What is the likelihood that Strattera (atomoxetine) will cause tachycardia in patients, particularly those with pre-existing heart conditions or cardiovascular risk factors?

Cardiovascular Effects of Strattera (Atomoxetine)

Direct Answer on Heart Rate Changes

Strattera causes statistically significant increases in heart rate in the majority of patients, with mean increases of 5 beats/minute in extensive metabolizers and 9.4 beats/minute in poor metabolizers, though these changes are generally not clinically significant for most patients. 1

Likelihood and Magnitude of Heart Rate Effects

Incidence of Tachycardia

• In pediatric placebo-controlled trials, 23.4% of atomoxetine patients experienced heart rate increases ≥20 bpm at some point during treatment, compared to 11.5% on placebo 1
• Tachycardia was identified as an adverse event in only 0.3% of pediatric patients (5/1,597) versus 0% on placebo (0/934), indicating that while heart rate increases are common, clinically significant tachycardia is rare 1
• In adult trials, tachycardia occurred in 1.5% (8/540) of atomoxetine patients compared to 0.5% (2/402) on placebo 1

Magnitude of Heart Rate Changes

• Extensive metabolizers: mean increase of 5 beats/minute 1
• Poor metabolizers (CYP2D6): mean increase of 9.4 beats/minute in pediatrics and 11 beats/minute in adults 1
• The heart rate effects are dose-proportional and could be clinically important in poor metabolizers 1, 2

Blood Pressure Effects

Incidence of Clinically Significant Changes

• 21.5% of pediatric patients experienced diastolic blood pressure increases ≥15 mm Hg versus 14.1% on placebo 1
• 12.5% experienced systolic blood pressure increases ≥20 mm Hg versus 8.7% on placebo 1

Magnitude in Poor Metabolizers

• Poor metabolizers show significantly higher blood pressure effects: mean diastolic increase of 4.21 mm Hg versus 2.13 mm Hg in extensive metabolizers 1
• Systolic blood pressure increased by 2.75 mm Hg in poor metabolizers versus 2.40 mm Hg in extensive metabolizers 1

High-Risk Populations

Patients with Pre-existing Cardiovascular Disease

Atomoxetine should generally not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to noradrenergic effects 1

• Sudden death has been reported in association with atomoxetine at usual doses in children and adolescents with structural cardiac abnormalities 1
• Adults with clinically significant cardiac abnormalities should be carefully evaluated before treatment, as sudden deaths, stroke, and myocardial infarction have been reported 1
• The medication should not be used in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate with clinically important increases in blood pressure or heart rate 1

Specific Contraindications

• Atomoxetine should be used with caution in patients with hypertension, tachycardia, or cardiovascular/cerebrovascular disease 1
• Patients with conditions that could be worsened by increases in blood pressure or heart rate require careful risk-benefit assessment 1

Cardiovascular Screening Algorithm

Pre-Treatment Assessment

1. Obtain detailed cardiac history including family history of sudden death or ventricular arrhythmia 1
2. Perform physical examination to assess for cardiac disease 1
3. Obtain baseline ECG and measure pulse and blood pressure 1
4. If findings suggest cardiac disease (e.g., abnormal ECG), obtain echocardiogram before initiating treatment 1

Monitoring During Treatment

• Measure pulse and blood pressure at baseline, following dose increases, and periodically during therapy 1
• Monitor for symptoms of cardiac disease including exertional chest pain, unexplained syncope, palpitations, or other cardiac symptoms 1
• Patients developing cardiac symptoms during treatment should undergo prompt cardiac evaluation 1

Additional Cardiovascular Risks

Orthostatic Hypotension and Syncope

• Orthostatic hypotension occurred in 0.2% (12/5,596) of atomoxetine-treated pediatric patients 1
• A case report documented syncope, orthostatic hypotension, and tachycardia in a patient on atomoxetine, likely related to increased noradrenergic tone 3

Serious Cardiac Events in Overdose

• Isolated atomoxetine overdose (2840 mg) resulted in seizure, sinus tachycardia (110 bpm), and QRS widening to 93 ms 4
• A case of life-threatening QT prolongation with Takotsubo cardiomyopathy was reported in an 11-year-old on chronic atomoxetine therapy, requiring transcutaneous pacing 5

Critical Caveats

CYP2D6 Poor Metabolizers

Poor metabolizers of CYP2D6 (approximately 7% of Caucasians, 2% of African Americans) experience significantly greater cardiovascular effects and require closer monitoring 1, 2

• These patients have 10-fold higher plasma concentrations of atomoxetine 2
• Concomitant use of CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) produces similar effects 1

Drug Interactions

• CYP2D6 inhibitors increase atomoxetine exposure and cardiovascular effects similar to poor metabolizers 1, 3
• Review all concurrent medications for potential interactions before initiating atomoxetine 1