Abstract

Background

Minocycline is an oral antibiotic used for acne vulgaris. Its use has lessened due to safety concerns (including potentially irreversible pigmentation), a relatively high cost, and no evidence of any greater benefit than other acne treatments. A modified‐release version of minocycline is being promoted as having fewer side‐effects.

Objectives

To assess new evidence on the effects of minocycline for acne vulgaris.

Search methods

Searches were updated in the following databases to November 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched trials registers and checked reference lists for further references to relevant randomised controlled trials (RCTs).

The Cochrane Skin Group's Trials Search Co‐ordinator undertook searches exploring minocycline's adverse effects in EMBASE and MEDLINE in February 2012.

Selection criteria

We selected randomised controlled trials (RCTs) comparing minocycline, at any dose, to an active or a placebo control, in participants with inflammatory acne vulgaris. For adverse effects, we selected additional studies that reported the number of adverse effects and the number of participants treated.

Data collection and analysis

Outcome measures used in the trials included lesion counts, acne grades/severity scores, doctors' and participants' global assessments, adverse effects, and dropout rates. Two authors independently assessed the quality of each study. Effect sizes were calculated, and meta‐analyses were undertaken where possible.

Sixteen studies met the inclusion criteria for the review of adverse effects.

Main results

We included 12 new RCTs for this update, giving a total of 39 RCTs (6013 participants). These additional 12 RCTs have not changed the original conclusions about the clinical efficacy of minocycline.

The identified RCTs were generally small and poor quality. Meta‐analysis was rarely possible because of the lack of data and different outcome measures and trial durations. Although minocycline was shown to be an effective treatment for moderate to moderately‐severe acne vulgaris, there was no evidence that it is better than any of the other commonly‐used acne treatments. One company‐sponsored RCT found minocycline to be less effective than combination treatment with topical erythromycin and zinc. No trials have been conducted using minocycline in those participants whose acne is resistant to other therapies. Also, there is no evidence to guide what dose should be used.

The adverse effects studies must be interpreted with caution. The evidence suggests that minocycline is associated with more severe adverse effects than doxycycline. Minocycline, but not other tetracyclines, is associated with lupus erythematosus, but the risk is small: 8.8 cases per 100,000 person‐years. The risk of autoimmune reactions increases with duration of use. The evidence does not support the conclusion that the more expensive extended‐release preparation is safer than standard minocycline preparations.

Authors' conclusions

Minocycline is an effective treatment for moderate to moderately‐severe inflammatory acne vulgaris, but there is still no evidence that it is superior to other commonly‐used therapies. This review found no reliable evidence to justify the reinstatement of its first‐line use, even though the price‐differential is less than it was 10 years ago. Concerns remain about its safety compared to other tetracyclines.

Author(s)

Sarah E Garner, Anne Eady, Cathy Bennett, John Norman Newton, Karen Thomas, Catalin Mihai Popescu

Abstract

Plain language summary

Minocycline for acne vulgaris: efficacy and safety

Acne is the most common skin disease of adolescence, and in most cases it clears spontaneously. However, in some people it persists in to adulthood. There are many different treatment options, but there is little good evidence to inform doctors and individuals about which to choose.

Minocycline was the most prescribed antibiotic used to treat acne because it was thought to be better than other options, despite the original version of this review finding no reliable evidence that it was any better than other treatments. Over recent years it has been used less, which was due to serious concerns about its safety, including skin pigmentation, which in some cases is irreversible. It was also more expensive than other treatments.

Since the first version of this review, minocycline's cost has fallen. In the UK, the daily cost of generic minocycline is now one third the cost of tetracycline. This update was undertaken to identify whether there was any new evidence that might change the conclusions of the original review or provide information on risks associated with minocycline therapy. Twelve new RCTs were identified, making a total of 39 RCTs (6013 participants).

In summary, there is no evidence to support the first‐line use of minocycline in the treatment of acne. All of the trials showed that, on average, people treated with minocycline experienced an improvement in their acne. However, no study conclusively showed any important clinical difference between minocycline or other commonly‐used therapies. The analysis found that minocycline may act more quickly than oxytetracycline or tetracycline, but there is no overall difference in the end. There is no evidence that it is more effective in acne that is resistant to other therapies, or that the effects last longer. Although it is often claimed that the more expensive once‐daily slow‐release preparation is a more attractive option to teenagers with acne, the evidence in this review does not show it to be any better or safer compared to other oral antibiotics that have to be taken more frequently.

Despite a thorough search for evidence, it is still not known which of the tetracyclines are the safest to take overall as they are all associated with side‐effects. The only conclusion that we could make was that people treated with minocycline for acne are at a significantly greater risk of developing an autoimmune (lupus‐like) syndrome than those given tetracycline or no treatment.

Author(s)

Sarah E Garner, Anne Eady, Cathy Bennett, John Norman Newton, Karen Thomas, Catalin Mihai Popescu

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

The additional 12 RCTs that were located for the update have not changed the original conclusions about the clinical efficacy of minocycline. The 39 RCTs now included in this review do not provide any evidence to support the first‐line use of minocycline in the treatment of acne. Although it has been shown to be an effective treatment for moderate to moderately‐severe acne vulgaris at a dose of 100 mg per day, no study has conclusively shown any important clinical difference between minocycline and other commonly‐used therapies. Meta‐analysis indicated that minocycline may have a more rapid onset of action than tetracycline or oxytetracycline, but overall efficacy in the longer‐term is similar. There is no evidence that minocycline is more effective in acne resistant to other therapies, or that it has a more prolonged effect. Insufficient information was found to make any recommendations concerning the appropriate dose that should be used.

The relative safeties of the tetracyclines have still not been adequately determined, and little further information could be derived from the included RCTs because of their inherent inability to detect rare events. Recent reviews of case reports and case series (Gough 1996; Shapiro 1997) suggest that minocycline therapy for acne may be associated with a broader spectrum and a higher incidence of severe adverse effects than other tetracyclines. The lack of a denominator in nearly all of the studies means that the risks for minocycline compared to other tetracyclines cannot be compared. Only in the case of lupus‐like syndrome has it been conclusively shown that acne participants treated with minocycline are at a significantly greater risk than those given tetracycline or no treatment (Sturkenboom 1999). The risk of developing pigmentation (which can be irreversible) and lupus‐like syndrome increases with cumulative dose.

Implications for research 

The poor methodological quality of the acne trials was highlighted in the original version of this review. This was also the case for many of the trials identified in this update, with a few notable exceptions. In order to enable comparison of acne treatment, either directly or indirectly through modelling, an agreed set of core outcome measures should be developed. Until this has been done, trialists are encouraged to include lesion counts and quality of life as outcome measures.

It is surprising that very basic information about acne therapy with the tetracycline group of antibiotics is still unavailable.

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