Light Therapy for Elderly Depression

Condition(s) targeted: Major Depressive Disorder

Intervention: 10.000lux blue 1 hour every day during three weeks (Procedure); 50lux dim red 1 hour every day during three weeks (Procedure)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: GGZ Buitenamstel

Official(s) and/or principal investigator(s):
Witte JG Hoogendijk, prof. dr., Study Director, 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
Eus van Someren, PhD, Study Chair, Affiliation: Netherlands Institute for Brain Research, Amsterdam, The Netherlands; VU University Medical Center, Amsterdam, The Netherlands
Marjan MA Nielen, PhD, 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
Ritsaert Lieverse, MD, Principal Investigator, 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

Overall contact:
Ritsaert Lieverse, MD, Phone: +31 20 7885507, Email: Ritsaerl@ggzba.nl

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.

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 design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome:

Montgomery-Asberg Depression Rating Scale (MADRS) at T0, T1 and at T2

29-item Structured Interview Guide for the Hamilton Depression Rating Scale, SAD version (SIGH-SAD) at T0, T1 and T2.

Secondary outcome:

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 at 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 during 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)at T0, T1 and T2.

Pittsburgh Sleep Quality Inventory (PSQI)at T0, T1 and T2.

Neuropsychological test battery at T0, T1 and T2.

fMRI at T0 and T1 (encoding task, recognition task, N-Back)

structural MRI scanning at T0 and T1 (brain and volumetry of adrenals)

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.

Minimum age: 60 Years. Maximum age: N/A. Gender(s): Both.

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.

Ritsaert Lieverse, MD, Phone: +31 20 7885507, Email: Ritsaerl@ggzba.nl

GGZ Buitenamstel, Amsterdam, Noord-Holland 1081HL, Netherlands; Recruiting
Ritsaert Lieverse, MD, Principal Investigator

Related publications:

Hoogendijk WJ, van Someren EJ, Mirmiran M, Hofman MA, Lucassen PJ, Zhou JN, Swaab DF. Circadian rhythm-related behavioral disturbances and structural hypothalamic changes in Alzheimer's disease. Int Psychogeriatr. 1996;8 Suppl 3:245-52; discussion 269-72. No abstract available.

Beekman AT, Penninx BW, Deeg DJ, Ormel J, Braam AW, van Tilburg W. Depression and physical health in later life: results from the Longitudinal Aging Study Amsterdam (LASA). J Affect Disord. 1997 Dec;46(3):219-31.

Deuschle M, Gotthardt U, Schweiger U, Weber B, Korner A, Schmider J, Standhardt H, Lammers CH, Heuser I. With aging in humans the activity of the hypothalamus-pituitary-adrenal system increases and its diurnal amplitude flattens. Life Sci. 1997;61(22):2239-46.

Kripke DF, Tuunainen A, Endo T. Benefits of light treatment for depression. Am J Psychiatry. 2006 Jan;163(1):162-3; author reply 163. No abstract available.

Kripke DF. Light treatment for nonseasonal depression: speed, efficacy, and combined treatment. J Affect Disord. 1998 May;49(2):109-17.

Golden RN, Gaynes BN, Ekstrom RD, Hamer RM, Jacobsen FM, Suppes T, Wisner KL, Nemeroff CB. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry. 2005 Apr;162(4):656-62.

Wirz-Justice A, Terman M, Oren DA, Goodwin FK, Kripke DF, Whybrow PC, Wisner KL, Wu JC, Lam RW, Berger M, Danilenko KV, Kasper S, Smeraldi E, Takahashi K, Thompson C, van den Hoofdakker RH. Brightening depression. Science. 2004 Jan 23;303(5657):467-9. No abstract available.

Wirz-Justice A, Benedetti F, Berger M, Lam RW, Martiny K, Terman M, Wu JC. Chronotherapeutics (light and wake therapy) in affective disorders. Psychol Med. 2005 Jul;35(7):939-44.

Martiny K, Lunde M, Unden M, Dam H, Bech P. Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales. Acta Psychiatr Scand. 2005 Aug;112(2):117-25.

Martiny K, Lunde M, Unden M, Dam H, Bech P. Adjunctive bright light in non-seasonal major depression: results from patient-reported symptom and well-being scales. Acta Psychiatr Scand. 2005 Jun;111(6):453-9.

Gordijn MC, Beersma DG, Korte HJ, Van den Hoofdakker RH. Testing the hypothesis of a circadian phase disturbance underlying depressive mood in nonseasonal depression. J Biol Rhythms. 1998 Apr;13(2):132-47.

Zhou JN, Riemersma RF, Unmehopa UA, Hoogendijk WJ, van Heerikhuize JJ, Hofman MA, Swaab DF. Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in depression. Arch Gen Psychiatry. 2001 Jul;58(7):655-62.

Starting date: January 2003
Last updated: May 31, 2006