Fluoxetine treatment of depression. Clinical effects, drug concentrations and monoamine metabolites and N-terminally extended substance P in cerebrospinal fluid.
In an open study of depressed inpatients, the effects of the selective serotonin uptake blocker fluoxetine on 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) and N-terminally extended substance P (SP) in cerebrospinal fluid (CSF) were measured. Thirteen unmedicated patients who met the DSM-III criteria for major depressive episode were included, and 9 completed the study. During treatment the 5-HIAA concentration decreased by 46%. The HVA and HMPG concentrations also decreased significantly, but to a lesser degree. The mean level of N-terminally extended SP was unaffected by fluoxetine treatment, but the pretreatment level correlated significantly with the pretreatment level of HMPG. The pretreatment level of HVA was the only biochemically variable that appeared to predict therapeutic outcome. The plasma concentrations of both fluoxetine and its metabolite norfluoxetine increased significantly between 3 and 6 weeks. Plasma and CSF levels of both the parent drug and its active metabolite were correlated.
Mårtensson
B
B
Department of Psychiatry, Karolinska Hospital, Stockholm, Sweden.
Nyberg
S
S
Toresson
G
G
Brodin
E
E
Bertilsson
L
L
D000328:Adult; D000368:Aged; D003866:Depressive Disorder / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006018:Glycols / Q000134:cerebrospinal fluid*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D013373:Substance P / Q000134:cerebrospinal fluid*
D006018:Glycols; D010446:Peptide Fragments; D005473:Fluoxetine; D013373:Substance P; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; C042612:substance P (1-4); C036139:norfluoxetine; D006719:Homovanillic Acid