The combination of bright light therapy plus an antidepressant significantly improves nonseasonal major depressive disorder, and light therapy alone is more effective than antidepressant monotherapy, a randomized, placebo-controlled trial suggests.

"I've studied bright light therapy in winter depression for a long time, but we always thought that winter depression was different from nonseasonal depression," Raymond Lam, MD, University of British Columbia, Vancouver, Canada, told Medscape Medical News.

"So this was the first study that was placebo-controlled, and I think that while light therapy could be used on its own for some patients, more severely ill patients need combination therapy, whether that combination be an antidepressant plus psychotherapy or psychotherapy plus light therapy or light therapy plus an antidepressant."

The study was published online November 18 in JAMA Psychiatry.

The trial randomly assigned 122 patients to light therapy alone for 30 minutes a day; a placebo device, which was a negative ion generator; the combination of light therapy plus fluoxetine (multiple brands), 20 mg a day; or a negative ion generator plus placebo. Approximately 30 patients were enrolled in each of the four treatment groups.

Patients had a score of 20 or higher on the Hamilton Depression Rating Scale at baseline. The mean duration of the current major depressive disorder episode ranged from a low of 45 weeks in the placebo group to a high of 90 weeks in the combination group.

The mean Montgomery-Åsberg Depression Rating Scale (MADRS) score at week 0 was approximately 22 in all treatment groups.

Light therapy consisted of 30 minutes a day of exposure to a fluorescent light box as soon as possible after awakening. The negative ion generator was modified to emit an audible quiet hum but was deactivated so that no ions were emitted.

At the end of the 8-week treatment interval, mean changes in MADRS score from baseline were significantly greater among those who received the combination of bright light plus fluoxetine than for any of the other treatment groups.

Table. Outcome Measures at the End of 8 Weeks

Placebo Fluoxetine Monotherapy Light Monotherapy Combination Therapy Significant Comparisons Change in MADRS score from week 0 to week 8 (mean) 6.5 8.8 13.4 16.9 Light > placebo (P = .006); combination > placebo (P < .001); combination > fluoxetine (P = .02) MADRS response at study endpoint 33.3% 29% 50% 75.9% Combination > placebo (P = .005) MADRS remission at study endpoint 30% 19.4% 43.8% 58.6% Combination > placebo (P = .02)

The number needed to treat (NNT) to achieve a response using the combination approach was only 2.4 compared with placebo; the NNT to achieve remission when using the combination approach was 3.5 compared with placebo.

Adverse Events

One patient in the combination treatment arm was hospitalized for worsening suicidal ideation after treatment week 4, but this was not judged to be treatment related.

Otherwise, the percentage of patients reporting at least one treatment-emergent adverse event was not significantly different between the four treatment groups, at about 54% for placebo, 80% for fluoxetine monotherapy, 62% for light therapy alone, and about 51% for the combination group.

According to investigators, most treatment-emergence adverse events were transient. No patients switched to hypomania.

The investigators speculate that light therapy resynchronizes circadian rhythms in seasonal depression or perhaps restores neurotransmitter dysfunction.

"Nonseasonal major depressive disorder may also be associated with disturbances in circadian rhythms," they write. "And bright light has predictable circadian phase-shifting effectives in humans."

Dr Lam noted that light therapy is quite accessible, inasmuch as many drug stores sell light devices and boxes, which are usually priced within the $100 to $300 range.

"Surveys of psychiatrists show psychiatrists are using these light devices, but predominantly for seasonal depression," Dr Lam said.

"But the main point of the study is that light therapy does seem to have an antidepressant effect in nonseasonal depression as well, particularly when added to an antidepressant, and light therapy could be considered an option now for patients with nonseasonal depression."

Rapid and Dramatic Improvement

Asked by Medscape Medical News to comment on the study, Michael Terman, PhD, professor of psychiatry, Columbia University, and director of the Comprehensive Chronotherapy Group, New York City, noted that as early as the 1970s, there were inklings that light had antidepressant effects in nonseasonal major depression, but because of the rapid — often within days — and dramatic improvement seen with light therapy in patients with seasonal affective disorder (SAD), attention was quickly diverted to the use of light therapy in SAD.

"Dr Lam's multicenter trial wraps up the loose ends with a comprehensive, 8-week comparison of light therapy and fluoxetine, separately and in combination," Dr Terman told Medscape Medical News.

"The major surprise was the failure of a standard therapeutic dose of fluoxetine to beat the placebo rate, while light therapy showed a large effect size within 4 weeks," he added.

This is particularly surprising given that an earlier study by Dr Lam and colleagues showed that fluoxetine and light had similar benefits in patients with SAD.

For patients with nonseasonal depression in the current study, Dr Terman still believes there was a subtle benefit of fluoxetine that emerged with extended treatment, and its effect was magnified when used in combination with light.

"This the most impressive clinical trial of light therapy I have seen, whether for SAD or non-SAD," Dr Terman said.

"It ran for 8 weeks ― longer than earlier studies ― it used two types of placebo control, and it pitted the response against standard antidepressant medication," he added.

"If light had proved ineffective or only weakly effective in comparison with fluoxetine, it would have consigned light therapy to the dustbin, but the dramatic, opposite result turns the tables on the choice of somatic treatment for major depression ― 10,000 lux light therapy upon awakening or, by implication, a walk outdoors if the sun is up ― now can be recommended to patients with recurrent depression, many of whom will respond without recourse to drugs."

More information on light therapy is available online from the University of British Columbia.

Dr Lam and his coauthors have a number of relationships with the healthcare industry, which are listed in the original article. Dr Terman has disclosed no relevant financial relationships.

JAMA Psychiatry. Published online November 18, 2015. Full text