Fluoxetine: First Test in Ages 4-6

Portrait by Mona Nelson

The first trial to test an antidepressant below age six

STUDY: Shakibaei F et al, Advanced Biomedical Research 2026

STUDY TYPE: Randomized, double-blind, placebo-controlled trial

FUNDING: Isfahan University of Medical Sciences (government/academic grant)

Background

Among antidepressants, fluoxetine has the best evidence in children, with FDA-approval down to age eight. This trial asked whether fluoxetine helps children as young as four.

The Study

• 40 children ages 4 to 6 with major depression, diagnosed by DSM-5 criteria and confirmed with the Depression scale (PFC-S).
• Fluoxetine (0.7 mg/kg daily, up to 15 mg) versus placebo for 60 days.
• Depression scores (PFC-S) checked at baseline, 30 days, and 60 days.

Results

Depression scores dropped sharply with fluoxetine, from about 4.9 to 3.1, while the placebo group barely moved, from 5.4 to 5.1. The gap showed up early, by 30 days, and held through 60 days. Parents reported no side effects on the antidepressant checklist (ASEC) in either group.

However, the report of “no side effects” is misleading. Two children on fluoxetine dropped out of the trial due to agitation, enough to leave the study entirely. The published safety numbers only count the 40 who finished, so the real side effect rate looks better on paper than what actually happened.

Limitations

Small, single-center pilot study with just two months of follow-up.

Practice Implications

1. A small study like this is a call for more research. Psychotherapy is first-line in this age group.
2. Parent-Child Interaction Therapy has the strongest empirical support for depression in children under age eight. Also consider the family history (is there bipolar?) and the context: sleep, diet, activity, and trauma.