Statins and Antidepressants: A Comprehensive Review and Clinical Outlook of the Risks and Benefits of Co-prescription (2022)

Abstract

Antidepressants are the most prescribed medications in the United States, and the most frequently prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs) followed by serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), serotonin antagonist and reuptake inhibitors (SARIs), and norepinephrine-dopamine reuptake inhibitors (NDRI). On the other hand, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are the most prescribed lipid-lowering medications, and because the majority of patients with cardiovascular disease (CVD) have depressive symptoms, it is essential to understand the possible drug-drug interactions these two classes of medications can have, their potential synergistic mechanisms, and possible risks. In our research, we tried to understand the facts and uncover any missing links regarding the potential risks and benefits of statins and antidepressant co-prescription in the current clinical scenario. We reviewed all the relevant information from inception up to October 2022 regarding the antidepressant and statin polypharmacy. The databases we used were PubMed and PubMed Central, and the 11 keywords were "statins," "SSRI," "SNRI," "selective serotonin reuptake inhibitors," "serotonin-norepinephrine reuptake inhibitors," "antidepressants," "HMG-CoA reductase inhibitors," "tricyclic antidepressants," "monoamine oxidase inhibitors," "serotonin antagonist and reuptake inhibitors," and "norepinephrine-dopamine reuptake inhibitors." We carefully screened each of the relevant articles, including animal and human studies. In our study, we concluded that co-prescription of statins and SSRIs/SNRIs was generally safe and should be encouraged due to the potential synergistic nature of their effects in patients with CVD and major depression, and caution is advised with all other classes of antidepressants. We would like to encourage the undertaking of large-scale observational studies and proactive postmarketing surveillance to improve our knowledge regarding this topic considering the immense clinical importance it holds by directly and indirectly affecting half the population worldwide.

Keywords: antidepressant drug; cardiovascular disease (cvd); pharmacotherapy education; rational polypharmacy; selective serotonin reuptake inhibitor; serotonin-norepinephrine reuptake inhibitors; statin use; tricyclic antidepressants.

Figure 1. Co-prescription of statins and antidepressants.

A minimum of 10% of patients are commonly prescribed both medications in the United States. It may be as high as 30%-40% in the near future. Figure credits: Sai Dheeraj Gutlapalli