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Side Effects: Telling the Real From the Imagined

Fear of side effects prompts many patients to stop taking their medicine

The long list of side effects rattled off at the end of TV drug ads and found on many websites is giving some doctors a headache.

Dr. Betul Hatipoglu, of the Cleveland Clinic, asks patients to record their symptoms in a journal to help determine if their perceived side effects to drugs are real or not. ENLARGE

Many people often believe, research shows, they are experiencing side effects even when they're not, ranging from minor dizziness to muscle pain and heart palpitations. That prompts some patients to stop taking their medicine, which can increase their health risk. Physicians say patient concerns about adverse effects from drugs are an issue they deal with almost every day.

"We take side effects seriously because it's the No. 1 reason why patients are noncompliant with their medications," said Magnus Ohman, associate director of the Duke Heart Center at Duke University. "They look up a medication on Google and they usually find every side effect known to man. Some patients are sensitive to that," he said.

One-third to one-half of U.S. patients on drugs for chronic illnesses don't take their medication as prescribed, health experts say.

Studies show reports of side effects often aren't valid. A review of 21 randomized clinical trials for depression, published in the journal Psychiatry Research last year, found that among 3,255 patients receiving placebo treatments about 45% reported at least one adverse effect, such as headache, dizziness or fatigue. In a similar meta-analysis looking at pain treatment, researchers found many patients were likely to report undesirable side effects, even when they were given a placebo. The analysis, published in the journal Pain this year, reviewed 10 separate studies involving a total of about 335 patients.

And in a March study in the Annals of Internal Medicine, eight patients taking cholesterol-lowering statins who reported muscle pain were tested to determine if the symptoms resulted from the medication. In none of the patients was this the case. Similar results have been found in patients taking beta blockers, a class of drugs commonly used for hypertension and cardiovascular problems, and medications used to treat migraine, fibromyalgia and other conditions.

"It's quite common," said Paul Enck, a professor of medical psychology at the University of Tübingen in Germany. "When patients take drugs they do attribute all the effects they feel to the drug rather than to their health, the environment, the weather or the beer they had last night."

To test a perceived side effect, many doctors instruct the patient to stop the drug for a week or two to see if the symptoms go away. Then they resume the drug. If the symptom comes back, doctors then often try to find a different medication. Side effects like rashes or fevers are relatively easy for a doctor to assess. It is the subjective ones, like aches and fatigue, that are harder to determine if they are caused by a medication or something else.

Betul Hatipoglu, an endocrinologist at Cleveland Clinic, said for difficult-to-evaluate symptoms she finds it helpful to ask patients to write in a journal how they feel every day for a week or two and to rank the severity on a scale of 1 to 10. Then she tells them to continue keeping the journal after stopping the medication and to see if the symptoms improve.

On the Side

Possible side effects of some common medications

  • Statins (for cholesterol): muscle pain, liver damage, digestive problems
  • Beta blockers (hypertension): blurred vision, chest pain, dizziness
  • Ibuprofen (mild pain): abdominal discomfort, sour stomach, bloating
  • Metformin (Type 2 diabetes): shortness of breath, chills, decreased appetite
  • Thyroid hormone (hypothyroidism): weight loss, trouble sleeping, tremors

Source: Mayo Clinic

Dr. Hatipoglu said in recent months some of her patients taking DPP-4 inhibitors, a class of drugs used by many Type 2 diabetes patients, have been concerned about a suspected association between the medication and pancreatitis. (Studies so far have failed to turn up evidence for such a link.) Some of the patients stopped taking the medication after a bout of indigestion. Dr. Hatipoglu said a blood test ruled out pancreatitis in these patients. "None of them had the side effect that they thought they were having," she said.

Michael Perskin, chief of geriatrics at Tisch Hospital, part of New York University Langone Medical Center, said sometimes it is pretty clear if a side effect is imagined. Some patients, for instance, report a side effect after one dose of a medication that is known to take several days to cause symptoms. Another clue: when a person reports having side effects with three different drugs that typically cause such symptoms in less than 1% of patients.

Eric Matteson, chair of the division of rheumatology at the Mayo Clinic in Rochester, Minn., said he tries to educate patients about the balance between the benefits and risks of taking certain drugs. For example, methotrexate, a drug used to treat some rheumatoid-arthritis patients, increases the chance of getting certain types of cancers. He tells these patients the disease itself puts them at greater risk for cancer, even without treatment.

"Then I discuss, 'If there's a doubling of your lymphoma risk, that means it goes from 1 in 4,000 to 1 in 2,000,' " he said. "It sounds dramatic to have a doubling in risk but the actual chance that you'll get that is still very low."

"Empowering the patient to feel like they're in control" can help when people refuse to take a drug for fear of side effects, Dr. Matteson said. He might start a patient on a very low dose and slowly increase it. Or he might negotiate with patients to allow them a medication-free day.

Cardiologists say fear of side effects makes it difficult to convince some heart patients to start on statins. Internet chat rooms are filled with talk about possible adverse effects, such as myalgia, or muscle pain, and cognitive dysfunction, also known as brain fog, the doctors say.

"This can be critically important because we have patients for whom statins have documented lifesaving benefits," said Steven Nissen, chairman of the department of cardiovascular medicine at Cleveland Clinic.

The dilemma for a physician is knowing how to approach the topic with patients, Dr. Nissen said. Describing too many possible side effects might be counterproductive because patients might want to stop taking the drug the first time they feel something.

Dr. Nissen said he always tells patients about potential side effects. But if it is a drug that could save someone's life, he is less likely to list myriad negative symptoms.

Write to Sumathi Reddy at

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