Can Atorvastatin Cause Mood Changes?
Atorvastatin can cause mood and behavioral changes in some individuals, though this is not a common or well-established adverse effect in major clinical guidelines. The evidence is mixed, with case reports documenting psychiatric symptoms while controlled trials show conflicting results.
Evidence from Clinical Guidelines
Major cardiovascular and lipid management guidelines do not list mood changes as a recognized adverse effect of atorvastatin or other statins 1. The 2016 ESC/EAS dyslipidemia guidelines focus primarily on muscular symptoms (myalgia, myopathy, rhabdomyolysis) and liver enzyme elevations as the main adverse effects requiring monitoring 1. The 2008 AHA/ASA stroke prevention guidelines note that atorvastatin was well-tolerated in the SPARCL trial, with no significant differences in serious adverse events between treatment groups, though psychiatric effects were not specifically assessed 1.
Evidence from Case Reports and Observational Studies
Case series and individual reports document psychiatric adverse reactions with atorvastatin, including:
- Depression, irritability, aggression, violent ideation, anxiety, and paranoia have been reported in temporal association with atorvastatin initiation 2, 3
- In a 12-patient case series, atorvastatin was associated with mood/behavioral changes that commenced following initiation and resolved with discontinuation 2
- Specific cases included: depression and irritability in a male in his 50s on atorvastatin 20 mg (probable causality); aggression/irritability in a male in his 30s on fenofibrate + rosuvastatin + atorvastatin (probable causality); and violent ideation/anxiety in a male in his 30s on escalating atorvastatin doses (probable causality) 2
- A 79-year-old woman developed paranoia, anxiety, and behavioral changes 2.5 weeks after starting atorvastatin 10 mg, with complete resolution 4 days after discontinuation (Naranjo score: 5, indicating "probable" causality) 3
Evidence from Controlled Trials
Randomized controlled trials provide conflicting evidence:
- A 12-week RCT in bipolar disorder and major depressive disorder patients (n=60) found no significant differences in depression relapse, manic episodes, or cognitive outcomes between atorvastatin and placebo groups 4
- An experimental medicine study in healthy volunteers (n=50) showed that 7-day atorvastatin 20 mg increased recognition and processing of fearful facial expressions compared to placebo, suggesting effects on emotional processing, though this did not translate to changes in subjective mood or anxiety 5
- Preclinical studies suggest atorvastatin may have antidepressant effects by preventing LPS-induced depressive-like behavior in mice, potentially through anti-inflammatory mechanisms 6
Clinical Implications and Monitoring
When prescribing atorvastatin, consider the following:
- Mood and behavioral changes are possible but uncommon adverse effects that may occur within days to weeks of initiation 2, 3
- Temporal relationship is key: symptoms that begin shortly after statin initiation and resolve with discontinuation suggest causality 2, 3
- Rechallenge typically reproduces symptoms when causality is present 2
- Risk factors that may increase susceptibility include pre-existing psychiatric conditions, other statin-associated adverse effects (suggesting individual susceptibility), and factors affecting statin metabolism 2
Common Pitfalls
- Do not dismiss psychiatric symptoms in patients recently started on statins, even though this is not a widely recognized adverse effect in guidelines 2, 3
- Consider discontinuation trial if temporal relationship suggests causality, particularly if symptoms are severe (violent ideation, suicidal thoughts, severe depression) 2
- Document carefully the timing of symptom onset relative to drug initiation and any improvement with discontinuation 2, 3
- Be aware that most large cardiovascular trials did not systematically assess psychiatric outcomes, potentially underestimating this adverse effect 1