The 30-second version

1. When the heart is the constraint, sertraline is your default. It has the strongest cardiac safety evidence (SADHART) and fewer clinically significant interactions with cardiac drugs than other SSRIs.
2. The antidepressants of greatest concern are citalopram and escitalopram — both classed by CredibleMeds as “known risk” of TdP (citalopram the larger effect) — and the TCAs (modest at therapeutic dose, lethal in overdose).
3. Don't forget trazodone. Formally only a “conditional risk” agent, but its FDA label warns against use in known QT prolongation, with torsades reported at doses as low as 100 mg — and it hides on med lists as a sleep aid, so it rarely gets counted in the QT tally.
4. The dose rules are the QT rules: citalopram and escitalopram ceilings drop with age, hepatic impairment, and CYP inhibition.
5. The newest high-QT agent is gepirone (Exxua, 2024). It's contraindicated above a baseline QTc of 450 ms and is the only antidepressant that mandates an ECG before starting, during titration, and periodically — stricter than citalopram.

Look up a drug

Tap a drug for its QT tier, dose and ECG rule, and notes.

High-risk scenarios

• ElderlyCitalopram max 20 mg over 60 (FDA); escitalopram 10 mg (US recommended dose; UK maximum over 65)
• Hepatic impairmentCitalopram caps at 20 mg; duloxetine avoided
• Polypharmacy / CYP inhibitionFluvoxamine, fluoxetine, paroxetine raise other drugs' levels
• On methadoneA major QT load — favor sertraline, avoid stacking
• Overdose risk / suicidalityAvoid TCAs — lethal in overdose
• Trazodone for sleepCount it as an active QT contributor
• Gepirone + strong CYP3A4 inhibitorContraindicated (~5× exposure); severe hepatic impairment also contraindicated

Monitoring

Apply the baseline-ECG logic from Chapter 1: a young, healthy patient starting sertraline does not need a screening ECG, while a patient with stacked risk factors does — and the threshold drops further for citalopram, trazodone, or a TCA. When you do monitor:

1. Check a baseline ECG
2. Correct potassium (> 4.0 mEq/L) and magnesium (> 2.0 mg/dL) first
3. Recheck after the drug reaches steady state or after a dose increase
4. Re-image any time you add a second QT-prolonging agent or the clinical picture shifts

Red flags — stop and escalate

Clinical pearls

• Sertraline is the default when cardiac risk drives the choice.Best evidence, no cardiac drug interactions, low QT.
• Trazodone is the silent contributor.Because it's prescribed for sleep, it rarely makes it onto the mental "QT drugs" list — but it belongs there, and TdP has occurred at low doses.
• Escitalopram is lower-risk than citalopram, not no-risk.Keep it at 10 mg in older patients (the US recommended dose; the UK maximum over 65) and respect QT risk factors. Its modeled QTc effect grows with age.
• Some SSRIs endanger the QT indirectly.Fluvoxamine (potent CYP1A2, plus CYP3A4, CYP2C9, and CYP2C19 — the CYP3A4 inhibition can raise trazodone levels) and fluoxetine/paroxetine (CYP2D6) can raise the levels of co-prescribed QT-prolonging drugs, on top of any direct effect.
• For TCAs, think overdose lethality, not just steady-state QT.In a depressed, potentially suicidal patient, that distinction can decide the agent.
• Newer doesn't mean lower-risk — check the label.Most recent approvals (Auvelity, esketamine, zuranolone) are low-QT, but gepirone (2024) carries the strictest QT requirements of any antidepressant. A 2025 network meta-analysis (Pillinger, Lancet) found little QTc change for most agents in trial data (only nortriptyline and amitriptyline stood out). A 2026 patient-level analysis (Ostinelli, BMJ) found escitalopram and amitriptyline separated from placebo at average values, and that age changed the picture. RCTs enroll younger, healthier patients, so real-world risk can run higher.

Patient script & EMR note

Antidepressant selected with QT risk considered: [agent/dose].
QT rationale: [low-risk agent chosen / dose capped for age/hepatic/CYP].
Baseline QTc: ____ ms (if obtained; indication: ____).
Risk factors: [age / cardiac hx / electrolytes / other QT drugs incl.
   trazodone-for-sleep, methadone / hepatic / CYP inhibitors].
K+ ___  Mg2+ ___ (corrected as needed).
Plan: [agent, dose]. Monitoring: repeat ECG at ____ if indicated.
Counseled on syncope/palpitations and on disclosing new meds; return
precautions given.

Last reviewed October 2026. Part of the Psychiatry Education Forum Academy; for clinician education — it supports, and does not replace, individual clinical judgment and current local protocols.