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Home , Light therapy

Bright for bipolar

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, , 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 disruption in Chief of Behavioral Indianapolis, Indiana Clinical manifestation. Patients with bipolar disorder (BD) Health Services Director of Interventional spend more time in depression than in .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 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 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 . 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 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 , 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 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 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 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 Patients who received BLT at midday had down to 12) compared with 16 patients the best outcome, while 3 of the 5 patients who received dim light (mean score of 24 who received morning BLT developed at baseline down to 18). The authors also unstable mood. The authors recommended reported remission in 4 out of 4 patients titrating the duration of light exposure so who had seasonal depression, compared that patients could skip a treatment if their with 3 out of 12 who did not have seasonal mood was trending toward hypomania. depression (the other 9 showed response Sit et al (2007)30 evaluated BLT in a case but not remission). series of 9 women with bipolar I or II disor- Zhou et al (2018)33 conducted a multi- der in the depression phase. Patients were center, randomized, single-blind clinical exposed to 50 lux of red light for 2 weeks, trial of 63 patients with bipolar depression. and then they received 7,000 lux BLT for Thirty-three patients received morning 15, 30, and 45 minutes daily for 2 weeks BLT, and 30 received dim red light therapy (4 patients received morning light and 5 (control group). The authors reported a received midday light). Mood was assessed significantly higher response rate in the using the Structured Interview Guide for BLT group (78%) compared with the con- the Hamilton Depression Rating Scale trol group (43%). with Supplement and Sit et al (2018)34 conducted a 6-week ran- the Mania Rating Scale. Of the 4 patients domized, double-blind, -controlled receiving morning BLT, one patient had trial of BLT vs dim red light in patients a full response and the other 3 developed with bipolar I or II depression. Twenty- Current Psychiatry 30 November 2018 hypomania. Of the 5 patients who received three patients were administered 7,000 lux bright white light, and 23 patients received 50 lux dim red light, at midday 5 days a Related Resource week. The light dose was increased by 15 • Mostert M, Dubovsky S. When bipolar treatment fails: what’s your next step? Current Psychiatry. 2008;7(1): MDedge.com/psychiatry minutes every week up to 60 minutes by 39-46. Week 4, unless the patient achieved remis- Drug Brand Name sion. Patients were maintained on their Lithium • Eskalith, Lithobid usual medications, which included mood stabilizers and/or . At Week 6, the group randomized to BLT had a significantly higher remission rate (68%) compared with patients who received dim Selecting a dose. The dose received is deter- red light (22%). Improvement was noted by mined by the intensity emitted from the Week 4. Patients receiving BLT also had sig- light source, distance from the light box, and nificantly fewer depressive symptoms, and duration of exposure.36 Begin with midday no mood polarity switch was noted. light therapy between 12 noon and 2 pm at a daily dose of 15 minutes, and increase by 15 minutes every 2 weeks until the patient Clinical Point 34 Prescribing bright light therapy has achieved a euthymic mood. Patients Use of BLT around Light box selection criteria. When select- need not stare directly into the light source ing a light box or related BLT treatment as long as the light is able to meet the eye noon is preferred for apparatus, the Center for Environmental at an angle of 30° to 60°.35 The upper limit patients with bipolar Therapeutics recommends consideration of of midday light is 45 to 60 minutes, beyond depression the following factors35: which patients are more likely to have diffi- • clinical efficacy culty with adherence. Because morning BLT • ocular and dermatologic safety also may be effective, consider a change to • visual comfort. morning light at a starting dose of 15 min- The intensity of the light hitting the cor- utes for patients who respond partially or nea depends on the distance from the light. minimally to 45 to 60 mins of midday light, In our experience, when the patient is facing then increase it every week by an additional the box it should provide 10,000 lux when 7 to 15 mins.35 For patients who respond to he or she is 1 foot away at approximately a BLT, it is reasonable to continue light ther- 45° angle (1 lux = 1 lumen per square meter). apy for 12 months after remission to prevent The light box selected should emit full spec- relapses, similar to the recommendations for trum white light with UV filter. The newest antidepressant therapy.34 filters use LED, which is less expensive and more durable. Typically, we’ve found that Monitor for adverse effects. Generally, it is most convenient for patients to use the BLT is well tolerated.37 Adverse effects are light box in the morning before 9 am, but rare; the most common ones include head- around noon is preferred for patients with ache, eyestrain, , and agitation.38 One BD. If using a light box is not feasible, we study found no adverse ocular effects from suggest the use of dawn light by the bed- light therapy after 5 years of treatment.39 side before waking in the morning. Again, it Adverse effects tend to remit spontaneously is preferable to get some sunshine outdoors or after dose reduction.35 Evening adminis- while taking a walk as long as geographical tration of BLT may increase the incidence location and weather conditions permit. of sleep disturbances.40 Like other biologic

Bottom Line Evidence suggests that bright light therapy is an effective, well tolerated, and affordable adjunct treatment for bipolar depression. Exposure to 5,000 to 7,000 lux Current Psychiatry around noon for 15 to 60 minutes will enhance the remission rate. Vol. 17, No. 11 31 treatments for bipolar depression, BLT can 19. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science. precipitate manic/hypomanic and mixed 2002;295(5557):1070-1073. states in susceptible patients, although the 20. Peirson S, Foster RG. Melanopsin: another way of signaling light. Neuron. 2006;49(3):331-339. light dose can be titrated against emergent 21. Anderson JL, Glod CA, Dai J, et al. Lux vs. wavelength symptoms of hypomania.41 in light treatment of seasonal affective disorder. Acta Psychiatr Scand. 2009;120(3):203-212. 22. Wirz-Justice A, Graw P, Kräuchi K, et al. Effect of Acknowledgements light on unmasked circadian rhythms in winter depression. 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