Tretinoin has been investigated the most out of all the topical retinoids for clinical effectiveness and safety, with over 20 randomised trials comparing it either to placebo or to other treatments.[1] Evidence of its effectiveness was first demonstrated in the 1980s. [2]

Certain genes, formed from sequences in our DNA, are sensitive to topical retinoids, which lead to changes in the function of the cell. They improve signs of ageing by: increasing cell division leading to increased thickness in the top layer of the skin (the epidermis); compaction of the outermost cells in the skin (stratum corneum); and production of glycosaminoglycans (complex chains of sugar molecules which attract water). [1][2]

Clinical trials looking at the effectiveness of tretinoin look at the various signs of ageing including fine wrinkles, coarse wrinkles, hyperpigmentation (brown marks), skin texture, laxity, and signs of ageing seen on skin samples under the microscope.

Three trials were published between 1988-1993 involving 55 patients between them; all showed statistically significant improvements with short-term (1-4 months) tretinoin use. [2]

As the short term studies showed continued improvements over time, five six-month trials were performed between 1989 and 1992 including 1,199 patients in total. All of these trials showed significant improvement in signs of ageing, even after six months. [2]

Since the six-month trials, longer-term trials have been performed, and consequently long term maintenance regimes have been recommended. [1]

There have been two American trials including over 80 patients comparing treatment with tretinoin to placebo. One of the trials showed a significant improvement of pigmentation with tretinoin, although the other trial did not report a significant difference with placebo. [3]

However tretinoin can be mixed with other ingredients to make it more effective in the treatment of melasma, including bleaching agents such as hydroquinone and fluocinolone acetate, which is a topical steroid. A recent systematic review of clinical trials, which looked at 20 studies of 2125 participants, has concluded that triple therapy with tretinoin, hydroquinone and fluocinolone acetate is more effective than hydroquinone alone, or dual combinations of tretinoin or hydroquinone with fluocinolone acetate. [3]

Topical retinoids are recommended as a first line treatment option either on their own or in combination with other treatments for mild acne. They are also recommended as a first line treatment option for moderate and severe acne in combination with other treatments. [4]

Tretinoin as a single therapy has been found to be effective in clinical trials for comedonal acne (blackheads and whiteheads) and inflammatory acne (papules (small bumps), nodules (large bumps) and pustules). [5][6]

Tretinoin is especially good in treating comedonal acne, and is also recommended to treat all acne variants when combined with other ingredients. [4] For example the combination of tretinoin with clindamycin (an antibiotic) has been shown to be more effective than either tretinoin or clindamycin alone. [7][8]

Topical antibiotics alone have been shown to be effective in treating acne but are no longer recommended as single therapy due to concerns of resistance. They can however be safely given in combination with other ingredients such as tretinoin.

Older studies have shown adapalene (a different topical retinoid) may be better tolerated than tretinoin; however, this is based on old formulations. Limitations of the existing studies makes direct comparison of the effectiveness of different topical retinoids difficult. [4]

1 Darlenski R, Surber C, Fluhr J. Topical retinoids in the management of photodamaged skin: from theory to evidence‐based practical approach. British Journal of Dermatology. 2010;163(6):1157-65.

2 Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clinical interventions in aging. 2006;1(4):327.

3 Rajaratnam R, Halpern J, Salim A, Emmett C. Interventions for melasma. The Cochrane Library. 2010.

4 Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, et al. Guidelines of care for the management of acne vulgaris. Journal of the American Academy of Dermatology. 2016;74(5):945-73. e33.

5 Krishnan G. Comparison of two concentrations of tretinoin solution in the topical treatment of acne vulgaris. The Practitioner. 1976;216(1291):106-9.

6 Christiansen J, Holm P, Reymann F. The retinoic acid derivative Ro 11-1430 in acne vulgaris. Dermatology. 1977;154(4):219-27.

7 Zouboulis C, Derumeaux L, Decroix J, Maciejewska‐Udziela B, Cambazard F, Stuhlert A. A multicentre, single‐blind, randomized comparison of a fixed clindamycin phosphate/tretinoin gel formulation (Velac®) applied once daily and a clindamycin lotion formulation (Dalacin T®) applied twice daily in the topical treatment of acne vulgaris. British Journal of Dermatology. 2000;143(3):498-505.

8 Richter J, Förström L, Kiistala U, Jung E. Efficacy of the fixed 1.2% clindamycin phosphate, 0.025% tretinoin gel formulation (Velac®) and a proprietary 0.025% tretinoin gel formulation (Aberela®) in the topical control of facial acne. Journal of the European Academy of Dermatology and Venereology. 1998;11(3):227-33.