Commentary - October 1998

A Turning Point for Seasonal Affective Disorder and Light Therapy Research?

The Studies of bright light therapy in the treatment of seasonal affective disorder (SAD; also known as winter depression) in this issue of the ARCHIVES[1-3] are sound studies that address important fundamental questions. Is bright light therapy more than a placebo effect? Is morning bright light therapy more effective than evening bright light?

IS BRIGHT LIGHT THERAPY MORE THAN A PLACEBO EFFECT?

Since bright light therapy was introduced as a treatment for SAD in the early 1980s, many have been concerned about the adequacy of the control conditions used in the treatment studies. Bright light therapy poses a special problem for blinding the patients to the active treatment: the patients see the bright light box. During the 1980s, the usual placebo condition was a light box of lower intensity, often of a different color. A pooled analysis of these data showed that bright light is superior to dim light controls.[4] However, expectations of the subjects sometimes predicted the clinical response. This placebo problem is not unique to phototherapy. Antidepressant medication trials can be criticized similarly for using inert pills as placebos; the relative lack of adverse effects in the placebo group may weaken the expectations for the placebo conditions.[5] Nonetheless, the question of the placebo effect clouded the interpretation of bright light therapy efficacy studies.

Led by Eastman,[6] light therapy researchers began to address this problem. Eastman et al[7] used a deactivated negative-ion generator as a placebo condition and found its efficacy to be no different from the bright light therapy. Like the bright light box, the negative-ion generator is a device, has a plausible mechanism for efficacy, and requires the subject to sit beside it. In the current study, Eastman et al[1] again used the deactivated negative-ion generator, this time bolstering the placebo effect with an enthusiastic endorsement of the device. Terman et al[2] followed up on this design and used high- and low-dose negative-ion generators as comparison conditions. Both studies show the superiority of bright light therapy over a plausible nonlight control condition.

These positive results occurred despite other therapeutic aspects of placebo response, such as ambient light exposure, that might confound studies of SAD. In the placebo-controlled 5-week study of fluoxetine by Lam et al,[8] the placebo responses markedly increased as the photoperiod increased. Rabkin et al[9] found that even among patients with depression (not selected for seasonality), the response rate to a 10-day administration of a placebo pill was significantly less from November through February than during the rest of the year. Terman et al[2] addressed this problem in their study by excluding patients from analysis who did not relapse following the treatment trial. In the Eastman et al[1] study in this issue, most of the subjects began the 4-week study in January and February and therefore were exposed to the increasing photoperiod of late winter and early spring.

Direct sunshine even during short photoperiods may also be important. Patients with SAD often report that they feel better on sunny days.[10] Because environmental light exposure is difficult to control, SAD studies of efficacy may be analogous to doing an efficacy study of Prozac with Prozac intermittently in the drinking water. Changes in ambient light may explain some of the previous negative studies of light therapy. In spite of this potential confound, both studies in this issue found bright light superior to the placebo conditions.

IS MORNING BRIGHT LIGHT THERAPY MORE EFFECTIVE THAN EVENING BRIGHT LIGHT?

The 3 studies in this issue[1-3] are the largest studies to compare morning and evening light therapy. Two studies support[2,3] and 1 partially supports[1] the conclusion of most previous studies[4] that morning light is superior. Some studies have found no significant difference.[11] No study has found evening light superior to morning light. If morning and evening light are equal in efficacy, one might expect a similar number of studies reporting superiority of morning and evening light.

In addition to the placebo confounds cited earlier, there are several possible reasons why some studies have not found differences between morning and evening bright light therapy. Most studies have had small sample sizes. Diagnostic heterogeneity among the patients with SAD could obscure real differences. Some studies have found that the presence of hypersomnia[12] or atypical symptoms[13] are good prognostic factors for response to morning bright light. The sample of patients with SAD studied by Terman et al[2] had more atypical symptoms than the sample of another study,[11] which did not show a difference. These selective predictive factors also argue against light therapy merely being a placebo response.[14]

Evening bright light can be considered a good "placebo." The light apparatus and intensity are the same. Only the timing is different. Subjects are almost always blind to the hypothesis of morning light superiority. Whether one considers the evening light a placebo condition or simply a lower dose of light treatment, evening light is probably a good control condition and the superiority of the morning light strongly suggests that bright light therapy is an active treatment.

The relative efficacy of morning and evening light is important for both practical clinical and theoretical reasons. Morning light superiority over evening light might be explained by the phase-shift hypothesis developed by Lewy et al.[15] Many patients with SAD have phase-delayed circadian rhythms.[15,16,17] In this issue, Lewy et al[3] present further data showing that morning bright light phase-advanced the melatonin onset and was more efficacious than evening bright light. If the phase-shift hypothesis is confirmed, clinicians might need to individualize the timing of the bright light therapy: for example, phase-advanced patients might benefit more from evening bright light.

CONCLUSION

The studies of Eastman et al[1] and Terman et al[2] provide good controls and adequate sample sizes and, together with the previous studies of bright light therapy, allow us to conclude that morning bright light therapy is effective in treating SAD. All 3 studies add to the literature suggesting that morning bright light is superior to evening bright light, a good control condition. Together, the placebo-controlled studies and the morning-vs-evening studies strongly support the efficacy of morning bright light in the treatment of SAD and help establish bright light therapy as a first-line treatment for SAD. Light therapy and SAD investigators may now turn their attention to other research questions. Does the phase-shift hypothesis explain the superiority of morning light over evening light? Is dawn simulation[18] effective in treating SAD? Is light therapy effective in other disorders[19] such as subsyndromal SAD, nonseasonal depression, premenstrual depression, circadian sleep-phase disorders, sleep-maintenance insomnia, jet lag, and problems resulting from shift work? In addition, the provocative finding by Terman et al[2] that exposure to high-density negative ions has antidepressant effects in SAD calls for replication and, if replicated, an exploration of possible mechanisms of action. All these future studies will require continued careful attention to potential placebo effects.

David H. Avery, MD
Harborview Medical Center
Box 359896
Department of Psychiatry and Behavioral Sciences
University of Washington School of Medicine
325 Ninth Ave
Seattle, WA 98104-2499

References

1. Eastman CI, Young MA, Fogg LF, Liu L, Meaden PM. Bright light treatment of winter depression: a placebo-controlled trial. Arch Gen Psychiatry. 1998;55:883-889.

2. 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.

3. Lewy AJ, Bauer VK, Cutler NL, Sack RL, Ahmed S, Thomas KH, Blood ML, Latham Jackson JM. Morning vs evening light treatment of patients with winter depression. Arch Gen Psychiatry. 1998;55:890-896.

4. Terman M, Terman J, Quitkin F, McGrath P, Stewart J, Rafferty B. Light therapy for seasonal affective disorder: a review of efficacy. Neuropsychopharmacology. 1989;2:1-22.

5. Fisher S, Greenberg RP. How sound is the double-blind design for evaluating psychotropic drugs? J Nerv Ment Disord. 1993;181:345-350.

6. Eastman CI. What the placebo literature can tell us about light therapy for SAD. Psychopharmacol Bull. 1990;26:495-504.

7. Eastman CI, Lahmeyer HW, Watell LG, Good GD, Young MA. A placebo-controlled trial of light treatment for winter depression. J Affect Disord. 1992;26:211-222.

8. Lam RW, Gorman CP, Michalon M, Steiner M, Levitt AJ, Corral MR, Watson GD, Morehouse RL, Tam W, Joffe RT. Multicenter, placebo-controlled study of fluoxetine in seasonal affective disorder. Am J Psychiatry. 1995;152:1765-1770.

9. Rabkin JG, Stewart JW, McGrath PJ, Markowitz JS, Harrison W, Quitkin FM. Baseline characteristics of 10-day placebo washout responders in antidepressant trials. Psychiatry Res. 1987;21:9-22.

10. Albert PS, Rosen LN, Alexander JR, Rosenthal NE. The effect of daily variation in weather and sleep on seasonal affective disorder. Psychiatry Res. 1990;36:51-63.

11. Wirz-Justice A, Graw P, Krauchi K, Gisin B, Jochum A, Arendt J, Fisch H, Buddeberg C, Poldinger W. Light therapy in seasonal affective disorder is independent of time of day or circadian phase. Arch Gen Psychiatry. 1993;50:929-937.

12. Terman M, Amira L, Terman JS. Predictors of response and nonresponse to light treatment for winter depression. Am J Psychiatry. 1996;153:1423-1429.

13. Avery DH, Khan A, Dager SR, Cohen S, Cox GB, Dunner DL. Morning or evening bright light treatment of winter depression? the significance of hypersomnia. Biol Psychiatry. 1991;29:117-126.

14. Terman M. Problems and prospects for use of bright light as a therapeutic intervention. In: Wetterberg L, ed. Light and Biological Rhythms in Man. Stockholm, Sweden: Pergamon Press; 1993:421-437.

15. Lewy AJ, Sack RL, Miller S, Hoban TM. Antidepressant and circadian phaseshifting effects of light. Science. 1987;235:352-354.

16. Sack RL, Lewy AJ, White DM, Singer CM, Fireman MJ, Vandiver R. Morning vs evening light treatment for winter depression: evidence that the therapeutic effects of light are mediated by circadian phase shifts. Arch Gen Psychiatry. 1990;47:343-351.

17. Avery DH, Dahl K, Savage MV, Brengelmann GL, Larsen LH, Kenny MA, Eder DN, Vitiello MV, Prinz PN. Circadian temperature and cortisol rhythms during a constant routine are phase-delayed in hypersomnic winter depression. Biol Psychiatry. 1997;41:1109-1123.

18. Avery DH, Bolte MA, Wolfson JK, Kazaras AL. Dawn simulation compared with a dim red signal in the treatment of winter depression. Biol Psychiatry. 1994;36:181-188.

19. Lam RW, ed. Seasonal Affective Disorder and Beyond. Washington, DC: American Psychiatric Press; 1998.

(Arch Gen Psychiatry. 1998;55:863-864)

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