Light therapy at the right time on the biological clock induces rapid remission in 80 percent of persons with winter depression, scientists at the New York State Psychiatric Institute (NYSPI) and Columbia University have found.
Morning is the optimal time for treatment—about 8.5 hours after the evening onset of melatonin secretion or 2.5 hours after the midpoint of sleep, report Jiuan Su Terman, Ph.D., Michael Terman, Ph.D., and colleagues in the January 15 Archives of General Psychiatry.
While earlier research by the Termans and others established the superiority of morning light therapy over that at other times for most people with winter depression, this study helps clinicians pinpoint the treatment time most likely to benefit individual patients. That’s a major advance for practitioners, according to Dan Oren, M.D., an associate professor of psychiatry at Yale University School of Medicine and past president of the Society for Light Treatment and Biological Rhythms. "The idea that ‘one time fits all’ is no more useful in psychiatry," Oren said, "than the idea that one clothing size fits everyone."
The Termans and their colleagues assessed daily plasma melatonin patterns and depression symptoms in 42 adults with recurrent winter depression, before and after light therapy. After a minimum two-week baseline observation, the volunteer subjects continued their usual schedules for the NIMH-funded study. They were asked to maintain consistent bedtimes and wake-up times. None was using antidepressant medication.
Participants used light boxes that provided 10,000 lux artificial light (equivalent to daylight about 40 minutes after sunrise) for 30 minutes daily at home for 10 to 14 days at two times: either soon after awakening or about two hours before bedtime. Light of this intensity and daily duration is widely used in research studies and as maintenance therapy for people with winter depression. Half the subjects in this study used their lighting devices first in the morning, and then the evening, while the others followed the reverse sequence. They had no break between therapy periods.
The researchers sampled subjects’ melatonin every 30 minutes on evenings before and after treatment under dim light conditions in their laboratory, using an in-dwelling venous catheter. They then used melatonin onset as a reference point to assess effects of treatment. The start of melatonin secretion, Terman said, varied by as much as four hours in different subjects.
While the subjects’ bedtime and wake-up time remained constant, morning light therapy shifted baseline melatonin onset earlier (that is, advanced) on the 24-hour clock by up to 2.65 hours. Evening light therapy delayed it—that is, shifted it to a later clock time—by up to 2.8 hours. The greater the advance in melatonin onset, the greater a patient’s improvement. Whether or not melatonin per se plays a role in a patient’s response to light or serves only to mark body time is not yet known, Terman said.
The 80 percent rate of improvement in patients whose melatonin onset advanced the most, he said, compares favorably with the rate seen with antidepressant drugs. Moreover, it often occurs within a few days of starting light treatment. Patients whose melatonin onset showed little or no advance with morning light, or delay with evening light, still experienced about a 35 percent improvement rate. The latter, he noted, "might be interpreted as nothing more than a placebo effect."
The placebo issue is one that has long bedeviled light therapy investigators. They have compared bright lights with dim lights, lights of different colors, air-cleaning negative ions (an environmental treatment alleged to boost moods), and even a sham negative-ion device, as well as with antidepressant medications.
Most of the antidepressant response to any treatment is a nonspecific placebo effect, notes Charmane Eastman, Ph.D., who directs the biological rhythms research laboratory at Rush-Presbyterian-St. Luke’s Medical Center in Chicago.
Alfred Lewy, M.D., Ph.D., vice chair of the department of psychiatry at Oregon Health Sciences University, reports that giving a small dose of exogenous melatonin in the afternoon, when the body does not normally produce melatonin, also advances the biological clock. He is investigating its mood-enhancing effects. Placebo melatonin capsules, he said, serve as a good control.
To schedule light therapy, Terman said, practitioners do not need to determine the exact time of melatonin onset. The blood and saliva assays used in research studies are not yet widely available. In people who habitually sleep at night, however, the midpoint of sleep predictably falls roughly six hours after melatonin onset, regardless of the length of sleep. Light 2.5 hours after the midpoint of sleep brought about the highest remissions in this study, Terman said.
That finding suggests short sleepers should use a lighting device right after their normal wake-up time. Long sleepers may benefit from getting up earlier than they customarily do (TAB1 at right).
The pros and cons of shortening sleep still prompt debate. While sleep loss itself may undermine mood, sleep deprivation, particularly in the latter half of the night, also has been reported to ease depression. People with typical daytime work hours often curtail sleep to make time for morning light therapy, Eastman said. In a study she and her colleagues reported in the October 1998 Archives of General Psychiatry, light therapy users rose one to two hours earlier than usual. "We wondered whether waking early was part of the treatment," she said, "but we didn’t have a comparison group who got light or placebo and didn’t wake up early." The Termans’ data, she said, show that early rising is not necessary.
People with winter depression often resist waking early, Lewy noted, although they usually become amenable to it when their mood improves after they use light therapy for a week or so. He suggests starting light therapy at the patient’s normal rise time. Lewy is investigating whether a small dose of melatonin in midafternoon—.5 mg or less—can serve as an alternative to light therapy or permit a reduction in duration of morning light exposure.
A small subgroup of people with winter depression responds best to light in the evening or melatonin in the morning to delay their rhythms, Lewy said. These people tend to be extreme morning types, who get up early year around.
Although most people with winter depression respond best to morning light, he said, finding the optimal time and length of exposure for light therapy for any one patient may involve some trial and error. ▪