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Kehinde Eniola, MD, MPH; Angela Bacigalupo, MD, MPH; Anne Light therapy for nonseasonal Mounsey, MD Cone Health Family Medicine Residency, major depressive disorder? Greensboro, NC (Drs. Eniola and Bacigalupo); Department of Family While bright light therapy already has a place in the Medicine, University of North Carolina, Chapel Hill treatment of seasonal affective disorder, a recent trial (Dr. Mounsey) spotlights its utility beyond the winter months.

DEPUTY EDITOR James J. Stevermer, MD, MSPH Department of Family and Community Medicine, PRACTICE CHANGER University of Missouri- cologic agents have a higher frequency of Columbia Consider treatment with bright light therapy, treatment-associated adverse effects than alone or in combination with fluoxetine, for fluorescent light therapy.4 patients with nonseasonal major depressive A Cochrane systematic review of 20 stud- disorder (MDD).1 ies (N=620) showed the effectiveness of com- bined light therapy and pharmacotherapy STRENGTH OF RECOMMENDATION in treating nonseasonal MDD, but found no B: Based on a single moderate-quality ran- benefit to light used as a monotherapy.5 How- domized control trial. ever, the majority of the studies were of poor Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, quality, occurred in the inpatient setting, and fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. lasted fewer than 4 weeks. 2016;73:56-63. In a 5-week, controlled, double-blind trial not included in the Cochrane review, 102 patients with nonseasonal MDD were ILLUSTRATIVE CASE randomized to receive either active treatment A 38-year-old woman recently diagnosed (bright light therapy) plus sertraline 50 mg with MDD without a seasonal pattern comes daily or sham light treatment (using a dim red to see you for her treatment options. Her light) plus sertraline 50 mg daily. The inves- Hamilton Depression Rating Scale (HAM-D) tigators found a statistically significant larger is 22, and she is not suicidal. Should you reduction in depression score in the active consider bright light therapy in addition to treatment group than in the sham light group, pharmacotherapy? based on the HAM-D, the Hamilton 6-Item Subscale, the Melancholia Scale, and the DD is one of the most common 7 atypical items from the Structured Interview psychiatric illnesses in the United Guide for the Seasonal Affective Disorder ver- States, affecting approximately sion of the HAM-D.6,7 M 2 one in 5 adults at some point in their lives. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reup- STUDY SUMMARY take inhibitors are considered effective first- Light therapy improves depression line pharmacotherapy options for MDD.2,3 without a seasonal component Despite their effectiveness, however, studies This latest study was an 8-week random- have shown that only about 40% of patients ized, double-blind, placebo- and sham- with MDD achieve remission with first- or controlled clinical trial evaluating the benefit second-line drugs.2 In addition, pharma- of light therapy with and without pharma-

486 THE JOURNAL OF FAMILY PRACTICE | JULY 2016 | VOL 65, NO 7 cotherapy for nonseasonal MDD.1 The in- sizes vs placebo were: fluoxetine, d=0.24 (95% vestigators enrolled 122 adult patients (ages confidence interval [CI], −0.27 to 0.74); light 19-60 years) from outpatient psychiatry clin- monotherapy, 0.80 (95% CI, 0.28 to 1.31); and ics with a diagnosis of MDD (as diagnosed by combination therapy, 1.11 (95% CI, 0.54 to a psychiatrist) and a HAM-D8 score of at least 1.64). Effect sizes of more than 0.8 are often 20. Subjects had to be off psychotropic medi- considered large.10 cation for at least 2 weeks prior to the first vis- The treatment response (≥50% MADRS it and were subsequently monitored for one improvement) rate was highest in the com- week to identify spontaneous responders and bination treatment group (75.9%) with re- to give patients time to better regulate their sponse rates to light monotherapy, placebo, sleep-wake cycle (with the goal of sleeping and fluoxetine monotherapy of 50%, 33.3%, only between 10:00 pm and 8:00 am daily). and 29%, respectively. There was a signifi- The investigators randomly assigned cant response effect for the combination vs patients to one of 4 treatment groups: active placebo treatment group (P=.005). Similarly, light monotherapy (10,000-lux fluorescent there was a higher remission rate in the com- white light for 30 min/d early in the morning) bination treatment group (58.6%) than in the plus a placebo pill; fluoxetine 20 mg/d plus placebo, light monotherapy, or fluoxetine sham light therapy; placebo pills with sham treatment groups (30%, 43.8%, and 19.4%, light therapy; and combined active light ther- respectively) with a significant effect for the apy with fluoxetine 20 mg daily. Sham light combination vs placebo treatment group Seventy-six therapy consisted of the use of an inactivated (P=.02). percent negative ion generator, used in the same fash- Combination therapy was superior to of patients ion as a light box. All patients were analyzed placebo in treatment response (≥50% re- treated with based on modified intention to treat. duction in the MADRS score) and remis- fluoxetine The investigators monitored patients sion (MADRS ≤10) with numbers needed to and light for adherence to active and sham treatment treat of 2.4 (95% CI, 1.6-5.8) and 3.5 (95% CI, therapy saw by review of their daily logs of device treat- 2.0-29.9), respectively. at least a 50% ment times. Pill counts were used to assess By the end of the 8-week study period, improvement in medication adherence. The primary outcome 16 of 122 patients had dropped out; 2 reported their depression at 8 weeks was the change from baseline in lack of efficacy, 5 reported adverse effects, and scores. the Montgomery-Asberg Depression Rating the remainder cited administrative reasons, Scale (MADRS), a 10-item questionnaire with were lost to follow-up, or withdrew consent. a worst score of 60.9 Secondary outcomes were treatment response (≥50% MADRS score reduction) and remission (≤10 MADRS WHAT’S NEW? score) at the final 8th-week visit. MADRS New evidence scoring was used because of its higher sen- on a not-so-new treatment sitivity to treatment-induced changes and its We now have evidence that bright light ther- high correlation with the HAM-D scale. apy, either alone or in combination with At the end of 8 weeks, the mean (stan- fluoxetine, is efficacious in increasing the re- dard deviation [SD]) changes in MADRS mission rate of nonseasonal MDD. scores from baseline were: light mono- therapy 13.4 (7.5), fluoxetine monotherapy CAVEATS 8.8 (9.9), combination therapy 16.9 (9.2), Choice of SSRI, geography, and trial and placebo 6.5 (9.6). The improvement was duration may have affected results significant in the light monotherapy treat- A single SSRI (fluoxetine) was used in this ment group vs the placebo group (P=.006), study; other more potent SSRIs might work in the combination treatment group vs the better. This study was conducted in southern placebo group (P<.001), and in the combina- Canada, and light therapy may not demon- tion group vs the fluoxetine treatment group strate as large a benefit in regions located far- (P=.02), but not for the fluoxetine treatment ther south. The study excluded pregnant and group vs the placebo group (P=.32). The effect breastfeeding women. CONTINUED

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The trial duration was relatively short, of the bright light devices, which can be found and the investigators did not attain their pre- in medical supply stores and online outlets, planned sample size for the study, which lim- ranges between $118 and $237.4,12 However, ited the power to detect clinically significant such devices are reusable, making the amor- seasonal treatment effects and differences tized cost almost negligible.13 JFP between the fluoxetine and placebo groups, regardless of whether they received active ACKNOWLEDGEMENT The PURLs Surveillance System was supported in part by Grant phototherapy. Number UL1RR024999 from the National Center for Research Also, it’s worth noting that there were Resources, a Clinical Translational Science Award to the Uni- versity of Chicago. The content is solely the responsibility of trends for some adverse events (nausea, heart- the authors and does not necessarily represent the official burn, weight gain, agitation, sexual dysfunc- views of the National Center for Research Resources or the tion, and skin rash) to occur less frequently in National Institutes of Health. the combination group than in the fluoxetine monotherapy group. Possible explanations References are that the study had inadequate power, that 1. Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treat- ment, fluoxetine, and the combination in patients with nonsea- the sham treatment did not adequately blind sonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73:56-63. patients, or that light therapy can ameliorate 2. Weihs K, Wert JM. A primary care focus on the treatment of pa- some of the adverse effects of fluoxetine. tients with major depressive disorder. Am J Med Sci. 2011;342:324- 330. 3. Gelenberg AJ, Freeman CMP, Markowitz JC, et al. Practice guide- We now have CHALLENGES TO IMPLEMENTATION line for the treatment of patients with major depressive disorder. 3rd edition. 2010. Available at: http://psychiatryonline.org/pb/ evidence that Commercial insurance doesn’t assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. bright light usually cover light therapy Accessed April 20, 2016. 4. Lam RW, Tam EM. A Clinician’s Guide to Using Light Therapy. therapy, Bright light therapy is fairly safe, and some New York, NY: Cambridge University Press; 2009. Available at: evidence exists supporting its use in the treat- http://www.ubcmood.ca/sad/SAD%20resources%20package% alone or in 202009.pdf. Accessed April 20, 2016. combination ment of nonseasonal MDD; however, the 5. Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal with fluoxetine, data for its use in this area are limited.11 Since depression. Cochrane Database Syst Rev. 2004;2:CD004050. 6. Martiny K. Adjunctive bright light in non-seasonal major depres- is efficacious in only a few studies have tested light therapy sion. Acta Psychiatr Scand Suppl. 2004;425:7-28. increasing the for nonseasonal MDD, significant uncertain- 7. Martiny K, Lunde M, Unden M, et al. Adjunctive bright light in non-seasonal major depression: results from clinician-rated de- remission rate ty remains about patient selection, as well as pression scales. Acta Psychiatr Scand. 2005;112:117-125. of nonseasonal optimal dose, timing, and duration of light 8. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62. major therapy in the management of nonseasonal 9. Montgomery SA, Asberg M. A new depression scale designed to depressive MDD.12 Although the risks associated with be sensitive to change. Br J Psychiatry. 1979;134:382-389. 10. Sullivan GM, Feinn R. Using effect size—or why the P value is not disorder. bright light therapy are minimal, the therapy enough. J Grad Med Educ. 2012;4:279-282. 3 can lead to mania or hypomania, so clini- 11. Oldham MA, Ciraulo DA. Use of bright light therapy among psy- chiatrists in Massachusetts: an e-mail survey. The Primary Care cians need to monitor for such effects when Companion for CNS Disorders. 2014;16. initiating therapy. 12. Sloane PD, Figueiro M, Cohen L. Light as therapy for sleep disor- Lastly, commercial insurance does not ders and depression in older adults. Clin Geriatr. 2008;16:25-31. 13. Kripke DF. A breakthrough treatment for major depression. J Clin usually cover light therapy. The average price Psychiatry. 2015;76:e660-e661.

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