Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine adversely affect bone mineral density (BMD) and turnover, thereby increasing the risk of fractures. The objective of the present systematic review and meta-analysis was to evaluate studies on animal models that assessed whether fluoxetine can influence orthodontic tooth movement (OTM).

Indexed databases (PubMed/Medline, EMBASE, Cochrane Library, Scopus and ISI Web of Knowledge) and Google Scholar were searched without time and language barriers up to and including June 2024. Original studies that assessed the influence of fluoxetine on OTM were included. Letters to the Editor, reviews, commentaries, perspectives and, in-vitro/ex-vivo studies were excluded. Study selection, and risk of bias (RoB) and quality assessments were assessed. Quantitative assessment (meta-analysis) was also performed using fixed-effects and random effects models.

Four studies performed on male rats were included. Rats in the experimental group underwent OTM with adjunct fluoxetine injections at concentrations ranging between 10–20mg/kg. Orthodontic forces applied ranged between 25–60grams. Three studies reported that fluoxetine does not influence OTM. All studies had a high RoB. Three studies demonstrated low certainty (weak) and two showed very low certainty of evidence. In the meta-analysis, the pooled SMD using a random effects model was 0.05 (95% CI: –0.42 to 0.52), indicating no significant overall effect of fluoxetine on OTM. The analysis revealed substantial heterogeneity across the included studies.

Further well-designed and power-adjusted prospective studies are needed to elucidate the role of SSRIs on OTM.

PROSPERO CRD42024563793.