Key result
Simvastatin fails to alter facial expression recognition versus placebo but increases anxiety scores.
Why the study?
Simvastatin may be a candidate for drug repurposing in depression, but its neuropsychological effects on mood and cognition are not known.
Does simvastatin alter emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers?
RCT (n=53)
Double-blind
Randomly assigned
No
Does simvastatin alter emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers?
p-value: p=>0.20
A 7-day course of simvastatin in healthy volunteers induced a positive emotional bias alongside increased anxiety, hinting at potential early antidepressant-like effects.
Short-term simvastatin shows no core effect on emotional recognition in healthy volunteers; leaves open longer-term mood effects in clinical populations.
Rationale Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin’s influence on mood and cognition. Objectives We aimed to investigate the effects of simvastatin on a battery of psychological tests and inflammatory markers in healthy volunteers. Methods Fifty-three healthy subjects were randomly assigned to 7 days of either simvastatin ( N = 27) or sucrose-based placebo ( N = 26) given in a double-blind fashion. Then, participants were administered questionnaires measuring subjective rates of mood and anxiety, and a battery of tasks assessing emotional processing, reward learning, and verbal memory. Blood samples for C-reactive protein were also collected. Results Compared to placebo, participants on simvastatin showed a higher number of positively valenced intrusions in the emotional recall task ( F 1,51 = 4.99, p = 0.03), but also an increase in anxiety scores ( F 1,51 = 5.37, p = 0.02). An exploratory analysis of the females’ subgroup ( N = 27) showed lower number of misclassifications as sad facial expression in the simvastatin arm ( F 1,25 = 6.60, p = 0.02). No further statistically significant changes could be observed on any of the other outcomes measured. Conclusions We found limited evidence that 7-day simvastatin use in healthy volunteer induces a positive emotional bias while also being associated with an increase in anxiety, potentially reflecting the early effects of antidepressants in clinical practice. Such effect might be more evident in female subjects. Different drug dosages, treatment lengths, and sample selection need consideration in further experimental medicine and clinical studies. Trial registration Clinicaltrials.gov: NCT04652089.
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Giorgi et al. (2022) conducted an RCT in Healthy volunteers (n=53). Simvastatin vs. Sucrose-based placebo was evaluated on Accuracy at recognising the correct emotion (Facial Expression Recognition Task) (p=>0.20). Simvastatin 20 mg daily for 7 days did not significantly alter accuracy in facial expression recognition compared to placebo in healthy volunteers, though it increased positively valenced intrusions and anxiety scores.
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