PERSPECTIVES The Psychiatry of Light Richard S. Schwartz, MD, and Jacqueline Olds, MD Abstract: Bright light therapy and the broader realm of chronotherapy remain underappreciated and underutilized, despite their empirical support. Efficacy extends beyond seasonal affective disorder and includes nonseasonal depression and sleep disorders, with emerging evidence for a role in treating attention-deficit/hyperactivity disorder, delirium, and dementia. A practical overview is offered, including key aspects of underlying biology, indications for treatment, parameters of treatment, adverse effects, and transformation of our relationship to light and darkness in contemporary life.

Keywords: chronotherapy, circadian rhythm, mood disorders, phototherapy, seasonal affective disorder

“Y

ou don’t hear a psychiatrist asking how much light you get,” Satchin Panda told a reporter for The Economist.1 “It affects so much of our physiology, psychology, and mood. But we take it for granted.” Panda is a scientist at the Salk Institute, who confirmed that melanopsin (a photopigment found in nonvisual retinal ganglion cells) is the primary light receptor for the regulation of circadian rhythm. He is an expert in the biology of light. He also recognizes how little the rapidly expanding body of knowledge about light and health has affected psychiatric practice, to the detriment of our patients. In contrast to the information available on how psychiatrists and other clinicians use medications and psychotherapy in treating patients, remarkably little data are available on the use of bright light therapy2—an absence that itself reflects a lack of attention to the clinical use of light. Only three studies have been published. Surveys of psychiatrists in Germanspeaking countries were conducted by the same group in 1994 and 2012. Over that time period, the number of psychiatrists using light therapy increased from 13% to 69.8%.3,4 Almost all use was for the treatment of depression. The only study of light therapy use in the United States is an email survey of Massachusetts psychiatrists, with a low survey response rate of 14%.5 Seventy-two percent of the psychiatrists reported that they recommend the use of bright light occasionally—most often for seasonal affective disorder (SAD), much less frequently for nonseasonal depression, and rarely for inpatients. Given the low survey response rate, the authors suggested that psychiatrists with an interest in light therapy were likely to be significantly overrepresented among the responders, leading to

From Harvard Medical School; McLean Hospital, Belmont, MA (Dr. Schwartz); Department of Psychiatry, Massachusetts General Hospital, Boston, MA (Dr. Olds). Original manuscript received 15 September 2014, accepted for publication subject to revision 28 October 2014; revised manuscript received 12 November 2014. Correspondence: Richard Schwartz, MD, 30 Hillside Ave., Cambridge, MA 02140. Email: [email protected] © 2015 President and Fellows of Harvard College DOI: 10.1097/HRP.0000000000000078

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an overestimate of the actual use of bright light therapy in clinical practice. Before reviewing the evidence of effectiveness for light therapy in depression and other syndromes, it is worth considering why an evidence-based treatment with an unusually benign side-effect profile remains in the shadows. With obvious parallels to psychotherapy, the lack of industrybased funding to supplement federal research grants has slowed the emergence of a compelling body of research on light-based treatments. Similarly, the lack of industry-based funding for advertising and speakers slows the dissemination of research findings to clinicians. Yet, in contrast to psychotherapy, bright light therapy lacks a large and established group of practitioners ready to enthusiastically rebroadcast news of positive research results. Other possible reasons have more to do with the nature of bright light therapy itself. Unlike swallowing a pill, bright light therapy requires time. The use of artificial light tethers a patient to a light box. The use of natural light stirs concerns about UV exposure. Absent an understanding of the importance of circadian rhythm to most bodily functions and behaviors—and of the importance of light to circadian rhythm—light therapy can seem on the alternative margins of scientific medicine. Moreover, our impression is that light just sounds less potent and less precise than a medication to many of our patients, a view supported by a recent study on the importance of pilltaking expectations in patients’ responses to antidepressant treatment.6 Finally, at the level of professional identity, an environmental approach to psychiatric treatment challenges the idea that depression is an illness that resides primarily “within” the patient—whether that notion is understood in biological, cognitive, or behavioral terms. We will return to these questions, which are extremely important in clinical practice, after a non-exhaustive review of the evidence supporting more widespread use of light therapy in psychiatric care.

BRIGHT LIGHT THERAPY FOR AFFECTIVE DISORDERS The use of bright light as a controlled intervention in psychiatry began in 1984. A groundbreaking study published by the Volume 23 • Number 3 • May/June 2015

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National Institute of Mental Health systematically described SAD and the use of bright light as an effective antidepressant in 11 patients.7 In 2005, the American Psychiatric Association Council on Research convened a work group to review the subsequent 20 years of research on light therapy for treating depression. The number of studies that met the rigorous inclusion criteria was small—eight for SAD and three for nonseasonal depression—but the group concluded that light therapy was an effective treatment for both types of depression.8 Notably, the effects sizes for light therapy were “equivalent to those in most antidepressant pharmacotherapy trials” (0.84 for SAD, and 0.53 for nonseasonal depression).* Subsequent research has supported, refined, and extended these conclusions.11 A standard treatment approach has emerged, one that uses a fluorescent light box that produces 10,000 lux of white light at a specified distance from the user’s eyes (the distance is dependent on the particular device), beginning with 30 minutes exposure in the early morning, as close to awakening as feasible.12 A dose-response curve has been defined, with a threshold of 2500 lux for an antidepressant effect. Two hours of exposure are required at 2500 lux and 45–60 minutes at 5000 lux (versus the recommended 30 minutes at 10,000 lux). Even at light intensities greater than 10,000 lux, however, the time required for effective treatment does not seem to decrease below the “standard” 30 minutes (a bright, sunny day can reach intensities of 50,000–100,000 lux). At the other end of the brightness curve, it is important to note that, other than sitting in a window with sunshine streaming in, indoor lighting, however bright it may seem (our eyes adjust effectively to immense variations in brightness), never approaches 2500 lux. Treatment parameters are adjusted based on individual response. Terman and Terman13 report that remission rates in SAD can be improved by timing the treatments to an individual’s evening melatonin onset, using a self-rating scale called the Morningness-Eveningness Questionnaire as a rough proxy for salivary melatonin assays. Preliminary evidence suggests that SAD patients have a less sensitive light-input pathway, which is related to variations in the melanopsin gene.14 This finding opens up the possibility of more fundamental and individualized approaches to dosing in the future. The key pathway for light in its role as primary timekeeper for circadian rhythm begins with melanopsin-containing, intrinsically photosensitive retinal ganglion cells. These cells project to the suprachiasmatic nuclei of the anterior hypothalamus—the body’s master biological clock. The system’s peak spectral sensitivity is in the blue range (460 nm). Two studies by the same group found low-intensity, blue-enriched light (750 lux) as effective as, but not superior to, standard bright light (10,000 lux) * In 2007, a Swedish advisory council concluded that the value of therapy with a light box for SAD could not be either confirmed or dismissed.9,10 When we invited Alfred Lewy to comment on the Swedish review, he noted that it included studies with too few subjects to demonstrate a meaningful difference from placebo (a problem in all antidepressant research) but that larger studies demonstrating efficacy are still convincing (Lewy A, personal communication, 2014).

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in treating SAD.15,16 Most experts still recommend white light, however, since the evidence base is better established, and the interplay of effects of differing wavelengths is complex and not yet fully understood.11 The identification of melanopsin and the associated neural pathways has had profound theoretical and practical implications for the use of light therapy. But these discoveries may not tell the whole story. One of the more intriguing hypotheses is humoral phototransduction, in which bloodborne hemoglobin and bilirubin in the central retinal vein act as photoreceptors; the resulting release of carbon monoxide serves as a signal and regulator of circadian and seasonal changes.17 Ongoing investigations in this area, along with lingering questions about a role for the visual rod and cone receptors in circadian regulation, may further refine our understanding of optimal spectra for light therapy. An additional complexity may also be emerging from yet-unpublished research. The presence of vitamin D appears to enhance serotonin synthesis in rat brain cells, an effect that would not explain the efficacy of light boxes (which should produce no UV radiation) but that could indicate a distinct additional mechanism of action for natural light.18 Although the American Psychiatric Association work group found no evidence for improved response from the combination of bright light and antidepressant medication, welldesigned trials not published within the defined time frame of the APA review show both superior response and remission rates over medication treatment alone in nonseasonal major depressive disorder.19 The combination of wake therapy (sleep deprivation at the start of treatment), bright light therapy, and medication is emerging as a particularly effective strategy in both major depressive disorder20–22 and bipolar depression.23,24 A recent study combining lithium with sleep deprivation and light therapy in drug-resistant bipolar patients showed not only rapid improvement but an immediate and persistent decrease in suicidality after the first sleep-deprivation cycle.25 Bright light treatment carries a low but significant risk of switching in bipolar depression. A small study suggests that initiating treatment with midday light—rather than the usual early morning light—may minimize that risk.26 Conversely, a pilot study on “dark therapy” (light deprivation) in acute mania suggests that this treatment may lead to more rapid improvement when added to standard treatments.27 Studies on other specialized patient populations have shown bright light to be an effective treatment for nonseasonal major depression in the elderly28,29 and a promising treatment in perinatal depression.30

BRIGHT LIGHT THERAPY FOR OTHER PSYCHIATRIC DISORDERS Bright light therapy has a conceptually straightforward and well-supported role in the treatment of circadian rhythm sleep disorders—disturbances in sleep that result from a misalignment of an individual’s sleep-wake pattern with his or her internal circadian system or with the demands of the www.harvardreviewofpsychiatry.org

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external world.31 The major categories are delayed sleep-phase disorder, advanced sleep-phase disorder, jet-lag disorder, shiftwork disorder, and free-running disorder in blind patients (some individuals with blindness are still responsive to light as a circadian regulator through the melanopsin–suprachiasmatic nucleus pathway).11 Early morning light is used to phaseadvance an individual’s sleep-wake cycle, and late afternoon/ evening light, to phase-delay the cycle. Low-dose melatonin (0.3–0.6 mg) is an alternative intervention when administered with the opposite timing—early morning for phase delay and late afternoon/evening for phase advance.32 The phase-shifting effects of bright light and melatonin appear to be additive.33 Beyond improving the immediate consequences of insomnia (fatigue, decreased performance in both cognitive and motor tasks, decreased alertness), the treatment of circadian rhythm sleep disorders links back to the treatment and prevention of mood disorders. Since a fundamental connection appears to exist between mood disturbances and the phase delay of internal circadian rhythms,28 the effectiveness of similar interventions (bright light and melatonin) in both conditions is not surprising. Evidence shows that poor sleep in the elderly is a considerable risk factor for suicide over a subsequent ten-year period, independent of the presence of other depressive symptoms.34 Attention deficit/hyperactivity disorder (ADHD) is another condition where evidence is emerging of improvement from exposure to bright light. An intriguing study looked at the relationship between ADHD prevalence and solar intensity (kilowatt hour/square meter/day) across nations and across US states. Higher solar intensity was strongly associated with a lower prevalence of ADHD in both children and adults.35 The authors suggest that the preventive effect of high solar intensity in ADHD is related to improvement of circadian clock disturbances. An open trial of bright light therapy in adult ADHD had positive results.36 And a recent pilot study found evidence for a range of circadian disturbances in ADHD, including sleep disruption, phase delays, and unstable circadian rhythms, along with seasonal effects on circadian rhythm stability and symptomatology.37 Given the importance of circadian rhythms to optimal function in normal states and the notable reduction in exposure to bright light in modern times (see below), the current paucity of research on the effect of bright light enhancement in nonclinical populations is surprising; we expect more research to be emerging. The available evidence suggests, however, that bright light treatment “improves vitality and alleviates distress” in healthy office employees during winter months,38 that bright light has important alerting effects (not only on patients with disordered states),39 and that these alerting effects directly improve cognitive function.40 The last study cited also suggests a new complexity: the response to a test dose of light was affected by the wavelength of light to which individuals had been exposed prior to the test (“photic memory”). Finally, a large study of healthy, older women (median age = 67) found that 190

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increased light exposure was associated with improved quality of life and social and emotional functioning.41

BRIGHT LIGHT THERAPY FOR MEDICAL/PSYCHIATRIC CONDITIONS Parkinson’s disease (PD) is an illness closely associated with depression. Patients with PD are at high risk for depression,42 and depression increases the risk of PD.43 PD is also associated with circadian desynchronization, and several studies have found that bright light therapy has positive effects not only on sleep and mood in PD patients but also on motor function.44 Circadian desynchronization is also a major problem in Alzheimer’s disease and related dementias. The use of bright light in a small number of studies has shown mixed results.45 A promising, new pilot study that used bluish-white light in the rooms of nursing home patients with Alzheimer’s disease found significant improvement in sleep quality, sleep efficiency, and total sleep time, along with reduced depression and agitation.46 Early studies of bright light as an adjunctive treatment for hospitalized patients with delirium have also been encouraging.47,48 The association between “winter blues” and weight gain raises questions about the use of bright light for weight loss. A single placebo-controlled, randomized trial found that morning bright light treatment reduced body fat and appetite in overweight women.49 Complicating the picture, evidence suggests that morning bright light improves the efficiency of carbohydrate digestion and absorption from an evening meal and that evening bright light has the opposite effect, decreasing the efficiency of carbohydrate digestion and absorption from an evening meal. Thus, bright light at supper—though unromantic—could be an aid to weight loss.50,51 A recent, careful correlational study, however, found that exposure to moderately bright light (above 500 lux) earlier in the day is associated with lower BMIs, independent of effects on sleep.52 Finally, one of the more intriguing new findings is that bright light (sunlight) in childhood may be an essential element for healthy eye development. Concern about an “epidemic” of myopia in urban east Asia (the prevalence of myopia in young adults is 80%)53 led researchers to investigate a possible association between myopia, educational pressure, and time spent outdoors. A strong correlation emerged between outdoor time and lower prevalence of myopia in children.47 A simple (randomized) program encouraging elementary school children to spend one hour of daily recess outdoors led to a significant reduction in new-onset cases of myopia by the end of the school year.54 CONTEMPORARY EXPOSURE TO LIGHT AND DARKNESS Over the past century, electric lighting has transformed the relationship between human activity and the natural cycles of light and darkness in which our physiology evolved. Most of our days are spent in light that is significantly dimmer than sunlight, and much of our nights are spent in light that is Volume 23 • Number 3 • May/June 2015

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significantly brighter than starlight or moonlight. As summarized in a 2008 review by Turner and Mainster: Young adults in industrialized countries typically receive only 20–120 min of daily light exposure exceeding 1000 lux. Elderly adults’ bright light exposures average only 1/3 to 2/3 that duration. Institutionalized elderly receive less than 10 min per day of light exposure exceeding 1000 lux, with median illuminances as low as 54 lux.55(p 1443) The effect of decreasing exposure to bright light in the elderly is amplified by the dramatic decline in light transmittance through the eye that comes with age, the result of both crystalline lens yellowing and pupillary miosis.49 The eyes of a 45-year–old, compared to those of a 10-year-old, transmit only half the light active in circadian photoreception to the retina, and by the age of 95 years, circadian photoreception has dropped to one-tenth the level of a 10-year-old. The relevance of decreasing circadian photoreception to sleep disorders, mood disorders, and cognitive decline in the elderly is a subject of active investigation. Wright56 has begun to examine changes in circadian function when individuals move from modern, electrically lit, “constructed environments” to environments with only natural lighting (during camping trips where no artificial light sources are available). His findings emphasize that natural sunlight is a more powerful zeitgeber (timing cue) for circadian rhythm than electric lighting and that without natural light, internal differences in circadian periodicity express themselves more strongly and move an individual away from a state of light-based entrainment to the 24-hour solar day. At night, the ubiquitous presence of electric light and illumination from electronic screens (which emit significant amounts of blue light at the peak sensitivity of intrinsically photosensitive retinal ganglion cells) has captured public attention.57 The upper limits of nighttime illumination that do not disrupt circadian function are unclear, but remarkably low levels appear to have significant effects.58 Light-based, nighttime disturbances of circadian rhythm and melatonin secretion not only may lead to sleep and mood problems but have also been associated with increased risk for breast cancer and intrinsic resistance to tamoxifen therapy in breast cancer.59 Technology can help with this problem. For patients who cannot avoid exposure to light from computer and smartphone screens as bedtime approaches, programs (e.g., the free program f.lux)60 and apps are now available that gradually red-shift the screen illumination based on time of day.60 One study of three mobile devices (two tablets and one smartphone, without any of the preceding programs or apps) found that illumination of the eyes could be kept below the presumptive threshold for melatonin suppression of 30 lux by reducing the screen brightness from the maximum or by keeping the device at least 14 inches from the eyes.61 Harvard Review of Psychiatry

ADVERSE EFFECTS Like all effective treatments of depression, bright light therapy can trigger a shift to mania or hypomania in patients with bipolar depression. Otherwise, immediate side effects are mild and can usually be managed by temporary reductions in light intensity or duration. Most common are reports of eye discomfort, headache, and feeling “wired.”12 Given the long-standing observation that suicide rates are highest in the spring, a new study investigated whether the seasonal change in suicide is directly related to increased sunshine.62 Looking at 40 years of Austrian data, the authors found that, independent of seasonal variation, increased hours of sunshine both on the day of the suicide and over the prior 10 days are positively correlated with the number of suicides on a given day. Increased hours of sunshine over the prior 14 to 60 days, however, is negatively correlated with suicide. All of the effect is on violent suicides. There is no effect on nonviolent suicides (e.g., overdoses). The authors speculate that the mechanism of sunshine’s effect on suicide is the same as that of antidepressant medication; both are mediated by changes in the serotonergic system, with an improvement in motivation sometimes preceding an improvement in mood (what is sometimes called an “activating” effect). The result would be the observed short-term increased risk of suicide, followed by a longer-term protective effect. A practical consequence is that even though bright light therapy is theoretically available to patients without the involvement of a treating clinician (unlike both prescription medications and psychotherapy), it should not be used by patients to treat their own severe depression. Long-term exposure to solar UVB radiation is associated with an increased risk of cataract formation. Therapeutic light boxes should effectively filter out all UV light. For patients using natural light, the UV component of sunlight is low in the early morning hours, when bright light treatment is optimal for most patients. Eye protection in the form of sunglasses and brimmed hats is recommended only during the middle of the day.63 A new retrospective study shows an association between lifetime solar exposure and exfoliation syndrome, a form of ocular aging associated with increased risk for various deleterious conditions, including cataract formation.64 The researchers in this study asked subjects about time outdoors only between the hours of 10 a.m. and 4 p.m., presumably positing the safety of early morning sunlight.† Since bright light therapy works through the eyes, protecting the skin from solar radiation does not reduce its efficacy. One early study directly compared the effect of bright light applied to the skin versus the eyes in treating SAD.65 The study, which supported a mechanism of action through the eyes, was never repeated; the clear efficacy of light boxes that are directed primarily at the eyes, coupled with the convincing † Regarding the importance of eye protection during the middle of the day, when UV radiation is high, sunglasses were protective against exfoliation syndrome in the United States but not Israel, and brimmed hats were not protective at all, perhaps because of significant reflected UV radiation.

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elucidation of underlying mechanisms of action, meant that researchers could move on. But as we noted earlier, ongoing research on a possible link between vitamin D and serotonin synthesis may lead to a circling back on these questions with regard to sunlight.18 Most manuals on light treatment offer cautions about using it in patients with underlying retinal disease; the manuals suggest guidance from an ophthalmologist, with baseline and annual follow-up eye exams.11,12 Patients with agerelated macular degeneration (AMD) are regularly cautioned against unprotected exposure to sunlight since environmental light exposure has long been suspected to be a risk factor in the development and progression of AMD. A current review, however, concludes that decades of research do not support the view that environmental light is a significant factor in AMD.66 Patients on photosensitizing medications—including lithium, phenothiazines, and St.-John’s-wort—should likewise obtain an ophthalmological assessment before treatment and be followed with regular eye exams. Melatonin also causes retinal photosensitization but can safely be combined with bright light therapy when used correctly. Since melatonin and bright light produce phase shifts in opposite directions, they cancel each other out when administered at the same time. They can be combined safely, with enhanced effect, when used at opposite ends of the day because of melatonin’s short half-life.11 In our own practices, the “side effect” that most often leads patients to discontinue light therapy is that it requires time. This comment from one patient is typical: “If you think my kids and wife will let me sit at the table in front of a light box while everyone else is getting ready for school or work, you just don’t understand my life.” By contrast, only a moment is required to take a pill. Better-engineered indoor light (both in the workplace and the home)67 and wearable sensors to “dose” natural light68 may eventually minimize practical obstacles to the use of bright light therapy.

CONCLUSIONS Our own experience with light therapy began in the mid1980s, soon after the publication of the earliest studies on SAD. In the absence of commercially manufactured light boxes, a colleague down the hall drew up a shopping list and wrote down instructions to help patients build their own light boxes with parts from their local hardware stores. Our colleague soon withdrew his instructions from circulation because of liability issues (so we are sadly unable to give credit for his work). Fortunately, a commercial light box shortly became available from a company that was started by a participant in the original National Institute of Mental Health study, who had been appalled to discover the impossibility of continuing effective treatment once the study was over. We have been fascinated by the emerging research over the past three decades that has not only extended our understanding of the use of light in psychiatry but helped us to appreciate the complex effects of light on circadian and seasonal 192

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regulation, the importance of circadian regulation in an expanding array of functions at both the cellular and organismic levels, and the unanticipated health effects from the transformation of our daily relationship to light in a modern, constructed environment. The story continues to unfold. Integrating the psychiatry of light and the indications for bright light therapy into the standard education of psychiatrists offers many benefits to our patients. Bright light therapy is not a panacea. The history of psychiatry is strewn with the overselling of favorite approaches to treatments. But bright light therapy can be both effective and uncommonly safe. It deserves more attention and more frequent use. Declaration of interest: Drs. Schwartz and Olds are board members and cofounders of GoodLux Technology, which manufactures a wearable device for keeping track of bright light exposure. REFERENCES 1. Blau R. The light therapeutic. Intelligent Life 2014; May/June. http:// moreintelligentlife.com/content/features/rosie-blau/light-and-health 2. Oldham MA, Domenic CA. Bright light therapy for depression: a review of its effects on chronobiology and the autonomic nervous system. Chronobiol Int 2014;31:305–19. 3. Fischer R, Kasper S, Pjrek E, Winkler D. On the application of light therapy in German-speaking countries. Eur Arch Psychiatry Clin Neurosci 2012;262:501–5. 4. Kasper S, Ruhrmann S, Neumann S, Möller HJ. Use of light therapy in German psychiatric hospitals. Eur Psychiatry 1994;9: 288–92. 5. Oldham MA, Domenic CA. Use of bright light therapy among psychiatrists in Massachusetts: an e-mail survey. Prim Care Companion CNS Disord 2014:16(2):doi:10.4088/PCC.14m01637. 6. Leuchter AF, Hunter AM, Tartter M, Cook IA. Role of pilltaking, expectation and therapeutic alliance in the placebo response in clinical trials for major depression. Br J Psychiatry 2014;205:443–9. 7. Rosenthal NE, Sack DA, Gillin C, et al. Seasonal affective disorder: a description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry 1984;41:72–80. 8. Golden RN, Gaynes BN, Ekstrom RD, et al. The efficacy of light therapy in the treatment of mood disorders: a review and metaanalysis of the evidence. Am J Psychiatry 2005;162:656–62. 9. Swedish Council on Technology Assessment in Health Care. Summary and conclusions: light therapy for depression, and other treatment of seasonal affective disorder: a systematic review. 2007. http://www.sbu.se/upload/Publikationer/Content1/1/ light_therapy_depression.pdf 10. Swedish Council on Technology Assessment in Health Care. Light therapy for depression, and other treatment of seasonal affective disorder: a systematic review [Full report, in Swedish]. 2007. http://www.sbu.se/upload/Publikationer/Content0/1/ Ljusterapi_2007.pdf 11. Wirz-Justice A, Benedetti F, Terman M. Chronotherapeutics for affective disorders: a clinician’s manual for light and wake therapy. Basel: Karger, 2013. 12. Lam RW, Tam EM. A clinician’s guide to using light therapy. Cambridge: Cambridge University Press, 2009. 13. Terman M, Terman JS. Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and side effects. CNS Spectr 2005;10:647–63.

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Volume 23 • Number 3 • May/June 2015

Copyright © 2015 President and Fellows of Harvard College. Unauthorized reproduction of this article is prohibited.

The psychiatry of light.

Bright light therapy and the broader realm of chronotherapy remain underappreciated and underutilized, despite their empirical support. Efficacy exten...
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