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. 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.


METHODS
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 < or = .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).


CONCLUSIONS
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 prolactin level.
Henderson
D C
DC
Schizophrenia Research Program, Massachusetts General Hospital, Boston, USA. dchenderson@partners.org
Goff
D C
DC
Connolly
C E
CE
Borba
C P
CP
Hayden
D
D
D000328:Adult; D017668:Age of Onset; D000553:Ambulatory Care; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D003024:Clozapine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000097:blood / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood* / Q000187:drug effects; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy / Q000523:psychology; D018967:Risperidone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D011388:Prolactin; D003024:Clozapine; D018967:Risperidone