Document Detail

Relationship between clinical effects of fluvoxamine and the steady-state plasma concentrations of fluvoxamine and its major metabolite fluvoxamino acid in Japanese depressed patients.
MedLine Citation:
PMID:  12682708     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: The relationship between clinical effects of fluvoxamine (FLV) and the steady-state plasma concentrations (Css) of FLV and its major metabolite fluvoxamino acid (FLA) was studied. METHODS: The subjects were 49 Japanese patients with major depressive disorder receiving FLV 200 mg/day for 6 weeks. Depressive symptoms and side effects were evaluated by the Montgomery Asberg Depression Rating Scale (MADRS), and the UKU Side Effect Rating Scale, respectively. The Css of FLV and FLA were measured by HPLC, and the CYP2D6 genotyping was performed by PCR methods. RESULTS: The Css of FLV and FLV+FLA showed significant negative correlations with the final MADRS score. The Css of FLV, FLA and FLV+FLA were significantly higher in the responders (final MADRS score < or =10) than in non-responders. The proportion of responders was significantly higher in the patients with the Css of FLV, FLA and FLV+FLA above 150, 55 and 180 ng/ml, respectively. In the multiple regression, the Css of FLV+FLA showed a significant negative correlation with the final MADRS score. In the logistic regression, the Css of FLA had a significant effect on the differentiation of responders from non-responders. The incidence of side effects was low, and the development of nausea, the most frequent one, was not dependent on any Css. The number of mutated CYP2D6 alleles causing absent or decreased enzyme activity was not related to the therapeutic response or development of nausea. CONCLUSIONS: The present study suggests that there is a therapeutic threshold for the Css of FLV and probably also for the Css of FLA, and the Css of FLV+FLA above 180 ng/ml best predicts a good therapeutic response.
Gisa Gerstenberg; Toshiaki Aoshima; Takashi Fukasawa; Keizo Yoshida; Hitoshi Takahashi; Hisashi Higuchi; Yoshiko Murata; Ritsuko Shimoyama; Tadashi Ohkubo; Tetsuo Shimizu; Koichi Otani
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article     Date:  2003-04-08
Journal Detail:
Title:  Psychopharmacology     Volume:  167     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-05-27     Completed Date:  2003-09-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  443-8     Citation Subset:  IM    
Department of Neuropsychiatry, Yamagata University School of Medicine, 990-9585 Yamagata, Japan.
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MeSH Terms
Amino Acids / blood*
Antidepressive Agents, Second-Generation / blood,  therapeutic use*
Cytochrome P-450 CYP2D6 / genetics,  metabolism
Depressive Disorder, Major / blood,  drug therapy*
Dose-Response Relationship, Drug
Fluvoxamine / analogs & derivatives,  blood*,  therapeutic use*
Middle Aged
Psychiatric Status Rating Scales
Serotonin Uptake Inhibitors / blood,  therapeutic use*
Treatment Outcome
Reg. No./Substance:
0/Amino Acids; 0/Antidepressive Agents, Second-Generation; 0/Serotonin Uptake Inhibitors; 0/fluvoxamino acid; 54739-18-3/Fluvoxamine; EC P-450 CYP2D6

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