PMID- 31587356
OWN - NLM
STAT- MEDLINE
DCOM- 20201204
LR  - 20201214
IS  - 1365-2710 (Electronic)
IS  - 0269-4727 (Linking)
VI  - 45
IP  - 2
DP  - 2020 Apr
TI  - Clinically relevant drug interactions between statins and antidepressants.
PG  - 227-239
LID - 10.1111/jcpt.13058 [doi]
AB  - 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.
CI  - (c) 2019 John Wiley & Sons Ltd.
FAU - Palleria, Caterina
AU  - Palleria C
AD  - Science of Health Department, School of Medicine, University of Catanzaro, 
      Catanzaro, Italy.
FAU - Roberti, Roberta
AU  - Roberti R
AD  - Science of Health Department, School of Medicine, University of Catanzaro, 
      Catanzaro, Italy.
FAU - Iannone, Luigi Francesco
AU  - Iannone LF
AD  - Science of Health Department, School of Medicine, University of Catanzaro, 
      Catanzaro, Italy.
FAU - Tallarico, Martina
AU  - Tallarico M
AD  - Science of Health Department, School of Medicine, University of Catanzaro, 
      Catanzaro, Italy.
FAU - Barbieri, Maria Antonietta
AU  - Barbieri MA
AD  - Department of Clinical and Experimental Medicine, University of Messina, Messina, 
      Italy.
FAU - Vero, Ada
AU  - Vero A
AD  - Science of Health Department, School of Medicine, University of Catanzaro, 
      Catanzaro, Italy.
FAU - Manti, Antonia
AU  - Manti A
AD  - Science of Health Department, School of Medicine, University of Catanzaro, 
      Catanzaro, Italy.
FAU - De Sarro, Giovambattista
AU  - De Sarro G
AD  - Science of Health Department, School of Medicine, University of Catanzaro, 
      Catanzaro, Italy.
FAU - Spina, Edoardo
AU  - Spina E
AD  - Department of Clinical and Experimental Medicine, University of Messina, Messina, 
      Italy.
FAU - Russo, Emilio
AU  - Russo E
AUID- ORCID: 0000-0002-1279-8123
AD  - Science of Health Department, School of Medicine, University of Catanzaro, 
      Catanzaro, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20191006
PL  - England
TA  - J Clin Pharm Ther
JT  - Journal of clinical pharmacy and therapeutics
JID - 8704308
RN  - 0 (Antidepressive Agents)
RN  - 0 (Cytochrome P-450 Enzyme Inhibitors)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*administration & dosage/pharmacokinetics/pharmacology
MH  - Cytochrome P-450 Enzyme Inhibitors/administration & dosage/pharmacology
MH  - Cytochrome P-450 Enzyme System/drug effects/metabolism
MH  - *Drug Interactions
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & 
      dosage/pharmacokinetics/pharmacology
OTO - NOTNLM
OT  - HMG-CoA reductase inhibitors
OT  - antidepressant drugs
OT  - drug-drug interactions
OT  - pharmacokinetic
OT  - statins
EDAT- 2019/10/07 06:00
MHDA- 2020/12/15 06:00
CRDT- 2019/10/07 06:00
PHST- 2019/07/30 00:00 [received]
PHST- 2019/09/05 00:00 [revised]
PHST- 2019/09/09 00:00 [accepted]
PHST- 2019/10/07 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2019/10/07 06:00 [entrez]
AID - 10.1111/jcpt.13058 [doi]
PST - ppublish
SO  - J Clin Pharm Ther. 2020 Apr;45(2):227-239. doi: 10.1111/jcpt.13058. Epub 2019 Oct 
      6.