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April 16, 1999
By Liz Lipton
Side effects secondary to hyper-pro-lactinemia have been well known since the introduction of antipsychotics in the 1950s, but they were largely ignored because not much could be done about them.
But now with the advent of newer antipsychotics such as olanzapine, quetiapine, and clozapine, "we can prevent these side effects and have an alternative way to treat them should they occur in the course of antipsychotic therapy," according to Ruth A. Dickson, M.D., an associate professor in the department of psychiatry at the University of Calgary.
Dickson spoke in February at the Manhattan medical writers' session titled "Prolactin: The Pandora's Box of Psychiatry." The session was sponsored by the University of Pennsylvania with funding from Eli Lilly and Company. The speakers limited their discussion to patients with schizophrenia.
"The elevations of prolactin are small and/or transient with clozapine, olanzapine, and quetiapine," commented Richard G. Petty, M.D., M.Sc., director of the integrated medicine program in the University of Pennsylvania's department of psychiatry. "Most effects associated with hyper-prolactinemia recede or even go away altogether when patients are switched to [these] atypicals. [However,] there is no specific figure available regarding the percentage of patients whose symptoms recede or go away altogether after making this transition."
In contrast, "many patients taking typical antipsychotics or risperidone develop hyperprolactinemia. The levels of prolactin seen in these patients are frequently found within the ranges found with prolactinomas, which are known to produce multiple endocrine disturbances. These disturbances include such sexual and reproductive ones as breast engorgement, amenorrhea, and decreased libido," said Petty, an attending psychiatrist at the Hospital of the University of Pennsylvania.
Furthermore, Dickson said, "Clinical studies support the occurrence of the above-mentioned dysfunctions, as well as anovulation, 'menstrual-chaos' decreased arousal, orgasmic dysfunction, nonpeurperal lactation, reduced fertility, and decreased bone density mediated by testosterone/estrogen deficiency."
When asked about such potential long-term side effects of hyperprolactinemia as breast cancer and accelerated atherosclerosis, Petty replied, "There are longer-term studies of hyperprolactinemia induced by prolactinomas and other medications that can elevate prolactin, and nobody yet knows whether these long-term side effects are real. We need to remain vigilant about this issue."
Dickson noted, "Side effects secondary to hyperprolactinemia do not correlate well with the severity of prolactin elevations. Some patients quite rapidly develop side effects such as amenorrhea or sexual dysfunction with relatively limited increases in prolactin levels, while others tolerate higher levels for extended periods before developing side effects."
Just how many psychotic patients develop hyperprolactinemia is not known. Dickson noted, "While there is agreement that all typical antipsychotics and risperidone cause hyperprolactinemia, there is no exact percentage of antipsychotic-treated patients who develop prolactin elevations and subsequent end organ side effects. Choice of drug, dose, duration of treatment, and poorly understood individual vulnerabilities influence this number."
Petty commented, "We calculate that 80 percent of the 2.5 million people with schizophrenia are on traditionals or risperidone." Petty is the author of "Prolactin and Antipsychotic Medications," published in the February supplement of Schizophrenia Research.
The previously mentioned clinical data-except for those on menstrual disturbances and galactorrhea-involved nonpsychiatric populations. Thus, the only figures available for studies involving psychotic patients on typical antipsychotics is 15 percent to 91 percent for menstrual disturbances and 10 percent to 50 percent for galactorrhea, according to William M. Glazer, M.D., president of Glazer Medical Solutions and an associate clinical professor of psychiatry at Massachusetts General Hospital and Harvard Medical School.
Glazer, who did not attend the workshop, cowrote with Dickson the review article "Neuroleptic-Induced Hyper-prolac-tine-mia," published in the February supplement of Schizophrenia Research.
Why, said, Glazer, are "there to date few, if any, good studies [on hyperpro-lactinemia] of psychotic patients treated with typicals or atypical medications? Two reasons for this are that the studies may involve self-reporting via patients or they are not designed to measure these side effects. For example, researchers might include women taking birth control pills, a small percentage of premenopausal women, or they might measure amenorrhea as a menstruation that is absent for three months in a six- to eight-week study.
"[In contrast], in nonpsychiatric literature there are thousands of reports describing clinical phenomena resulting from hyperprolactinemia secondary to medical conditions such as pituitary tumors. I strongly feel that hyperprolactinemia has the same clinical consequences whether caused by antipsychotic medications or other medical problems."
Increasing medical professionals' awareness of hyperprolactinemia in patients taking antipsychotics is important because these side effects may influence the patient's compliance in taking medication. Furthermore, medical professionals should realize they often must use direct inquiry to elicit information on sexual and reproductive dysfunctions, said Kimberly Littrell, an advanced practiced registered nurse and president and CEO of the Promedica Research Center in Atlanta.
"Other recommendations included improved monitoring for these side effects in clinical trials of new antipsychotics. Also, health care professionals should routinely screen for side effects known to occur secondary to hyperprolactinemia via history taking and, when indicated, serum prolactin levels, as well as educate patients about these side effects," said Dickson, who is also chief of the specialized programs division in the regional clinical department of psychiatry, Calgary Regional Health Authority.
Norman Sussman, M.D., a clinical professor of psychiatry at New York University School of Medicine, offered additional information on hyperprolactinemia and schizophrenic patients.
"People need to be mindful of short- and long-term effects of elevated prolactin. [However], it really needs to be proven that elevated prolactin does cause as many possible consequences in psychotic patients as the researchers were implying." Furthermore, there are other important factors that must be reviewed when prescribing anti-psychotic medications such as "sedation, the consequences of weight gain including poor body image and risk of diabetes, as well as the effects on metabolism of other drugs."
Another consideration, according to Sussman, is switching patients from typicals to atypicals. If a patient is stable on an existing drug, however, it may not be a good idea to switch even if he or she has elevated levels of prolactin.