Effect of coadministration of clozapine and fluvoxamine versus clozapine monotherapy on blood cell counts, plasma levels of cytokines and body weight.
BACKGROUND
Clozapine treatment is associated with side-effects such as blood cell dyscrasias and weight gain. Increased plasma levels of the cytokines and soluble cytokine receptors leptin, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors p55 and p75, as well as toxic metabolites of clozapine, have been suggested as the basis for these side-effects,


OBJECTIVE
This study examined whether the coadministration of the selective serotonine reuptake inhibitor fluvoxamine, which interferes with clozapine's hepatic metabolism, affects the immunomodulation by clozapine and some of its side-effects.


METHODS
The following parameters were measured: circulating levels of the cytokines and soluble receptors, plasma concentrations of clozapine and its metabolite N-desmethylclozapine, body weight and blood cell counts in 11 and 12 schizophrenic inpatients on combined and monotherapy, respectively, before and during the first 6 weeks of medication.


RESULTS
On the basis of comparable plasma levels of clozapine and N-desmethylclozapine, the coadministration of fluvoxamine 1) attenuated and delayed the clozapine-induced increase in TNF-alpha plasma levels, 2) enhanced and accelerated the clozapine-induced increase in leptin plasma levels without significant effect on clozapine-induced weight gain, and 3) decreased granulocyte counts.


CONCLUSIONS
As clozapine, its metabolite N-desmethylclozapine and fluvoxamine are unlikely to make these differences, other metabolites might be responsible. The coadministration of clozapine and fluvoxamine offers the opportunity to investigate further the putative associations between certain metabolites, immunomodulation and these side-effects.
Hinze-Selch
D
D
Max-Planck-Institute of Psychiatry, Munich, Germany.
Deuschle
M
M
Weber
B
B
Heuser
I
I
Pollmächer
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001772:Blood Cell Count / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology* / Q000627:therapeutic use; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
D014150:Antipsychotic Agents; D003024:Clozapine; D016207:Cytokines; D016666:Fluvoxamine; D020738:Leptin; D017367:Selective Serotonin Reuptake Inhibitors