Efficacy of oral azithromycin versus oral doxycycline in treating moderate acne vulgaris and their effects on patients’ quality of life

Abstract

This study aimed to compare the efficacy of oral azithromycin with oral doxycycline in moderate acne vulgaris and to assess the corresponding changes in patient-reported quality-of-life. In this open label, randomised controlled trial conducted at a university student clinic, Muscat, Oman, 163 patients with moderate and severe acne vulgaris were assigned equally to receive either oral azithromycin or oral doxycycline. Treatments were administered over a three-month period with monthly clinical assessments. Acne severity was quantified using a validated acne severity scale, and quality of life was measured at baseline and at study end via a standardised questionnaire. Analyses were performed using univariate statistics. The cohort comprised 163 participants (mean age 20.2 ± 1.7 years; 67.3% female). Both groups experienced significant and comparable reductions in acne severity after three months. Parallel, statistically significant improvements were observed in quality-of-life scores across domains related to symptoms, emotional well-being, and social functioning. Oral azithromycin and doxycycline demonstrate equivalent efficacy in reducing moderate acne vulgaris and both confer substantial enhancements in patients’ quality of life. These findings support either antibiotic as an appropriate option for addressing both the dermatological and psychosocial burdens of moderate acne. The trial was registered with the Australia New Zealand Clinical Trial Registry (ACTRN12619000073101; Date: 18^th of January 2019).

Introduction

Acne vulgaris is an inflammatory disorder of the pilosebaceous unit, in which proliferation of Cutibacterium acnes is precipitated by increased androgen activity during adolescence¹. Clinically, it manifests as a mixture of comedones, papules, pustules and nodules on the face, upper arms, trunk, and back, with global prevalence estimates among adolescents ranging from approximately 35% to over 90%².

When moderate to severe inflammatory lesions fail to response adequately to topical therapies, systemic antibiotics such as doxycycline and azithromycin are indicated³. Doxycycline, a tetracycline derivative, has long been considered first-line but is frequently associated with photosensitivity and gastrointestinal upset⁴. In contrast, azithromycin, a macrolide, offers a more favorable side-effect profile and is deemed safe for use during pregnancy and lactation^4,5. Comparative studies have yielded mixed outcomes: some report superior lesion-count reductions with doxycycline, while others demonstrate equivalent efficacy for azithromycin^5,6.

Although often dismissed as a transient adolescent condition, acne vulgaris imposes a substantial psychosocial burden that extends well beyond cutaneous involvement⁷. Affected individuals frequently experience diminished quality of life, impaired self-esteem and increased symptoms of anxiety and depression⁸. In adults, acne has also been linked to higher unemployment rates and, in severe cases, elevated risk of suicidal ideation⁹.

Multiple investigations confirm that stigmatization and peer teasing further exacerbate psychosocial distress in acne patients^10,11. Epidemiological data consistently show greater impairment among females⁸, with one study at King Abdulaziz University Hospital in Jeddah identifying the role-social domain as most compromised among female students¹². Research at Sultan Qaboos University in Oman similarly found the role-emotional domain to be the most affected across both genders¹³.

Evaluating both clinical efficacy and psychosocial outcomes is essential for comprehensive acne management. This study thus compares oral doxycycline and azithromycin in moderate acne vulgaris, examining patterns of dropout and loss of follow-up, and assesses changes in health-related quality of life before and after treatment.

Methods

This phase IV, open-label, randomised controlled trial was conducted at the Sultan Qaboos University hospital student clinic, Muscat, Oman, from July 2023 to March 2024. Based on power calculations to detect an absolute difference in response rates of 25–50% with 90% power at an alpha of 0.05, a sample size of 170 patients (85 per arm) was required.

Students aged 17–25 years with newly diagnosed moderate acne vulgaris (per the Acne Severity Scale) were screened. Exclusion criteria included systemic antibiotic use within the preceding 3 months, pregnancy, current topical anti-acne or systemic steroid therapy, oral contraceptive use, active liver disease, or known allergy to azithromycin or doxycycline. Eligibility was confirmed by detailed history and complete physical examination.

Participants were stratified by gender and randomised—using a computer-generated sequence managed by an independent physician—to one of two treatment arms. Patients in the azithromycin arm received 500 mg once weekly (on Fridays) for the following 12 weeks, while those in the doxycycline arm were administered 100 mg once daily after meals throughout the 12-week treatment period. Monthly follow-up visits with an independent assessor documented acne severity and adverse events. Lesion clearance was categorised by percentage reduction—excellent (100%), good (80–90%), moderate (50–79%), mild (30–49%), and no response (< 30%)—and side effects reported using the hospital adverse drug reaction (ADR) form. The primary response to treatment was assessed by using the difference in the Global Acne Assessment Scale (GEA)¹⁴ before treatment and after 3 months of treatment.

All participants completed the validated Arabic acne-specific quality of life questionnaire (Acne-QoL) before treatment initiation and at week 12, assessing four domains: self-perception, role-social, role-emotional, and acne symptoms¹⁵. A total of 18 questions were distributed between these four domains. Permission to use the Acne-QoL was also obtained.

All participants were fully informed of the experimental procedures and possible risks (including, medications side effects) at time of recruitment. They were advised of their right to withdraw unconditionally at any time during the study period. A written informed consent was obtained from all the participants, plus from the parents or legal guardians if the participant’s age is less than 18 years old prior to enrolment. The study strictly adhered to the Declaration of Helsinki and was approved by the Medical Research Ethics Committee of the College of Medicine & Health Sciences (MREC#1914; 2/6/2019) and the trial was registered with the Australia New Zealand Clinical Trial Registry (ACTRN12619000073101; 18/1/2019).

Data were analysed using the Statistical Package for the Social Science (SPSS), Version 23 software (IBM Corp, Armonk, New York, USA). Quantitative variables are presented as mean ± standard deviation. Between-group differences were assessed by independent t-test when comparing genders and paired t-test for pre and post treatment. and one-way ANOVA for comparing the means as appropriate, with P < 0.05 denoting statistical significance.

Results

A total of 163 participants were randomised, with 83 (50.9%) assigned to the azithromycin group and 80 (49.1%) to the doxycycline group. Overall, 68.7% (n = 112) were female; the mean age was 19.75 ± 1.73 years (Table 1).

Table 1.

Age and gender distribution of study participants by treatment group (N = 163).

Characteristic	Azithromycin Group	Doxycycline Group	P Value
Age (mean ± SD)	19.95 ± 1.710	19.54 ± 1.743	0.550
Gender
Male	26%	25%	0.984
Female	57%	55%

SD standard deviation.

Baseline acne severity was comparable between groups (68 versus 64 moderates, 14 versus 16 severe, and 1 versus 0 very severe in the azithromycin versus doxycycline groups; P = 0.911; Table 2). After 12 weeks, both regimens produced marked improvement: in the azithromycin group, 35 participants achieved clear skin, 19 had mild and 7 had moderate residual lesions, with none remaining in severe or very severe categories; in the doxycycline group, 37 achieved clear skin, 16 mild and 3 moderate severity, with one patient each in the severe and very severe categories (P = 0.704). The mean acne severity score decreased steadily over the 12-week treatment period in both groups, with nearly identical trajectories observed for azithromycin and doxycycline recipients (Fig. 1).

Table 2.

Distribution of acne severity grades before intervention and after 12 weeks of treatment in the azithromycin and doxycycline groups (N = 163).

	Clear	Mild	Moderate	Severe	Very severe	P Value
Before intervention						0.911
Azithromycin group	0	0	68 (81.9%)	14 (16.9%)	1 ((1.2%)
Doxycycline group	0	0	64 (80.0%)	16 (20.0%)	0
After 3 months						0.704
Azithromycin group	57 (68.7%)	19(22.9%)	7 (8.4%)	0	0
Doxycycline group	59(73.8%)	16 (20.0%)	3 (3.8%)	1(1.2%)	1 (1.2%)

Fig. 1.

Percentage reduction in acne lesion count over 12 weeks in the azithromycin and doxycycline treatment groups.

Quality-of-life scores improved significantly across all Acne-QoL domains in both groups. In the azithromycin group, self-perception scores rose from 3.41 ± 1.55 to 4.56 ± 1.06 (P < 0.001), while in the doxycycline group they increased from 3.51 ± 1.10 to 4.68 ± 1.12 (P < 0.001). Role-emotional scores improved from 2.97 ± 1.27 to 5.07 ± 1.06 (P < 0.001); and symptom domain from 3.31 ± 1.14 to 4.49 ± 0.90 and from 3.26 ± 0.95 to 4.59 ± 0.90 (P < 0.001). No significant intergroup differences were observed in any QoL domain post-treatment (Table 3).

Table 3.

Pre- and post-treatment Acne-Specific Quality of Life (Acne-QoL) domain scores in azithromycin versus doxycycline recipients.

Subscale-level for the Acne-QoL	Group	Before	After	P Value
Self-perception	A	3.41 ± 1.55	4.56 ± 1.06	< 0.001*
	D	3.51 ± 1.1	4.68 ± 1.12	< 0.001*
Role emotional	A	2.97 ± 1.27	4.31 ± 1.15	< 0.001*
	D	3.11 ± 1.14	4.45 ± 1.03	< 0.001*
Role Social	A	3.76 ± 1.32	4.89 ± 1.03	< 0.001*
	D	3.93 ± 1.34	5.07 ± 1.06	< 0.001*
Acne Symptoms	A	3.31 ± 1.14	4.49 ± 0.9	< 0.001*
	D	3.26 ± 0.95	4.59 ± 0.9	< 0.001*

A azithromycin group; D doxycycline group.

Out of the total patients one patient from doxycycline group reported epigastric pain and 2 patients from azithromycin group reported diarrhoea and nausea, all of them completed the treatment. Regarding dropouts, two patients (2.5%) from doxycycline group stopped treatment because of lack of adherence while all patients in azithromycin group completed the treatment.

Discussion

This randomized controlled trial demonstrated comparable clinical efficacy between oral azithromycin and doxycycline in reducing acne lesions among young adults with moderate acne vulgaris after 12 weeks. The absence of statistically significant differences in treatment outcomes between these antibiotics aligns with prior literature. A meta-analysis of multiple randomized trials similarly concluded no discernible superiority between azithromycin and doxycycline, reinforcing their clinical interchangeability in treating inflammatory acne^16,17. Both antibiotics effectively reduce the growth and inflammatory activity of Cutibacterium acnes, highlighting their similar therapeutic profiles^5,16–18.

Pharmacological differences between these agents may influence clinician choice, despite similar efficacy outcomes. Doxycycline, a tetracycline-class antibiotic, requires consistent daily administration, and is commonly associated with gastrointestinal disturbances and photosensitivity, potentially influencing patient adherence and comfort^19,20. In contrast, azithromycin, a macrolide antibiotic, exhibits a longer tissue half-life allowing less frequent dosing^21,22. The current study’s high adherence rates in both groups underscore both regimens’ acceptability; however, azithromycin’s intermittent dosing potentially offers superior patient convenience and compliance, particularly relevant for students or young adults managing complex schedules²³. Literature consistently highlights the adherence benefits of simplified dosing regimens, especially among adolescent and young adult populations who typically display variable adherence behaviors^22–24.

Importantly, the current trial reported minimal adverse events, aligning with other studies emphasizing favorable safety profiles for both azithromycin and doxycycline in acne therapy^19,24. Nonetheless, doxycycline’s higher propensity for gastrointestinal side effects and photosensitivity reactions remains clinically relevant, particularly in geographical regions with significant sun exposure or in patients susceptible to these side effects^19,20. Conversely, azithromycin’s comparatively mild adverse effect profile, absence of significant photosensitivity risks, and reduced pill burden may favor its selection in specific patient contexts, facilitating optimal antibiotic stewardship and patient satisfaction.

In addition to clinical efficacy, this study demonstrated significant and parallel improvements in acne-related QoL across multiple domains—self-perception, role-social, role-emotional, and acne symptoms—highlighting the broad psychosocial impact of acne management. Prior research consistently documents the substantial psychological morbidity associated with acne, including diminished self-esteem, anxiety, and depression^25–28. The current findings support evidence suggesting that effective acne treatment significantly alleviates these psychosocial burdens. For instance, studies by Kaikati et al. and Gallitano and Berson reported substantial QoL gains among acne patients upon clinical improvement, regardless of antibiotic regimen employed^25,26. The use of a culturally validated Arabic Acne-QoL questionnaire strengthens the reliability and relevance of these findings, underscoring the real-world significance of clinical improvements in acne for patient psychological and emotional health²⁹.

The high adherence and minimal dropouts observed further affirm favorable patient acceptance and manageable treatment regimens in this trial. A retention rate approaching 100% is uncommon in acne trials, particularly within adolescent and young adult demographics, which typically show substantial dropout rates due to adherence issues or side effects³⁰. Such high retention likely reflects effective patient counseling, manageable dosing regimens, and minimal adverse events observed in this study. Notably, the brief (12-week) treatment duration aligns with current dermatological guidelines advocating limited antibiotic use duration, contributing to adherence and minimizing resistance risks^31–33.

Antimicrobial resistance remains a critical global concern, mandating judicious antibiotic use in dermatology. Current acne treatment guidelines strongly advocate limiting systemic antibiotics to a maximum of three to four months, combined with topical agents such as benzoyl peroxide or retinoids, to mitigate antimicrobial resistance risks^32–35. Nevertheless, evidence suggests that prolonged antibiotic treatments exceeding recommended durations remain widespread, exacerbating resistance concerns^21,35. The current trial underscores that a short, guideline-concordant antibiotic regimen can achieve clinically meaningful results without extended exposure, emphasizing the feasibility and effectiveness of stewardship-compliant prescribing practices.

Clinically, the current findings advocate flexibility in antibiotic selection, enabling clinicians to personalize acne therapy based on patient-specific factors, such as adherence potential, side effect susceptibility, and lifestyle considerations. While doxycycline remains a traditionally preferred oral antibiotic for acne, azithromycin presents a valuable alternative, especially when considering its pharmacological benefits, favorable tolerability, and convenient dosing schedule. Furthermore, azithromycin’s demonstrated safety during pregnancy and lactation represents a critical therapeutic advantage over doxycycline, contraindicated in these scenarios due to teratogenic risks and potential impacts on fetal bone and dental development^36–38. Although the current study did not include pregnant or lactating patients, the broader implications of these safety considerations underscore azithromycin’s utility, particularly among reproductive-age female patients.

The findings also highlight the critical importance of addressing acne’s psychosocial dimensions during treatment planning. Acne’s profound impact on patient quality of life is well-documented, with patients frequently experiencing feelings of embarrassment, anxiety, and social withdrawal^25–27. Clinicians should therefore consider both dermatological and psychological outcomes when selecting acne therapies. The substantial QoL improvements observed reinforce the comprehensive benefit of achieving adequate acne clearance, promoting both dermatological and psychological well-being.

This study’s primary strengths include its randomized controlled design, use of validated and culturally appropriate QoL measurement tools, excellent adherence, and comprehensive assessment of both clinical and patient-reported outcomes. These elements significantly enhance internal validity, providing robust, reliable evidence supporting azithromycin and doxycycline’s comparable efficacy and tolerability in moderate acne.

However, several limitations warrant consideration. First, the open-label design inherently introduces expectation bias as it may lead to inflated outcomes and observer bias risks in terms of participants selection bias, provision of unequal care and outcome reporting bias, particularly relevant for subjective QoL outcomes. A double-blind approach would better control such biases, though differing dosing schedules of the medications presented practical challenges to blinding. Second, the single-center design and focused young adult population potentially limit external validity and generalizability. Broader multicenter studies involving diverse demographics could further validate the findings across varied clinical settings and populations. Third, the slight shortfall in participant enrollment (163 out of a planned 170 participants) marginally impacts statistical power, though the negligible difference observed between groups reduces the clinical relevance of this limitation. Lastly, the absence of longer-term follow-up precludes evaluating sustained treatment efficacy, durability of remission, and possible differences in relapse rates between the two antibiotics.

Conclusion

This randomized controlled trial substantiates oral azithromycin and doxycycline’s comparable clinical efficacy and significant QoL improvements in treating moderate acne vulgaris in young adults. Both antibiotics represent effective therapeutic options, with clinical decisions guided by patient-specific considerations, pharmacological properties, and stewardship guidelines. Adhering to short-duration antibiotic regimens, incorporating topical therapies, and closely monitoring psychosocial impacts ensure comprehensive, responsible, and effective acne management.

Author contributions

A.SH : Idea and design formulation, data analysis and interpretation, manuscript writing, over all supervision Y.A: data analysis and interpretation, manuscript writing J.S: data analysis and interpretation, manuscript writing A.S: Idea and design formulation M.K: design formulation, data analysis and interpretation, manuscript writing I.Z: Idea and design formulation, manuscript writing Z.B: design formulation, manuscript writing A.M: design formulation, manuscript writing.

Funding

No funding was received for this study.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.