May 31, 2006 – A statistical "signal" links Risperdal and other schizophrenia drugs to pituitary tumors, FDA researchers report.
The finding is not proof that these extremely useful drugs cause these benign (noncancerous) tumors. And it does not tell how often patients develop drug-linked pituitary tumors, says Duke University psychiatrist P. Murali Doraiswamy, MD. Doraiswamy was a member of the research team led by the FDA's Ana Szarfman, MD.
The researchers used a highly sophisticated computer program to analyze the FDA's database of 40 million combinations of drugs and side effects reported by doctors and patients. They found 77 reports of pituitary tumors in patients using seven different antipsychotic drugs. Seventy percent of these reports were in patients taking Risperdal.
"When you put all the data together, you get a strong biochemical plausibility that this is a Risperdal effect," Doraiswamy tells WebMD. "But we cannot rule out the possibility it is a spurious association. No one should stop Risperdal because of this. Even if Risperdal is linked to pituitary tumors, it may turn out to be fairly rare."
Szarfman, Doraiswamy, and colleagues report the findings in the June 2 issue of the journal Pharmacotherapy.
Small Risk, Benign Tumors
The tumors linked to Risperdal and other drugs are not necessarily dangerous. Many are microscopic. Few are larger than 1 millimeter.
"These are benign tumors, better thought of as a cyst," Doraiswamy says. "They grow slowly and, generally, locally. Most are very tiny. But sometimes they grow, and when they do, they press on surrounding tissue and cause hormonal problems. Or they can press on the optic nerve and cause some loss of vision."
Janssen, the Johnson & Johnson subsidiary that makes Risperdal, is already telling patients about animal studies and human case reports that link antipsychotic drugs to pituitary tumors, or, as doctors call them, adenomas.
"Last year, we updated our labeling to ensure that health care professionals are aware of reports of benign pituitary adenomas in patients using antipsychotic medications," Janssen spokeswoman Theresa Gaines tells WebMD. "Benign pituitary adenomas are present in 10% to 25% of the general healthy population."
Expensive MRI scans are the only way to detect a pituitary tumor. It may be that these tumors are seen in patients taking Risperdal because that is where doctors are looking, says Glenn W. Currier, MD, medical director for psychiatry at the University of Rochester, N.Y. Currier is not affiliated with Janssen but has been lead researcher in Janssen-funded clinical trials and has served on Janssen's Risperdal speakers' board.
"Are we finding these tumors in Risperdal patients because we wouldn't be looking for it if they weren't taking the drug?" Currier asks.
Johnson & Johnson is a WebMD sponsor.
Sexual Symptoms May Warn of Tumor Risk
The pituitary gland is a small organ in the center of the brain. It secretes hormones that have direct actions on the body, and/or regulate other hormones in your body.
How could schizophrenia drugs cause pituitary tumors? The pituitary gland makes a hormone called prolactin. Prolactin tells women's breasts to enlarge and make milk. Normally, a brain chemical called dopamine puts the brakes on prolactin production.
Risperdal and several other antipsychotic drugs block dopamine. This reduces their psychotic symptoms -- but it also takes the brakes off the pituitary's prolactin machinery. Overproduction of prolactin, over time, can make the pituitary grow larger, which ups the risk for tumor growth.
"A quarter of all patients who take Risperdal have prolactin elevations," Doraiswamy says. "Most are mild and fairly transient, so those people don't need to worry at all. Many, many people have taken Risperdal for years without any problem. But Risperdal is far more likely to cause prolactin problems than many other drugs in its class."
Those who do have problems, Doraiswamy says, usually have sexual symptoms: male impotence, breast tenderness, breast enlargement, and/or abnormal milk secretion in a child, a man, or a nonpregnant woman.
"We just had a call from a patient who had a pituitary tumor while on Risperdal, and then switched to another drug and the tumor went away," Doraiswamy says. "But if any drug switching is done, it must be done with a psychiatrist's care. If you suddenly switch from one drug to another, psychotic symptoms may flare up."
Currier says that sexual side effects in most Risperdal patients will go away if a lower dose of the drug is used. That's why he's glad to see doctors becoming concerned about too-high prolactin levels in patients taking antipsychotic drugs. He's not worried about pituitary tumors -- he's worried that the sexual side effects will cause patients to stop taking their meds.
"Sexual side effects are taboo to talk about, even in psychiatry," Currier tells WebMD. "This is one reason people go off their antipsychotic drugs. If this causes psychiatrists to be mindful of it, and talk about it with patients, it is a good thing."