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Comment on: The relationship between statins and depression: a review of the literature

You et al. comprehensively reviewed the relationship between statins and depression. They concluded that statins may cause depressive symptoms, although they point out that a number of issues still need to be addressed [1]. Some comments may be of interest. Some of the evidence supporting a possible association between statins and depression comes from fragmented reports and relatively small-scale studies with selected samples. Further, a recent meta-analysis involving seven controlled trials (n = 2105) found that statins had no significant effect on the development of depression compared with placebo, while statins were associated with statistically significant improvements in mood scores in the sensitivity analyses [2]. In addition, no significant differences were found when such effects were compared by longterm (3 -4 years), intermediate (3 -6 months) and short-term (4 weeks) use of statins. In 14 registration trials of pravastatin [3], the incidence of depression did not differ in 2485 patients treated with pravastatin or resin for up to 2 years; depression was reported in 1.6% (9/572) of resin-treated patients and 1.1% (21/1913) of patients receiving pravastatin. Further, a cohort study including 46,249 patients from 2003 to 2010 [4] created 6972 statin users and 6972 non-users by a propensity score-matched cohort design among the data of statin users (13,626 patients) and non-users (32,623 patients). In this study, the odds ratio of statin users for developing depression was only 1.02 (95% confidence interval: 0.94 -1.11) [4]. The risk of developing depression was also similar after 4.5 years of follow up in this cohort between users and non-users of statin [4]. The safety and tolerability data from post-marketing surveillance may produce a more complete picture of the overall safety profile of a certain drug, compared with controlled trials. In this context, Bristol-Myers Squibb’s post-marketing surveillance of over 1.5 million patients treated with pravastatin has shown only occasional reports of depression but no relation between pravastatin and depressive symptoms [3]. A number of epidemiological and preclinical studies have proven the potential benefit and role of omega-3 fatty acids (another lipid lowering agent) in the development and management of depression [5]. As for biological aspects, pravastatin was found to significantly increase plasma adiponectin levels, which has been involved in depressive-like behaviors and innovative therapeutic approach for depression [6]. An enhancement of the proteolytic cleavage of pro-brain-derived neurotrophic factor by statins has been suggested to be beneficial for treating depression and cognitive impairment [7]. Pravastatin is relatively hydrophilic and is not significantly metabolized by cytochrome P450 enzymes and is safe to use with antidepressants [8]. Further, the neurorestorative effect of some statins has been proposed to be mediated through activation of the Akt-mediated signaling pathway, subsequently upregulating the expression of growth factors as well as neurogenesis of the hippocampus, which should be beneficial in a recovery of cognitive function in patients with depression [9]. Statins may prevent metabolic syndrome associated with psychotropics [10] and may reduce the risk associated with metabolic syndrome. Maintaining safe