Prospect of Bright Light Therapy for MDD in Parkinson Dims

Damian McNamara

March 07, 2019

Bright light therapy (BLT) appears to have little impact in the treatment of major depression for patients with Parkinson disease (PD), new research shows.

The findings from the randomized clinical trial showed that PD patients with major depressive disorder (MDD) responded no better to BLT than to a control light condition. The findings call into question the value of the treatment to improve mood in this population.

"Based on our results, we cannot recommend bright light therapy as a treatment option for depressive disorder in Parkinson disease patients," principal investigator Sonja Rutten, MD, PhD, from Amsterdam UMC and Vrije Universiteit Amsterdam, Department of Psychiatry and Amsterdam Neuroscience, Department of Research and Innovation, told Medscape Medical News.

Although BLT was not found to be superior with regard to MDD, the trial revealed some benefits. "The results of our study do indicate that bright light therapy is effective in improving subjective sleep quality in Parkinson disease patients," she added. "A positive effect of BLT on sleep and excessive daytime sleepiness in Parkinson disease patients has been found in other clinical trials as well.

"We therefore recommend BLT for sleep problems in Parkinson disease patients."

The study was published online February 15 in Neurology.

Depression, Insomnia Common

Nearly 1 in 5 patients with PD also have MDD. Insomnia affects at least 30% of these patients.

Some previous research suggests that BLT has a positive impact on mood. However, to date, there have been no randomized trials to provide class I evidence for an effect of BLT on depression in PD.

For the study, the investigators assessed 389 potential candidates. The final cohort included 83 adults who had been diagnosed with idiopathic PD and who met DMS-IV-TR criteria for MDD. The mean age was 64 years, and 44% were women; 58% of participants had stage 2 PD, as measured by the Hoehn and Yahr scale.

The mean Hamilton Depression Rating Scale (HDRS) score was 14.6, suggesting that most study participants had moderately severe depression at baseline. Some participants withdrew by the end of the first week of the study; the modified intent-to-treat cohort comprised 72 participants.

The trial ran from July 2012 to January 2017.

BLT consisted of 30 minutes each morning and evening of treatment with the Brazil Lightbox (Lumie, Cambridge, United Kingdom). This device emits daylight spectrum light with an intensity of 10,000 lux at a distance of 30 to 40 cm.

Those participants who were randomly assigned to the control group took the device home and fitted it with a neutral density filter (Lee Filters, type 209.03ND, Hampshire, United Kingdom). The filters cut light transmission to 200 lux.

Researchers kept participants in the dark about group assignment.

"Because the appearance of the device or the characteristics of the emitted light might provide our participants with clues about the treatment condition and influence study outcomes, we did not inform our study participants about the exact details of the two light devices and the expected therapeutic effect," they note.

The investigators controlled for seasonal changes of daylight exposure by randomly assigning patients per season. "We also checked whether season was a confounder in our analyses, but this was not the case," Rutten said.

No Between-Group Differences

The researchers controlled for other possible confounders, including age, treatment expectancy, compliance with treatment, dose of dopaminergic medication (converted to the levodopa equivalent daily dose), and use of antidepressants and hypnotic/anxiolytic medications.

Participants maintained a sleep diary and wore a light sensor and actigraphy watch for 7 days following baseline assessments. They also collected saliva samples at home at regular intervals to measure cortisol and melatonin levels.

After a 3-month treatment phase, the investigators monitored participants for an additional 6 months of naturalistic follow-up.

Severity of depression at 3 months was the primary outcome. The total score on the 17-item HDRS decreased in both the intervention and control groups. However, there was no significant between-group difference (B [SE] = −0.58 [1.06]; 95% confidence interval, −2.66 to 1.51; P = .59).

In contrast, 6 months after treatment, the HDRS score was significantly lower in the control group than the intervention group (P = .03). This improvement in depressive symptoms in the control participants was unexpected, Rutten said.

"We had anticipated at least some benefit from the structuring of sleep-wake cycles due to fixed timing of light therapy, but we did not expect such a large effect on depression," she added.

The proportion of patients who achieved clinical remission of the depressive episode at 3 months was 63% in the intervention group and 52% in the control group. This corresponded to an absolute risk reduction of 0.11 and a number needed to treat of 9.

At the end of the follow-up period, 72% of participants in the treatment group had recovered from their depressive episode, compared to 87% of control patients. This translated to an absolute risk reduction of 0.15 and a number needed to treat of 7.

At both time points, the differences were not statistically significant.

Likewise, researchers found no significant between-group differences in the secondary outcome of mean 30-item Geriatric Depression Rating Scale score.

Another Trial Planned

Some similar findings emerged regarding sleep. For example, the Scales for Outcomes in Parkinson's Disease–Sleep total and subscale scores decreased in both groups during the intervention, but there were no significant between-group differences.

Furthermore, the researchers found no significant between-group differences in sleep except for the subjective quality of sleep at 3 months, which intervention participants rated better on the Consensus Sleep Diary measure (P = .04).

The researchers report a few logistic problems with the research. For example, they were unable to perform the Dim Light Melatonin Onset measure as expected because of an error in the salivary melatonin concentration measurement.

In addition, the assay to determine the salivary cortisol concentration had a minimum detection limit of 2.0 pg/mL, and for some of samples, the results were nondetectable.

Rutten and colleagues imputed these measures with a value of 1.9 pg/mL. Also, because the number of evening cortisol concentrations was too low for reliable area under the curve calculations, they calculated the mean evening cortisol concentration using the salivary cortisol concentration at bedtime and 1 and 2 hours before bedtime.

Ocular symptoms, headache, and gastrointestinal complaints were the most common adverse events. In all reports, these events were mild and transient. In the intervention group, 66% experienced adverse effects, compared to 46% of the control group (χ2 = 2.68; df = 1; P = .10).

The lack of significant difference in depression severity between groups at 3 months was unexpected. "We were a bit surprised," said Rutten.

"However, we were pleased to see that there was such a strong reduction of depressive symptoms in both the BLT and control groups," she added. "The response rate in both groups was higher than would be expected from a placebo effect."

The structuring of the sleep-wake cycle due to the scheduled timing of light therapy sessions may be responsible for the antidepressant effects observed in both groups, Rutten said, "but more research is necessary to support this hypothesis."

The investigators are planning another trial.

"Our study results suggest a strong positive effect of sleep-wake structuring on depressive symptoms in Parkinson disease patients with major depressive disorder. We intend to study the effects of sleep-wake structuring in depressed Parkinson disease patients in another randomized clinical trial," Rutten said.

"Encouraging" Effects

This study represents the first clinical trial of BLT as a treatment of depressive symptoms in Parkinson disease, Aleksandar Videnovic, MD, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, and Lambros Messinis, PhD, University Hospital of Patras, University of Patras Medical School, Rio, Greece, note in an accompanying editorial.

"Although the trial did not achieve significant differences between bright light therapy and the control light, it is important to note that both active and control conditions improved depression and sleep," the editorialists write.

"The main challenges of this clinical trial are failure to meet its recruitment goals and failure to collect and analyze circadian markers as originally proposed," they note. Despite this and other limitations, "Rutten and colleagues designed and executed an important clinical trial using a well-tolerated intervention that targeted a large unmet need in Parkinson disease.

"This trial represents an important contribution to a growing body of literature centered on chronotherapeutics of Parkinson disease. While reported effects of light therapy on depressive symptoms in Parkinson disease are encouraging, further studies are needed to better define the role of light therapy in the management of Parkinson disease," Videnovic and Messinis write.

The study was supported by research grants from Hersenstichting Nederland, Stichting Parkinson Fonds, and de Parkinson Vereniging. Rutten and Messinis have disclosed no relevant financial relationships. Videnovic has received research support from the National Institutes of Health; publishing royalties from Springer; and has been a consultant for Acorda, Acadia, Jazz, Pfizer, Theranexus, and Wilson's Therapeutics.

Neurology. Published online February 15, 2019. Abstract, Editorial

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