Major depressive disorder (MDD) affects at least 5% of the population, with a lifetime prevalence estimated at 14%. It is the second-ranked cause of disability worldwide and is associated with impairment in quality of life, increased risk of mortality, and societal burden. Treatments for MDD include psychotherapies and antidepressants, but remission rates remain low despite adequate treatment and more therapeutic options are needed.
Light therapy, an effective treatment for seasonal affective disorder (SAD), may also be appropriate for MDD. Bright light is a safe, well-tolerated, nonpharmacological treatment that can be used alone or combined with medications. Light can correct disturbed circadian rhythms, which have been implicated in the pathophysiology of MDD. Previous metaanalyses of light therapy for nonseasonal MDD, however, have yielded only equivocal and conflicting evidence for efficacy. Two more recent systematic reviews both concluded that the quality and methods of the identified studies were too heterogeneous to conduct a meta-analysis. They each found insufficient evidence for efficacy of bright light monotherapy, although 1 review found low-quality evidence for bright light as adjuvant treatment to antidepressants.
In summary, these systematic reviews indicate that the evidence for benefits of bright light therapy for nonseasonal MDD is inconclusive and well-designed studies are required to resolve this issue.
So begins a new paper on depression. I like these opening paragraphs and, in particular, the first paragraph (and its bluntness). For the clinicians among us, the final phrase is hauntingly true: “more therapeutic options are needed.”
This week’s Reading: “Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial” by Dr. Raymond W. Lam et al., which was just published online (ahead of print) in JAMA Psychiatry.
This is a big paper in a big journal with big clinical implications. It’s also very Canadian – every co-author lives north of the 49th parallel; the first author hails from Vancouver.
We know that light therapy works for those with a seasonal pattern to their depression. But could we use the light therapy for other people suffering from depression? The authors attempt to answer this question.
You can find the paper here:
Here’s what they did:
· Essentially, the authors designed a randomized, double-blind controlled study.
· Participants were recruited in 5 psychiatric outpatient clinics, with data collected between October 2009 and March 2014.
· Participants were eligible if they had a diagnosis of depression (assessed by a psychiatrist, confirmed with a MINI, and with a HAM-D score over 20).
· Exclusion criteria included people with seasonal depression patterns, substance use issues and treatment resistance in their depression (i.e., having failed 2 med trials).
· Participants were randomly allocated to 1 of 4 treatment groups for 8 weeks: (1) Light: light monotherapy using a fluorescent light box (10,000 lux, with people encouraged to use it between 7 and 8 am daily) plus a placebo pill; (2) Prozac: fluoxetine monotherapy using an inactive ion generator (but one that makes an “audible quiet hum”) with fluoxetine hydrochloride, Prozac, at 20 mg daily; (3) Placebo: placebo treatment with an inactive ion generator plus a placebo pill; or (4) Light + Prozac: combined treatment using a light box plus fluoxetine hydrochloride at 20 mg daily.
· Several scales were used with the primary measure of depression being the Montgomery-Åsberg Depression Rating Scale, or MADRS.
· Statistical analysis was done, including with an ANOVA.
Here’s what they found:
· Of 372 people who had the original telephone screening, 164 had psychiatric assessments. 122 were randomized to the 4 groups: Light (32 assigned, with 28 having completed), Prozac (31, 27), Placebo (30, 24), Light + Prozac (29, 27)
· The 5 original sites were reduced to 3 because of patient numbers.
· The mean change in MADRS score from baseline to the 8-week end point: Light: 13.4; Prozac: 8.8; Placebo: 6.5; and Light + Prozac: 16.9. (See figure below.)
· At the 8-week end point, response was achieved for: Light: 50.0% of participants; Prozac: 29.0%; Placebo: 33.3%; and Light + Prozac: 75.9%.
· The number needed to treat for response for Light + Prozac vs. Placebo was 2.4.
· Remission was achieved for: Light: 43.8% of participants; Prozac: 19.4%; Placebo: 30.0%; and Light + Prozac: 58.6%. (!!)
· The number needed to treat for remission for Light + Prozac vs. Placebo was 3.5.
The authors write:
The main result of this study was that both light monotherapy and the combination treatment had significant benefits compared with a sham-placebo condition in adults with nonseasonal MDD. The combination treatment showed significant results for both the primary outcome (change in MADRS total score) and key secondary outcomes (including MADRS response and remission rates).
This trial represents, to our knowledge, the first adequate duration, placebo-controlled comparison of light monotherapy and combination light and antidepressant treatment.
A few thoughts:
1. This is a smart study.
2. This study is very relevant to practice. In the management of depression, this paper suggests that there is an additional tool in the toolkit: light therapy. For the patient who isn’t willing to take medications or the patient who isn’t getting better on medications, light therapy could be considered.
3. It’s striking how ineffective SSRI monotherapy proved to be – far inferior to the Light and the Light + Prozac groups, and basically offering patients the benefits of placebo. Ouch. Of course, the Prozac dosing was low and wasn’t adjusted. (!) And another potential problem: the relatively small numbers of participants with this intervention. We should thus take the result with a pinch of salt.
4. That said, we can add this paper to a growing list of papers showing that psychiatry needs to be more than a doctor and his prescription pad.
Reading of the Week. Every week I pick a reading — often an article or a paper — from the world of Psychiatry.