What interventions must a patient fail before being considered for isotretinoin (13-cis-retinoic acid) for acne treatment?

Interventions to Fail Before Isotretinoin for Acne

According to the 2024 American Academy of Dermatology guidelines, patients must fail standard treatment with oral or topical therapy before being considered for isotretinoin, unless they have severe acne, psychosocial burden, or scarring. 1

First-Line Treatments to Try Before Isotretinoin

Topical Therapies (First-Line)

• Topical retinoids (tretinoin, adapalene, tazarotene, trifarotene) - strongly recommended with moderate evidence 1
• Benzoyl peroxide - strongly recommended with moderate evidence 1
• Combination therapies (strongly recommended):
  • Fixed-dose combination topical retinoid with benzoyl peroxide 1
  • Fixed-dose combination topical antibiotic with benzoyl peroxide 1
  • Fixed-dose combination topical retinoid with topical antibiotic (with concomitant benzoyl peroxide to prevent antibiotic resistance) 1

Additional Topical Options

• Azelaic acid (conditional recommendation) 1
• Clascoterone (conditional recommendation) 1
• Salicylic acid (conditional recommendation) 1

Second-Line Treatments to Try Before Isotretinoin

Oral Antibiotics

• Doxycycline - strongly recommended with moderate evidence 1
• Minocycline - conditionally recommended with moderate evidence 1
• Sarecycline - conditionally recommended with high evidence 1

Important: Systemic antibiotics should be used concomitantly with benzoyl peroxide and other topical therapy to reduce antibiotic resistance 1

Hormonal Therapies (for females)

• Combined oral contraceptive pills - conditionally recommended with moderate evidence 1
• Spironolactone - conditionally recommended with moderate evidence 1

Adjunctive Therapy

• Intralesional corticosteroid injections for larger acne papules or nodules at risk of scarring 1

When to Consider Isotretinoin

Isotretinoin is recommended for:

1. Patients with severe acne
2. Patients who have failed standard treatment with oral or topical therapy
3. Patients with psychosocial burden or scarring (should be considered as having severe acne) 1

Treatment Algorithm Before Isotretinoin

1. Start with topical therapies:

   • Topical retinoid + benzoyl peroxide combination
   • If inadequate response after 6-8 weeks, add topical antibiotic to the regimen

2. If inadequate response to topical therapy:

   • Add oral antibiotics (preferably doxycycline) while continuing topical therapy
   • For females with hormonal acne patterns, consider combined oral contraceptives or spironolactone

3. If inadequate response to oral antibiotics after 3 months:

   • Try a different oral antibiotic (minocycline or sarecycline)
   • Consider hormonal therapy if not already tried (for females)

4. If still inadequate response:

   • Consider isotretinoin, especially if there is:
     • Severe acne
     • Scarring or risk of scarring
     • Significant psychosocial burden
     • Failure of multiple standard treatments

Important Considerations

• Topical antibiotic monotherapy is not recommended due to risk of antibiotic resistance 1
• Systemic antibiotics should be limited when possible to reduce antibiotic resistance 1
• For patients with severe acne, traditional daily dosing of isotretinoin is conditionally recommended over intermittent dosing 1
• Higher cumulative dosage of isotretinoin (≥120 mg/kg) may potentially reduce risk of acne relapse and need for retreatment 2

By following this treatment algorithm, clinicians can ensure patients have tried appropriate standard therapies before moving to isotretinoin, which carries more significant monitoring requirements and potential side effects.