methylphenidate: minor increases in heart rate and blood pressure, uncertain long-term effects on cardiovascular health 5, 7.
• Atomoxetine: potential for increases in blood pressure and heart rate, uncertain effects on QTc interval 5, 7.