A Time to Heal: Chronotherapy Tunes In to Body's Rhythms

Successful treatment of diseases may depend on the time of day or month that a medicine is taken or surgery performed. Asthma and arthritis pain are examples of conditions now being treated by the clock or calendar.

How our bodies marshal defenses against disease depends on many factors, such as age, gender and genetics. Recently, the role of our bodies' biological rhythms in fighting disease has come under study by some in the medical community.

Our bodies' rhythms, also known as our biological clocks, take their cue from the environment and the rhythms of the solar system that change night to day and lead one season into another. Our internal clocks are also dictated by our genetic makeup. These clocks influence how our bodies change throughout the day, affecting blood pressure, blood coagulation, blood flow, and other functions.

Some of the rhythms that affect our bodies include:

• Ultradian, which are cycles shorter than a day (for example, the milliseconds it takes for a neuron to fire, or a 90-minute sleep cycle)



• Circadian, which last about 24 hours (such as sleeping and waking patterns)



• Infradian, referring to cycles longer than 24 hours (for example monthly menstruation)



• Seasonal, such as seasonal affective disorder (SAD), which causes depression in susceptible people during the short days of winter.

"The biology of human beings is not constant throughout the day, the menstrual cycle, and the year," says Michael Smolensky, Ph.D., director of the Chronobiology Center at the University of Texas. "Instead, it varies predictably in time."

Coordinating biological rhythms (chronobiology) with medical treatment is called chronotherapy. It considers a person's biological rhythms in determining the timing--and sometimes the amount--of medication to optimize a drug's desired effects and minimize the undesired ones.

According to Smolensky, patients are more likely to follow schedules for taking their medications when those medications are formulated as chronotherapies because of better medical results and fewer adverse side effects. "With better compliance, the disease can be better contained, which means fewer doctor visits and potential trips to the hospital because of acute flare- ups," he says.

The area in which chronotherapy is most advanced--drug chronotherapy--for the most part does not involve new medicines but using old ones differently. Revising the dosing schedule, reformulating a drug so its release into the bloodstream is delayed, or using programmable pumps that deliver medicine at precise intervals are some of the simple changes that may reap enormous benefits. Drugs that are reformulated as chronotherapeutics are regulated by the Food and Drug Administration.

Here's a look at how chronotherapy is being used or studied for various diseases.

Asthma

Normal lung function undergoes circadian changes and reaches a low point in the early morning hours. This dip is particularly pronounced in people with asthma.

Chronotherapy for asthma is aimed at getting maximal effect from bronchodilator medications during the early morning hours. One example is the bronchodilator Uniphyl, a long-acting theophylline preparation manufactured by Purdue Frederick Co. of Norwalk, Conn., and approved by FDA in 1989. Taken once a day in the evening, Uniphyl causes theophylline blood levels to reach their peak and improve lung function during the difficult early morning hours. There are other bronchodilators that act similarly to address the early morning dip in lung function, but the manufacturers have not sought or received FDA approval for chronotherapeutic labeling.

Writing in the April 15, 1996, issue of Hospital Practice, Richard Martin, M.D., who directs the division of pulmonary medicine at the National Jewish Center for Immunology and Respiratory Medicine in Denver, stated his belief that "the key to managing [asthma] cases is chronotherapy. I have found that unless treatment improves nighttime asthma, it is hard to improve its daytime manifestations." For people with severe asthma who wake up several times a night gasping for breath, a good night's sleep can be a dream come true.

Arthritis

Chronobiological patterns have been observed with arthritis pain. People with osteoarthritis, the most common form of the disease, tend to have less pain in the morning and more at night. But for people with rheumatoid arthritis, the pain usually peaks in the morning and decreases as the day wears on. Recent animal studies showing that joint inflammation in rats fluctuates over a 24-hour period support these observations by both patients and physicians.

Chronotherapy for all forms of arthritis uses standard treatment, nonsteroidal anti-inflammatory drugs and corticosteroids; however, the dosages are timed to ensure that the highest blood levels of the drug coincide with peak pain.

For osteoarthritis sufferers, the optimal time for a nonsteroidal anti-inflammatory drug such as ibuprofen would be around noon or mid-afternoon. The same drug would be more effective for people with rheumatoid arthritis when taken after the evening meal. The exact dose would depend on the severity of the patient's pain and his or her individual physiology.