Risperidone added to clozapine: Impact on serum prolactin levels

Background: Several years ago, we reported that the addition of risperidone to clozapine improved response in some patients with schizophrenia. Risper idone, 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 m atched for age and gender with 20 patients treated with clozapine monothera py. Demographic information was gathered along with clozapine and risperido ne 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 a t clozapine initiation, age at onset, Abnormal Involuntary Movement Scale s cores, 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 c ombination therapy patients. The 2 medication categories showed a significa nt difference in log prolactin values (t = -7.97, df = 38, p less than or e qual to .0001). Sixteen combination therapy patients (80%) exhibited elevat ed prolactin levels (range for entire group, 9.7-69.8 ng/mL) while only 2 c lozapine monotherapy patients (10%) exhibited prolactin elevation levels (r ange 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 elevation s of serum prolactin level.