Clinically relevant drug interactions between statins and antidepressants

Abstract

What is known and objective Statins, also known as 3‐hydroxy‐3‐methylglutaryl‐CoA reductase inhibitors, and antidepressant drugs are frequently used in combination due to the high and growing incidence of cardiovascular diseases and psychiatric disorders worldwide. Several aspects on management, the risk of adverse events (AEs) occurrence and the potential clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) drug‐drug interactions (DDIs) between these two classes have not been well investigated. The aim of the present review was to describe the PK and PD interactions, of clinical relevance, between statins and antidepressant drugs and provide a comprehensive overview of their pharmacological features for appropriate multiple drug regimens. Methods Relevant studies were identified through a literature search of PubMed and the Cochrane databases focusing on clinically relevant DDIs between statins and antidepressants. Only papers in English were included in the search. Results and discussion Pharmacodynamic (PD) drug‐drug interactions (DDIs) are unlikely to occur as statins are highly selective inhibitors of HMG‐CoA reductase with no relevant effect on other enzymes or receptor systems. Despite the numerous PK studies on individual drugs belonging to statins and antidepressant agents, only a few case reports regarding specific DDIs are present in the literature and no clinical studies have been performed. PK data allow to speculate on potential DDIs, comparing the metabolic pathways, intestinal and liver transporters and elimination routes. Overall, second‐generation antidepressants, in particular citalopram, escitalopram, mirtazapine, reboxetine and venlafaxine, have weak inhibitory effects on various cytochrome (CYP) isozymes and seem to have a more advantageous DDIs profile in vivo. Conversely, nefazodone, fluoxetine, paroxetine and fluvoxamine influence considerably CYPs activity with potential effects on statins plasma levels, although pravastatin, pitavastatin and rosuvastatin are not susceptible to inhibition by any CYP. Albeit no studies have been performed on P‐glycoprotein (P‐gp), interactions of clinical relevance are unlikely. What is new and conclusion Although DDIs with antidepressants are potentially, but rarely clinically significant, the use of antidepressants with a more favourable drug interaction profile is advisable. An evaluation on DDIs between these drugs can be useful for future PK/PD studies on drug‐drug interaction to provide clinicians with more data for appropriate multiple drug regimens.

Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use

“…This is an essential research and clinical question that will require dedicated analysis. Future work will require careful consideration of variable medication prescription frequencies across regions and patient care networks (e.g., combined statin and antidepressant prescription 45 ), generalizability outside the United Kingdom (i.e., prescription combinations may differ by country), and how to classify medications containing more than one active compound (e.g., combined opioid and acetaminophen analgesics). Third, pharmacogenes are occasionally duplicated/deleted and the frequency of these events varies by population and genomic region.…”

Biobank scale pharmacogenomics informs the genetic underpinnings of simvastatin use

“…Indeed, many UKB participants endorse use of more than one medication and addressing this observation is an essential research and clinical question but is a tricky topic to address. Future work will require careful consideration of variable medication prescription frequencies across regions and patient care networks (e.g., combined statin and antidepressant perscription 42 ), generalizability outside the UK (i.e., prescription combinations may differ by country), and how to classify medications containing more than one active compound (e.g., combined opioid and acetaminophen analgesics). Third, PGx loci are occasionally duplicated/deleted and the frequency of these events various by population and genomic region.…”

Pharmacokinetic Aspects of Statins

“…With respect to the norepinephrine-dopamine reuptake inhibitor (NDRI), bupropion is a moderate CYP2D6 inhibitor and is metabolized by CYP2D6. Considering the lacking of in vitro and in vivo pharmacokinetics studies and the metabolic pathway of statins, with only fluvastatin metabolized to a lesser extent by CYP2D6 and the high rate of renal excretion (>85%), the intereactions pharmacokinetics are no probable [39].…”