Initial increase of plasma serotonin: a biological predictor for the antidepressant response to clomipramine?
Hypofunction of the serotonin (5-HT) system might be involved in depression. Initial effects of the 5-HT reuptake inhibitor clomipramine (CMI) on plasma 5-HT have never been assessed. On Day 1, 27 depressed patients received either a 25-mg CMI slow infusion or a 25-mg CMI tablet in a randomized, double-blind, double-dummy design. The daily dose was subsequently titrated up to 75 mg i.v. or 150 mg orally. The Montgomery-Asberg Depression Rating Scale (MADRS) was rated on Days 1, 4, 7 and 14. High-performance liquid chromatography (HPLC-EC) assays of plasma 5-HT, platelet 5-HT, and CMI were performed on Day 1 before and after the infusion. On Day 1, both groups experienced a mean (nonsignificant) plasma 5-HT increase; in the i.v. group this initial increase correlated with MADRS decrease over 14 days (r = 0.76, p = .0025). Correlations between platelet 5-HT and MADRS decrease were not significant. These preliminary data show that: i) CMI administration results in initial changes in plasma 5-HT; and ii) i.v. CMI-induced initial plasma 5-HT increase is consistent with the CMI 5-HT profile, and might predict the clinical response to CMI.
Spreux-Varoquaux
O
O
Centre Hospitalier de Versailles, Département de Biochimie-Pharmacologie-Toxicologie, Hopital A. Mignot, Le Chesnay France.
Gailledreau
J
J
Vanier
B
B
Bothua
D
D
Plas
J
J
Chevalier
J F
JF
Advenier
C
C
Pays
M
M
Brion
S
S
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002997:Clomipramine / Q000008:administration & dosage / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000097:blood*
D000929:Antidepressive Agents, Tricyclic; D015415:Biomarkers; D012701:Serotonin; D002997:Clomipramine