Once a patient has moved beyond the honeymoon phase of levodopa therapy, the drug-dosing schedule that the doctor prescribes is designed to keep blood levels of dopamine on an even keel throughout the day. Too little dopamine may leave your family member stiff and frozen in the middle of the grocery store; too much dopamine, and the wriggly dyskinesias kick in. So it's critical for her to try to always take the meds on time.

After roughly five years of taking levodopa, about 40 to 50 percent of people with Parkinson's disease develop long-term side effects called motor complications:

• Motor fluctuations. The benefit of each pill lasts a shorter time, and as the effect fades at the end of the dose, the patient's stiffness, slowness, or shakiness returns. This "wearing off" phenomenon seems to be connected with the continuing loss of dopamine-producing brain cells, which would otherwise store the dopamine supplied by levodopa therapy and release it in a natural way. So patients become highly sensitive to changes in their blood levels of the drug.

Over time, the "wearing off" turns unpredictable, occurring even in the middle of a dosing cycle when you wouldn't expect it, says nurse practitioner Julie Carter, who is associate director of the Parkinson Center of Oregon in Portland. Patients suddenly fluctuate from being "on" -- where symptoms are controlled -- to being "off," where symptoms worsen. Or sometimes they don't respond to a dose at all, Carter says.

• Dyskinesias. When "wearing off" begins, the physician will either give the patient more levodopa or shorten the interval between doses from one pill every, say, eight hours to one every six hours. But having too much dopamine in the blood can produce a side effect known as dyskinesia: involuntary and random fidgety, writhing movements of the patient's head, face, torso, arms, or legs. Although dyskinesias aren't painful, for some patients, they may be as troublesome as the Parkinson's disease itself.

To deal with these motor complications, the doctor may add on one or two drugs from the other classes of medications -- the dopamine agonists, MAO-B inhibitors, or COMT inhibitors -- to increase "on" time. That could reduce the amount of levodopa needed.

Gradually, over several years, the patient typically has to take more and more doses of medicine per day to squelch motor fluctuations, up to the point where it may be necessary, in advanced Parkinson's disease cases, to take levodopa every couple of hours.