A breakthrough treatment for major depression.

I this issue, Özdemir and colleagues1 have shown that treatment of severe major depression can now be greatly improved by safe, simple, and readily available bright light treatment. Patients may benefit within a week. Moreover, the benefit persisted throughout 8 weeks of observation even after the bright light treatment was discontinued. What seemed unique in this new study is the focus on hospitalized patients with severe non-seasonal unipolar depression and the treatment combination of bright light with the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine, contrasted with venlafaxine alone. Also unusual is the well-constructed design with just 1 week of treatment followed by 7 more weeks of observed remission. When bright light was combined with venlafaxine, substantially faster amelioration of symptoms began in the first week, and the advantage of 1 week of bright light treatment persisted throughout 8 weeks. In the first week, the benefit of bright light added to venlafaxine was more than double the benefit of venlafaxine as indicated by Beck Depression Inventory (BDI) and Profile of Mood States (POMS) depression ratings, and almost double for the Hamilton depression rating Scale (HDRS) scores. Mean HDRS score was reduced from 29.9 at baseline to 5.7 at 8 weeks in the combination group, a most excellent response. No substantial adverse effects were observed attributable to bright light. The cost of inpatient bright light treatment is almost negligible since light treatment devices may be reused many times, whereas the cost savings of faster remissions could be considerable. It is estimated that, worldwide, perhaps a million patients have tried bright light treatment (much of it unsupervised at home), so we have considerable experience with bright light’s safety. For the good of our patients, there now seems to be an evidence base sufficient to immediately incorporate bright light combined with an antidepressant into our routine treatment of depression. As Özdemir and colleagues review, there have previously been a substantial number of clinical trials of bright light demonstrating efficacy—indeed, a larger number of successful trials than are usually available when antidepressant drugs are first marketed. Both non-seasonal major depression and seasonal (winter) depression receive benefit with or without combination with antidepressants, as does bipolar depression, but the preponderance of evidence has come from outpatients with winter depression.2,3 If bright light trials have tended to be relatively small and of short duration compared to antidepressant drug trials, that may be because bright light benefits are manifest more rapidly and sometimes have larger effect sizes, so that contrasts of hundreds of patients and controls followed for 8 to 16 weeks have not been needed to demonstrate efficacy. Though I do not believe we need more studies before incorporating bright light into routine practice, as Özdemir et al emphasize, much could be gained from more exploration of bright light treatment in combination with antidepressants. Combinations of bright light treatment should be explored with a wider variety of antidepressants, with lithium, and with thyroid supplementation. Concealing expectations from patients in light treatment studies controlled by dummy treatments is practical. Masking treatments from the staff performing mood ratings is feasible, although neither form of blinding was attempted in this study. Wellblinded studies have previously demonstrated the efficacy of bright light treatments, but more blinded studies will be welcome. Studies with follow-up observations continuing for 6 months or even years would be desirable. I do not know why the authors thought there would be substantial ocular risk in extending treatment beyond 1 week. The combination of bright light and venlafaxine might produce even faster remission if continued for several weeks. For selected patients, many clinicians recommend daily use of bright light for months or years. Despite considerable vigilance for adverse effects, it is generally believed that bright light treatment is extremely safe (far safer than drugs or drug combinations). Documented instances of permanent eye damage of clinical importance seem almost unknown. Alert follow-up and monitoring remain advisable. The timing and intensity of light treatment used in this study are consistent with the consensus of many experts. However, several senior investigators have recommended combining bright light treatment with acute advances of sleep timing and various patterns of wake therapy (sleep restriction).4,5 As yet, we do not have well-randomized contrasts that explore if this triple therapy is superior to bright light treatment alone. Many variations of light timing and triple therapy could be explored in comparison with standard bright light therapy to further optimize the benefits. Some have thought that lighting systems mounted on the head, eg, bright light visors, would be more convenient than sitting near a lighting box or fixture, despite early controlled tests that were disappointing. Head-mounted devices are being marketed, but I have not seen sufficient empirical evidence of their efficacy. Some investigators have argued that blue light (eg, 450–500 nm) of lower perceived intensity would be less disturbing and as effective as bright white light. It is likely that the main therapeutic effects of bright light are mediated by intrinsically photosensitive retinal ganglion cells exciting the Submitted: November 10, 2014; accepted November 14, 2014. Corresponding author: Daniel F. Kripke, MD, 8437 Sugarman Drive, La Jolla, CA 92037 ([email protected]).