Spironolactone Non-Responder Profile: Who Doesn't Respond and Why

What Counts as Non-Response?

Non-response is not a fixed category, and the results depend on the endpoint. In SAFA, 410 women were randomized (201 to spironolactone, 209 to placebo). Investigator's Global Assessment success at week 12 was 18.5% with spironolactone vs 5.6% with placebo (adjusted OR 5.18, 95% CI 2.18 to 12.28). At 24 weeks, 81.9% of the spironolactone group and 63.3% of the placebo group rated themselves improved [1]. Many women in the placebo group also reported improvement, because topical treatments were continued in both groups [1].

In a retrospective series of 110 women, 94 improved and 61 cleared completely; 16 did not improve and 6 relapsed after initial improvement [2]. That gives a non-improvement rate of 14.5% in that clinic population. A separate series of 403 women found reduction or complete clearance in 75.5% of those with face data at first follow-up [3]. These are uncontrolled observations, not predictor analyses.

Do the Studies Show Who Will Not Respond?

SAFA was designed to test whether spironolactone works overall, not to build a non-responder profile [1]. The 2017 systematic review found 10 randomized trials and 21 case series, all trials at high risk of bias, with low or very low quality evidence [5]. The two case series above report outcome rates, not baseline characteristics that predict who will not respond [3][2]. A woman whose acne does not improve therefore cannot be placed into a validated category from these data.

What About Dose and Timing?

The best randomized evidence used 50 mg/day for the first 6 weeks, then 100 mg/day through week 24 [1]. The Acne-Specific Quality of Life symptom difference favoring spironolactone was 1.27 (95% CI 0.07 to 2.46) at 12 weeks and 3.77 (95% CI 2.50 to 5.03) at 24 weeks [1]. The 2017 systematic review found that evidence for the usual doses of 100 mg/day or less was of limited quality; one crossover trial showed 200 mg/day was superior to placebo for inflamed lesions [5].

What the Label Says to Watch

Acne is not an FDA-labeled use of spironolactone. The labeled uses are heart failure, add-on therapy for hypertension, edema in cirrhosis or nephrotic syndrome, and primary hyperaldosteronism [4]. The label says to monitor serum potassium within 1 week of starting or changing the dose and regularly thereafter; risk rises with impaired kidney function, potassium supplements, potassium-containing salt substitutes, ACE inhibitors, and ARBs [4].