Risperidone Added to Clozapine: Impact on Serum Prolactin Levels
J Clin Psychiatry 2001;62(8):605-608
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Background: Several years ago, we reported that
the addition of risperidone to clozapine improved response in
some patients with schizophrenia. Risperidone, in general, is
well tolerated when administered as monotherapy, but has been
linked to a persistent elevation of serum prolactin and
associated symptoms. The goal of this study was to determine
whether the addition of risperidone to clozapine results in an
elevation of serum prolactin levels in patients with chronic
schizophrenia or schizoaffective disorder.
Method: Twenty patients on clozapine-risperidone
combination therapy were matched for age and gender with 20
patients treated with clozapine monotherapy. Demographic
information was gathered along with clozapine and risperidone
dose and the length of time on risperidone. Serum prolactin
levels were measured from a single blood sample.
Results: The 2 groups did not differ in age,
race, gender, diagnosis, age at clozapine initiation, age at
onset, Abnormal Involuntary Movement Scale scores, or clozapine
dose. The mean ± SD serum prolactin level was 8.42 ± 4.17 ng/mL
for clozapine monotherapy patients and 35.76 ± 17.43 ng/mL for
combination therapy patients. The 2 medication categories showed
a significant difference in log prolactin values (t = -7.97, df =
38, p <= .0001). Sixteen combination therapy patients (80%)
exhibited elevated prolactin levels (range for entire group,
9.7-69.8 ng/mL) while only 2 clozapine monotherapy patients (10%)
exhibited prolactin elevation levels (range for entire group,
2.4-20.2 ng/mL; df = 1, p < .0001).
Conclusion: The combination of risperidone and
clozapine appears to result in a moderate elevation of serum
prolactin levels. Additionally, controlled prospective studies
are needed to clarify the risks of long-term elevations of serum