Can spironolactone cause insomnia, restlessness, or sexual dysfunction (decreased libido)?

Spironolactone and Sexual/Sleep Side Effects

Spironolactone frequently causes decreased libido due to its potent anti-androgenic effects, but insomnia and restlessness are not recognized side effects of this medication. 1, 2

Decreased Libido: Well-Established Side Effect

Decreased libido is a frequent and dose-dependent side effect of spironolactone, particularly in men, caused by its anti-androgenic mechanism. 1

Mechanism of Action

• Spironolactone potently inhibits testosterone and dihydrotestosterone binding to androgen receptors at target tissues 1, 3
• The drug decreases testosterone production directly at the testicular level and may inhibit 5-alpha-reductase activity 1, 3
• This dual mechanism—blocking both androgen synthesis and receptor binding—explains the high frequency of sexual side effects 3, 4

Clinical Frequency by Population

• In men with cirrhosis and ascites, the British Society of Gastroenterology identifies decreased libido as one of the most frequent side effects, occurring alongside impotence and gynecomastia 1
• In women treated for acne, decreased libido is acknowledged but less prominently featured than menstrual irregularities and breast tenderness 1, 5
• In ophthalmology patients treated for central serous chorioretinopathy, decreased libido is listed among the most common side effects 1

Dose-Dependency

• Sexual side effects are strongly dose-dependent, with substantially higher risk at doses ≥150 mg/day 1, 6
• Gynecomastia incidence demonstrates this relationship: 52.2% at ≥150 mg/day versus only 6.9% at 50 mg/day 1, 6
• Lower doses (75-100 mg daily) are as effective as higher doses (150-300 mg daily) for acne treatment but with substantially fewer sexual side effects 1, 5

Insomnia and Restlessness: Not Documented Side Effects

Insomnia and restlessness are not listed among the documented side effects of spironolactone in current guidelines. 2

Recognized Side Effects Instead Include:

• Headache (>10% of patients) 2
• Diarrhea (>10% of patients) 2
• Fatigue (1-2% of patients)—note this is the opposite of restlessness 2
• Menstrual disruption (15-30% in women, dose-dependent) 2
• Breast tenderness (3-5%) 2
• Dizziness (3-4%) 2
• Nausea (2-4%) 2
• Polyuria/diuresis (1-2%) 2

Clinical Pitfall to Avoid

• If a patient reports insomnia or restlessness while taking spironolactone, investigate alternative causes rather than attributing these symptoms to the medication 2
• Review concomitant medications that may cause these symptoms (e.g., stimulants, decongestants, other medications) 2

Management Strategies for Sexual Side Effects

When decreased libido occurs, consider dose reduction as the first-line strategy, as lower doses maintain efficacy while reducing anti-androgenic effects. 1, 5

Specific Approaches:

• Start with the lowest effective dose (75-100 mg daily for acne; 50 mg daily for other indications when possible) 1, 5
• Consider alternative aldosterone antagonists such as eplerenone, which has 3- to 10-fold reduced affinity for androgen and progesterone receptors, resulting in fewer sexual side effects 1, 7, 6
• Potassium canrenoate may also produce fewer sexual side effects compared to spironolactone 1

Key Distinction Between Agents:

• Eplerenone's selective mineralocorticoid receptor antagonism (lacking the 17-alpha-thioacetyl group present in spironolactone) substantially reduces the likelihood of endocrine side effects including loss of libido, menstrual irregularities, gynecomastia, and impotence 7