A number of commonly prescribed older antipsychotic drugs, and some newer ones, are associated with a significant increase in risk of breast cancer.
Previous research uncovered the link between antipsychotic drug use, prescribed for a wide array of mental health problems, and breast cancer risk. This study compared newer antipsychotics to older drugs, and examined how the drugs affect prolactin levels, which have been associated with breast cancer. However, many antipsychotics elevate prolactin levels and can produce side effects such as menstrual cycle irregularities, abnormal breast milk production and abnormal breast tissue growth.
The findings are published online in the Journal of Clinical Psychopharmacology.
“Many women with psychiatric illnesses such as schizophrenia and bipolar disorder will take antipsychotics for decades, and they are essential to keeping symptoms in check,” said first author Tahir Rahman, MD. “But both older antipsychotic medicines and some newer drugs raise levels of prolactin and increase the risk of breast cancer, which is concerning. Our study confirms findings from a smaller European study that advised women and their doctors to first try drugs that don’t affect prolactin levels. We agree with that advice and believe psychiatrists should start to monitor prolactin levels in their patients taking antipsychotics.”
Antipsychotic drugs were classified into three categories, based on their established effects on prolactin. Category 1 included drugs associated with high prolactin levels, such as haloperidol, paliperidone and risperidone. Category 2 had mid-range effects and included iloperidone, lurasidone and olanzapine. Category 3 had low-effect drugs such as aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, quetiapine and ziprasidone.
Comparing the three drug categories to anticonvulsant drugs and lithium, the relative risk of breast cancer was 62% higher for women who took Category 1 drugs and 54% higher for those taking Category 2 drugs, whereas Category 3 antipsychotics were not associated with any increase in breast cancer risk.
“Certain drugs are known to elevate prolactin, and the women taking those drugs were more likely to have breast cancer,” Dr Rahman said. “But we didn’t detect any increased risk in women taking antipsychotics that don’t raise prolactin levels.”
In mouse models, prolactin can help weaken systems keeping precancerous lesions from becoming breast cancer. In humans, prolactin levels tend to be lower in women who have had more children at a younger age than in women who have fewer children or wait until they are older to do so.
In this study using data collected from 2012 through 2016, the research team performed a retrospective, observational study of breast cancer risk in women ages 18 through 64 who took antipsychotics.
The researchers identified which patients were treated for breast cancer during a 12-month period and matched that information to patients taking antipsychotic drugs. Of the 540 737 women in the database taking antipsychotics, only 914 were identified as having breast cancer – a significant number of whom were taking drugs known to increase prolactin.
“Antipsychotic medications can be lifesaving for patients who have psychotic episodes where they experience symptoms such as hallucinations and delusions,” Dr Rahman said. “In recent years, the drugs have been approved to treat other conditions, too, including depression and bipolar disorder. As those high-prolactin agents are used more widely, the number at risk could increase. We’ve been advising against using these high-prolactin agents in women who already have breast cancer, but we’d like to investigate whether keeping prolactin levels lower even might prevent some of these cancers.”
In another recent study, the antipsychotic drug aripiprazole did not increase prolactin levels in women and that a few women who began the study with high prolactin levels experienced decreases in prolactin levels after 12 weeks of treatment.
Those findings, combined with preclinical evidence of the anticancer effects of some antipsychotics, have inspired Dr Rahman and colleagues to propose repurposing some antipsychotic drugs in the fight against breast cancer.
“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr Rahman said.