Risperidone increased prolactin

Hypothalamus and Endocrine Systems Endocrine changes occur because of effects of antipsychotic drugs on the hypothalamus or pituitary, including their antidopaminergic actions. Most older antipsychotics and risperidone increase prolactin secretion, probably due to a blockade of the pituitary actions of the tuberoinfundibular dopaminergic neurons. These neurons project from the arcuate nucleus of the hypothalamus to the median eminence, where they deliver DA to the anterior pituitary via the hypophyseoportal blood vessels. Dj receptors on lactotropes in the anterior pituitary mediate the tonic prolactin-inhibiting action of DA (see Chapter 55). 

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. 

Fluoxetine and paroxetine inhibit the cytochrome P450 isoenzyme CYP2D6 by which risperidone is metabolised, hence risperidone levels rise. This can lead to extrapyramidal adverse effects and, it has been suggested, the increased prolactin levels and gynaecomastia seen in one patient. Sertraline is thought to have a dose-dependent effects on CYP2D6 inhibition. ... 

In a review of the use of risperidone in autistic disorder in children and adolescents it was stressed that somnolence, increased appetite, increased prolactin concentrations, and fatigue were the most common adverse events [117 ]. 

Observational studies An open-label, long-term study of patients switched to oral paliperidone from either risperidone or other antipsychotics found that extrapyramidal symptoms improved significantly for all patients [192 ]. Akathisia and weight gain were the main adverse events, and increased prolactin levels in female patients from the nonrisperidone group. 

Another case of priapism in a 45-year-old male on risperidone and sodium valproate is reported [267 ]. Musculoskeletal A study of risperidone-associated prolactin elevation and markers of bone turnover found that prolactin levels significantly increased and N-telopeptide cross-links (markers of bone resorption) significantly decreased [268 ]. No differences were noted between men and women osteocalcin, N-telopeptide cross-links osteocalcin ratios, oes-tradiol and testosterone did not significantly change and there were no significant associations between risperidone dose and prolactin levels. 

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. 

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). 

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). 

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). 

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). 

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. 

In an 8-week study, pre-school-age children with bipolar disorder (aged 4-6 years) took either olanzapine (n = 15 mean age 5.0 years 10 boys mean dose 6.3 mg/day) or risperidone (n = 16 mean age 5.3 years 12 boys mean dose 1.4 mg/day) (59). There were significantly more dropouts with olanzapine (6 versus 1), including one patient who withdrew because of adverse events (increased appetite and hand tremor). The main adverse events, found with both treatments, were significant increases in prolactin concentrations and weight gain. With both treatments, increased appetite, flu-like symptoms, headaches, and sedation were the most commonly reported adverse effects. 

A 34-year-old woman developed dyskinesia after starting risperidone, with a marked increase in prolactin concentrations (95). 

Risperidone and blonanserin In a randomised comparison of risperidone and blonanserin in 206 patients with schizophrenia the mean change in the Positive and Negative Syndrome Scale (PANSS) total score at the final evaluation time point was —24 with blonanserin and -25 with risperidone [125 ]. Dysarthria, dizziness, increased alanine aminotransferase and aspartate aminotransferase activities, and increased blood prolactin concentrations were more frequent with risperidone hand tremor was more frequent with blonanserin. 

Increases in serum prolactin concentrations after the administration of risperidone have been attributed by some to its active metabolite, 9-hydroxyrisperidone (paliperidone). Serum prolactin concentrations after the administration of paliperidone extended-release and risperidone immediate-release tablets have therefore been compared in a double-bund, randomized, paraUel-group study in patients with schizophrenia [iso ll. On day 6, serum prolactin concentration-time profiles were similar with both treatments, with overaU higher serum prolactin concentrations than on day 1. 

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