Depression and hypercholesterolemia are two of the most commonly treated conditions in the developed countries, while the lipid–lowering agents and antidepressants are among the most widely prescribed drugs in the world. There is a common concern that selective serotonin reuptake inhibitors (SSRIs) can trigger statin adverse effects, especially myopathy. However, the supporting evidence originates from studies in-vitro and big epidemiological studies. Recent pharmacokinetic insights indicate that the magnitude of pharmacokinetic interaction between SSRIs and statins is likely to be below the threshold for clinical significance.

Explorative study on pharmacokinetic effects of SSRIs on statin drugs.

We performed a detailed literature review through PubMed, EMBASE and Cochran's Library to assess the clinical relevance of combined SSRIs and statin use. To address pharmacokinetic interactions between two drug groups, we focused on:

– cytochrome P450 enzyme metabolism of statins;

– CYP enzyme inhibition by SSRIs;

– SSRIs–statin drug interactions;

– non-CYP pharmacokinetic pathways.

With regard to pharmacokinetic drug interactions and the risk of statin related myopathy, escitalopram, citalopram, and paroxetine are to be safe in co-therapy with all statins. Rosuvastatin and pravastatin are almost certain to be safe in co-therapy with all SSRIs. Fluoxetine and sertraline are also likely to be safe, even when combined with atorvastatin, simvastatin, and lovastatin.

Though the absolute risk of concomitant use of SSRIs with statins seems to be negligible, even this risk can be minimized by using lower statin doses and monitoring the patient.