Prolactin risperidone

Antipsychotic-induced elevations in prolactin levels with associated galactorrhea and menstrual irregularities are common. These effects may be dose related and are more common with the use of FGAs and risperidone. 

Risperidone produces at least as much sexual dysfunction as FGAs, but other SGAs (which have a weaker effect of prolactin) are less likely to have this effect. 

Nevertheless, some dopamine-blockade side effects can still be found with the atypicals. Prolactin elevation still occurs, particularly with risperidone. The risk of... 

Given that limitation, the only ways to counteract elevated prolactin are to lower the dose of the antipsychotic or to switch to another antipsychotic that does not elevate prolactin. We prefer switching (especially if the problem has been encountered with an older style typical antipsychotic) to an atypical antipsychotic if side effects of elevated prolactin become problematic. Most atypical antipsychotics, with the exception of risperidone when used in high doses, do not elevate prolactin. There are few compelling reasons to use a typical antipsychotic compared to the newer atypical agents. 

Older typical antipsychotic drugs, as well as risperidone and paliperidone, produce adverse effects marked by elevations of prolactin, see Adverse... 

Risperidone (1) has high affinity for D2, 5-HT2c and tti receptors and a very high affinity for the 5-HT2a receptor. Risperidone is the most likely of the atypical antipsychotics to cause prolactin increases, but has a lower weight gain liability than olanzapine or quetiapine. Risperidone has a relatively narrow therapeutic window since doses above 6 mg/day cause EPS in a dose-dependent manner. 

Quetiapine also has a chemical structure related to that of clozapine (Fig. 11—36), but it has several differentiating pharmacologic (Fig. 11—41) and clinical features, not only as compared with clozapine (Fig. 11—37) but also as compared with risperidone (Fig. 11-39) and olanzapine (Fig. 11-40). Quetiapine is very atypical in that it causes virtually no EPS at any dose and no prolactin elevations. Thus, quetiapine tends to be the preferred atypical antipsychotic for patients with Parkinson s disease and psychosis. It is also useful in schizophrenia, bipolar disorder, and other types of psychosis, in which it has few extrapyramidal side effects. 

A number of antidepressant drugs, particularly SSRIs, can increase plasma prolactin concentrations, although galactorrhea is uncommon. In a prescription event monitoring survey of about 65 000 patients, compared with SSRIs, moclobemide was associated with a relative risk of galactorrhea of 6.7 (95% Cl = 2.7, 15) (727). However, this was substantially less than the risk associated with the dopamine receptor antagonist risperidone (relative risk compared with SSRIs 32 95% Cl = 14, 70). 

Three women, aged 61, 53, and 21 years, developed delusions of pregnancy while taking risperidone their blood prolactin concentrations were 49, 78, and 52 ng/ ml, respectively (reference range 2-26) (760). 

A 34-year-old woman, who developed amenorrhea while taking risperidone, regained her normal menstrual pattern along with a marked fall in serum prolactin concentration 8 weeks after being switched to olanzapine, whereas amantadine had failed to normalize the menses and had apparently reactivated the psychotic symptoms (856). 

There was a significant rise in baseline serum prolactin concentration in 10 patients after they had taken risperidone for a mean of 12 weeks compared with 10 patients who were tested after a neuroleptic drug-free wash-out period of at least 2 weeks (1014). A non-significant increase in serum prolactin has also been observed in an open comparison of risperidone with other neuroleptic drugs in 28 patients (1015). However, in a meta-analysis of two independent studies (n = 404), prolactin was greatly increased by risperidone (mean change 45-80 ng/ml), a larger effect than with olanzapine and haloperidol (1016). 

Five patients (four women and one man, aged 30-45 years), who were evaluated for risperidone-induced hyperprolactinemia, had significant hyperprolactinemia, with prolactin concentrations of 66-209 pig/1 (1017). All but one had manifestations of hypogonadism, and in these four patients, risperidone was continued and a dopamine receptor agonist (bromocriptine or cabergoline) was added in three patients this reduced the prolactin concentration and alleviated the hypogonadism. 

The relation of prolactin concentrations and certain adverse events has been explored by using data from two large randomized, double-blind studies (n = 2725 813 women, 1912 men) (1018). Both risperidone and haloperidol produced dose-related increases in plasma prolactin concentrations in men and women, but they were not correlated with adverse events such as amenorrhea, galactorrhea, or reduced libido in women or with erectile dysfunction, ejaculatory dysfunction, gynecomastia, or reduced libido in men. Nevertheless, in five patients risperidone (1-8 mg/day) caused amenorrhea in association with raised serum prolactin concentrations (mean 122 ng/ml, range 61-230 ng/ml reference range 2.7-20 ng/ml) (1019). 

Furthermore, risperidone-induced galactorrhea associated with a raised prolactin has been reported (1020,1021), as have amenorrhea and sexual dysfunction (1022). 

Galactorrhea associated with a rise in prolactin occurred after a few weeks of treatment with risperidone in two women aged 24 and 39 (1021). One of them was switched to thioridazine, with an improvement in the galactorrhea, and the other continued to take risperidone owing to a robust response her galactorrhea was partially treated with bromocriptine. 

In 41 schizophrenia patients who took either risperidone (11 men, 9 women mean dose 4 mg/day) or peros-pirone (10 men, 11 women mean dose 24 mg/day) for at least 4 weeks, prolactin concentrations increased only in those taking risperidone (5.3-fold in women and 4.2-fold in men) (1029). 

Hyperprolactinemia was found after about 30 months in 12 premenopausal women with schizophrenia or schizoaffective disorder (aged 15-55 years) taking risperidone but not in those taking olanzapine (n = 14) (1030). Prolactin concentrations were significantly higher in the first group than in the second (123 ng/ml versus 26 ng/ml). 

In a randomized, double-blind, 12-week study in 78 inpatients with schizophrenia assigned to either risperidone 6 mg/day (73% men n — 41) or haloperidol 20 mg/day (81% men n = 37), prolactin concentrations increased significantly in men in both groups (1033). Adjusted for haloperidol dose equivalents (risperidone 6 mg/day equivalent to haloperidol 12 mg/day), risperidone caused a significantly larger rise in prolactin than haloperidol. The study was limited by the small number of women in the sample, which allowed the comparison of prolactin concentrations by sex but without consideration of treatment the women had a significantly larger rise in prolactin than the men. 

A 35-year-old woman who had taken lithium carbonate 800 mg/day for 2 years was also given risperidone 6 mg/ day for a manic relapse. She missed two menstrual periods and had galactorrhea. A head CT scan showed a pituitary microadenoma and the prolactin concentration was 125 pig/l (reference range up to 20 pg/1). Risperidone withdrawal resulted in disappearance of the prolactinoma. Her other symptoms persisted and did not change with olanzapine 2.5 mg/day however, bromocriptine 12.5 mg/day for 2 weeks relieved her symptoms and the prolactin concentration normalized. 

Kleinberg DL, Davis JM, de Coster R, Van Baelen B, Brecher M. Prolactin levels and adverse events in patients treated with risperidone. J Clin Psychopharmacol 1999 19(1) 57-61. 

David SR, Taylor CC, Kinon BJ, Breier A. The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. Clin Ther 2000 22(9) 1085-96. 

Popli A, Gupta S, Rangwani SR. Risperidone-induced galactorrhea associated with a prolactin elevation. Ann Clin Psychiatry 1998 10(l) 31-3. 

Kim KS, Pae CU, Chae JH, Bahk WM, Jun TY, Kim DJ, Dickson RA. Effects of olanzapine on prolactin levels of female patients with schizophrenia treated with risperidone. J Clin Psychiatry 2002 63(5) 408-13. 

Togo T, Iseki E, Shoji M, Oyama I, Kase A, Uchikado H, Katsuse O, Kosaka K. Prolactin levels in schizophrenic patients receiving perospirone in comparison to risperidone. J Pharmacol Sci 2003 91 259-62. 

Ceskova E, Prikryl R, Kasparek T, Ondrusova M. Prolactin levels in risperidone treatment of first-episode schizophrenia. Int J Psych Clin Pract 2004 8 31-6. 

Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC. Prolactin levels in male schizophrenic patients treated with risperidone and haloperidol a double-blind and randomized study. Psychopharmacology 2005 178 35 10. 

After a baseline period of treatment with fluphenazine for a minimum of 2 weeks, 29 patients with chronic schizophrenia participated in a randomized, double-blind, 6-week comparison of clozapine and risperidone (15). Clozapine was superior to risperidone for positive symptoms and parkinsonian adverse effects. In addition, clozapine produced fewer effects on plasma prolactin than risperidone. The mean daily doses during week 6 of the trial were 404 mg of clozapine and 5.9 mg of risperidone. 

---