Quetiapine and norquetiapine in plasma and cerebrospinal fluid of schizophrenic patients treated with quetiapine: correlations to clinical outcome and HVA, 5-HIAA, and MHPG in CSF.
This study investigated concentrations of quetiapine and norquetiapine in plasma and cerebrospinal fluid (CSF) in 22 schizophrenic patients after 4-week treatment with quetiapine (600 mg/d), which was preceded by a 3-week washout period. Blood and CSF samples were obtained on days 1 and 28, and CSF levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were measured at baseline and after 4 weeks of quetiapine, allowing calculations of differences in HVA (ΔHVA), 5-HIAA (Δ5-HIAA), and MHPG (ΔMHPG) concentrations. Patients were assessed clinically, using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale at baseline and then at weekly intervals. Plasma levels of quetiapine and norquetiapine were 1110 ± 608 and 444 ± 226 ng/mL, and the corresponding CSF levels were 29 ± 18 and 5 ± 2 ng/mL, respectively. After the treatment, the levels of HVA, 5-HIAA, and MHPG were increased by 33%, 35%, and 33%, respectively (P < 0.001). A negative correlation was found between the decrease in PANSS positive subscale scores and CSF ΔHVA (r(rho) = -0.690, P < 0.01), and the decrease in PANSS negative subscale scores both with CSF Δ5-HIAA (r(rho) = -0.619, P = 0.02) and ΔMHPG (r(rho) = -0.484, P = 0.038). Because, unfortunately, schizophrenic patients experience relapses even with the best available treatments, monitoring of CSF drug and metabolite levels might prove to be useful in tailoring individually adjusted treatments.
Nikisch
Georg
G
Department of Psychiatry and Psychotherapy, Klinikum Fulda gAG, Fulda, Germany. georg.nikisch@klinikum-fulda.de
Baumann
Pierre
P
Wiedemann
Georg
G
Kiessling
Bernhard
B
Weisser
Heike
H
Hertel
Andreas
A
Yoshitake
Takashi
T
Kehr
Jan
J
Mathé
Aleksander A
AA
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D003987:Dibenzothiazepines / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D005260:Female; D006719:Homovanillic Acid / Q000097:blood / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D000069348:Quetiapine Fumarate; D012559:Schizophrenia / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid