Citalopram and Escitalopram: QT Prolongation Risks and Dose Limits

When you're prescribed an antidepressant, the goal is simple: feel better. But for some people, especially those over 65 or with heart conditions, the very medication meant to lift their mood might quietly affect their heart rhythm. Two commonly used SSRIs-citalopram and escitalopram-carry a known, measurable risk: QT interval prolongation. It’s not a common event, but it’s serious enough that regulators around the world changed the rules on how these drugs are prescribed.

What QT Prolongation Really Means

Your heart beats because of electrical signals. The QT interval on an ECG measures how long it takes for the heart’s lower chambers to recharge between beats. If this interval gets too long, it can trigger a dangerous rhythm called Torsade de Pointes, which can lead to fainting, seizures, or even sudden death. The risk isn’t theoretical-it’s been measured in clinical trials and confirmed by real-world data.

Both citalopram and escitalopram block a specific ion channel in heart cells (the hERG potassium channel). This slows down the heart’s recovery phase, stretching out the QT interval. The longer the interval, the higher the chance of an arrhythmia. But here’s the catch: not every small increase matters. Regulatory agencies define clinical concern as either:

• A QTc interval of 500 milliseconds or more
• A change from baseline of 60 milliseconds or more

These thresholds aren’t arbitrary. They’re based on studies showing when the risk of serious arrhythmias starts to climb.

Dose-Dependent Risk: The Numbers Don’t Lie

Both drugs increase QTc in a clear, dose-dependent way. But the amount of increase differs-and that difference matters.

For citalopram:

• 20 mg/day: +8.5 ms (95% CI: 6.2-10.8)
• 40 mg/day: +12.6 ms (95% CI: 10.9-14.3)
• 60 mg/day: +18.5 ms (95% CI: 16.0-21.0)

For escitalopram:

• 10 mg/day: +4.5 ms (95% CI: 2.5-6.4)
• 20 mg/day: +6.6 ms (95% CI: 5.3-7.9)
• 30 mg/day: +10.7 ms (95% CI: 8.7-12.7)

Notice something? At the highest approved doses, citalopram pushes the QTc nearly twice as much as escitalopram. That’s not a small difference. It’s why regulators took different approaches.

Why Regulators Took Different Paths

In 2011, the U.S. Food and Drug Administration (FDA) issued a safety alert specifically for citalopram after reviewing data showing QT prolongation at doses above 40 mg. They didn’t mention escitalopram by name-but the data was there. By 2012, the UK’s MHRA and New Zealand’s Medsafe went further: they warned about both drugs.

Here’s what changed:

• U.S. FDA: Citalopram capped at 40 mg/day for adults under 65; 20 mg/day for those over 65. Escitalopram was not restricted at the time.
• UK MHRA: Citalopram limited to 40 mg/day (under 65) and 20 mg/day (65+). Escitalopram limited to 20 mg/day (under 65) and 10 mg/day (65+).
• Canada and Europe: Followed the UK’s more cautious approach.

Why the difference? European regulators looked at the totality of evidence and decided that even escitalopram’s modest effect was enough to warrant limits-especially since elderly patients metabolize these drugs slower. Their bodies build up higher concentrations, increasing risk even at lower doses.

Who’s at Highest Risk?

It’s not just about the dose. Certain people should avoid these drugs altogether-or use them with extreme caution:

• Patients with known congenital long QT syndrome
• Those with a history of heart failure, bradycardia, or recent heart attack
• People taking other QT-prolonging drugs (like certain antibiotics, antifungals, or antiarrhythmics)
• Those with low potassium, low magnesium, or severe dehydration
• Patients over 65, especially if they have kidney or liver impairment

It’s also risky to combine these SSRIs with other medications that slow their breakdown-like fluvoxamine or cimetidine. That can push blood levels into dangerous territory.

How Do Other Antidepressants Compare?

Not all antidepressants carry the same cardiac risk. Here’s a quick snapshot:

Tricyclic antidepressants (TCAs) like amitriptyline are even riskier than citalopram. But among SSRIs, citalopram stands out as the highest-risk option. That’s why many clinicians now choose escitalopram over citalopram when cardiac risk is a concern-even though escitalopram costs more.

Is the Risk Real-or Overblown?

You might hear conflicting opinions. Some experts say the QTc increases seen with these drugs are too small to matter. After all, a 18.5 ms rise from citalopram 60 mg sounds minor next to the 500 ms threshold.

But here’s the problem: thresholds aren’t safety zones. They’re warning signs. A 60 ms increase from baseline could push someone with a pre-existing long QT interval into the danger zone. And in people with multiple risk factors-elderly, on multiple meds, low electrolytes-that small change can be enough to trigger a dangerous rhythm.

Studies show that while serious events like Torsade de Pointes are rare, they do happen. And they’re often preventable. The key is knowing who’s at risk and avoiding the high doses that push them over the edge.

What Should You Do?

If you’re on citalopram or escitalopram:

• Never increase your dose without talking to your doctor.
• If you’re over 65, your dose should be lower-no exceptions.
• If you have heart disease, ask whether an alternative antidepressant might be safer.
• Get an ECG if you’re starting a high dose or have multiple risk factors.
• Watch for symptoms: dizziness, palpitations, fainting, or sudden shortness of breath.

Doctors now routinely check for these risks before prescribing. If you’ve been on one of these drugs for years without issues, you’re likely fine. But if you’re newly prescribed, or your dose has been increased recently, make sure your provider has considered your full health picture.

Bottom Line: Safer Choices Exist

Citalopram and escitalopram are effective. But they’re not equally safe. Citalopram’s higher risk at doses above 40 mg means it’s no longer the first choice for many patients-especially older adults or those with heart conditions. Escitalopram, with its lower QTc effect and better safety profile, has become the preferred SSRI in these cases.

The takeaway? Dose matters. Age matters. Health history matters. And when it comes to antidepressants and heart rhythm, what seems like a small change on paper can mean the difference between safety and a life-threatening event.