Sir: Evidence from randomized trials suggests that statins are very safe.1 Consequently, their widespread use is highly promoted, even in high doses, and among adults of all ages. However, we feel caution is warranted, particularly when striving for aggressive low-density lipoprotein (LDL) cholesterol targets. In general, subjects in statin trials have been free of many chronic diseases, such as prevalent cancer, severe renal impairment, and neurodegenerative and depressive disorders. In clinical practice, individuals with the aforementioned problems and other chronic ailments are commonly treated with statins to achieve LDL cholesterol–lowering targets. Hence, it is sometimes dangerous to extrapolate trial results to real-world practice. High-dose simvastatin alters cholesterol turnover in the brain.2 Low-dose simvastatin has caused significant decreases in positive affect in elderly volunteers.3 Additionally, violent behavior has been associated with hypocholesterolemia resulting from a novel apolipoprotein B gene mutation.4 Furthermore, victims of violent suicides were found to have lower frontal cortex gray-matter cholesterol content than victims of nonviolent suicides.5 Statins were introduced in 1987. During the 1990s, in Scotland, there was a sharp increase in antidepressant prescribing by physicians.6 It is certainly plausible that the increase in the use of antidepressants might have occurred as a result of statin- induced lower cholesterol levels, leading to more depression. As the prescribing of statins becomes more widespread and cholesterol-lowering goals more aggressive, practicing clinicians must be vigilant in recognizing behavior changes, particularly in elderly and depressed individuals. Mark R. Goldstein, M.D. Private Practice, Bonita Springs, Florida Luca Mascitelli, M.D. Medical Service, “Julia” Alpine Brigade, HQ, Udine, Italy Francesca Pezzetta, M.D. Cardiology Department, Hospital of Tolmezzo, Tolmezzo, Italy