Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors.
OBJECTIVE
The selective serotonin reuptake inhibitor (SSRI) fluoxetine can increase serum levels of clozapine and norclozapine, but effects of other SSRIs are unknown. Thus, the authors evaluated interactions of clozapine with fluoxetine, paroxetine, and sertraline.


METHODS
Serum clozapine and norclozapine concentrations were assayed in 80 psychiatric patients, matched for age and clozapine dose, given clozapine (mean dose = 279 mg/day) alone or with fluoxetine (mean dose = 39.3 mg/day), paroxetine (mean = 31.2 mg/day), or sertraline (mean = 92.5 mg/ day). Each patient's dose of clozapine was stable for at least a month before serum sampling.


RESULTS
Concentrations of clozapine plus norclozapine averaged 43% higher, and the risk of levels higher than 1000 ng/ml was 10-fold greater (25%), in the patients taking SSRIs, with minor differences between patients taking the individual SSRIs.


CONCLUSIONS
SSRIs can increase circulating concentrations of clozapine and norclozapine, sometimes to potentially toxic levels.
Centorrino
F
F
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Baldessarini
R J
RJ
Frankenburg
F R
FR
Kando
J
J
Volpicelli
S A
SA
Flood
J G
JG
D015057:1-Naphthylamine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000341:Affective Disorders, Psychotic / Q000097:blood / Q000188:drug therapy; D000368:Aged; D000553:Ambulatory Care; D003024:Clozapine / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D020280:Sertraline; D013268:Stimulation, Chemical
D015057:1-Naphthylamine; D003024:Clozapine; D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C058272:norclozapine