Antipsychotic Drugs May Raise the Risk of Fatal Blood Clots
United Press International
October 07, 2000
Boston, Oct. 7 (UPI) -- Drugs prescribed for conditions such as schizophrenia or manic depression may increase the risk of life-threatening blood clots, say the authors of a new study here.
The clots, known as venous thromboembolic (VTE), "are potentially fatal but eminently treatable," said Gwen Zornberg, assistant professor of epidemiology and Biostatistics at Boston University School of Public Health. Zornberg is lead author of the study, published in The Lancet.
The clots form in the lungs or the legs, from where they can break away and travel to the lungs. Risk of death comes when they block the flow of oxygen-rich blood from the lungs to the rest of the body. Traditionally, people who are overweight, extremely sedentary, or who have a history of conditions such as heart attacks or diabetes have a particularly high risk of developing such emboli. But doctors have long suspected that antipsychotic drugs, such as chlorpromazine (Thorazine) or thioridazine (Mellaril), might contribute to the risk of VTE as well. Earlier studies claiming a link had too many confounding factors, however, to permit firm conclusions, Zornberg said.
For their study, she and her co-author Hershel Jick looked at the records of nearly 30,000 people who were part of a general-practice database in Britain. All of the subjects had taken at least one type of antipsychotic drug between 1990 and 1998. To eliminate the influence of confounding variables, they studied only patients who were under age 60 and had none of the medical conditions associated with an increased risk of VTE.
From this group, the authors identified 42 people who developed VTE for the first time while taking the drugs. They compared each patient with four other people from the database of similar age, sex, and health status, who had not been on any antipsychotic medication, and compared the risk of VTE between the two groups. No one in the comparison group developed VTE.
Because the two groups were similar in every major respect except the use of antipsychotic drugs, the authors calculated that the risk of VTE was seven times greater in current users of antipsychotic drugs than in non-users. Ironically, the risk was higher with low-potency drugs than with high-potency drugs, and was greatest during the first three months of use. "This is good evidence that there's a link" between antipsychotic drugs and VTE, said Victor Tapson, associate professor of medicine at Duke University, Chapel Hill, N.C. "It really does suggest that we should look at this more carefully."
Nevertheless, according to Los Angeles psychiatrist Mark Graff, the practical significance of these findings is yet to be determined. Although the findings are "thought-provoking," he said, "I can't recall the last case of VTE that I've seen, and I have about 1,000 patients."
How these drugs contribute to VTE is still unknown, said Zornberg. VTE often is seen in the legs of elderly or immobile people, because lack of activity causes blood to pool in the leg veins, where it can form clots. Since low-potency antipsychotics also have a sedative effect, she suggested that people who take them may become less active. There is some evidence that the drugs increase the adhesiveness of platelets, the clotting elements of the blood. It is also possible that "there is something about 1/8psychotic illness3/8 itself that causes VTE," Graff warned.
It is known, for example, that with schizophrenia, "the frequency of death from all causes is higher." Because virtually everyone with schizophrenia is placed on drugs, it would be impossible -- as well as unethical -- to compare risks of patients who take the drugs to those who do not. Symptoms of VTE include pain or swelling of the legs or calves, shortness of breath, chest pain, and a feeling of apprehension, Zornberg said. This can make diagnosis tricky, because doctors often prescribe these drugs to relieve anxiety, so if a patient complains of apprehension, the doctor may assume it's due to an anxiety attack, she explained. "There's no need for people to panic," said Tapson, who wrote an editorial about the study, which appears in The Lancet. "But for individuals taking care of these patients, it's important to keep this possibility in mind."
VTE is easily treated with anticoagulant drugs such as heparin or warfarin, added Zornberg. "One of the best preventive factors is good health," she said. "Just make sure the person stays active. Even a bedridden patient can engage in physical rehabilitation to remain active and prevent blood clots."
"If you are concerned, speak to the practitioner who prescribed these drugs to you or your loved one," said Graff. "Just because you see something in the newspaper doesn't mean you should stop taking the medication abruptly." (Reported by Norra MacReady in Los Angeles.)
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This news story is not produced by the American Psychological Association and does not necessarily represent the opinions of the association.