# Individualizing isotretinoin dosing in acne: comparable 24-week efficacy and better tolerability at lower daily doses

## TL;DR

Lower doses of isotretinoin for acne show similar effectiveness to higher doses but with better tolerability and higher patient satisfaction.

## Contribution

Demonstrates that low-dose isotretinoin is as effective as conventional doses for acne with better tolerability.

## Key findings

- Low-dose isotretinoin showed comparable 24-week efficacy to conventional doses.
- Low-dose regimens had higher patient satisfaction and better tolerability.
- Post-treatment worsening did not differ significantly between the two dosing strategies.

## Abstract

The optimal isotretinoin dosing strategy for acne vulgaris remains debated, balancing efficacy against dose-dependent toxicity.

To compare the efficacy, safety, and post-treatment outcomes of low-dose (≤0.5 mg/kg/day) versus conventional-dose (0.5–1.0 mg/kg/day) isotretinoin.

We searched PubMed, Embase, CENTRAL, and Web of Science for randomized controlled trials (RCTs). The primary outcome was the change in Global Acne Grading System (GAGS) score at 24 weeks. Secondary outcomes included post-treatment worsening quantified as GAGS score deterioration, adverse events, and patient satisfaction. Certainty of evidence was assessed using GRADE.

Four trials (210 randomized; 202 analyzed) were included. At 24 weeks, the pooled mean difference favored neither regimen [MD = −1.87, 95% CI (−4.38, 0.64); p = 0.15; I2 = 85.67%]. Heterogeneity was predominantly attributable to one trial that enrolled more severe cases and used adjunctive antibiotics/corticosteroids; excluding it reduced heterogeneity and maintained no significant difference under a random-effects model [MD = −0.92, 95% CI (−2.62, 0.77); p = 0.28; I2 = 44.97%]. Post-treatment worsening did not differ overall and, in sensitivity analyses excluding the co-intervention trial, showed no statistically significant difference with no heterogeneity [MD = 0.10, 95% CI (−1.67, 1.86); p = 0.91; I2 = 0%]. Low-dose regimens had higher patient satisfaction [SMD = 0.99, 95% CI (0.63, 1.34); p < 0.001] and better tolerability. Certainty of evidence was low for efficacy and moderate for safety and satisfaction (GRADE).

In RCTs conducted predominantly in moderate acne and in contexts minimizing co-interventions, low-dose isotretinoin provides comparable 24-week efficacy to conventional dosing while offering superior tolerability and higher patient satisfaction. Conventional dosing may yield a modestly faster early response; however, the absolute differences were small and evidence in substantially more severe acne remains limited and context-dependent.

Registered in PROSPERO (ID: CRD42024536322), URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024536322.