Light Therapy for Elderly Depression

Study Overview
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Brief Summary
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The purpose of this study is to investigate the following two hypotheses: Treatment with bright light improves their sleep, mood, concentration and self-sufficiency of elderly depressed subjects. This clinical improvement is accompanied by decreases in cortisol/DHEA ratio and increases in melatonin concentration in urine and saliva. The eventual beneficial effect of bright light treatment can be predicted by the presence of sleep-wake rhythm disturbances as found using muscle activity registration, and by cortisol/DHEA and melatonin concentrations in saliva and urine over the day and the night.

Detailed Description
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Background: Depression frequently occurs in the elderly. In normal aging, and in depression, the functioning of the suprachiasmatic nucleus (SCN) is impaired, as evidenced by an increased prevalence of day-night rhythm perturbations, e.g. sleeping disorders. Also, the normal inhibition of SCN neurons on corticotrophin-releasing hormone (CRH) producing cells is decreased, which could be responsible for the hyperactive hypothalamus-pituitary adrenocortical axis (HPA-axis). This raises the question whether elderly patients with depression have more impaired SCN activity and whether HPA-activity is enhanced. Using bright light therapy (BLT) the SCN can be stimulated. And, the beneficial effects of BLT on seasonal depressive disorders are well accepted. Nevertheless, the effects of BLT in aged depressed patients have never been studied, as yet. Aims: The aim of this study is to test the hypothesis that BLT improves sleep, mood, concentration and self-efficacy of older people with depression and this improvement is accompanied by a normalization of HPA-indices. Methods: Randomised double blind placebo controlled trial in 120 subjects of 60 years and older with a diagnosis of major depressive disorder (DSM-IV/SCID-I). Subjects are recruited through referrals of psychiatric outpatient clinics and from case-finding from databases of general practitioners and old-people homes in the Amsterdam region. After inclusion subjects are randomly allocated to bright blue light vs. dim red light groups using two Philips Bright Light Energy boxes type HF 3304 per subject from which the light bulbs have been covered with bright blue or dim red light permitting filters. Criteria for stratification are the use of SSRIs. Prior to treatment a 1-week run-in period without treatment will be used as a baseline condition. At three time points several endocrinological, psychophysiological, psychometrically, neuropsychological, and neuroimaging measures are performed: just before start of light therapy (T0), after completion of the three week light therapy period (T1), and three weeks thereafter (T2). Relevance: This study is designed to show whether light therapy can reduce depressive symptoms of elderly patients with a major depressive disorder. If this is the case, then additional lightning may easily be installed in the homes of patients to serve as a maintenance treatment. Also, if our data support the role of a dysfunctional biological clock in depressed elderly subjects, such a finding may guide the further development of drugs that inhibit the HPA axis.

Official Title
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High Cortisol Levels as a Risk Factor for Depression in the Elderly and the Effect of Bright Light Treatment on Mood, Sleep-Wake Pattern and Self-Sufficiency

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Procedure: 10.000lux blue 1 hour every day during three weeks
* Procedure: 50lux dim red 1 hour every day during three weeks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understanding and speaking Dutch language 60 years of age or older Presence of a Major Depressive Disorder according to DSM-IV (SCID-based) When under treatment of an ophthalmologist, his / her approval for participation. Exclusion Criteria: Progressive eye diseases, glaucoma or cataract for which an operation is scheduled in near future, aphakia, retinopathies like maculopathy, retinitis pigmentosa or ablatio retina. Physical problems or disorders which require specific medical treatment like Lupus, untreated diabetes, malignancies, organic brain disorders, chronic infections, thyroid disorders not adequately treated, thyroid associated ophthalmopathies, M. Parkinson. Presence of any concurrent substance abuse problem Presence of other actual axis-I disorders like bipolar disorder, dementias, delirium, all psychotic disorders, Posttraumatic stress disorder. Use of tricyclic antidepressants, MAOIs. Use of corticosteroids. Use of tetracyclic antibiotics. Treatment with antidepressants shorter than 2 months Use of oral contraceptives. Treatment with light therapy in the past.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>10.000lux bright blue light 1hour every morning 1 hour after wake-up time during three weeks | Procedure: 10.000lux blue 1 hour every day during three weeks<br>* 10.000lux during 60 minutes, starting 1 hour after wake-up, during 3 weeks<br>* Other names: Bright light;|
| Placebo Comparator: 2<br>50lux dim red light 1 hour every morning 1 hr after wake-up time during 3 weeks | Procedure: 50lux dim red 1 hour every day during three weeks<br>* 50 lux red light, 60 minutes every morning, starting 1 hour after wake-up, during three weeks<br>* Other names: Dim red light;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale (HADRS-17) |  | at T0, T1 and T2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actimetry |  | continuous measurement during complete 7 week study period | 
| 24-hour urinary cortisol measurements |  | at T0, T1 and T2 (saliva melatonin evening curve (bedtime minus 4 hours, minus 3 hours, minus 2 hours, minus 1 hour). | 
| saliva cortisol daytime curve |  | T0, T1 and t2 (get-up time plus 30 minutes, plus 60 minutes, plus 90 minutes, plus 120 minutes,bedtime minus 4 hours, minus 3 hours, minus 2 hours, minus 1 hour) | 
| Social Rhythm Metric |  | complete 7-week study period. | 
| Groningen Activity Restriction Scale (GARS) |  | at T0, T1 and T2 | 
| Algemene Competentieverwachtingen Schaal (ALCOS) |  | at T0, T1 and T2 | 
| Social Support List interactions, discrepancies and negative (SSL-i, SSL-d, SSL-n) |  | at T0, T1 and T2 | 
| MOS-short form General Health Survey (SF-20) |  | T0, T1 and T2 | 
| Pittsburgh Sleep Quality Inventory (PSQI) |  | at T0, T1 and T2 | 
| Neuropsychological test battery |  | at T0, T1 and T2 | 
| fMRI (encoding task, recognition task, N-Back) |  | at T0 and T1 | 
| structural MRI scanning (brain and volumetry of adrenals) |  | at T0 and T1 | 
| MADRS |  | at T0, T1 and t2 | 
| Adverse effects inventarisation |  | 3-5 times during treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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(Non-seasonal) Depression, bright light therapy, randomized controlled trial, suprachiasmatic nucleus, HPA-axis, DHEA, melatonin, actigraphy, elderly, self-efficacy, social support