By Ellen Feldman, MD

Altru Health System, Grand Forks, ND

Dr. Feldman reports no financial relationships relevant to this field of study.

EXECUTIVE SUMMARY

This Netherlands-based, randomized controlled study involving 72 patients with Parkinson’s disease (PD) and major depressive disorder (MDD) aimed to see if bright light therapy (BLT) showed efficacy in treatment of depressive symptoms in this population.

Participants were treated with BLT (10,000 lux twice daily) in their homes for three weeks. Follow-up continued for six weeks.

Control group used the same light device as the BLT group but with a filter, thereby reducing light intensity to 200 lux.

The Hamilton Depression Rating Scale (HDRS) decreased in both the control and intervention arms without significant difference, except for a significantly lower score in the control arm at the conclusion of the six-month follow-up period.

Secondary outcome measurements showed a significant improvement in subjective sleep quality in the intervention group at the end of the three-week intervention period (P < 0.001).


SYNOPSIS: Bright light therapy (10,000 lux intensity for 30 minutes twice daily) and a low intensity control light showed similar efficacy in treatment of depression associated with Parkinson’s disease; the bright light therapy showed some advantages in improving subjective quality of sleep.

SOURCE: Rutten S, Vriend C, Smit JH, et al. Bright light therapy for depression in Parkinson disease: A randomized controlled trial. Neurology 2019;92:e1145-e1156.

“Sleep that knits up the ravell’d sleave of care

The death of each day’s life, sore labour’s bath

Balm of hurt minds, great nature’s second course,

Chief nourisher in life’s feast.”

William Shakespeare, Macbeth

Shakespeare did not need medical training to recognize a connection between sleep quality and mood! However, it took several centuries for medical science to catch up with the observations of this 17th century bard. The pivotal work of Kleitman in the 1950s and his discovery of rapid eye movement (REM) sleep sparked renewed interest in the essential role of sleep in health.1 Sleep medicine, a new branch of medicine devoted to the study and treatment of sleep disorders, emerged from Kleitmans work and other related work of the time. With advances in technology, a new understanding of the electrical activity of the brain during wake and sleep cycles propelled investigation of the science behind the link between sleep and mental health disorders.1,2

Over the last 20 years, a growing recognition of a bidirectional relationship (think chicken and egg) between sleep and disorders of mood led to a focus on improving sleep in treatment and prevention of mood disorders.3 Rutten et al designed a randomized controlled trial investigating bright light therapy (BLT) to treat depression in Parkinson’s disease (PD). The researchers noted the high prevalence of both depression (17%) and insomnia (30%) in this population, as well as the significant functional impairment associated with each of these states. The group also noted the likelihood that disruptions in circadian rhythm (known to be associated with PD) may be a key factor in the development of both of these states. The researchers postulated that BLT would be more effective than a control light in treating patients with depression associated with PD. Secondary outcomes in the study included measuring markers of circadian rhythm (including cortisol) and sleep quality.

Previous studies have shown a positive impact of BLT on sleep, mood, and motor improvement in PD, but this is the first known randomized controlled trial to review the effects on depression in PD with the use of BLT.

To be included in this Norwegian study, patients needed to have a diagnosis of idiopathic PD and major depressive disorder (MDD) and be stable on medications used for these conditions. Exclusion criteria revolved around comorbid medical factors that could contraindicate use of BLT (such as photosensitivity from medication and bipolar disorder) or instability of PD or MDD. The study was controlled to account for the impact of seasonal changes on ambient light.

There were significant difficulties recruiting and retaining participants for the study. Out of 389 volunteers over a five-year period (between 2012 and 2017), only 83 met the inclusion criteria. Of those 83 volunteers, 11 withdrew before the end of the first week of the study, resulting in only 72 participants.

After randomizing into two groups, all participants received a light box and were instructed to use it for 30 minutes twice daily at specified times.

Light boxes for the intervention arm emitted daylight spectrum light at 10,000 lux; a filter placed in the boxes for those in the control arm lowered the light intensity to 200 lux. In addition, members of both groups were asked to keep a sleep diary and collect and submit saliva samples periodically during the study.

Severity of depression as measured by the Hamilton Depression Rating Scale (HDRS) and several other measurements of secondary outcomes were assessed at baseline, midway, and at the conclusion of the three-month study. After the study period, patients were encouraged to assume care as usual, and researchers continued to follow up for six months, with assessments at months one, three, and six.

primary outcome measures

Scores on the HDRS are one way to measure and follow the severity or intensity of symptoms of MDD. Individuals with scores under 10 are generally not reporting depressive symptoms; scores between 10 and 13 represent mild distress; scores between 14 and 17 represent mild to moderate distress; and scores above 17 represent moderate to severe distress. In this study, mean HDRS at baseline was 14.5 for the control group and 14.7 for the BLT group.

At the three-month endpoint of the active intervention, both groups showed a decrease in HDRS, to 8.3 for the control group and 7.6 for the BLT group. These values were not significantly different, but both were under the threshold measurement for the diagnosis of MDD.

At the conclusion of the six-month follow-up period, the mean HDRS in the control group had dropped to 5.9, while the mean HDRS in the BLT group remained close to the last measured value at 8.5. This difference was significant with a P = 0.03. (See Table 1.)

Table 1: Results for Depression, Sleep Scales, and Serum Cortisol for Control and Intervention Groups at Baseline, Three Months, and Six Months

 

Baseline

Three-month mark (end of active intervention)

End of six-month naturalistic follow-up (treatment as usual)

Mean HDRS

Control: 14.5

BLT: 14.7

Control: 8.3

BLT: 7.6

P = 0.59

Control: 5.9

BLT: 8.3

P = 0.03

Geriatric Depression Rating Scale

Control: 17.1

BLT: 17.9

Control: 14.9

BLT: 13.7

P = 0.80

Control: 12.3

BLT: 13.2

P = 0.90

Scales for Outcomes
in PD — Sleep

Control: 2.0

BLT: 1.7

Control: 2.1

BLT: 2.2

P < 0.05

Control: 2.2

BLT: 2.0

P = 0.46

Total Cortisol (estimate)

Control: 25

BLT: 23.1

Control: 26.9

BLT: 19.6

P = 0.04

Control: 28.4

BLT: 27.2

P = 0.81

HDRS = Hamilton Depression Rating Scale; PD = Parkinson’s disease; BLT = Bright light therapy

Significant findings are in bold.

SECONDARY OUTCOME MEASURES

Geriatric Depression Rating Scale: There were decreases in both groups without significant difference between the two groups.

Subjective quality of sleep (measured with the Scales for Outcomes in Parkinson’s Disease Sleep): After correcting for confounders at the end of the three-month study period, scores improved in both groups but improved more significantly in the BLT arm (P < 0.05). This difference was no longer significant at the conclusion of the six-month follow-up period.

Circadian rhythm markers: Measurements reflected estimates of total cortisol secretion and of cortisol level on awakening. Cortisol has a complex relationship to sleep and depression; in general, sleep disruption is associated with elevated levels of cortisol, as are some forms of depression.5

Estimated total cortisol levels decreased in the intervention arm and increased in the control arm during the study period, with the BLT group having a significant decrease at the end of the intervention period (P = 0.04). This difference was no longer significant at the end of the six-month follow-up period, with both arms showing an increase in cortisol levels from baseline.

Adverse effects were mild and occurred less in the control group than the intervention group. These included mild nausea, dizziness, and transient photophobia.

COMMENTARY

This Rutten et al randomized controlled trial not only provides Class I evidence that BLT is not more effective than control light in treatment of depression associated with PD, but also gives rise to other thought-provoking results.

It is interesting to consider the results in a different light. Although there was no significant difference, results from both the control and BLT arms showed a reduction in mean HDRS values to non-depressed levels at the end of the three-month intervention period. While the low light intensity of the control group (200 lux) is thought to be too low to impact circadian rhythm, it certainly is possible that the use of the light box itself was helpful in addressing symptoms of depression. Rutten et al note that proper use of the box required a participant to structure their day, and that the schedule imposed at least an outline of a daily routine. A regular sleep and wake time can be helpful in re-establishing circadian rhythms and is an established adjunct tool for treating depression. The group recommends that future work incorporates a control arm without a scheduled time for the light box as well as another arm with scheduled sleep and wake times without use of the box. Such a study will help distinguish the actual active intervention.

It is useful to note that the improvement in HDRS scales occurred in both arms, but the sleep quality measures were significantly improved in the BLT arm only. It makes sense that this improvement in sleep is linked with the decrease in cortisol levels seen in the BLT arm as well. However, it does give rise to question how the control arm patients noted a decrease in depressive symptoms without an improvement in sleep and if depressive disorder linked to PD is unique in this regard. Again, this clearly is an area for future investigation.

Finally, it is notable that at the six-month follow-up point, the HDRS scores in the control group were significantly lower than the comparable scores for the intervention group. As there was no control in place regarding treatment during the six-month period, it is difficult to know how to interpret this finding.

Again, future studies with long-term follow-up and active intervention during a longer period could be very useful.

It is important to keep in mind that the mean HDRS of patients in both groups at baseline indicated a mild to moderate severity of depression. Therefore, findings from this study cannot be generalized to those with more severe depressive disorder.

Given that this is a Norwegian study, it is worth considering that geographic factors (long winters with short daylight hours) affected results. Replication of this work in diverse locations and latitudes will help clarify this possibility.

Obtaining a light box may be a challenge for some patients. Guidelines can be found online and many online vendors have a range of devices with prices well under the $100 mark.7 There may be some insurances that will reimburse for the boxes with a prescription indicating that 10,000 lux is to be used up to 40 minutes daily.

What is the take-home message from this study? It appears that in patients with PD who have mild to moderate MDD, use of any intensity light in the morning and evening may be associated with lowering depressive symptom intensity. Additionally, use of BLT at 10,000 lux for 30 minutes, twice daily may have the added advantage of improving subjective quality of sleep. With a relatively low cost and few adverse effects, the risk of recommending such a treatment is quite low and seems well worth the potential benefit.

The results remind providers to be attentive to the role that depression and insomnia play in functional impairment in PD, and to consider the potential for functional improvement by addressing the symptoms of these states.

REFERENCES

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  3. Zhao X, Ma J, Wu S, et al. Light therapy for older patients with non-seasonal depression: A systematic review and meta-analysis. J Affect Disord 2018;232:291-299.
  4. Hamilton M. Development of a rating scale; for primary depressive illness. Br J Soc Clin Psychol 1967;6:278-296. Available at: http://www.npcrc.org/files/news/hamilton_depression_scale.pdf. Accessed Sept. 22, 2019.
  5. Li S, Wang Y, Wang F, et al. A new perspective for Parkinson’s disease: Circadian rhythm. Neurosci Bull 2017;33:62-72.
  6. Dienes KA, Hazel NA, Hammen CL. Cortisol secretion in depressed, and at-risk adults. Psychoneuroendocrinology 2013;38:927-940.
  7. Mayo Clinic Staff. Seasonal affective disorder treatment: Choosing a light therapy box. Mar. 16, 2016. Available at: https://www.mayoclinic.org/diseases-conditions/seasonal-affective-disorder/in-depth/seasonal-affective-disorder-treatment/art-20048298. Accessed Oct. 10, 2019.