Michael Terman, PhD; Jiuan Su Terman, PhD; Donald C. Ross, PhD Arch Gen Psychiatry. 1998;55:875-882. Background Artificial bright light presents a promising nonpharmacological treatment for seasonal affective disorder. Past studies, however, have lacked adequate placebo controls or sufficient power to detect group differences. The importance of time of day of treatment—specifically, morning light superiority—has remained controversial. Methods This study used a morningxevening light crossover design balanced by parallel-group controls, in addition to a nonphotic control, negative air ionization. Subjects with seasonal affective disorder (N=158) were randomly assigned to 6 groups for 2 consecutive treatment periods, each 10 to 14 days. Light treatment sequences were morning-evening, evening-morning, morning-morning, and evening-evening (10000 lux, 30 min/d). Ion density was 2.7x106 (high) or 1.0x104 (low) ions per cubic centimeter (high-high and low-low sequences, 30 min/d in the morning). Results Analysis of depression scale percentage change scores showed low-density ion response to be inferior to all other groups, with no other group differences. Response to evening light was reduced when preceded by treatment with morning light, the sole sequence effect. Stringent remission criteria, however, showed significantly higher response to morning than evening light, regardless of treatment sequence. Conclusions Bright light and high-density negative air ionization both appear to act as specific antidepressants in patients with seasonal affective disorder. Whether clinical improvement would be further enhanced by their use in combination, or as adjuvants to medication, awaits investigation. From the Department of Psychiatry, Columbia University, New York, NY (Dr M. Terman); and the Clinical Chronobiology Program (Drs M. and J. S. Terman) and Computer Center (Dr Ross), New York State Psychiatric Institute, New York.