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Chronotherapy: For Some Treatments, It's About Time
Many of our body’s internal processes are cyclical. There are daily patterns, like waking and sleeping, monthly patterns, like a woman’s menstrual cycle, and even seasonal patterns, like those that cause seasonal-affective disorder (SAD) during the winter months. But doctors are only recently beginning to understand these rhythms’ impact on other conditions well enough to more effectively treat their patients.
The idea that medical treatments can be improved based on when they are given to a patient is called chronotherapy. And by making use of this good timing, doctors are finding that they are more effectively treating a wide-range of diseases such as asthma, arthritis and cancer, all while reducing side effects.
"Chronomedicine can help you cope better with short-lasting illnesses such as colds and flu, episodic ones such as headaches and back pain and persistent ailments such as arthritis, high blood pressure, heart disease, cancer and more." says Dr. Michael Smolensky, co-author of the book The Body Clock Guide to Better Health.
Treating By the Clock
Asthma was the first condition to benefit from a little clock watching. Doctors noted that lung function is at its lowest point in the wee hours of the morning, so it would be most ideal for asthma patients to take their bronchodilator medication at this time. However, it is not reasonable to expect someone to wake up at 3 a.m. to pop some pills, so researchers developed long-acting drugs that can be taken before bedtime, yet begin to work much later. One such drug, Uniphyl, is taken only once in the evening but has proven to be a better asthma reducer than more traditional medications, as it acts when the patient is most likely to need it.
"Chronotherapy is the key to [asthma] management." says Dr. Richard Martin, an asthma specialist at National Jewish Center for Immunology and Respiratory Medicine in Denver, in the April 15, 1996 edition of Hospital Practice.
Because asthma symptoms are substantially reduced when taking a drug like Uniphyl, doctors report that patients are more likely to keep using the medication, a major challenge for chronic conditions.
But sometimes, different types of the same condition have different daily patterns, and by recognizing subtle differences, better treatment practices can be implemented. For example, osteoarthritis tends to be most painful in the evening, while rheumatoid arthritis is usually more painful in the morning. Once doctors began to notice these differences, they advised patients with osteoarthritis to take arthritis medications—usually, non-steroidal anti-inflammatory drugs (NSAID)—around noon, but patients with rheumatoid arthritis would be directed to take the same drug in the evening. This way, the medication would kick in at the appropriate time for each condition.
Chronotherapy has also been used to lower the amount of side effects from chemotherapy drugs. Over the years, doctors have realized that by giving two of these drugs, Adriamycin and cisplatin, in the morning and evening, respectively, side effects could be cut in half.
Further understanding of the cancer cell cycle would be the next step. A few studies have shown that cancer cells function on a cycle independent of the rest of the body. Therefore, if researchers can pinpoint the best time to administer cancer-killing drugs, these treatments would be more effective and do less harm to the rest of the body.
"When cancer medications are given in a chronobiological manner, patients may be able to tolerate higher, more potent doses than would be possible otherwise." says Dr. Smolensky.
Even tumor-removing surgery may benefit from some clever timing. While the idea is still fervently debated, some small studies have shown that women’s menstrual cycles are important in breast tumor removal. One study in particular, presented at the 1996 International Conference on Breast Diseases, showed that removing a tumor during the week following ovulation improved the five-year cancer-free rate by 13 percent over patients whose surgeries occurred earlier in the menstrual cycle. It is assumed that the differences in hormone levels produced in the latter stages of a woman’s cycle play a role in inhibiting the spread of cancer after surgery. Larger studies are needed, however, to prove this idea.
Developing Timed Technology
While researchers have a long way to go to determine the cycles that govern other conditions, drug companies are realizing that chronotherapy has a future.
A doctor will often prescribe a drug to be taken with meals or before bed simply because it is easy for a patient to remember to take the medicine at these times. However, symptoms may peak at other times of the day. So, drug companies are trying to develop ways of delivering medication that will allow patients to take their drugs at convenient times but won’t impact the body until the medication will be most effective.
One company, Egalet, is working on two new types of pills. One allows for a drug to be released at a constant level over many hours, eliminating the need for patients to take multiple doses of a drug that may result in inconsistent therapeutic levels. The other pill has a built-in delay that slowly erodes to deliver one large burst of a drug at a set time. Ultimately, these two pills can be used to release medication in the manner it will most benefit the patient.
Programmable pumps, which have already shown utility in diabetes treatment, may also prove useful in delivering chemotherapy drugs at the appropriate time in the cancer cycle, without any extra work for the patient.
While technology is slowly being developed to help doctors administer medicine at the best times, more knowledge about chronotherapy is needed. In a 1996 poll, the American Medical Association found more than half of the physicians in the U.S. were not familiar with chronotherapy.
Still, there have been thousands of studies and articles written on the topic. Chronotherapy may be a fairly new concept, but it is certainly not an outlandish one.
"The evidence [for chronotherapy] is solid and growing." says Dr. Smolensky.
