Isotretinoin 3 Times Per Week Is Not Recommended
Intermittent dosing regimens, including 3 times per week administration, are explicitly not recommended by the American Academy of Dermatology due to significantly higher relapse rates compared to continuous daily dosing. 1, 2
Evidence Against Intermittent Dosing
The strongest guideline evidence clearly demonstrates that intermittent dosing produces inferior outcomes:
- Daily continuous dosing produces significantly greater reductions in inflammatory lesions (mean difference 3.87) and non-inflammatory lesions (mean difference 4.53) compared to intermittent dosing at 24 weeks 1
- Intermittent regimens are associated with higher relapse rates despite having lower withdrawal rates due to adverse effects 1
- A 2022 meta-analysis confirmed that conventional daily dosing improves the odds of prolonged remission compared to pulsed/intermittent doses in mild-to-moderate acne 3
What the Literature Actually Shows About Intermittent Regimens
While one older study from 2006 examined weekly pulse dosing (1 week on, 3 weeks off) and reported 82.9% complete improvement in 41 patients with mild-to-moderate acne 4, this approach contradicts current guideline recommendations and has been superseded by higher-quality evidence showing inferior long-term outcomes.
Recommended Alternative Approaches
For mild-to-moderate acne, low-dose daily isotretinoin (0.25-0.4 mg/kg/day) is the evidence-based alternative that provides:
- Comparable efficacy to conventional dosing 1, 2
- Significantly fewer side effects while maintaining therapeutic benefit 1, 2
- Equal relapse rates compared to higher-dose regimens 1
- Better outcomes than any intermittent dosing strategy 3
For severe acne, the standard approach remains:
- Start at 0.5 mg/kg/day for the first month 1, 2
- Increase to 1.0 mg/kg/day thereafter as tolerated 1, 2
- Target cumulative dose of 120-150 mg/kg to minimize relapse 1, 2
Critical Administration Requirements
Regardless of dosing strategy selected:
- Isotretinoin must be taken with meals in two divided daily doses to ensure adequate absorption, as the medication is highly lipophilic and bioavailability decreases significantly without food 1, 2
- Continue treatment for at least 2 months after achieving clear skin to reduce relapse frequency 2
Common Pitfall to Avoid
The appeal of intermittent dosing (fewer side effects, lower cost) is understandable but misguided—the significantly higher relapse rates mean patients ultimately require retreatment, negating any perceived benefits and exposing them to additional treatment courses with cumulative teratogenic risk and monitoring burden.