Hyperprolactinemia with antipsychotics

Hyperprolactinemia can lead to hypogonadism secondary to prolactin s inhibitory effects on the hypothalamic-pituitary-gonadal hormonal axis. A 35-year-old female with psychosis and history of 7years of treatment with different antipsychotics presented with hypogonadism and radiological evidence of a pituitary microadenoma while on amisulpride and aripiprazole [53 ]. The authors did not relate the microadenoma to the hyperprolactinema and commented on the difficulty of treating these disorders. 

Ari pi prazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). 

Atypical antipsychotics cause fewer EPS than do conventional antipsychotics. Clozapine and quetiapine are the least likely to cause EPS and are therefore recommended for treatment of psychosis in patients with Parkinson s disease. With the notable exception of risperidone, atypical antipsychotics cause substantially less hyperprolactinemia than do conventional antipsychotics. Weight gain is a side effect of all atypical antipsychotics except ziprasidone and aripiprazole. Concerns about cardiac conduction delay with ziprasidone therapy exist and warrant consideration in patients who have... 

Serotonin pathways are involved in the regulation of prolactin secretion. Amenorrhea, galactorrhea, and hyperprolactinemia have been reported in a patient who was already taking an antipsychotic drug after starting treatment with fluvoxamine (SEDA-17, 20). 

The relation between antipsychotic drug-induced hyperprolactinemia and hypoestrogenism has been studied in 75 women with schizophrenia (762). Serum estradiol concentrations were generally reduced during the entire menstrual cycle compared with reference values. There was hypoestrogenism, defined as serum estradiol concentrations below 30 pg/ml in the follicular phase and below 100 pg/ml in the periovulatory phase, in about 60%. 

The authors suggested that olanzapine may offer advantages for selected patients in whom hyperprolactinemia occurs during treatment with other antipsychotic drugs. 

Canuso CM, Hanau M, Jhamb KK, Green AI. Olanzapine use in women with antipsychotic-induced hyperprolactinemia. Am J Psychiatry 1998 155(10) 1458. 

Kinon BJ, Gilmore JA, Liu H, Halbreich UM. Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. Psychoneuroendocrinology 2003 28 55-68. 

In the in-vitro kinetic experiments, the rates of association (Kon) and dissociation (Kan) of various (labeled) antipsychotic compounds to dopamine D2 receptors were determined. Kapur and Seeman found that antipsychotics substantially differ (almost 1000-fold) in their Koff rate (whereas only 10-fold differences were found in the Kon rate), and that this value is highly correlated with their affinity to D2 receptors. These authors also demonstrated that Koff for clozapine, olanzapine and quetiapine was 1.386 min"1, 0.039 min"1, and 3.013 min"1, respectively, and assumed that the rate of how rapidly they left the receptor was an important mechanism in their atypical antipsychotic action. Indeed, this fully explained the lack of extrapyramidal symptoms (EPS) and hyperprolactinemia and the low risk for tardive dyskinesia [34—36]. In this regard, quetiapine (which has the lowest affinity to D2 receptors) seems to be the most atypical among all tested antipsychotics, followed by clozapine and olanzapine (nevertheless, olanzapine s Koff value is close to those of raclopride and chlorpromazine). 

In one study, the prevalence of hyperprolactinemia among women taking risperidone was 88% (n = 42) versus 48% (n = 105) in those taking conventional antipsychotic drugs 48% of these women of reproductive age taking risperidone had abnormal menstrual cycles (137). In the whole sample (147 women and 255 men) there were trends towards low concentrations of reproductive hormones associated with rises in prolactin patients taking concomitant medications known to increase prolactin had been excluded. Raised prolactin concentrations were also observed in 13 (9 women and 4 men) of 20 patients (13 women and 7 men mean age 36 years) (138). In premenopausal women there was a good correlation between prolactin concentrations and age, but there was no clear correlation between duration of treatment, dose, prolactin concentration, and prolactin-related adverse effects. 

C Risperidone. Although the incidence of adverse effects associated with hyperprolactinemia is rare with atypical antipsychotics, risperidone can inaease prolactin levels in a dose-dependent manner. Blockade of the dopaminergic tone in the hypothalamus and 5HT-2 antagonism by risperidone may explain this effect. Other adverse eff associated with persistent prolactin elevation include sexual dysfunction, female menstrual disorders, and reduced bone mineral density. 

Sexual Side Effects and Hyperprolactinemia. Clinical evaluation of the sexual function effects of antipsychotic agents are fraught with methodological difficulties including reduced sexual performance in unmedicated schizophrenics. The few well-con-trolled studies that have appeared have involved male subjects (74,75). 

The potential risk of osteoporosis is of concern with the longterm use of medications that cause osteoporosis. Inadequate evidence is currently available regarding the potential effects on bone density of long-term antipsychotic-related hyperprolactinemia. 

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