Bryan M McClarty1, Daniel W Fisher2, Hongxin Dong1. 1. Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA. 2. Department of Neurology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Abstract
PURPOSE OF THE REVIEW: Antipsychotics are commonly prescribed for the treatment of psychosis as well as behavioral and psychological symptoms of dementia (BPSD) in elderly patients. However, elderly patients often experience decreased antipsychotic efficacy and increased side effects, though the mechanisms underlying these changes with age are not clear. RECENT FINDINGS: Although aging can affect drug metabolism and clearance through changes in renal and hepatic function, additional pharmacokinetic and pharmacodynamic changes due to aging-induced epigenetic alterations also impact processes important for antipsychotic function. Epigenetic mechanisms account for some of the altered efficacy and increased side effects seen in elderly patients. SUMMARY: Both clinical and animal studies from our group and others have demonstrated a plausible epigenetic mechanism involving histone modifications that can adversely affect the efficacy of antipsychotics and increase their side effects in elderly patients. Hopefully, further investigation of this mechanism will benefit elderly patients who need treatment for psychosis and BPSD.
PURPOSE OF THE REVIEW: Antipsychotics are commonly prescribed for the treatment of psychosis as well as behavioral and psychological symptoms of dementia (BPSD) in elderly patients. However, elderly patients often experience decreased antipsychotic efficacy and increased side effects, though the mechanisms underlying these changes with age are not clear. RECENT FINDINGS: Although aging can affect drug metabolism and clearance through changes in renal and hepatic function, additional pharmacokinetic and pharmacodynamic changes due to aging-induced epigenetic alterations also impact processes important for antipsychotic function. Epigenetic mechanisms account for some of the altered efficacy and increased side effects seen in elderly patients. SUMMARY: Both clinical and animal studies from our group and others have demonstrated a plausible epigenetic mechanism involving histone modifications that can adversely affect the efficacy of antipsychotics and increase their side effects in elderly patients. Hopefully, further investigation of this mechanism will benefit elderly patients who need treatment for psychosis and BPSD.
Entities:
Keywords:
Aging; Antipsychotics; Drug efficacy; Epigenetics; Histone modification; Side effects
Authors: Janitza L Montalvo-Ortiz; Daniel W Fisher; Guadalupe Rodríguez; Deyu Fang; John G Csernansky; Hongxin Dong Journal: Psychopharmacology (Berl) Date: 2017-04-18 Impact factor: 4.530
Authors: N Kemppainen; M Laine; M P Laakso; V Kaasinen; K Någren; T Vahlberg; T Kurki; J O Rinne Journal: Eur J Neurosci Date: 2003-07 Impact factor: 3.386