bright light therapy for regular depression

 

a recent meta-analysis found that using bright light therapy (BLT) as an adjunctive therapy is associated with decreased depression symptoms even in individuals without seasonal affective disorder (see depression bright light in nonseasonal JAMApsych2025 in dropbox, or doi:10.1001/jamapsychiatry.2024.2871). thanks to Talya Salant for bringing this to my attention.

 

Details:

--11 unique randomized controlled trials were found from 2000-2024 with 858 patients assessing the effect on depression response with vs without added BLT

    -- 7 of these studies were in patients with major depressive disorder: one study of patients with severe MDD, most others had patients with moderate or severe depression; 3 had patients with bipolar disorder, and 1 had both

    -- intervention group: 9 studies exposed the intervention group to 10,000 lux bright light therapy (BLT) for 30-60 minutes, one study used 7000 lux, and 1 study 2000 lux

    -- control group: most studies had controls using other light sources (8 studies with red lights of various intensities, 2 with negative ion generators as sham BLT, one with antidepressant med)

    -- 426 patients received BLT and 389 were in the control groups

-- 75.6% female (649 patients). No comment on other demographic/medical/psychosocial issues (which undoubtedly varied from study to study)

-- Depression scales used:

    -- HAM-D (Hamilton Rating Scale for Depression)

    -- MADRS (Montgomery-Asberg Depression Rating Scale)

    -- CGI (Clinical Global Impressions Scale)

-- risk of bias in the studies was assessed using the Cochrane Risk of Bias tool

 

Main outcomes: full remission of symptoms, and response to treatment but not full remission of symptoms

Secondary outcomes: comparison of scales used to assess depression

 

Results:

-- remission rate for depression:

    -- BLT group: 40.7%

    -- control group: 23.5%

​ -- odds ratio [OR] 2.42 (1.50-3.91); P <.001

-- response rate for depression:

    -- BLT group: 60.4%

    -- control group: 38.6%

        -- OR 2.34 (1.46-3.75); P <.001

 

 Forest plot revealing that there was considerable consistency of results from the individual studies

 

-- subgroup analyses, by follow-up times:

        -- remission rate for depression, <4 weeks:

           -- BLT group: 27.4%

           -- control group: 9.2%

               -- OR 3.59 (1.45-8.88); P =0.005

        -- response rate for depression, <4 weeks:

           -- BLT group: 55.6%

           -- control group: 27.4%

               -- OR 3.65 (1.81-7.33); P<0.001

 

        -- remission rate for depression, >4 weeks:

           -- BLT group: 46.6%

           -- control group: 29.1%

               -- OR 2.18 (1.19-4.00); P=0.01

      -- response rate for depression, >4 weeks:

           -- BLT group: 63.0%

           -- control group: 44.9%

               -- OR 1.79 (1.01-3.17); P=0.04

 

-- BLT-associated reduction of depression, by the depression assessment scales:

    -- HAM-D: mean difference (MD): -1.44 (-2.40 to -0.48), p=0.003

    -- MADRS: MD 0.36 (-2.60 to 3.31), p=0.81, not statistically significant

    -- CGI: MD -0.06 (-0.29 to 0.16), P=0.56, not statistically significant

-- Meta-regression analysis (assessing how the study design affected the results of  the study, to make sure that the overall analysis is reasonable despite the methodological diversity of the included studies):

    -- age of onset of MDD and remission rate: p=0.06, suggesting the possibility of a true link between the covariate (characteristics of the patients) and the outcome

    -- age of onset and response rate: not statistically significant

    -- duration of MDD and remission rate: not statistically significant

    -- duration of MDD and response rate: not statistically significant

-- quality assessment: all of the included RCTs were felt to be of low risk of bias, as well as low probability of publication bias affecting the overall remission and response rates

Commentary:

-- per the World Health Organization, about 5% of the global adult population suffers from depression (4% of men and 6% of women), and 5.7% of those >60yo; >700K people depressed people die from suicide annually, with suicide being the 4^th leading cause of death in 15-29yo people; and overall depression is a leading cause of functional disability: https://www.who.int/news-room/fact-sheets/detail/depression

-- general response rates with initial treatment of depression is about 50%, with many people needing modifications of treatment after 4-8 weeks

  

-- the results of this study were impressively positive regarding BLT's role as adjunctive therapy for depression. Prior meta-analyses were inconclusive, likely from the older studies having had small sample sizes (the current study had 3 times the prior sample size) and limited statistical analyses

    -- ie, BLT seems to have a huge benefit as add-on therapy

    -- and it seemed that the HAM-D depression scale was the one changing significantly with BLT. this scale includes patient-reported scales of depressed mood, feelings of guild, feeling suicidal, insomnia at different times of the evening, effects on work and activities, slowness of thought and speech as well as ability to concentrate and psychomotor retardation, agitation, anxiety, somatic GI symptoms, general somatic symptoms, low libido and menstrual abnormalities, hypochondriasis, low weight, and insight into being depressed.

 

-- other studies have found other benefits of BLT, many presumably related to shifts in circadian rhythm and alterations in serotonin uptake:

    -- a study that included information on other conditions benefiting by BLT besides those with seasonal affective disorder (SAD), specifically non-seasonal unipolar major depression (including antepartum depression, depression in adolescents), bipolar depression, eating disorders, and ADHD: https://pmc.ncbi.nlm.nih.gov/articles/PMC6746555/

        -- studies have suggested that the effect of BLT on mood disorders were evident within 1 week: https://pmc.ncbi.nlm.nih.gov/articles/PMC6405415/

    -- a study of BLT as an adjunctive therapy in patients with bipolar disease on appropriate medical therapy, finding that adding BLT vs control arm with dim red light therapy found a pretty dramatic response rate of 78.19% vs 43.33% after a median onset of 4.33 days, and no episodes of hypomania or adverse effects of BLT: see bipolar dz bright light therapy JAffectDisord2018 in dropbox, or http://dx.doi.org/10.1016/j.jad.2017.09.038

    -- a study on cognitive function finding modest benefit in improving some cognitive symptoms of dementia

        -- eg, in elderly patients with dementia who are often deprived of much sunlight, bright lights improved daytime activity (https://pubmed.ncbi.nlm.nih.gov/9110101/), with some studies suggesting mild improvement in cognitive function. Another study in hematopoietic stem cell transplant survivors documented improved cognition with BLT: https://pmc.ncbi.nlm.nih.gov/articles/PMC9645769

        -- a systematic review of patients with sleep problems found improvement in circadian rhythm sleep disorders, insomnia, and sleep problems related to Alzheimer’s: https://pubmed.ncbi.nlm.nih.gov/26606319/

    -- a randomized controlled study in patients with insomnia, excessive daytime sleepiness, and other sleep disorders in people with Parkinson's disease found that BLT was associated with small but significant improvement: https://pubmed.ncbi.nlm.nih.gov/34052783/

    -- a study found that BLT had a consistent and significant anxiolytic effect in low anxiety individuals https://bmcpsychiatry.biomedcentral.com/articles/10.1186/1471-244X-7-62

    -- another study found that correcting delayed circadian phase by BLT led to improvement in ADHD symptoms: https://pmc.ncbi.nlm.nih.gov/articles/PMC7959333/

    -- ‎and, as a sort of interesting aside, BLT improves the jet lag syndrome better than zolpidem, with rapidly regularizing circadian TSH secretion (https://pubmed.ncbi.nlm.nih.gov/8784082/)

-- when to use BLT: the SAD studies generally preferred using BLT in the early morning for 30-60 minutes, as a means to simulate normal exposure to bright light in the summer. For circadian rhythm, use in the AM to simulate the summer and reset the circadian rhythm and make sleep easier at night; use in the PM to reset the sleep time to later in the night

-- potential mechanisms of the BLT benefit on mood and cognitive function include stimulation of retinal ganglion cells, which connect with areas of the brain involved in mood regulation (eg amygdala, suprachiasmatic nucleus, and dorsal raphe nucleus)

    -- BLT suppresses melatonin secretion from the pineal gland, thereby resetting the sleep-wake rhythm in those with insufficient morning light exposure

    -- the effects of BLT on depression happen quickly, within 1 week (https://pmc.ncbi.nlm.nih.gov/articles/PMC6405415/), much faster than meds.

-- many of the symptoms of sleep deprivation overlap the clinical presentation of depression, reflecting that both sleep deprivation and depression are associated with abnormal sleep patterns (and many of us in medical training can attest to the effect of sleep deprivation in altering one's mood, and this gets better pretty quickly with normal sleep...). In this light (so to speak), it would be useful to have a trial of just BLT vs antidepressant meds and/or psychological intervention in patients with depressive symptoms. or perhaps first trying BLT and adding meds if inadequate response (easy to do since in only takes a week to see if BLT works, at least in the above studies using BLT as an add-on therapy). these studies would help differentiate just lack of restful sleep from major depressive disorder, the latter might well need medical/behavioral health therapies. But this should be studied

-- Adverse effects of BLT: only occasional, and almost all mild problems of jitteriness (8.8%), headache (8.4%), nausea (15.9%), though the benefits for seasonal affective disorder outweigh the risks when using 10,000 lux 30 minutes daily in the morning for 10-14 days (https://pubmed.ncbi.nlm.nih.gov/10584776/ ). In non-depressed individuals, the adverse effects were not increased by a single exposure to 10,000 lux bright lights https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0075893 .

Limitations:

 -- as per usual with meta-analyses, this study is aggregating 11 different individual studies, all with different inclusion criteria, exclusion criteria, baseline age/demographics/medical problems/social problems/other medications: all of this may limit the accuracy and generalizability of the results

-- the researchers above did not include the baseline antidepressant medications (or dosages) used in the patients, nor the specifics of their response to the pre-trial meds or other interventions, the amount of time it took for the BLT intervention to work (it was notable that for bipolar disease it was only 4 days, and other studies suggest response within one week)

-- per the study design, the studies in patients on meds included those on antidepressant monotherapy and not adding other antidepressants into the therapeutic mix (which is often what we do in clinical practice to improve the clinical response). however, there are advantages to using BLT as the add-on therapy since it is so cheap, nontoxic, and effective and may not lead to the adverse effects of added medications

so,

-- the advantage of BLT as an adjunct to treatment for major depressive disorders include the fact that it is cheap, easily available, and hasminimal adverse effects

-- perhaps we should be suggesting BLT more widely: especially in the elderly, who typically have altered sleep patterns (https://pmc.ncbi.nlm.nih.gov/articles/PMC5841578/) and less restful sleeps (more naps), BLT really seems to improve sleep and decrease fatigue quite often. maybe worth a try??

-- similar to vitamin D (which has myriad effects throughout the body, including on the immune system, through sunlight exposure), this issue of not having enough bright sunlight brings up yet again whether prehistoric hominids should ever have left the bright, warm fertile crescent...

geoff

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