QT Interval Prolongation: Lamotrigine vs Lurasidone
Lurasidone increases QT interval minimally while lamotrigine does not prolong QT interval at all—in fact, lamotrigine is associated with small reductions in QTc and has no association with QT prolongation at therapeutic doses.
Lamotrigine and QT Interval
Lamotrigine does not cause QT prolongation and is considered safe from a cardiac standpoint. The evidence is clear and consistent:
- A thorough QT/QTc study in healthy subjects demonstrated that therapeutic doses of lamotrigine (50-200 mg twice daily) were not associated with QT prolongation 1
- In fact, lamotrigine was associated with small reductions in QTcF (maximum mean difference from placebo -7.48 ms) rather than increases 1
- No subjects in the lamotrigine group had QTcF >450 ms or increases from baseline >60 ms 1
- European Heart Journal guidelines classify anticonvulsants including lamotrigine as mood stabilizers that have generally not been associated with severe arrhythmia 2
Lurasidone and QT Interval
Lurasidone causes minimal to no clinically significant QT prolongation and is among the safest antipsychotics regarding cardiac risk:
- Multiple sources identify lurasidone as having the lowest risk of QT prolongation among antipsychotics 3, 4, 5
- A 2023 pharmacovigilance study analyzing real-world data from VigiBase found that lurasidone was associated with the lowest risk of QT prolongation reporting among 20 antipsychotics studied 3
- Lurasidone and aripiprazole are specifically recommended as preferred antipsychotics when QTc prolongation is a concern 6
- Clinical studies show no association between lurasidone and prolonged QTc interval 5
Clinical Context and Risk Stratification
The distinction matters because:
- Antipsychotics as a class carry varying degrees of QT prolongation risk, with sertindole, ziprasidone, and thioridazine causing the most prolongation (13-30 ms mean increase) 6
- Lurasidone sits at the safest end of the antipsychotic spectrum, comparable to aripiprazole and brexpiprazole 6, 3
- Lamotrigine, as an anticonvulsant mood stabilizer, belongs to a different drug class entirely with no QT prolongation concerns 2, 1
Monitoring Recommendations
When either medication is used in patients with cardiac risk factors:
- Obtain baseline ECG before initiating any psychotropic therapy 2, 6
- Correct electrolyte abnormalities, particularly hypokalemia and hypomagnesemia, before starting treatment 2, 6
- Perform follow-up ECG after dose titration 2, 6
- Consider medication adjustment if QTc exceeds 500 ms or increases by >60 ms from baseline 2, 6
Key Clinical Pitfalls
- Do not confuse lurasidone with other antipsychotics that significantly prolong QT (ziprasidone causes 5-22 ms prolongation, quetiapine causes 6 ms, haloperidol causes 7 ms) 6
- Avoid combining multiple QTc-prolonging medications, as the risk increases exponentially with polypharmacy 6, 7
- Female sex, age >65 years, and pre-existing cardiovascular disease are high-risk situations requiring heightened vigilance 6
- Route of administration matters for some antipsychotics (IV haloperidol carries higher risk than oral), but this is not relevant for lamotrigine or lurasidone 6