Genetic and pharmacokinetic factors affecting the initial pharmacotherapeutic effect of paroxetine in Japanese patients with panic disorder.
OBJECTIVE
The objective of this study was to evaluate genetic and pharmacokinetic factors affecting the initial pharmacotherapeutic effect of paroxetine (PAX) in Japanese patients with panic disorder (PD).


METHODS
Plasma concentration of PAX was determined by high performance liquid chromatography. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) variants were determined by polymerase chain reaction techniques. PD severity was assessed using the Panic and Agoraphobia Scale (PAS).


RESULTS
Multiple regression analysis revealed that the plasma concentration of PAX, 5-HTTLPR genotype, and comorbid physical illness were significant factors affecting the initial pharmacotherapeutic effect of PAX in PD and indicated that these factors accounted for 52.4% (R(2) = 0.524) of the variability in the percent reduction in PAS score. The final model was described by the following equation (P = 0.001): percent reduction in PAS score (%) = 68.5 - 1.2 x [plasma concentration of PAX (ng/ml)] - 33.0 x (L/S = 1, S/S = 0) - 21.8 x (with comorbid physical illness = 1, without comorbid physical illness = 0).


CONCLUSIONS
The high plasma concentration of PAX, the L/S genotype of 5-HTTLPR, and comorbid physical illness might be associated with a poor response to the initial phase of pharmacotherapy of PD with PAX.
Saeki
Yoshinori
Y
Department of Psychiatry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga, Tochigi, 321-0293, Japan.
Watanabe
Takashi
T
Ueda
Mikito
M
Saito
Atsushi
A
Akiyama
Kazufumi
K
Inoue
Yoshimasa
Y
Hirokane
Genta
G
Morita
Sachiyo
S
Yamada
Naoto
N
Shimoda
Kazutaka
K
D000328:Adult; D000368:Aged; D000379:Agoraphobia / Q000150:complications / Q000523:psychology; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000627:therapeutic use*; D044466:Asian People / Q000706:statistics & numerical data*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D017374:Paroxetine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
D018687:Antidepressive Agents, Second-Generation; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D017374:Paroxetine