By Daniel F. Kripke, MD

The outlook is bright for patients with sleep disorders and/or depression who undergo light treatment

Ancient writings show how the benefits of light have been time-tested in human experience. Today, experimental science points to specific ways that bright light can be used to treat sleep clinic patients. Bright light should be considered for two kinds of clinical problems: circadian rhythm sleep disorders and depression.

Circadian Rhythm Sleep Disorders Case Report
A 42-year-old man has had difficulty falling asleep since childhood, and getting up for school then was always a struggle, as is getting up for work now. He finds it difficult to fall asleep before 4-6 am and to get up before noon. He is lethargic until early afternoon but full of energy in the late evening.

This patient has a problem with his body clock, which controls the daily interval of sleepiness—when we feel like falling asleep and when we feel like waking up. His body clock is running very late, and as a result his sleep-onset and wakening times are markedly delayed.

Our bodies contain about-24-hour clocks called circadian oscillators (circa + dian means “about a day”). Circadian oscillators are composed of recently discovered genes, related RNA, and proteins with interesting names such as period, timeless, clock, cryptochrome, and doubletime.1,2 Expression of these genes seems to cycle up and down each day like the turning of watch gears. The most important body clock is the suprachiasmatic nucleus of the anterior hypothalamus, a tiny area of about 10,000 nerve cells located just above the optic chiasm.3 Bright light striking the retinas resets the timing of the suprachiasmatic nucleus, much like the adjustment of the time on a wristwatch. Incidentally, most experts doubt that light striking the skin has much effect.

Figure 1

Figure 1. The phase-response curve is the dotted red line, which shows how advance and delay occur in response to bright light at different times. The time of sleepiness in the 24-hour cycle corresponds to the 7-8 hour bedtime for a normal person, but the interval of sleepiness will be before desired bedtime in advanced-sleep-phase syndrome and after desired bedtime in delayed-sleep-phase syndrome. The white sun symbols and arrows illustrate the directions in which light exposures at different times push the interval of sleepiness.

The diagnosis for patient one was delayed sleep-phase syndrome.4 The treatment for this can be understood best by visualizing the phase-response curve5 (PRC) of the body clock. The PRC illustrated in Figure 1 demonstrates the times when the body clock is sensitive to resetting. For a few hours before and just after our usual awakening time, bright-light exposure will advance the body clock, causing us to fall asleep earlier and to arise earlier. In this case, because the patient’s body clock is delayed, his PRC is also delayed. Thus, the advancing portion of his PRC would start after 8 am. Exposure to bright light after 8-10 am, especially soon after noon, will tend to set his body clock earlier so he can fall asleep earlier.

Here is how we would treat this patient.6 We would advise him to purchase a bright-light box, which he can use at home after awakening or just after he arrives at work. His problem is so disabling that the expense of owning a light box is well justified. He should expose himself to bright light (10,000 lux for at least 30 minutes or 2,500 lux for at least 2 hours) as soon as possible after he awakens, day after day, until he finds himself falling asleep earlier and arising earlier. As he arises earlier, he should also use his bright light earlier—as soon as possible after arising. Once his bedtime and arising time advance to his preferred schedule (with sleep occurring perhaps from midnight to 7 am), he might be able to stabilize his circadian rhythm with a shorter duration of daily bright light. Some patients find that taking 1 mg of oral vitamin B12 daily increases the benefit of bright light.7

Patients who are in a hurry to reset their body clocks could spend the entire daytime outdoors for 2-3 days, which may be of great benefit. Unfortunately, patients with delayed-sleep-phase syndrome tend to relapse whenever they miss exposure to bright light for several days in a row or stay up for social occasions. An important part of treatment is motivating patients to accept the idea that they may need morning bright light most of their lives, as well as a consistent rising time.

Campbell8 showed that within a couple of weeks, bright-light boxes next to the television can make dramatic improvements in the early awakening insomnia. Unfortunately, light this bright may not be well tolerated. Sometimes modest augmentation of ordinary room lighting is well accepted and sufficient to relieve phase-advance symptoms. A good choice might be a fluorescent torchère placed next to the television-viewing chair for evening use. Fluorescent torchères use little electricity, have long-lasting bulbs, and present less danger of fire than halogen lighting. This is such an easy, safe, and inexpensive treatment that patients who might have phase-advance have little to lose by trying brighter room lighting.

Shift Work
For decades, studies in all parts of the world have shown that most people working the night shift sleep poorly.9,10 Partly because of poor daytime sleep, night workers often fall asleep during the night shift, a problem creating inefficiency and posing grave risks.

There are now sufficient data from short-term research to prove that use of bright light on the night shift can help workers adjust to this shift.11 Wearing dark glasses when driving home from work in the morning may also be important—the darker the glasses the better (welder’s goggles are optimal), as long as driving safety is not compromised.11 Studies of ways to use bright light in actual night-shift workplaces are only beginning, and much experimentation will be needed to find the best approaches for a very complex range of work schedules. Unfortunately, there has been little study of the long-term effects of bright light on persons who work nights week after week. It is possible that improvement in night alertness will be counterbalanced by greater difficulties in sleeping during time off.

Jet Lag
People fly so much these days that everybody knows what jet lag feels like. The sleep-wake pattern may be stuck in the departure time zone, causing sleep disruption.12 Today’s frequent travelers sometimes consult a sleep clinic for help. Most travelers will not find it convenient to use light boxes on arrival at their destination, but they can use the most readily available tools: daylight and dark glasses. Unfortunately, recommendations for treatment of jet lag are based mainly on theory, since no extensive field trials have been performed.

People flying from east to west may arrive with symptoms of advanced-sleep-phase syndrome. Air travelers can make good use of the PRC to accelerate adjustments. Before a flight from east to west, they can wear dark glasses whenever they are outdoors on the morning before departure. It is good to be outdoors for 1 or 2 hours before sundown on the day of arrival and then to use as much bright light as available in the evenings until the body clock adjusts. Bright light in the morning should be avoided until early awakening disappears. West-going travelers may also wish to use bright light for one or two evenings before departure to begin adjusting their body clocks, especially if they will be traveling across one to 12 time zones.

People flying from west to east may arrive with symptoms of delayed-sleep-phase syndrome. Adjustment will be speeded if the traveler is exposed to bright outdoor light on the morning of departure and perhaps for a day or two in advance. Exposure to bright outdoor light in the morning should continue until problems with falling asleep at night are resolved, but because of the position of the PRC, it is not necessary to use dark glasses outdoors except in the longest evenings of midsummer. This approach usually works for travel across one to six time zones. When flying east across six to 11 time zones, travelers may find it easier to delay than to advance their body clocks, depending partly on the time of day and conditions of the flights. It may be difficult to predict which way the body clock will adjust, and it is even possible for some body system clocks to advance while others delay. For travelers on long east-going flights, morning outdoor light on the day immediately after arrival may fall on the delay portion of the PRC and push the sleepiness time in the wrong direction.13 After long east-going flights, it may be wisest to go outdoors in mid-afternoon for a day or two after arrival. A day or two after arrival (once the PRC has advanced a bit), exposure to morning bright outdoor light is preferable.

Bright-light Treatment of Depression
A high percentage of sleep clinic patients with chronic insomnia are depressed.14 Moreover, depression is often a secondary problem with sleep apnea,15 narcolepsy, and idiopathic hypersomnias. Therefore, sleep clinicians often arrange treatment of depression.

Antidepressant drugs are well accepted worldwide because they are effective and relatively safe and affordable. The scientific evidence of their benefit after 8-16 weeks of use is overwhelming, but the limitations of that benefit are often not recognized. A recent analysis of records of the US Food and Drug Administration showed that after 8 weeks, use of antidepressant drugs reduced Hamilton Depression Ratings only 10%-11% more than placebo.16 A comprehensive meta-analysis of published trials suggested that the conditions of patients given antidepressants might improve 19% more often than those of patients given placebo, but because of a significant bias toward publishing good results, the true figure is probably less than that.17 Since the indolence and effectiveness of psychotherapeutic treatments may be similar to those of antidepressant drugs, augmentation and acceleration of therapy for depression are needed.

Bright light offers a remarkable new option for treatment of depression. This officially approved treatment18 reduces depressive symptoms more promptly and substantially than placebo treatments.19-21 The majority of studies have shown that it produces significant benefit within 1 week. Increases in benefits have been measured in controlled studies in which light treatment was continued for up to 4 weeks, but because of the rapid response, controlled studies have not been extended beyond 1 month. Case reports suggest that bright light may continue to benefit patients for many years, though relapse is common when bright light is withdrawn. The great majority of controlled bright-light trials have shown net benefits (reductions in symptoms) of >12% (20%-30% reductions within 1-2 weeks). In other words, bright light has a more rapid and possibly larger antidepressant benefit than antidepressant drugs. Moreover, the benefits of bright light appear to be additive or synergistic with antidepressant medication, so the clinician should usually combine these treatments rather than trying to choose between them.19

The indications for bright light are about the same, whether a patient has nonseasonal depression or SAD. Bright light works well for either pattern of depression. It is possible that patients with SAD may have somewhat greater response to bright light, but this has never been proven in well-balanced, placebo-controlled comparisons. It appears that almost any depressed patient is likely to benefit from bright-light treatment.

Risks of light treatment
In general, bright light is extremely safe for treatment, but there is one serious risk. Bipolar patients (those with a history of mania) often experience sudden mania when treated with bright light. The mania may be worse than the depression it relieves. The risk of mania seems to be moderated for bipolar patients if they are taking a mood stabilizer such as lithium and receive light treatment in the evening; thus cautious use of bright light in such cases may be worthwhile. Apart from mania, bright light has few serious risks. Although eye irritation and headache have been reported as adverse effects, they may be just as common among patients treated with placebo.22 Since modern light boxes filter out ultraviolet light, the risk of eye damage is probably less than that associated with bright sunlight.

Light boxes
When bright-light treatment is initiated, it is most important that the light be bright. Illumination of about 10,000 lux (about the same as illumination striking the cornea on a sunny day at noon) works best. The sun at noon might be as bright as 100,000 lux if we were to look at it directly, but of course we never do so; we know we should avoid illumination >10,000 lux so as not to risk eye damage. For practical reasons, since bright sunlight is not usually available at the times needed, a patient should buy a light box designed to deliver the illumination required. In our experience, patients are unable to build or buy other lighting that is as satisfactory as the boxes specially manufactured to provide bright light. The cost of a special bright-light box, which will last for years, is roughly equivalent to the cost of 1-3 months’ worth of modern antidepressant prescription drugs.

There is some evidence that light boxes work best when they are placed somewhat above the center of vision, for example, on a tilted stand almost like a desk light. This orientation may allow the patient to read, eat, or watch television while receiving treatment.

Researchers have found no advantage of “full spectrum” light over ordinary bright white light for therapy. Since ultraviolet light is associated with known risks (of cataracts and cancer) and no known benefit for depression, light with the true, full spectrum of sunlight (including ultraviolet) should actually be avoided. In addition, although light visors sound like a good idea, controlled trials have not shown visor light treatments to be superior to placebo treatments.23

Timing and Duration
Many patients have a satisfactory antidepressant response to treatment with 10,000 lux of light for 30 minutes per day, although for severe depression a longer duration early in the course of treatment will likely yield more rapid progress. Some patients prefer less intense light (2,500 lux) but the duration of treatment may then need to be increased to 2 hours per session. There is some indication that light treatment works best very early in the morning, immediately after the patient arises. Early morning timing is certainly a good choice for patients who tend to sleep late and have trouble waking up since such patients probably benefit from using bright light in the advanced portion of the PRC. Patients suffering from early awakening might be more comfortable using evening bright light.

Usually, patients should continue with bright-light treatment at least until their symptoms fully resolve. Patients may be able to reduce the duration of daily treatment once a response occurs. As with antidepressant drugs, discontinuation of treatment is often followed by relapse, so some patients may find that they need long-term bright-light treatment. In addition, as with any medical treatment, the clinician must often individualize the dose and duration of light treatment to balance benefits and side effects. Light can bring joy to patients as well as to the clinicians who watch their conditions improve.

Daniel F. Kripke, MD, is professor of psychiatry at the University of California, San Diego, where he founded one of the first sleep clinics in the United States. He is now director of the Circadian Pacemaker Laboratory. Richard T. Loving, RN, DNSc, is an assistant project scientist at the University of California, San Diego, where he is working on antidepressant benefits of bright light combined with half-night sleep deprivation.

References
1. Barinaga M. Two feedback loops run mammalian clock. Science. 2000;288:943-944.
2. Shearman LP, Sriram S, Weaver DR, et al. Interacting molecular loops in the mammalian circadian clock. Science. 2000;288:1013-1019.
3. Klein DC, Moore RY, Reppert SM, eds. Suprachiasmatic Nucleus. New York: Oxford University Press; 1991.
4. Regestein QR, Pavlova M. Treatment of delayed sleep phase syndrome. Gen Hosp Psychiatry. 1995;17:335-345.
5. Johnson CH. Phase response curves: what can they tell us about circadian clocks? In: Hiroshige T, Honma K, eds. Circadian Clocks from Cell to Human. Sapporo, Japan: Hokkaido University Press; 1992:209-250.
6. Chesson AL Jr, Littner M, Davila D, et al. Practice parameters for the use of light therapy in the treatment of sleep disorders. Sleep. 1999;22:641-660.
7. Okawa M, Uchiyama M, Shirakawa S, et al. Favourable effects of combined treatment with vitamin B12 and bright light for sleep-wake rhythm disorder. In: Kumar VM, Mallick HN, Nayar U, eds. Sleep—Wakefulness. New Delhi, India: Wiley Eastern Ltd; 1993:71-77.
8. Campbell SS. Bright light treatment of sleep maintenance insomnia and behavioral disturbance. In: Lam RW, ed. Seasonal Affective Disorder and Beyond: Light Treatment for SAD and Non-SAD Conditions. Washington, DC: American Psychiatric Press Inc; 1998:289-304.
9. Monk TH. What can the chronobiologist do to help the shift worker? J Biol Rhythms. 2000;15:86-94.
10. van Reeth O. Sleep and circadian disturbances in shift work: strategies for their management. Horm Res. 1998;49:158-162.
11. Eastman CI, Martin SK. How to use light and dark to produce circadian adaptation to night shift work. Ann Med. 1999;31:87-98.
12. Graeber RC, Dement WC, Nicholson AN, Sasaki M, Wegmann HM. International cooperative study of aircrew layover sleep: operational summary. Aviat Space Environ Med. 1986;57:B10-B13
13. Cole RJ, Kripke DF. Amelioration of jet lag by bright light treatment: effects on sleep consolidation. Sleep Res. 1989;18:411.
14. Sateia MJ, Doghramji K, Hauri PJ, Morin CM. Evaluation of chronic insomnia. Sleep. 2000;23:243-308.
15. Aikens JE, Vanable PA, Tadimeti L, Caruana-Montaldo B, Mendelson WB. Differential rates of psychopathology symptoms in periodic limb movement disorder, obstructive sleep apnea, psychophysiological insomnia, and insomnia with psychiatric disorder. Sleep. 1999;22:775-780.
16. Khan A, Warner HA, Brown WA. Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials. Arch Gen Psychiatry. 2000;57:311-328.
17. Mulrow CD, Williams JW, Trivedi M, et al. Treatment of Depression: Newer Pharmacotherapies. Evidence Report/Technology Assessment 7. Rockville, Md: USPHS AHCPR; 1999.
18. Depression Guideline Panel. Depression in Primary Care: Volume 2. Treatment of Major Depression. Washington, DC: US Government Printing Office; 1993:1-175. Agency for Health Care Policy and Research, HHS, AHCPR publication 93-0551.
19. Kripke DF. Light treatment for nonseasonal depression: speed, efficacy, and combined treatment. J Affect Dis. 1998;49:109-117.
20. Lam RW, Levitt A. Canadian Consensus Guidelines for the Treatment of Seasonal Affective Disorder. Vancouver, Canada: Clinical and Academic Publishing; 1999.
21. Terman M, Terman JS, Ross DC. A controlled trial of timed bright light and negative air ionization for treatment of winter depression. Arch Gen Psychiatry. 1998;55:875-882.
22. Terman M. On the specific action and clinical domain of light treatment. In: Lam RW, ed. Seasonal Affective Disorder and Beyond: Light Treatment for SAD and Non-SAD Conditions. Washington, DC: American Psychiatric Press Inc; 1998:91-116.
23. Teicher MH, Glod CA, Oren DA, et al. The phototherapy light visor: more to it than meets the eye. Am J Psychiatry. 1995;152:1197-1202.