title: Effects of the serotonin 1A, 2A, 2C, 3A, and 3B and serotonin transporter gene polymorphisms on the occurrence of paroxetine discontinuation syndrome.
abstract: Paroxetine discontinuation symptoms can at times be severe enough to reduce the quality of life. However, it is currently not possible to predict the occurrence of discontinuation syndrome before the initiation or discontinuation of paroxetine treatment. In this study, we investigated the effects of genetic polymorphisms in the serotonin 1A, 2A, 2C, 3A, and 3B receptor, the serotonin transporter, and the cytochrome P450 2D6 (CYP2D6) genes on the occurrence of paroxetine discontinuation syndrome. A consecutive series of 56 Japanese patients who had a diagnosis of major depressive or anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were treated with paroxetine. Paroxetine discontinuation syndrome was found in 35.7% of the patients by direct interview. Patients who stopped taking paroxetine abruptly experienced paroxetine discontinuation syndrome significantly more often than patients who had a tapering off of the dosage of medication. Patients who had the -1019C allele experienced paroxetine discontinuation syndrome more frequently than patients who had the -1019G homozygote (nominal P = 0.0423) of the serotonin 1A receptor gene. However, this result did not remain significant after the Bonferroni correction for multiple comparisons. The findings suggest that the abrupt stoppage of medication is a major risk factor for the occurrence of paroxetine discontinuation syndrome and that C(-1019)G polymorphism of the serotonin 1A receptor gene may be related to the occurrence of the syndrome.
authors.affiliation: Department of Psychosomatic Medicine, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Nanae
authors.initials: N
authors.lastname: Imuta
authors.forename: Koichi
authors.initials: K
authors.lastname: Haraguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ieiri
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nishimura
authors.forename: Susumu
authors.initials: S
authors.lastname: Koyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Mine
mesh_terms: D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D004334:Drug Administration Schedule; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects* / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics*; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000235:genetics*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D017374:Paroxetine; D019389:Cytochrome P-450 CYP2D6