Spironolactone and Anxiety: Evidence-Based Assessment
Spironolactone does not cause anxiety as a recognized adverse effect; in fact, limited evidence suggests it may have anxiolytic properties, though decreased libido and other hormonal side effects are well-documented.
FDA-Approved Adverse Effects
The FDA drug label for spironolactone lists the following nervous system and psychiatric adverse reactions: lethargy, mental confusion, ataxia, dizziness, headache, and drowsiness 1. Anxiety is notably absent from the official adverse effect profile 1.
The reproductive and hormonal side effects that are well-established include 1:
- Decreased libido (occurring in >10% of patients) 2, 3
- Inability to achieve or maintain erection in men 1
- Irregular menses or amenorrhea in women 1
- Breast and nipple pain 1
Guideline-Based Side Effect Profile
The American Academy of Dermatology's 2024 guidelines on acne management identify the common side effects of spironolactone as 4:
- Diuresis
- Breast tenderness and enlargement
- Gynecomastia
- Fatigue
- Headache
- Dizziness
- Menstrual irregularities (40.6% vs 0% compared to placebo)
Anxiety is not mentioned among the documented side effects in these comprehensive guidelines 4.
Research Evidence on Anxiety and Mood
Interestingly, the available research suggests spironolactone may have anti-anxiety effects rather than anxiety-inducing properties:
Animal and Human Experimental Studies
- A 2007 study in healthy men found that MR blockade with spironolactone (300 mg) did not affect experimentally induced panic symptoms after CCK-4 administration, though it did impair cognitive function 5.
- Animal research from 2019 demonstrated that blocking MR with spironolactone induced anxiety-like behavior in rats with intact adrenal glands, but this effect was mediated through inhibition of hippocampal neurogenesis 6.
Clinical Observations
- A 2014 observational study in women with fibromyalgia found that spironolactone improved anxiety and depression scores: anxiety decreased significantly, and negative mood improved from 35.4 to 10.0 on a 60-point scale over 12-14 months 7.
- A 1978 case series reported successful prophylactic use of spironolactone in six manic-depressive patients who had been maintained on lithium, suggesting mood-stabilizing rather than anxiety-inducing properties 8.
Clinical Context and Caveats
The confusion about spironolactone causing anxiety may stem from its well-documented sexual side effects, which can secondarily affect mood and quality of life 2, 3:
- Decreased libido is dose-dependent and occurs more frequently at higher doses 3
- Sexual dysfunction may indirectly contribute to psychological distress 2, 3
- Starting with lower doses (50-100 mg daily) minimizes these hormonal side effects 3
Important Monitoring Considerations
- The cognitive impairments documented with spironolactone include selective attention deficits, visuospatial memory problems, and reduced mental flexibility 5
- These cognitive effects, rather than direct anxiogenic properties, may be misinterpreted as anxiety symptoms 5
If a patient reports anxiety while taking spironolactone, consider alternative explanations including the underlying condition being treated, concurrent medications, or the psychological impact of sexual side effects rather than a direct pharmacological anxiety-inducing effect 2, 3, 1.