Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology.
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Abstract
Objective: Psychiatric disorders burden the peripartum period, often requiring psychopharmacological treatment, including antidepressants. Efficacy and tolerability of antidepressants are influenced by the physiological changes of the peripartum and individual metabolic profiles, which in turn can be modified by pregnancy. The objective of this study is to assess the relationship between antidepressants' pharmacokinetic profiles during pregnancy and individual metabolic profiles, along with the efficacy of the treatment.
Methods: In total 87 outpatients with diagnoses of bipolar disorder, major depression, anxiety, obsessive-compulsive disorder and post-traumatic stress disorder who required antidepressant treatment during pregnancy were recruited. Genotyping analysis of hepatic cytochrome P450 (CYPs) individual isoforms was performed. Antidepressants' blood concentrations and psychometric assessments were collected at five time points. Antidepressants' cord blood concentrations were assessed at birth.
Results: Sertraline showed greater stability in plasma concentrations and a lower placental penetrance index. Most of the antidepressants' concentrations below the therapeutic range were found in women with an extensive/ultrarapid metabolic profile. Antidepressants mainly metabolized by CYP2C19 were less frequently below the therapeutic range compared with antidepressants metabolized by CYP2D6.
Conclusions: Pregnancy modulates cytochrome activity and drugs' pharmacokinetics. Genotyping analysis of CYPs isoforms and therapeutic drug monitoring might be used to guide clinicians in a well-tolerated treatment of psychiatric symptoms in pregnant women.
期刊介绍：
International Clinical Psychopharmacology provides an essential link between research and clinical practice throughout psychopharmacology. It reports on studies in human subjects, both healthy volunteers and patients, which relate the effects of drugs on psychological processes.
A major objective of the journal is to publish fully refereed papers which throw light on the ways in which the study of psychotropic drugs can increase our understanding of psychopharmacology. To this end the journal publishes results of early Phase I and II studies, as well as those of controlled clinical trials of psychotropic drugs in Phase II and IV. Other topics covered include the epidemiology of psychotropic drug prescribing and drug taking, the sociology of psychotropic drugs including compliance, and research into the safety and adverse effects of these compounds.
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