Can lurasidone cause bradycardia in an adult with bipolar II disorder, particularly at higher doses or in patients with existing conduction abnormalities or on other bradycardic agents, and should a baseline electrocardiogram be obtained with regular heart‑rate monitoring?

Can Lurasidone Cause Bradycardia?

Yes, lurasidone can cause bradycardia, though this is an uncommon adverse effect that has been documented in case reports rather than large-scale clinical trials.

Evidence for Lurasidone-Associated Bradycardia

The most direct evidence comes from a 2023 case report of a 46-year-old woman with bipolar disorder who developed sinus bradycardia (heart rate 48 beats/min) within 5 days of starting lurasidone 80 mg/day, which resolved 5 days after discontinuation 1. This represents a probable causal relationship based on temporal association and resolution upon drug withdrawal 1.

While large clinical trials of lurasidone for bipolar depression and schizophrenia reported minimal cardiovascular effects—with the most common adverse events being headache, nausea, somnolence, and akathisia—bradycardia was not specifically highlighted as a common side effect 2, 3, 4. However, the absence of bradycardia in controlled trial data does not exclude its occurrence in real-world practice, particularly in vulnerable populations 2.

Risk Factors and High-Risk Populations

Patients at highest risk for lurasidone-induced bradycardia include those with:

• Pre-existing conduction abnormalities (sinus node dysfunction, AV block, or wandering atrial pacemaker) 5, 6
• Concurrent use of other bradycardic agents including beta-blockers, calcium channel blockers, digoxin, amiodarone, sotalol, or lithium 5, 7
• Structural heart disease (ischemic heart disease, heart failure, cardiomyopathy) 5
• Electrolyte disturbances (hypokalemia, hypomagnesemia) 6
• Advanced age (>60 years), where conduction system disease is more prevalent 5

The mechanism of antipsychotic-induced bradycardia remains poorly understood, though it may involve reflex bradycardia or direct effects on cardiac conduction 8. Notably, other atypical antipsychotics (ziprasidone, aripiprazole) have also been associated with symptomatic bradycardia in case reports 8.

Clinical Monitoring Recommendations

Before initiating lurasidone in patients with risk factors:

• Obtain a baseline 12-lead ECG to assess heart rate, PR interval, QRS duration, and QT interval, and to rule out higher-degree AV block 6, 5
• Verify normal electrolytes, particularly potassium and magnesium 6
• Review all concurrent medications for potential additive bradycardic effects 7, 6

During treatment:

• Monitor heart rate after the first dose and during the first week of therapy, particularly in high-risk patients 1, 7
• Perform regular vital sign checks for 24-48 hours after initial dosing or dose escalation 7, 6
• Reassess ECG after dose changes to evaluate conduction intervals 6
• Target heart rate >50 bpm if asymptomatic; higher if symptomatic 7

Management of Lurasidone-Induced Bradycardia

If symptomatic bradycardia develops (heart rate <50 bpm with dizziness, lightheadedness, syncope, confusion, or hypotension):

• Immediately discontinue or reduce the dose of lurasidone 7, 1
• Implement continuous cardiac monitoring 7, 6
• For acute symptomatic management, administer atropine 0.5 mg IV every 3-5 minutes up to a total of 3 mg 7, 6
• For refractory cases with severe symptoms, consider transcutaneous pacing and cardiology consultation 7
• Monitor for resolution of bradycardia over 3-5 days after discontinuation (as occurred in the documented case) 1

If bradycardia persists despite medication adjustments:

• Consult cardiology or electrophysiology for evaluation of underlying conduction disease 7, 6
• Consider permanent pacemaker implantation if symptomatic bradycardia is recurrent or severe 5, 7

Clinical Caveats

While lurasidone has a favorable metabolic profile compared to other atypical antipsychotics (minimal weight gain, lipid changes, or glycemic disturbances), clinicians should not assume complete cardiovascular safety 2, 3, 4. The case report emphasizes that even medications with "not significant" cardiovascular effects in trials can cause clinically meaningful bradycardia in individual patients 1.

Do not proceed with lurasidone if:

• The patient has symptomatic bradycardia with hemodynamic compromise at baseline 6
• There is evidence of second- or third-degree heart block on ECG 6, 5
• Sinus node dysfunction extends beyond simple wandering pacemaker 6