Reduction of clozapine-induced hypersalivation by pirenzepine is safe.
BACKGROUND
Hypersalivation is known as a frequent, disturbing, and socially stigmatizing side effect of therapy with the atypical antipsychotic clozapine. It has been shown that the addition of the anticholinergic pirenzepine is able to reduce clozapine-induced hypersalivation, probably by blocking M4-receptors. Nevertheless, a pharmacokinetic interaction between both compounds cannot be excluded.


METHODS
In this pilot study, 29 schizophrenic patients (ICD-10; 51.7 % female; age: 36.7 +/- 8.7 years [mean +/- SD]) were included. Serum concentrations of clozapine and its pharmacologically active metabolite N-desmethylclozapine were determined under steady-state conditions by automated HPLC with UV detection before and after addition of pirenzepine for 3 days.


RESULTS
Significantly fewer patients reported hypersalivation after addition of pirenzepine (69 % vs. 34.5 %, P = 0.002). No significant differences of clozapine and N-desmethylclozapine serum levels before (329 +/- 181 ng/ml and 218.0 +/- 123.4 ng/ml, respectively) and 3 days after (336 +/- 215 ng/ml and 235.9 +/- 164.4 ng/ml, respectively) addition of pirenzepine were found. In three patients, however, clozapine serum levels increased; this was probably unrelated to pirenzepine.


CONCLUSIONS
In conclusion, treatment of clozapine-induced hypersalivation with pirenzepine is a recommendable combination with low risk of additional side effects.
Schneider
B
B
Center of Psychiatry, Department of Psychiatry and Psychotherapy I, Johann Wolfgang Goethe-University of Frankfurt/Main, Germany. B.Schneider@em.uni-frankfurt.de
Weigmann
H
H
Hiemke
C
C
Weber
B
B
Fritze
J
J
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003024:Clozapine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D010865:Pilot Projects; D010890:Pirenzepine / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy; D012798:Sialorrhea / Q000139:chemically induced / Q000188:drug therapy*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
D014150:Antipsychotic Agents; D018727:Muscarinic Antagonists; C058272:norclozapine; D010890:Pirenzepine; D003024:Clozapine