The long-term treatment of chronic illnesses is challenging on many levels. Among other issues, how can physicians manage dosing over many years, when some drugs can be habit-forming or become less effective over time?

Preliminary research published Monday from scientists at the University of Pennsylvania's Perelman School of Medicine suggests that placebos, currently used mainly for control groups in clinical trials, may be worth another look for treatment.

For chronic illnesses such as insomnia, they might be a key to increasing a drug's lifetime effectiveness.

Clinicians and researchers agree that when certain medications seem to have good long-term efficacy, "what they mean is three, six, or 12 months," said Michael Perlis, associate professor in psychiatry at Penn and lead author of the new study.

"If these medications do not cure, which they don't, how do you treat patients with chronic insomnia for years or decades" with medication that stops working after 12 months?

The new study, published in the journal Sleep Medicine, introduces a new line of thinking about maintenance therapy, specifically for insomnia, but the results might have wider applications, such as for chronic pain management, Perlis said.

Certain sleep medications are not recommended for daily use because they could cause dependence and also lose effectiveness over time. One way to deal with that is intermittent dosing: a patient takes medication three to five nights a week, not every night.

This, however, presents a problem. An insomniac who takes pills only three nights a week might expect that the other four nights are going to be less than restful.

"The intermittent dosing schedule may be a good way to be conservative about drugs," Perlis said, "but half the week will be lousy and the other half the week is OK. Ultimately, your insomnia is going to get worse."

Earlier research suggested that the mind might be a powerful mediator for the immune system. Perlis had a hunch that the human body might be trained into having a physiological response to a placebo.

He wondered: If every time a patient swallows a red pill with a yellow stripe he or she experiences some physiological effect of sleepiness and sleep, is it possible that doing so 30 times or 1,000 times could evoke a similar response to any red pill with a yellow stripe?

Perlis' study tested this idea using different dosing strategies for Ambien, the popular sleep medication, to see which would lead to the best long-term management of chronic insomnia.

Although preliminary - the analysis was based on just 55 patients - the results suggest that the best option might be a strategy that trains the body to respond to a pill and then bridges the nights when a patient is not medicated with a placebo.

Karl Doghramji, director of the Sleep Disorders Center at Thomas Jefferson University Hospital, said the results were not surprising, although he said the Penn team should repeat the study with more patients. He said that patients who use intermittent dosing can do it wrong, which could increase their anxiety, leading to more insomnia.

"We know that there is a very strong placebo response in insomnia," said Doghramji, who was not involved with the study. "So taking something every night is a good idea, even if it's a placebo."

Perlis hopes that his findings on insomnia, if reproducible, have wider applications. Might this have benefits for pain medication?

"Habituation is your destiny," Perlis said regarding pain medication. "You cannot maintain any effects of opiates without dose escalation."

This new strategy, he said, might help.

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