Design: Individual-participant-data network meta-regression of double-blind randomised trials
Population: 8,679 adults with major depression for QTc; 52,398 for cardiovascular events
Primary outcome: QTc change over eight weeks; early major cardiovascular events
Effect: Escitalopram +8.7 ms, amitriptyline +5.3 ms vs placebo; no excess events (risk difference 0.01%)

This individual-participant-data network meta-regression pooled double-blind randomised trials to compare the effect of ten antidepressants on the QTc interval in the first eight weeks of treatment for major depression, and separately looked for early cardiovascular events.

The QTc effect varied by drug. Escitalopram and amitriptyline were associated with the largest prolongations, around 8.7 and 5.3 milliseconds against placebo, while venlafaxine and vortioxetine were among the lowest. Effects varied considerably between individuals, which is where baseline risk factors come in. Across an aggregate of 139 trials and 52,398 patients, antidepressant use was not associated with any excess of early major cardiovascular events or non-suicidal sudden death.

The practical reading is reassuring on hard outcomes and useful for choice: in a patient with a long baseline QTc or other risk factors, the lower-QTc agents are a rational preference, without treating the whole class as cardiotoxic.

Individual-participant-data analysis of double-blind trials covering ten antidepressants.
Escitalopram (+8.7 ms) and amitriptyline (+5.3 ms) had the largest QTc effects versus placebo.
Venlafaxine and vortioxetine were among the lowest for QTc prolongation.
Across 52,398 patients, antidepressant use showed no excess of early cardiovascular events.
Let a patient's baseline QTc and risk factors guide the choice of agent.

Why it matters

It replaces a blanket worry about antidepressant cardiotoxicity with a drug-specific, risk-factor-based choice.

The statistics, in plain English

A mean QTc rise of 8.7 ms is modest for most patients but matters when the baseline is already near 450 to 500 ms. The near-zero risk difference for cardiovascular events (0.01%) across tens of thousands of patients is strong reassurance about hard outcomes, distinct from the surrogate QTc measure.