Spironolactone Regret, Stopping, and Restarting: What Actually Happens

What the trials measured

Spironolactone is approved for NYHA Class III-IV heart failure with reduced ejection fraction, as add-on therapy for hypertension, for edema in cirrhosis or nephrotic syndrome, and for primary hyperaldosteronism; acne is off-label [2].

SAFA, a 2024 double-blind randomized trial, gave 410 women spironolactone 50 mg/day for 6 weeks then 100 mg/day to week 24, or placebo, alongside usual topical treatment [4]. At week 12, 18.5% versus 5.6% on placebo reached treatment success on the Investigator's Global Assessment (adjusted OR 5.18, 95% CI 2.18 to 12.28); participant-rated improvement at 24 weeks was 81.9% versus 63.3%. Headache was more frequent, 20.4% versus 12.0%, and there were no serious adverse reactions [4]. SAFA enrolled women aged 18 or older whose facial acne had persisted for at least 6 months and was judged to potentially warrant oral antibiotic treatment [4].

In a 403-woman case series, 75.5% had reduction or clearance of facial acne at first follow-up (84.0% chest, 80.2% back), and mean drug survival was 470.7 days [3]. A separate 110-woman series reported 94 improved, 61 cleared and 6 relapsed after improving [1].

Does acne come back when you stop?

The data above do not answer this directly. The 110-woman series counted six women who relapsed after initial improvement [1]. The 403-woman series records how long women stayed on the drug, not what happened after they left it [3]. SAFA ran to week 24 and reported outcomes while women were on treatment [4].

What a restart involves on the label

The Aldactone label says to monitor serum potassium within 1 week of starting or titrating and regularly afterward [2]. Potassium risk rises with impaired kidney function, potassium supplements, potassium-containing salt substitutes, ACE inhibitors and angiotensin receptor blockers; NSAIDs, heparin and trimethoprim are also named as potassium-raising drugs, and the label calls for a potassium check when ACE inhibitor or ARB therapy changes [2]. Contraindications are hyperkalemia, Addison's disease and concomitant eplerenone [2].

The label says to avoid spironolactone in pregnant women or advise them of the potential risk to a male fetus, based on anti-androgenic properties and rat data showing feminization of male fetuses; limited human case reports did not show an association with major malformations [2].

In 974 healthy young women taking spironolactone for acne, 13 of 1802 potassium measurements were abnormal (0.72%), close to a 0.76% baseline rate in a comparison group that included women taking and not taking spironolactone, and 6 of the 13 repeated normal; the authors concluded routine monitoring has low usefulness in that group, which excluded women with heart or kidney disease and those on drugs acting on the renin-angiotensin system [5].