Objectives : Risperidone, an atypical antipsychitics which blocks both dopaminergic
and serotonergic receptors, have a good response to the negative symptoms as well as
positive symptoms, and improve cognitive dysfunction of schizophrenic patients.
Furthermore, it has few extrapyramidal side effects and tardive dyskinesia. Although it
had been reported that the atypical antipsychotics have less effect on prolactin(PRL)
than the classical antipsychotics, we could experience PRL-associated symptoms such as
amenorrhea, galactorrhea and hyperprolactinemia in practice. Therefore we tried to
identify the sex differences of risperidone-induced hyperprolactinemia, to evaluate factors
affecting PRL levels, and to know the association between cognitive disorders and PRL.
Methods : The baseline levels of PRL and TSH prior th risperidone administration
were measured by enzyme immunoassay method for 50 patients (25 males and 25
females) admitted with schizophrenia, schizoaffective disorder or schizophreniform
disorder according to the DSM-IV classification, and the measurements of PRL were
repeated on the 2nd and the 4th wks of risperidone administration. Concomitantly, the
severity of psychotic symptoms using CGI, BPRS and PANSS, and the cognitive
dysfunction using PANSS-CF were assessed prior to, on the 2nd and the 4th wks of
risperidone administration. The PRL and TSH levels of 54 healthy controls(29 males and
25 females) who had no medical, neurological and psychiatric illnesses were also
evaluated. Furthermore, the correlation with the psychiatric diagnosis, education, age,
sex, duration of illnesses, risperidone dosage, duration of risperdone administration, TSH
concentration, cognitive function, severity of psychotic symptoms were also identified.
Results : 1) The baseline PRL levels of female schizophrenics(74.3±49.6ng/ml) were
significantly(p<0.005) higher than those of males(36.3±24.6ng/ml), which wee
significantly(p<0.0001 respectively) higher than those of controls(females 16.9±6.1ng/ml,
males 13.3±4.9ng/ml). The PRL levels measured on the 2nd wks(females 133.7±
47.8ng/ml, males 56.9±23.6ng/ml) and on the 4th wks(females 146.1±45.9ng/ml, males
70.0±31.5ng/ml) after risperidone administration were significantly(p<0.0001 respectively)
higher in females. The mean dosages of risperidone on the 2nd wks were 3.8±
1.7mg(2-6mg) for the females and 4.0±1.6mg(2-6mg) fore the males, and on the 4th
wks were 4.5±2.1mg(2-8mg) fore the females and 5.4±2.2mg(2-8mg) for the males.
2) The rise of PRL levels were positively correlated with increased risperidone dosage
in males(y=0.307 on the 2nd wks and y=0.280 on the 4th wks), while they were not
correlated with dosages in females. For the females, the PRL levels were negatively
correlated(y=-0.320) with decrease of TSH concentration. The baseline PRL levels were
not correlated with age, education, duration of illnesses, psychopathology, cognitive
disorders in both males and females, while it was negatively correlated with TSH levels
only in females(y=-0.320).
3) The cognitive dysfunction was correlated with PRL levels in males, while
PANSS-CF scores were negatively correlated with PRL levels(y=-0.220 on the 2nd wks
and y=-0.366 on the 4th wks) in females. The psychopathology was positively correlated
with cognitive dysfunction in both males and females. Therefore, the risperdone-induced
cognitive improvement seemed to be correlated with improvement of psychopathology in
both males and females, and with increase in PRL levels only in females.
Conclusions : The fact that the serum PRL levels of schizophrenics were higher than
those of controls, especially in females suggested that it could be related with
risperidone dosage in males and with primary pathological process in females. The
risperidone-associated cognitive improvement seemed to be related with general
improvement of psychopathology as well as the rise of PRL levels especially in females.
The facts that the effect of risperidone-induced hyperprolactinemia and the cognitive
function were more in females suggested that somewhat different mechanisms could be
exerted on them.
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