QT interval prolongation is one of the most important — and often misunderstood — safety issues in psychiatric prescribing.
While rare, significant prolongation can lead to Torsades de Pointes, syncope, and even sudden cardiac death.

Because many psychiatric medications influence cardiac repolarisation, every clinician should know how to evaluate, prevent, and manage QT prolongation safely.

This article provides a clear, practical, real-world guide for psychiatrists, physicians, and mental health professionals.

What Exactly Is the QT Interval?

The QT interval on an ECG represents how long the heart’s ventricles take to depolarise and repolarise — essentially, how long they need to “reset” before the next beat.

Since heart rate affects QT, we use a corrected value:

QTc = QT interval corrected for heart rate

Typical safe values:

• Men: < 450 ms

• Women: < 470 ms

• QTc ≥ 500 ms: significantly increased risk of arrhythmia (especially Torsades)

Why Psychiatric Medications Can Prolong QT

Many psychotropics block the IKr (hERG) potassium channels in the heart, delaying repolarisation.
This effect can be:

• dose-dependent

• amplified by drug interactions

• worsened by electrolyte imbalance

• dangerous when multiple QT-prolonging medications are combined

Understanding which medications carry higher risk helps protect patients.

Psychiatric Medications With Higher QT Risk

Higher-Risk Antipsychotics

• Ziprasidone

• Haloperidol (especially IV)

• Thioridazine

• Chlorpromazine

• Pimozide

Moderate-Risk Antipsychotics

• Quetiapine

• Risperidone

• Paliperidone

• Amisulpride

• Olanzapine (mild)

Low-Risk Antipsychotics

• Aripiprazole

• Lurasidone

• Brexpiprazole

• Cariprazine

Higher-Risk Antidepressants

• Citalopram

• Escitalopram

• Tricyclics (Amitriptyline, Imipramine, Clomipramine)

Lower-Risk Antidepressants

• Sertraline

• Mirtazapine

• Bupropion

• Vortioxetine

• Agomelatine

Non-Medication Factors That Increase QT Risk

These factors dramatically increase the likelihood of dangerous QT prolongation:

• Low potassium (hypokalaemia)

• Low magnesium (hypomagnesaemia)

• Bradycardia

• Female sex

• Older age (> 65)

• Pre-existing heart disease

• Renal or liver failure

• Eating disorders / malnutrition

• Alcohol use

• Vomiting, diarrhoea, dehydration

• Diuretic use

• Polypharmacy

You can often reduce QTc simply by correcting electrolytes and stopping interacting medications.

When Should a Psychiatrist Order an ECG?

Baseline ECG recommended when:

• starting high-risk antipsychotics or antidepressants

• starting two or more QT-prolonging medications

• patient is elderly

• patient has cardiac history

• electrolyte abnormalities suspected

• dose will exceed usual range

Follow-up ECG recommended when:

• increasing dose significantly

• adding another QT-prolonging drug

• patient develops syncope, palpitations, dizziness

• QTc borderline at baseline

How to Interpret QTc Like a Clinician

QTc < 450 ms (men) / < 470 ms (women)

→ Safe
Continue treatment.

QTc 450–500 ms

→ Caution

• Recheck electrolytes

• Review all medications

• Avoid dose increases

• Repeat ECG in 1–2 weeks

QTc ≥ 500 ms

→ High risk

• Stop the QT-prolonging drug

• Switch to safer alternatives

• Consider cardiology referral

Drug Interactions That Dramatically Increase QT Prolongation

Be especially cautious when psychotropics are combined with:

Antibiotics

• Azithromycin

• Levofloxacin

• Ciprofloxacin

Antiemetics

• Ondansetron

• Domperidone

Antihistamines

• Hydroxyzine

Other risky combinations

• SSRI + antipsychotic

• TCA + antipsychotic

• Multiple antipsychotics

• Antipsychotic + methadone

Many QT events happen because clinicians (or other specialists) unknowingly combine these.

Safe Substitutions in Patients With QT Prolongation

If antipsychotic needed:

Replace high-risk agents with:

• Aripiprazole

• Lurasidone

• Brexpiprazole

• Cariprazine

If antidepressant needed:

Replace high-risk agents with:

• Sertraline

• Mirtazapine

• Vortioxetine

• Agomelatine

• Bupropion

These medications have minimal or negligible QT effects.

Symptoms Suggesting QT Prolongation (Tell Patients to Watch For)

Patients should be educated to report:

• sudden dizziness

• fainting / near-fainting

• rapid or irregular heartbeat

• “fluttering” in the chest

• unexplained anxiety

• seizures

Early reporting prevents dangerous events.

Key Takeaways for Clinicians

• QT prolongation is real but rare.

• The 500 ms threshold is the most important actionable cut-off.

• Always check electrolytes before adjusting psychotropics.

• Avoid unnecessary polypharmacy.

• Aripiprazole, Lurasidone, Sertraline, and Mirtazapine are the safest choices when QT risk exists.

• ECG monitoring is simple and prevents catastrophic events.

Thoughtful prescribing protects both mental health and cardiac health.

About the Author

Dr. Srinivas Rajkumar T, MD (AIIMS), DNB, MBA (BITS Pilani)
Consultant Psychiatrist & Neurofeedback Specialist
Mind & Memory Clinic, Apollo Clinic Velachery (Opp. Phoenix Mall)
✉ srinivasaiims@gmail.com 📞 +91-8595155808