A Comparative Review of the Efficacy and Tolerability of Retinoid-Containing Combination Regimens for the Treatment of Acne Vulgaris

June 2007 | Volume 6 | Issue 6 | Original Article | 625 | Copyright © June 2007

James L. Campbell Jr. MD MS

Adjunct Assistant Professor, Dartmouth Medical School, Hanover, NH

Many physicians regularly prescribe combination therapy involving a retinoid for their acne patients. The most common retinoid-containing regimens include either oral antibiotics or topical benzoyl peroxide and antibiotic products. A fair number of studies have been conducted to evaluate the efficacy of these combination therapies, but there is a lack of comparative studies examining different regimens head-to-head. Also, many of the noncomparative studies have very similar trial designs. A review of these studies was conducted in order to organize the available data side by side from the different regimens. Although not derived from comparative studies, this presentation of data is expected to provide dermatologists with valuable information from which they can easily make their own comparisons among similarly designed trials.


Acne vulgaris is a common, chronic skin disorder that affects 70% to 87% of the adolescent population.1-3 While acne occurs mostly in pubescent teens, older individuals may also be afflicted.4 Moreover, it has been reported that suffering from acne may have psychological impact leading to anxiety, depression, and suicide.5
Acne vulgaris is characterized by several abnormalities in sebum production, follicular epithelial desquamation, bacterial proliferation, and inflammation.6 Because acne is a multifactorial disease, effective treatment may involve different combination therapies to control the disease. Such combination regimens are sometimes necessary to address the individual needs of each patient, particularly in more severe cases.
The US FDA has approved several agents to treat acne vulgaris. Adapalene, tazarotene, and tretinoin are topical retinoids that exhibit safe profiles for the treatment of facial acne. Local effects from the use of retinoids, especially prevalent in the early course of treatment, include peeling, erythema, dryness, burning, and itching; however, these effects can be reduced by limiting exposure to sunlight, extreme temperatures, and increasing use of moisturizers.7 Retinoids in particular have played an important role in the treatment of acne because they target the microcomedone—the primary lesion of acne.
Therapies involving retinoids in combination with oral and/or topical antibiotics have proven to be effective and safe for the treatment of acne vulgaris. Previously published studies have reported that the combination of a retinoid, such as adapalene gel 0.1% or tazarotene gel 0.1%, with an oral antibiotic is more effective in improving both inflammatory and noninflammatory acne lesions as compared to monotherapy with an antibiotic alone.8,9 Likewise, combination therapies with these retinoids and topical antibiotics also result in more beneficial effects compared to treatments with only the topical antibiotic.10-12 Although studies have reported similar efficacious results, differences in tolerability, safety, and patient satisfaction may suggest that one combination treatment regimen may exhibit more preferable outcomes than another. Understanding these differences will help the treating physician make appropriate choices for each individual patient.

Retinoids and Oral Antibiotics

Adapalene gel 0.1% and doxycycline
In a 12-week study, 467 patients with severe acne were randomized to receive doxycycline (100 mg capsule) once daily in the morning and either adapalene gel 0.1% or adapalene gel vehicle once daily in the evening.8
Reductions in lesions were statistically in favor of the combination regimen for both inflammatory (P=.02), and noninflammatory (P<.001) lesions (Figure 1a). At the end of the study, the percent of patients rated as success (clear or almost clear) was significantly higher with adapalene gel 0.1% and
table 1