Onset of clinical effects and plasma concentration of fluvoxamine in Japanese patients.
It is widely accepted that selective serotonin reuptake inhibitors (SSRIs) require 2 to 4 weeks of administration before improvements in emotional symptoms of depression are seen. We evaluated whether early monitoring of Hamilton Rating Scale for Depression (HAMD) scores in patients treated with the SSRI fluvoxamine could predict antidepressant response, and also assessed the relationship between the onset of clinical response following the start of fluvoxamine administration and its plasma concentration. Twelve depressed patients (baseline HAMD score ≥15) received an initial dose of fluvoxamine (50 mg/d) followed by an optimized maintenance dose according to their clinical symptoms after 7 d. HAMD scores and plasma drug concentrations were determined at 7 and 28 d after the first administration. There were 7 responders and 5 non-responders on day 28, as evaluated by HAMD scores. The HAMD score for the responders was significantly lower than that for the non-responders on day 7 (mean±S.D., 11.6±6.1 vs. 26.6±6.5, p=0.006). Thus, the reduction in HAMD score on day 7 was clearly divided between responders and non-responders. On day 28, the plasma concentration of fluvoxamine in responders was lower than that in non-responders (14.2±10.5 ng/ml vs. 44.2±28.1 ng/ml, p=0.051). Furthermore, receiver operating characteristic curve analysis conducted on day 28 revealed an upper concentration threshold of 28.2 ng/ml (p=0.042), with none in the responder group above that level. Our results suggest that HAMD score after the first week of treatment with fluvoxamine and the upper threshold of plasma drug concentration could predict whether a patient is a non-responder.
Department of Pharmacy Practice and Science, University of Shizuoka, Japan. y-kato@u-shizuoka-ken.ac.jp
Yasuhiro
Y
Katoh
Shinya
S
Uchida
Masayoshi
M
Kawai
Noriyoshi
N
Takei
Norio
N
Mori
Junichi
J
Kawakami
Yoshiyuki
Y
Kagawa
Shizuo
S
Yamada
Noriyuki
N
Namiki
Hisakuni
H
Hashimoto
D000328:Adult; D000928:Antidepressive Agents / Q000097:blood / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000097:blood / Q000188:drug therapy*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D001068:Feeding and Eating Disorders / Q000097:blood / Q000188:drug therapy*; D005260:Female; D016666:Fluvoxamine / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000097:blood / Q000188:drug therapy*; D012372:ROC Curve; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors