Clinical trial NCT00332670: Light Therapy for Elderly Depression
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Major Depressive Disorder
Keywords: (Non-seasonal) Depression
bright light therapy
randomized controlled trial
suprachiasmatic nucleus
HPA-axis
DHEA
melatonin
actigraphy
elderly
self-efficacy
social support
Lead sponsor: GGZ Buitenamstel
Sponsor class: OTHER
Collaborators: name: Netherlands Institute for Brain Research, Amsterdam, The Netherlands.
First posted: 2006-06-02
Enrollment: 89
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the following two hypotheses:

1. 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.
2. 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hamilton Depression Rating Scale (HADRS-17)
timeFrame: at T0, T1 and T2
Secondary outcomes:
measure: Actimetry
timeFrame: continuous measurement during complete 7 week study period
measure: 24-hour urinary cortisol measurements
timeFrame: at T0, T1 and T2 (saliva melatonin evening curve (bedtime minus 4 hours, minus 3 hours, minus 2 hours, minus 1 hour).
measure: saliva cortisol daytime curve
timeFrame: 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)
measure: Social Rhythm Metric
timeFrame: complete 7-week study period.
measure: Groningen Activity Restriction Scale (GARS)
timeFrame: at T0, T1 and T2
measure: Algemene Competentieverwachtingen Schaal (ALCOS)
timeFrame: at T0, T1 and T2
measure: Social Support List interactions, discrepancies and negative (SSL-i, SSL-d, SSL-n)
timeFrame: at T0, T1 and T2
measure: MOS-short form General Health Survey (SF-20)
timeFrame: T0, T1 and T2
measure: Pittsburgh Sleep Quality Inventory (PSQI)
timeFrame: at T0, T1 and T2
measure: Neuropsychological test battery
timeFrame: at T0, T1 and T2
measure: fMRI (encoding task, recognition task, N-Back)
timeFrame: at T0 and T1
measure: structural MRI scanning (brain and volumetry of adrenals)
timeFrame: at T0 and T1
measure: MADRS
timeFrame: at T0, T1 and t2
measure: Adverse effects inventarisation
timeFrame: 3-5 times during treatment
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: GGZ Buitenamstel
state: Noord-Holland
Study officials:
affiliation: Center for Neurogenomics and Cognitive Research, Free University, Amsterdam, the Netherlands; Department of Psychiatry VU University Medical Center, Amsterdam, The Netherlands; GGZ Buitenamstel, Amsterdam, The Netherlands
name: Witte JG Hoogendijk, prof. dr.
role: STUDY_DIRECTOR
affiliation: Netherlands Institute for Brain Research, Amsterdam, The Netherlands; VU University Medical Center, Amsterdam, The Netherlands
name: Eus van Someren, PhD
role: STUDY_CHAIR
affiliation: Center for Neurogenomics and Cognitive Research, Free University, Amsterdam, the Netherlands; Department of Psychiatry VU University Medical Center, Amsterdam, The Netherlands; GGZ Buitenamstel, Amsterdam, The Netherlands
name: Marjan MA Nielen, PhD
role: STUDY_CHAIR
affiliation: Center for Neurogenomics and Cognitive Research, Free University, Amsterdam, the Netherlands; Department of Psychiatry VU University Medical Center, Amsterdam, The Netherlands; GGZ Buitenamstel, Amsterdam, The Netherlands
name: Ritsaert Lieverse, MD
role: PRINCIPAL_INVESTIGATOR
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citation: Lieverse R, Van Someren EJ, Nielen MM, Uitdehaag BM, Smit JH, Hoogendijk WJ. Bright light treatment in elderly patients with nonseasonal major depressive disorder: a randomized placebo-controlled trial. Arch Gen Psychiatry. 2011 Jan;68(1):61-70. doi: 10.1001/archgenpsychiatry.2010.183.
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