Is less more with isotretinoin and acne?

Clinical question

Is low-dose isotretinoin as effective and tolerable as conventional doses in the treatment of acne?

Bottom line

Studies show that acne improvement with low-dose (about 20 mg/d) isotretinoin is similar to that with conventional doses. Low-dose isotretinoin might reduce common side effects by 16% to 35%; it might also be associated with higher relapse rates, particularly with severe acne, possibly owing to lower total accumulated doses.

Evidence

• Three RCTs compared conventional with low dosing.

  • -For 24 weeks, 60 patients with moderate acne used low (0.25 to 0.4 mg/kg daily) or conventional doses (0.5 to 0.7 mg/kg daily).¹ The low-dose group showed equivalent efficacy (acne grading and lesion counts); increased patient satisfaction (76% very satisfied vs 31%); and a higher (non-significant) 1-year relapse rate (18% vs 13%).

  • -For 20 weeks, 150 patients with treatment-resistant nodulocystic acne used 0.1, 0.5, or 1 mg/kg daily.² There was equivalent improvement with all doses; 18-month relapse rates were 42%, 20%, and 10%, respectively.

  • -Lower doses reduced common side effects (chapped lips, dry skin, and epistaxis) by 16% to 35%.^1,2

  • -In 120 patients with mild to severe acne using high (1 mg/kg daily) or low (20 mg/d) doses on alternating days for 16 weeks,³ the low-dose group had a decrease in acne load (81% vs 95%) and fewer side effects.

• A large prospective study (638 patients with moderate acne; 20 mg/d for 24 weeks) reported “good results” in about 94% of patients, decreased incidence of side effects, and a 5% relapse rate at 4 years.⁴

• Smaller observational studies (doses about 20 mg/d) support these findings^5–7; 2 studies report improved outcomes with a total cumulative dose of 120 mg/kg.^5,7

Context

• Isotretinoin is approved for the treatment of severe acne in patients aged 12 and older; the recommended dosage is 0.5 to 1 mg/kg divided into 2 doses daily for 4 to 5 months.⁸

• In many studies lower-dose groups reach lower total accumulated doses than the higher-dose treatment arms do, which might partly explain higher relapse rates.^1–3

• Recommended laboratory monitoring includes triglyceride, cholesterol, and liver transaminase levels, and complete blood count.^9,10

• Although there are reports of mood changes, suicidal thoughts, and suicide, no causal relationship has been proven.^9,10

• Isotretinoin is teratogenic and pregnancy must be prevented 1 month before, during, and after treatment.^9,10

Implementation

Isotretinoin is used in patients with severe, nodulocystic acne that is refractory to other treatments (eg, oral antibiotics). It is generally believed a cumulative isotretinoin dose ranging from 120 to 150 mg/kg is most effective in inducing acne remission.¹¹ If acne is less severe or if adverse effects are a concern, then a lower daily dose is a reasonable option. Handouts on acne¹² and websites on oral isotretinoin¹³ can help patients understand treatment options. A 2009 RxFiles article, accompanied by a patient follow-up sheet,¹⁴ might be helpful to clinicians.