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Light For Nonseasonal Major Depressive Disorder? While bright therapy already has a place in the treatment of seasonal affective disorder, a recent trial spotlights its utility beyond the winter months.

Kehinde Eniola, MD, MPH, Angela Bacigalupo, MD, MPH, Anne Mounsey, MD

fective firstline pharmacotherapy Interview Guide for the Seasonal PRACTICE CHANGER options for MDD.2,3 Despite their Affective Disorder version of the Consider treatment with bright effectiveness, however, studies HAM-D.6,7 light therapy, alone or in have shown that only about 40% of combination with , patients with MDD achieve remis- STUDY SUMMARY for patients with nonseasonal sion with firstline or secondline Light therapy improves major depressive disorder.1 drugs.2 In addition, pharmaco­ nonseasonal STRENGTH logic agents have a higher fre- This latest study was an eight- OF RECOMMENDATION quency of treatment-associated week, randomized, double-blind, adverse effects than fluorescent - and sham-controlled B: Based on a single moderate- 4 quality randomized controlled light therapy. clinical trial evaluating the ben- trial.1 A Cochrane efit of light therapy with and of 20 studies (N = 620) demon- without pharmacotherapy for strated the effectiveness of com- nonseasonal MDD.1 The investi- A 38-year-old woman recently bined light therapy and pharma- gators enrolled 122 adult patients diagnosed with major depressive cotherapy in treating nonseasonal (ages 19 to 60) from outpatient disorder (MDD) without a sea- MDD but found no benefit to light psychiatry clinics who had a di- sonal pattern presents to discuss used as monotherapy.5 However, agnosis of MDD (diagnosed by a treatment options. Her Hamilton the majority of the studies were of psychiatrist) and a HAM-D8 score Depression Rating Scale (HAM-D) poor quality, occurred in the inpa- of at least 20. Subjects had to be score is 22, and she is not suicidal. tient setting, and lasted less than off psychotropic medication for Should you consider bright light four weeks. at least two weeks prior to the therapy in addition to pharmaco- In a five-week, controlled, first visit; they were subsequently therapy? double-blind trial not included in monitored for one week to iden- the Cochrane review, 102 patients tify spontaneous responders and DD is one of the most with nonseasonal MDD were ran- give patients time to better regu- common psychiatric domized to receive either active late their sleep-wake cycle (with M illnesses in the United treatment (bright light therapy) the goal of sleeping only between States, affecting approximately plus (50 mg/d) or sham 10 pm and 8 am daily). one in five adults at some point light treatment (using a dim red The investigators randomly in their lives.2 Selective light) plus sertraline (50 mg/d). assigned patients to one of four reuptake inhibitors (SSRIs) and The investigators found a statisti- treatment groups: serotonin-norepinephrine reup- cally significant reduction in de- • Active light monotherapy take inhibitors are considered ef- pression score in the active treat- (10,000-lux fluorescent white ment group compared to the sham light for 30 min/d early in the Kehinde Eniola and Angela Bacigalupo light group, based on the HAM-D, morning) plus a placebo pill are with Cone Health Family Medicine Resi- dency in Greensboro, NC. Anne Mounsey the Hamilton 6-Item Subscale, the • Fluoxetine (20 mg/d) plus is in the Department of Family Medicine at Melancholia Scale, and the seven sham light therapy the University of North Carolina, Chapel Hill. atypical items from the Structured • Placebo pills with sham light continued on page 30 >>

28 Clinician Reviews • AUGUST 2016 clinicianreviews.com PURLs®

>> continued from page 28 therapy; or therapy (29%). There was a signifi- detect clinically significant sea- • Combined active light thera- cant response effect for the com- sonal treatment effects and dif- py with fluoxetine (20 mg/d). bination versus placebo treatment ferences between the fluoxetine Sham light therapy consisted of group. and placebo groups, regardless of the use of an inactivated negative Similarly, there was a higher whether they received active pho- ion generator, used in the same remission rate in the combination totherapy. fashion as a light box. All patients treatment group (58.6%) than in were analyzed based on modi- the placebo, light monotherapy, CHALLENGES fied intention to treat. Adherence or fluoxetine treatment groups TO IMPLEMENTATION was assessed through review (30%, 43.8%, and 19.4%, respec- Commercial insurance doesn’t of patients’ daily logs of device tively). Combination therapy was usually cover light therapy treatment times and through pill superior to placebo in treatment Bright light therapy is fairly safe, counts. response (≥ 50% reduction in the and some evidence exists support- The primary outcome at eight MADRS score) and remission ing its use in the treatment of non- weeks was the change from (MADRS ≤ 10), with numbers seasonal MDD; however, the data baseline in the Montgomery- needed to treat of 2.4 and 3.5, re- for its use in this area are limited.10 Asberg Depression Rating Scale spectively. Since few studies have tested light (MADRS), a 10-item question- By the end of the eight-week therapy for nonseasonal MDD, naire with a worst score of 60.9 study period, 16 of 122 patients uncertainty remains about patient Secondary outcomes were treat- had dropped out. Two reported selection, as well as optimal dose, ment response (≥ 50% reduction lack of efficacy, five reported ad- timing, and duration in the man- in MADRS score) and remission verse effects, and the remainder agement of nonseasonal MDD.11 (MADRS score ≤ 10) at the final cited administrative reasons, were Although the associated risks are eighth-week visit. MADRS scoring lost to follow-up, or withdrew minimal, bright light therapy can was used because of its sensitiv- consent.­ lead to or ; cli- ity to treatment-induced changes nicians need to monitor for such and its high correlation with the WHAT’S NEW effects when initiating therapy.3 HAM-D scale. New evidence on Lastly, commercial insurance At the end of eight weeks, the a not-so-new treatment does not usually cover light thera- mean changes in MADRS scores We now have evidence that bright py. The average price of the bright from baseline were: light mono- light therapy, either alone or in light devices, which are available therapy, 13.4; fluoxetine mono- combination with fluoxetine, is ef- in medical supply stores and on- therapy, 8.8; combination ther- ficacious for increasing the remis- line, ranges from $118 to $237.4,11 apy, 16.9; and placebo, 6.5. The sion rate of nonseasonal MDD. However, such de­vices are reus- improvement was significant in able, making the amortized cost the light monotherapy treatment CAVEATS almost negligible and perhaps ne- group and in the combination Variables may have affected gating this concern.12 CR therapy group, compared with the results placebo group, and in the com- Among the study’s limitations: REFERENCES bination group, compared with use of a single SSRI (other, more 1. Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the the fluoxetine treatment group; potent SSRIs might work better); combination in patients with nonseasonal improvement was not significant location (southern Canada; ben- major depressive disorder: a randomized for the fluoxetine treatment group efits may differ in regions farther clinical trial. JAMA Psychiatry. 2016;73: 56-63. compared with the placebo group, south); and exclusion of pregnant 2. Weihs K, Wert JM. A primary care focus on the however. and breastfeeding women from treatment of patients with major depressive The treatment response (≥ 50% the study population. disorder. Am J Med Sci. 2011;342:324-330. 3. Gelenberg AJ, Freeman CMP, Markowitz JC, MADRS improvement) rate was Furthermore, the trial dura- et al. American Psychiatric Association prac- highest in the combination treat- tion was relatively short, and the tice guideline for the treatment of patients ment group (75.9%), followed by investigators did not attain their with major depressive disorder. 3rd ed. 2010. http://psychiatryonline.org/pb/assets/raw/ light monotherapy (50%), placebo preplanned sample size for the sitewide/practice_guidelines/guidelines/ (33.3%), and fluoxetine mono- study. This limited the power to mdd.pdf. Accessed July 5, 2016. continued on next page >>

30 Clinician Reviews • AUGUST 2016 clinicianreviews.com PURLs®

>> continued from previous page 4. Lam RW, Tam EM. A Clinician’s Guide to Using 8. Hamilton M. A rating scale for depression. ACKNOWLEDGEMENT Light Therapy. New York, NY: Cambridge J Neurol Neurosurg Psychiatry. 1960;23: The PURLs Surveillance System was supported in University Press; 2009. www.ubcmood.ca/ 56-62. part by Grant Number UL1RR024999 from the sad/SAD%20resources%20package%20 9. Montgomery SA, Asberg M. A new depres- National Center For Research Resources, a Clinical 2009.pdf. Accessed July 5, 2016. sion scale designed to be sensitive to change. Translational Science Award to the University of 5. Tuunainen A, Kripke DF, Endo T. Light thera- Br J Psychiatry. 1979;134:382-389. Chicago. The content is solely the responsibility of py for non-seasonal depression. Cochrane 10. Oldham MA, Ciraulo DA. Use of bright light the authors and does not necessarily represent the Database Syst Rev. 2004;2:CD004050. therapy among psychiatrists in Massachu- official views of the National Center For Research 6. Martiny K. Adjunctive bright light in non- setts: an e-mail survey. Prim Care Companion Resources or the National Institutes of Health. seasonal major depression. Acta Psychiatr CNS Disord. 2014;16(3). Epub 2014 Jun 26. Scand Suppl. 2004;425:7-28. 11. Sloane PD, Figueiro M, Cohen L. Light as Copyright © 2016. The Family Physicians Inquiries 7. Martiny K, Lunde M, Unden M, et al. Adjunc- therapy for sleep disorders and depression in Network. All rights reserved. tive bright light in non-seasonal major older adults. Clin Geriatr. 2008;16:25-31. depression: results from clinician-rated 12. Kripke DF. A breakthrough treatment for Reprinted with permission from the Family Physi- depression scales. Acta Psychiatr Scand. major depression. J Clin Psychiatry. 2015; cians Inquiries Network and The Journal of Family 2005;112:117-125. 76:e660-e661. Practice. 2016;65(7):486-488.

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