Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous units that represents one of the most prevalent dermatological conditions worldwide, affecting an estimated 9.4% of the global population and ranking as the eighth most common disease globally[1]. The condition primarily manifests during adolescence and young adulthood, with prevalence rates ranging from 35% to over 90% among teenagers, though it can persist into or develop de novo during adulthood[2]. The pathophysiology of acne involves four primary factors: excessive sebum production driven by androgen stimulation, follicular hyperkeratinization with abnormal desquamation, proliferation of Cutibacterium acnes (formerly Propionibacterium acnes) within the pilosebaceous units, and subsequent inflammatory cascade activation[3].

The economic burden of acne is substantial, with direct costs in the United States estimated at over $3 billion annually, while individual patients typically spend $150-200 yearly on over-the-counter treatments[4]. Beyond financial implications, acne significantly impacts quality of life, particularly affecting self-esteem, body image, and psychosocial functioning. Studies demonstrate strong associations between acne severity and depression, anxiety, and social withdrawal, with patients showing 2.28 to 6.14 times higher odds of developing depressive symptoms compared to those with mild acne[5].

Topical antibiotics have traditionally formed a cornerstone of acne treatment, primarily targeting C. acnes colonization while providing anti-inflammatory effects through inhibition of bacterial protein synthesis and reduction of proinflammatory mediators[6]. Clindamycin phosphate, a lincosamide antibiotic, has been extensively utilized as a 1% topical gel formulation for moderate acne management. It demonstrates bacteriostatic activity against C. acnes and possesses anti-inflammatory properties that help reduce lesion formation and associated erythema[7]. However, widespread and prolonged use of topical clindamycin has contributed to increasing antimicrobial resistance, with studies reporting resistance rates exceeding 50% in some regions[8].

Minocycline, a second-generation tetracycline antibiotic, has emerged as an alternative therapeutic option with distinct advantages. Unlike oral minocycline, which poses systemic side effects including potentially irreversible pigmentation and autoimmune syndromes, the topical 4% minocycline gel formulation provides localized delivery with minimal systemic absorption[9]. The mechanism of action involves binding to the 30S ribosomal subunit, inhibiting bacterial protein synthesis, while additionally demonstrating potent anti-inflammatory effects through suppression of matrix metalloproteinases, cytokine production, and inflammatory cell migration[10]. Recent clinical trials have shown topical minocycline to be highly effective in treating moderate to severe acne, with the United States Food and Drug Administration approving 4% minocycline foam in 2019 for patients aged 9 years and older[11].

Comparative studies between topical minocycline and clindamycin phosphate have demonstrated superior efficacy of minocycline in reducing both inflammatory and non-inflammatory lesions. Indian population studies revealed significantly greater lesion reduction with minocycline 4% compared to clindamycin 1%, with better tolerability profiles and higher patient satisfaction rates[12]. Given the growing concerns about antibiotic resistance and the need for more effective topical treatments, comprehensive evaluation of these agents' comparative efficacy and safety profiles is essential for optimizing acne management strategies.

The present study aims to provide evidence-based data comparing the therapeutic efficacy and safety of topical 4% minocycline gel versus topical 1% clindamycin phosphate gel in patients with acne vulgaris, contributing to the development of more effective treatment protocols for this prevalent dermatological condition.

Study Design

This was a single-center, prospective, comparative, observational study conducted to evaluate and compare the efficacy and safety of topical 4% minocycline gel versus topical 1% clindamycin phosphate gel in patients with acne vulgaris. Participants were allocated in a 1:1 ratio to two treatment arms and followed over 12 weeks from baseline to final assessment.

Study Setting and Ethics

The study took place in the Department of Dermatology, Venereology, and Leprosy at Amaltas Institute of Medical Sciences, Dewas, Madhya Pradesh, India. Patients presenting to the outpatient dermatology clinic with clinically diagnosed acne vulgaris were screened for eligibility. Ethical approval was obtained from the Institutional Ethics Committee of Amaltas Institute of Medical Sciences, and the study adhered to the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from all participants, with parental consent for those under 18 years of age.

Study Population and Eligibility Criteria

Male and female patients aged 13 years and above with a clinical diagnosis of acne vulgaris were enrolled. Each potential participant underwent a detailed history, dermatological examination, and acne severity grading using the Comprehensive Acne Severity System (CASS).

Inclusion Criteria

• Age ≥ 13 years
• Male or female gender
• Clinically confirmed acne vulgaris
• Written informed consent (and parental consent for minors)

Exclusion Criteria

• Severe acne variants (acne conglobata, acne fulminans)
• Use of topical or systemic anti-acne therapy within 30 days prior to enrollment
• Secondary acne or acneiform eruptions
• Pregnancy or lactation
• Known allergy to minocycline or clindamycin
• Age < 13 years
• Inability or refusal to provide informed consent

Treatment Groups and Allocation

Participants were allocated to one of two groups by mutual discussion with the investigator after detailed counseling on benefits and potential side effects:

• Group A (n = 38): Topical 4% minocycline gel applied once nightly
• Group B (n = 38): Topical 1% clindamycin phosphate gel applied twice daily (morning and night)

All participants were instructed to use non-comedogenic sunscreen and moisturizer and to avoid any other acne treatments during the study.

Sample Size

Using standard statistical formulas for proportion estimates and a 95% confidence interval, the required sample size was determined to be 76 participants, with 38 in each treatment arm.

Outcome Measures

Primary Outcome

• Percentage reduction in total acne lesion count and improvement in CASS grading from baseline to Week 12

Secondary Outcomes

• Safety and tolerability, assessed by recording adverse effects (erythema, dryness, burning, peeling, photosensitivity, pruritus) at each follow-up visit
• Treatment adherence, evaluated via self-reported logs and assessment of returned unused medication
• Patient satisfaction, measured by a 5-point Likert scale at Week 12

Study Procedures and Data Collection

Baseline Assessment: Collection of demographic data, medical history, lesion counts (inflammatory and non-inflammatory), CASS grading, and standardized digital photographs under consistent conditions.

Follow-Up Visits: Scheduled at Weeks 2, 4, 8, and 12 to assess lesion counts, CASS grading, clinical photography, adverse events, adherence logs, and return of unused medication. At the final visit, patient satisfaction was recorded.

Statistical Analysis

Data were analyzed using Stata version 17. Descriptive statistics summarized baseline characteristics. Paired t-tests assessed within-group changes from baseline, while independent t-tests compared outcomes between groups at each time point. Categorical variables (adverse effects, satisfaction) were compared using chi-square tests. Multivariate logistic regression adjusted for potential confounders such as age, gender, and baseline severity.

Equipment and Materials

• Digital camera for clinical photography
• CASS grading charts
• Structured data collection proformas
• Visual analogue scales for subjective irritation assessment

Study Duration and Timeline

The study spanned 18 months, including a 12-month recruitment period and a 6-month follow-up completion. Individual participation lasted 12 weeks from baseline to final visit.

Funding and Conflicts of Interest

The study received institutional support without external funding. All costs were covered by the Principal Investigator. No financial compensation was provided to participants. The investigators declare no conflicts of interest, and no external party influenced the study design, conduct, or analysis.

Table 1 Demographic and Baseline Characteristics of study participants

Both groups had an equal gender distribution (68.4% female, 31.6% male). The minocycline group had more participants aged 26–30, while the clindamycin group had more aged 16–20.

Table 2 Acne Severity: Baseline vs. 12 Weeks post treatment

At 12 weeks, a higher proportion in the minocycline group achieved clear or almost clear skin (84.2% vs 57.9%), with no moderate or severe cases remaining. The difference was statistically significant.

Table 3 Lesion of study participants Count Over Time

Both groups started with similar lesion counts. The minocycline group showed a more rapid and greater reduction in lesions by week 12.

Table 4 Side Effects profile of study participants

Dryness, burning, peeling, and pruritis were notably more frequent in the clindamycin group, while other side effects were similar or less common.

Table 5 Patient Satisfaction and Adherence

Patient satisfaction was higher in the minocycline group, with 39.5% very satisfied compared to 7.89% in the clindamycin group. Adherence was also higher with minocycline, though the difference was not statistically significant.

The results of the study negate the findings of previous studies and show that topical minocycline 4% is more effective, safe, and patient-friendly than clindamycin 1%, in reproducing acne vulgaris. Although it can be characterized as a limitation of the study, the fact of the observed difference in the age distributions of the treatment groups perfectly coincides with the existing sources on the therapeutic benefits of minocycline and the rising issues of clindamycin resistance. The efficacy results in the study resoundingly support those of various Phase 3 clinical trials of topical minocycline foam (FMX101 4%). Minocycline 4% was shown to be considerably and superior to vehicle in both Investigator Global Assessment (IGA) success and reduction in the rate of inflammatory lesions in the critical studies conducted by Raoof et al. and Stein Gold et al.; both articles examined the topic of reduction of inflammatory lesions[13][14]. The statistically significant effect of minocycline treatment on skin and the percentage of respondents that have experienced clear or almost clear skin (a report of 84.2 percent for the treatment compared to 57.9 percent with clindamycin) is a close match with the high-reliability in these mass studies and the sample sizes of more than 1,500 enrolled participants. Shiva Kumar et al. performed a multicentric study on the use of topical minocycline 4 percent gel in India and compared this with clindamycin 1 percent gel, showing statistically significant better results in terms of improvement in the inflammatory and non-inflammatory lesions (p < 0.0001)[15]. The treatment success of the IGA treatment reported higher in the group of minocycline at week 9 and 12 with results similar to the one in the current study. On a positive note, in this Indian study, minocycline was established to be superior to clindamycin in adolescent subgroups implying that the treatment benefit is not limited to only one age group. The noticeably reduced frequencies of adverse effects of minocycline 4% (especially the dryness, as 7.89% compared to 31.6% of clindamycin) correlate with a considerable amount of safety information obtained during a clinical trial. The Phase 3 trials were also in agreement that there was less than 1 percent of those treated with minocycline 4 percent who experienced adverse events involving the skin[14]. Conversely, there are very high select rates of irritation with its clindamycin-based formulation so that research reported 55 percent dry skin patients on clindamycin-benzoyl peroxide combinations[16]. Its tolerability benefit is of high significance to minocycline, as the side effects in their opinion are the main cause of treatment withdrawal in 37.7 percent of patients that drop out of acne treatment [17] The high level of safety which was initially recorded that supported the current study is attributed to dermal safety studies which demonstrated the topical minocycline foam to have no phototoxicity, photo allergy, skin sensitization, and substantial irritation[18]. Patient Satisfaction/Compliance There is a considerable greater satisfaction with minocycline (39.5 percent very satisfied as compared with 7.89 percent with clindamycin). International research shows that the compliance with acne treatments is only 50 percent in average[19]. The most important reasons which preclude compliance are the side effects. The higher rates of adherence rates with minocycline (47.37 percent valid adherence >90 percent versus 28.95 percent recipients obtain >90 percent adherence clindamycin) are consistent with the study that simplifying treatment, enhancing tolerability of treatment, and make improvements in adherence[17]. A research in a group of 428 Japanese patients with acne revealed that treatment satisfaction and side effects represented the most influential constructs affecting adherence[20]. The finding of this relationship is corroborated by the current study where high tolerability of minocycline was reflected in enhance patient satisfaction levels and adherence patterns. The research results fall under the environment of increasing concerns on antibiotic resistance in acne therapy. Even global surveillance statistics have indicated that the rates of clindamycin resistance are widely different depending on the geographical location with the rates resting at 16.7 percent in Israel and 65.8 percent in India[21]. Minocycline on the other hand exhibits the lowest resistance rate in all the groups it was studied and often has a rate of less than 11 percent in most high-resistance-to-otherantibiotics regions[21]. Resistance The resistance profile of Cutibacterium acnes isolates in India was 73.7 percent to azithromycin, 65.8 percent to clindamycin but only 5.3 percent to minocycline[22]. The clinical preference towards the use of minocycline that has been observed in the present study will be strongly supported through this resistance pattern, because, minocycline does not only offer an immediate therapeutic boost, but also offers sustainability. The limitation of the study that had unbalanced selection between the age groups (minocycline group had more 26-30 year-olds, while clindamycin group had more 16-20 year-olds) worked in favor of the study when one considers the literature of treatment response to older adults against younger ones. In a number of fundamental ways adult acne is quite different to adolescent acne, including being generally more resistant to treatment, associated with higher frequencies of inflammatory lesions and of scarring[23][24]. It was found that the skin of an adult is more susceptible to topical treatment, and this aspect of tolerability is very important to the success of the treatment[25]. The excellent tolerability profile in minocycline is even more beneficial in adult populations, where the compliance of treatment is also likely (due to increased linear sensitivity of skin). The clinical significance of these findings is even increased by the fact that even though some more potentially resistant to treatment adult patients were included in this minocycline group, its efficacy outperformed the cannabis-based one. The 12 weeks is the normal regulation time to check the acne trials, but a longer study would give fascinating knowledge as to long-term performance and the likelihood of relapse. Topical minocycline foam extension studies beyond 2 months have shown a continuing efficacy and safety up to 52 weeks[26] that would benefit from long-term treatment. The results of the study are very important to clinical practice especially when it comes to the changing acne treatment guidelines. The latest guidelines focus on the less than 12-week restriction on antibiotic use and are not worried with antibiotic monotherapy[21]. Minocycline is a viable alternative because its higher efficacy and tolerability offers the potential of reaching initial control quickly and with low risk of the development of resistance. This is because the resistance rates of minocycline in the world population is low and therefore it might be a longer-term cure than clindamycin. It is of special concern, considering that long-lasting antibiotics consumption is still prevalent in the clinical practice, where 64 percent of patients are treated longer than 3 months [21].

This comparative study has shown that topical minocycline proved to be more efficient, more tolerable, and patient satisfaction, than clindamycin in a 12-week acne vulgaris case. These findings indicate that in clinical practice, minocycline can be a better alternative with higher patient preference in treating moderate acne. It should be noted that these findings may require further studies of bigger and heterogeneous cohorts as well as higher follow-up intervals.

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