Fluoxetine vs Escitalopram — a clear, practical comparison

Picking between fluoxetine (Prozac) and escitalopram (Lexapro) comes up a lot. Both are SSRIs that treat depression and anxiety, but they act differently in ways that matter day-to-day. This page breaks down the main differences so you can talk with your doctor with a little more confidence.

Key differences at a glance

Mechanism: both boost serotonin, but escitalopram is the more selective S-enantiomer of citalopram — often meaning fewer off-target effects. Fluoxetine is less selective and stays in the body much longer.

Onset and dosing: typical starting dose is fluoxetine 20 mg daily and escitalopram 10 mg daily. Both can take 2–6 weeks for mood to improve, though some people notice energy or sleep changes sooner.

Half-life and washout: fluoxetine has a very long half-life (plus an active metabolite). That means missed doses are less likely to cause withdrawal, but it also means you may need a 5-week wait before starting an MAOI. Escitalopram clears faster — usual washout is about 2 weeks before MAOIs.

Side effects and feel: fluoxetine is often described as more activating — it can increase energy or anxiety in some people and may cause less early weight gain. Escitalopram tends to be calmer and may be better if you feel very anxious or have trouble sleeping.

Drug interactions: fluoxetine is a stronger CYP2D6 inhibitor — it can interact with more meds (some pain meds, certain antipsychotics, beta-blockers). Escitalopram has fewer major CYP interactions but still can interact with other serotonergic drugs.

How to choose and practical tips

What are you treating? For depression with low energy or when bulimia or certain OCD symptoms are present, fluoxetine is often chosen. For generalized anxiety, panic disorder, or when you need a gentler start, escitalopram is a common pick.

Worried about withdrawal? If missing doses or future switching is likely, fluoxetine’s long tail can make stopping easier. If you need fewer drug interactions, escitalopram may be safer.

Watch common effects: nausea, headache, sleep changes, and sexual side effects can happen with either drug. If you’re under 25, monitor mood and suicidal thoughts closely during the first weeks — contact your prescriber if anything changes.

Practical steps: start at a low dose, give a medication 6–8 weeks unless side effects prevent continuation, report sexual problems or severe insomnia, and never mix with MAOIs. If switching, follow your doctor’s timeline for washout to avoid serotonin syndrome.

Questions to ask your prescriber: Which fits my symptoms better? How will this interact with my other meds? What side effects should I expect and when should I call? Those answers make the choice personal and safer.

If you want a quick summary: choose fluoxetine when you need a more activating option or longer washout safety; choose escitalopram when you want a cleaner interaction profile and a calmer effect. Talk it over with your clinician — personal health factors matter most.