An index of 5-HT synthesis changes during early antidepressant treatment: alpha-[11C]methyl-L-tryptophan PET study.
The antidepressant selective serotonin transporter inhibitors (SSRIs) are clinically active after a delay of several weeks. Indeed, the rapid increase of serotonin (5-HT) caused by SSRIs, stimulates the 5-HT(1A) autoreceptors, which exert a negative feedback on the 5-HT neurotransmission. Only when autoreceptors are desensitized, can SSRIs exert their therapeutic activity. The 5-HT(1A) receptor antagonist pindolol has been used to accelerate the clinical effects of antidepressant by preventing the negative feedback. Using the alpha-[(11)C]methyl-L-tryptophan/positron emission tomography (PET), the goal of the present double-blind, randomized study was to compare the changes in alpha-[(11)C]methyl-L-tryptophan trapping, an index of serotonin synthesis, in patients suffering from unipolar depression treated with the SSRI citalopram (20 mg/day) plus placebo versus patients treated with citalopram plus pindol (7.5 mg/day). PET and Hamilton depression rating scale (HDRS-17) were performed at baseline, and after 10 and 24 days of antidepressant treatment. Results show that the combination citalopram plus pindol, compared to citalopram alone shows a more rapid and greater increase of an index of 5-HT synthesis in prefrontal cortex (BA 9). This research is the first human PET study demonstrating that, after 24 days, the combination SSRIs plus pindolol produces a greater increase of the metabolism of serotonin in the prefrontal cortex, an area associated to depressive symptoms.
Berney
Alexandre
A
Department of Psychiatry, McGill University, Que., Canada.
Nishikawa
Masami
M
Benkelfat
Chawki
C
Debonnel
Guy
G
Gobbi
Gabriella
G
Diksic
Mirko
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000339:Affect / Q000187:drug effects; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015283:Citalopram / Q000494:pharmacology* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000494:pharmacology / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D019275:Radiopharmaceuticals; D012701:Serotonin / Q000096:biosynthesis*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000097:blood
D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D015283:Citalopram; D010869:Pindolol; D019275:Radiopharmaceuticals; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan; C020774:alpha-methyltryptophan