Antipsychotics and QT-Prolonging Drugs: What You Need to Know About Heart Risks

When you’re taking an antipsychotic for schizophrenia, bipolar disorder, or severe depression, your doctor focuses on calming your mind. But there’s another system in your body that’s quietly at risk: your heart. Mixing certain antipsychotics with other common medications can stretch out your heart’s electrical cycle-known as QT prolongation-and that’s not just a lab result. It can lead to a life-threatening rhythm called torsades de pointes, or even sudden cardiac death.

What QT Prolongation Really Means

Your heart beats because of electrical signals. The QT interval on an ECG measures how long it takes for your heart’s lower chambers to recharge after each beat. If that interval gets too long-over 450 ms in men, 460 ms in women-it creates a dangerous window where the heart can misfire. The result? A chaotic, twisting rhythm called torsades de pointes. It doesn’t always cause symptoms, but when it does, you might feel dizzy, faint, or have your heart racing. In severe cases, it can turn into ventricular fibrillation and kill you within minutes.

This isn’t theoretical. Between 2010 and 2022, the FDA documented 128 cases of torsades linked to combinations of antipsychotics and other QT-prolonging drugs. And here’s the kicker: nearly half of all people on antipsychotics are also taking at least one other medication that does the same thing. That includes antibiotics like moxifloxacin, anti-nausea drugs like ondansetron, and even some antidepressants. When these drugs stack up, the effect isn’t just added-it’s multiplied.

Not All Antipsychotics Are Created Equal

Some antipsychotics are far riskier than others. It comes down to how strongly they block the hERG potassium channel, which controls the heart’s repolarization. The lower the IC50 value, the stronger the blockade-and the higher the risk.

• High-risk: Thioridazine (IC50 0.04 μM), ziprasidone (0.13 μM), haloperidol (0.15 μM). Thioridazine was pulled from the U.S. market in 2005 for this reason, but it’s still used elsewhere. Ziprasidone carries an FDA black box warning.
• Moderate-risk: Quetiapine (2.5 μM), risperidone (3.1 μM), olanzapine (4.2 μM). These are the most commonly prescribed. Quetiapine alone was prescribed over 24 million times in 2023.
• Low-risk: Aripiprazole (11.7 μM), brexpiprazole (15.3 μM), lurasidone (18.9 μM). These are becoming preferred choices for patients with heart risks.

When you add another QT-prolonging drug to a moderate-risk antipsychotic like quetiapine, studies show the QT interval can stretch 38.7 milliseconds longer than if you were on the antipsychotic alone. That’s more than double the increase seen with single-drug use.

Who’s Most at Risk?

It’s not just the drugs. Your body matters too. Certain factors make QT prolongation more likely and more dangerous:

• Age over 65: Adds 15.3 ms to QTc
• Female sex: Adds 12.8 ms
• Low potassium (hypokalemia): Adds 22.7 ms
• Slow heart rate (bradycardia): Adds 18.4 ms
• Genetics: Poor metabolizers of CYP2D6 (7-10% of Caucasians) build up higher drug levels, increasing risk 2.4-fold

One case from Cleveland Clinic tells the story: a 68-year-old woman on quetiapine 300 mg started ciprofloxacin for a urinary infection. In just 72 hours, her QTc jumped from 448 ms to 582 ms. She went into torsades. She survived-but barely. That’s the kind of timeline we’re talking about. Risk doesn’t build over months. It can explode in days.

What Doctors Should Do (And Often Don’t)

Guidelines from the American Heart Association and American Psychiatric Association are clear: baseline ECG before starting high- or moderate-risk antipsychotics, then follow-up ECGs at 1 week, 4 weeks, and quarterly. For high-risk combinations-like antipsychotic plus antibiotic or antiemetic-you need weekly ECGs for the first month.

But here’s the reality: in community clinics, fewer than 35% of patients get even one follow-up ECG. Why? Insurance denies coverage. Rural clinics don’t have ECG machines. Doctors are overwhelmed. A 2023 survey found 68% of providers had ECG requests denied by insurers. Another 42% said their clinic didn’t have the equipment.

Meanwhile, patients are scared. Nearly 30% of people on antipsychotics have stopped taking them because they feared heart problems. And 61% say their doctor never explained how real-or how small-the actual risk was.

The Numbers Don’t Always Match the Fear

Some experts argue the warnings are overblown. Dr. John Csernansky, editor of The American Journal of Psychiatry, points out that the actual incidence of torsades is incredibly rare: about 1 in 25,000 patient-years for QT-prolonging antipsychotics versus 1 in 28,000 for non-prolonging ones. That’s not statistically different.

But here’s what matters: when you combine drugs, the risk skyrockets. The 2018 JAMA Internal Medicine study found that pairing an antipsychotic with an antidepressant increased torsades risk 4.3-fold. And while the absolute risk might be low, the consequences are catastrophic. One death is one too many.

And then there’s the cost of over-testing. Dr. Joseph Goldberg estimates that unnecessary ECGs for low-risk patients cost the U.S. system $1.2 billion a year. So the challenge isn’t just about safety-it’s about smart safety.

How to Reduce Risk Without Overdoing It

There’s a middle path. You don’t need to avoid antipsychotics. You don’t need to ECG everyone. You need to stratify.

• Start with low-risk drugs: Aripiprazole, brexpiprazole, and lurasidone are now preferred for patients with heart disease, older adults, or those on multiple medications.
• Check electrolytes: Potassium and magnesium are critical. A 2023 JAMA Cardiology study found that keeping potassium above 4.0 mmol/L prevented 82% of torsades cases in high-risk patients.
• Avoid dangerous combos: Never pair haloperidol or ziprasidone with moxifloxacin, ondansetron, or certain antidepressants like citalopram.
• Use tools: New ECG patches like Zio XT (FDA-approved in May 2024) can monitor for 14 days continuously-perfect for catching early QT changes in high-risk patients.
• Use risk calculators: Coming in early 2025, the American Psychiatric Association will release a validated calculator that factors in age, sex, drugs, and electrolytes to give a personalized risk score.

The Future Is Already Here

The market is shifting. In 2019, only 22% of new antipsychotic prescriptions were for low-risk drugs. By 2023, that jumped to 38%. Projections say it’ll hit 52% by 2027. Why? Because Medicare is starting to tie reimbursement to proper QT monitoring. Starting in 2025, 2.3% of Medicare Part D payments could be withheld if clinics don’t follow cardiac safety guidelines.

And it’s not just about money. The FDA now requires all new antipsychotic trials to include cardiac safety sub-studies. The European Medicines Agency now demands specific combination risk tables on drug labels. This isn’t just regulation-it’s evolution.

The goal isn’t to scare people away from treatment. It’s to make sure they can stay on the medication they need without risking their heart. The American College of Cardiology and American Psychiatric Association say it clearly: with proper risk stratification, torsades can be reduced to fewer than 1 case per 100,000 patient-years. That’s not just safe. That’s excellent care.

What You Should Do

If you’re on an antipsychotic:

• Ask your doctor: Is this drug high, moderate, or low risk for QT prolongation?
• Make a list of every medication you take-including over-the-counter drugs and supplements.
• Ask: Could any of these interact with my antipsychotic to stretch my QT interval?
• Request a baseline ECG if you’re over 65, female, or on more than one medication.
• If you feel dizzy, faint, or have palpitations-call your doctor immediately. Don’t wait.

If you’re a clinician:

• Use low-risk antipsychotics as first-line when possible.
• Check potassium before and during treatment.
• Use electronic alerts in your EHR to flag dangerous combinations.
• Don’t dismiss ECG requests because of insurance denials-advocate for your patient.
• Explain the real risk: not zero, but manageable with simple steps.