Table 5.

RCTs comparing oral tetracycline versus placebo.

Ref	Number of people	Treatment, dose, duration	Results	Comment
	108 people with mild to moderate acne	Oral tetracycline 500 mg twice daily v clindamycin phosphate 1% twice daily v placebo, for 8 weeks	Severity: No data reported Inflammatory lesions: Within-group comparison found that oral tetracycline significantly reduced inflammatory lesions from baseline, whereas placebo did not (mean inflammatory lesion count: 2.66 with tetracycline; P = 0.0001; mean inflammatory lesion count with placebo: 6.24; reported as NS, CI not reported) Patient perception of improvement: “Markedly improved” or “improved” from baseline: 72% with tetracycline v 3% with placebo; P values not reported Adverse effects: 1 person taking tetracycline and 1 taking placebo had diarrhoea	No direct comparison of tetracycline v placebo, as trial designed to compare oral tetracycline v topical clindamycin. Completer analysis in 87 people, no intention-to-treat analysis performed
	367 people with moderate to severe acne	Clindamycin phosphate 1% v oral tetracycline v placebo, for 8 weeks	Severity: Tetracycline significantly increased the proportion for whom physician assessment of treatment was “excellent” or “good” compared with placebo (64% with tetracycline v 46% with placebo; P less than 0.05) Inflammatory lesions: No data reportedPatient perception of improvement: Tetracycline significantly increased the proportion of people who thought their acne was “markedly improved” or “improved” compared with placebo (84% with tetracycline v 57% with placebo; P less than 0.05)Adverse effects: 9 people taking tetracycline v 6 people taking placebo had diarrhoea. 4 people taking tetracycline had epigastric pain	Completer analysis in 305/367 [83%] people who completed the trial. Unclear how assessments by physician or patient were defined
	75 people with moderate acne	Oral tetracycline 250 mg twice daily plus topical placebo v topical tetracycline 0.5% plus oral placebo v topical plus oral placebo, for 13 weeks	Severity: Tetracycline significantly reduced severity compared with placebo at 6 weeks (mean reduction in acne severity grade measured or a scale from 0 [least severe]–8 [most severe]: 1.14 with tetracycline v 0.43 with placebo; P less than 0.05) and 13 weeks (mean reduction in acne severity grade: 1.91 v 0.62; P less than 0.05)Inflammatory lesions: No data reported Patient perception of improvement: No data reported Adverse effects: No data reported	Observer blinded only. Results should be interpreted with caution because intention-to-treat analysis not performed, and 11/75 [15%] people withdrew from the trial
	60 male adolescents with mild to moderate acne	Oral tetracycline plus topical vehicle v oral placebo plus topical tetracycline v oral placebo plus topical vehicle, for 8 weeks	Severity: Improvement from baseline of 1 or more on a scale from 0 to 8: 12/18 [67%] with oral tetracycline v 14/19 [74%] with topical tetracycline v 6/17 [35%] with placebo Inflammatory lesions: No data reportedPatient perception of improvement: No data reported Adverse effects: No data reported	Did not assess the significance of the difference among groups
	135 people aged 18–25 years with mild to moderate acne, Cook's grades 0 to 8)	Topical tetracycline 0.22% plus oral placebo v oral tetracycline plus topical vehicle v topical vehicle plus oral placebo, for 12 weeks	Severity: Tetracycline significantly reduced acne severity at 7, 10, and 12 weeks compared with placebo (P less than 0.05) Inflammatory lesions: No data reported Patient perception of improvement: No data reported Adverse effects: No data reported	Absolute results presented graphically
	51 people (severity of acne unclear)	Tetracycline 250 mg twice daily v placebo, for 12 weeks	Severity: Tetracycline significantly reduced severity compared with placebo at 12 weeks (change in Pillsbury modified score –2 with tetracycline v 0 with placebo; P = 0.001). Tetracycline significantly increased the proportion of people assessed as “improved” at 12 weeks (23/24 [96%] with tetracycline v 15/27 [56%] with placebo; P = 0.01) Inflammatory lesions: No data reported Patient perception of improvement: Reported in discussion section of article that patient perception of improvement “close” to clinical assessment; no further data provided Adverse effects: No data reported	Pillsbury modified score: assigns 1 point for a change equivalent to half a grade. Score of +1 to +4 = ''improved'', 0 = ''no change'' and –1 to –4 = ''worse''
	68 people with mild to moderate acne	Tetracycline plus placebo v ibuprofen plus placebo v tetracycline plus ibuprofen v placebo for 8 weeks	Severity: No data reported Inflammatory lesions: No significant difference in inflammatory lesions between tetracycline and placebo (% reduction: 26% with tetracycline v 16% with placebo; P = NS, CI not reported) Patient perception of improvement: No data reported Adverse effects: No data reported	May have lacked power to detect a clinically important difference among groups

NS, not significant; Ref, reference