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Bright Light Therapy for Bipolar Depression

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Bright Light Therapy for Bipolar Depression Bright light therapy for bipolar depression Evidence suggests efficacy as an adjunctive treatment right light therapy (BLT) refers to the use of bright light to treat symptoms of depression. BLT was initially pre- scribed as a treatment for patients with seasonal affec- B 1 tive disorder. It was later found helpful for nonseasonal depression,2 premenstrual dysphoric disorder, postpartum depression, and phase shift circadian disorders, including for patients with dementia whose cognitive function improved after treatment with BLT.3 More recent studies suggest year- round benefit for nonseasonal depression.2 The American Psychiatric Association practice guidelines for the treatment of depression list BLT as an alternative and/or addition to pharmacologic and psychological treatment.4 BLT also may be beneficial for patients who are in the depressive phase of bipolar illness. This article describes the evidence, rationale for use, ANDRZEJ WOJCICKI mechanism of action, benefits, and safety profile of BLT for Suhayl J. Nasr, MD Ahmed Z. Elmaadawi, MD treating patients with bipolar depression. Professor of Psychiatry Adjunct Assistant Professor Indiana University School of Psychiatry of Medicine Indiana University School Indianapolis, Indiana of Medicine Circadian rhythm disruption in bipolar disorder Chief of Behavioral Indianapolis, Indiana Clinical manifestation. Patients with bipolar disorder (BD) Health Services Director of Interventional spend more time in depression than in mania.5 Sleep distur- Beacon Health System Psychiatry Division South Bend, Indiana Beacon Health System bance is a core symptom of BD; patients typically have little South Bend, Indiana need for sleep during a manic episode, and excess sleepiness Rikinkumar Patel, MD, during a depressive episode. Sleep complaints can be both pre- MPH cipitating factors and consequences of mood disorders. Patients Department of Psychiatry with seasonal depression have excess sleepiness and weight Griffin Memorial Hospital gain in the winter followed by hypomanic-like symptoms in Norman, Oklahoma the spring, including decreased need for sleep and weight loss with psychomotor activation. In a recent review of sleep Disclosures Current Psychiatry The authors report no financial relationships with any company whose products are mentioned in 28 November 2018 this article, or with manufacturers of competing products. problems in patients with BD, Steinan et al6 season, or other factor. For patients who reported that 20% of patients with euthymic live in areas that receive frequent sunshine, mood in bipolar disorder experience a sleep an outside stroll for half an hour will likely disorder. Circadian disruption and “evening- achieve similar benefit to BLT. MDedge.com/psychiatry ness” (being more active during the evening) The precise mechanism of action of BLT have been associated with mood episodes, for bipolar depression has not yet been functional impairment, poor quality of life, determined. It may be attributed to a phase- and treatment resistance.7-10 resetting effect via melanopsin and the suprachiasmatic nucleus (Box,18-24 page 30). Pathophysiology. Existing hypotheses for the biological mechanism underlying dys- regulation of circadian rhythm in BD include BLT for BD: What’s the evidence? changes in melatonin levels, expression of Several studies and case reports have evalu- melatonin receptors in the CNS, and daily ated the use of BLT for bipolar depression. cortisol profiles.11 Genetic evidence also The number of participants in these studies links circadian rhythm dysregulation with is small, and there is no uniformity of meth- BD. Two polymorphisms on the circadian odology or patient selection. Clinical Point 25 locomotor output cycles kaput (CLOCK) Dauphinais et al (2012) randomly Circadian rhythm gene that control circadian rhythm—aryl assigned 44 patients with bipolar depres- hydrocarbon receptor nuclear translocator- sion to BLT or a high-density or low-density dysregulation is like (ARNTL) and timeless circadian clock negative ion generator for 8 weeks. They associated with (TIMELESS)—have been linked to lithium reported no difference in outcome between metabolic problems responsiveness in BD.12 In addition, Per2, the various groups (50% vs 55.6%, remis- in patients with Cry1, and Rev-Erbα expression—all com- sion and response rate). Only one patient in bipolar disorder ponents of the circadian clock—have been each group showed a switch to hypomania. found to increase individual susceptibil- Carmadese et al (2015)26 reported an ity to the therapeutic effects of lithium in open-label study of adjunctive BLT in 31 mice.13 In addition, circadian rhythm dys- difficult-to-treat patients with depression regulation is associated with metabolic (16 unipolar and 15 bipolar). Significant problems encountered by patients with BD, improvement was noted within 3 weeks including weight gain, diabetes mellitus, and was sustained in 1 patient with bipolar and cardiovascular disease.14 depression 5 weeks after cessation of BLT. Papatheodorou and Kutcher (1995)27 treated 7 adolescents with bipolar depres- Rationale for use sion with adjunctive BLT (10,000 lux twice Regulation of a patient’s circadian rhythm per day). Three patients showed a marked disruption is a potential treatment for BD. response (>70% decrease from baseline Hashimoto et al15 demonstrated that mid- Beck Depression Inventory and Symptom day bright light exposure can phase advance Check List scores). Two patients had a mod- and increase the amplitude of nocturnal erate response (40% to 47% decrease) and melatonin production in healthy individu- 2 patients obtained mild to no response. als. Morning light therapy has been shown There were no reported adverse effects. to increase blood serotonin throughout Benedetti et al (2014)28 studied 141 the day in both healthy individuals and in patients with treatment-resistant bipolar patients with nonseasonal depression; the depression. Approximately one-quarter effect was apparent with light intensities as (23%) had a history of attempted suicide, Discuss this article at low as 50 lux.16 Lithium may exert its thera- and 83% had a history of drug resistance. www.facebook.com/ MDedgePsychiatry peutic effect through its influence on the The authors found a combination of total retino-hypothalamic-pineal tract and thus sleep deprivation, BLT, and lithium rap- its effect on melatonin secretion.17 idly decreased suicidality and improved BLT is a logical choice to treat the depres- patients’ depressive symptoms. sion phase of BD when exposure to sunlight Liebenluft et al (1995)29 administered 13 Current Psychiatry is not feasible due to geographical location, trials of BLT to 9 patients with rapid-cycling Vol. 17, No. 11 29 Box midday BLT, 2 achieved full response, 2 Bright light therapy: showed early improvement but required a How it works dose increase, and one remained depressed but had a full response when she was he mechanism of action of bright light switched to morning BLT. Ttherapy is yet to be elucidated. The Tseng et al (2016)31 reported a meta- suprachiasmatic nucleus (SCN) in the hypothalamus is the center of circadian analysis of BLT for bipolar depression that BLT for bipolar rhythm regulation and receives direct input included a total of 567 patients from 11 stud- from the retina through the retinohypothalamic ies. They reported significant improvement depression tract.18 Melanopsin, a short-wavelength, light-sensitive G-protein–coupled receptor with BLT alone or in combination with anti- located in human retinal ganglion cells, is depressants or total sleep deprivation. They known to transduce short-wavelength light also reported significant improvement with signals into neural signals.19 Since melanopsin is primarily responsible for resetting the BLT in 130 patients who were not receiving timing of the SCN, suppressing pineal gland other treatments. There was no difference melatonin secretion and improving alertness in the frequency of mood shifts between and electroencephalogram-derived correlates of arousal,20 short-wavelength light with a low patients on BLT alone or in combination Clinical Point light intensity might be a better stimulator with other modalities. The authors reported for melanopsin-containing retinal ganglion no mood shift in any of the patients receiv- BLT can be used cells and the behaviors mediated via this 21,22 ing concurrent mood stabilizers. They also to treat bipolar photoreceptor system. Whether the antidepressant effect of light is also related to reported no difference with the color of 23 depression when its alerting property is unclear. However, the light, gender, or duration of illness. acute alerting and performance-enhancing 32 exposure to sunlight effects of light are increasingly taken into Yorguner et al (2017) conducted a account for the design of indoor light 2-week randomized, single-blind study of is not feasible due 24 standards in office environments. Response BLT as an add-on treatment for 32 patients to geographical to light therapy is thus attributed to its phase- resetting effect. with bipolar depression. Patients were ran- location or season domly assigned to BLT or dim light, which they were administered each morning for 30 mins for 2 weeks. Sixteen patients who BD during a 3-month period. Five patients received BLT showed a significantly greater received the treatment in the morning, reduction in Hamilton Depression Rating 5 around midday, and 3 in the evening. Scale scores (mean score of 24 at baseline
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