Light Therapy for Elderly Depression

Major Depressive Disorder Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00332670
• Other study ID #: SOW 014-91-049
• Secondary ID: ZonMw SOW nr 014
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: May 31, 2006
• Last updated: August 12, 2008
• Start date: January 2003
• Est. completion date: June 2007

Study information

• Verified date: August 2008
• Source: GGZ Buitenamstel
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 89
• Est. completion date: June 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Procedure:
• 10.000lux blue 1 hour every day during three weeks
10.000lux during 60 minutes, starting 1 hour after wake-up, during 3 weeks
• 50lux dim red 1 hour every day during three weeks
50 lux red light, 60 minutes every morning, starting 1 hour after wake-up, during three weeks

Locations

Country	Name	City	State
Netherlands	GGZ Buitenamstel	Amsterdam	Noord-Holland

Sponsors (2)

Lead Sponsor	Collaborator
GGZ Buitenamstel	Netherlands Institute for Brain Research, Amsterdam, The Netherlands.

Country where clinical trial is conducted

Netherlands, 

References & Publications (12)

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. — View Citation

Deuschle M, Gotthardt U, Schweiger U, Weber B, Körner 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Kripke DF, Tuunainen A, Endo T. Benefits of light treatment for depression. Am J Psychiatry. 2006 Jan;163(1):162-3; author reply 163. — View Citation

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

Martiny K, Lunde M, Undén 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. — View Citation

Martiny K, Lunde M, Undén 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hamilton Depression Rating Scale (HADRS-17)		at T0, T1 and T2	No
Secondary	Actimetry		continuous measurement during complete 7 week study period	No
Secondary	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).	No
Secondary	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)	No
Secondary	Social Rhythm Metric		complete 7-week study period.	No
Secondary	Groningen Activity Restriction Scale (GARS)		at T0, T1 and T2	No
Secondary	Algemene Competentieverwachtingen Schaal (ALCOS)		at T0, T1 and T2	No
Secondary	Social Support List interactions, discrepancies and negative (SSL-i, SSL-d, SSL-n)		at T0, T1 and T2	No
Secondary	MOS-short form General Health Survey (SF-20)		T0, T1 and T2	No
Secondary	Pittsburgh Sleep Quality Inventory (PSQI)		at T0, T1 and T2	No
Secondary	Neuropsychological test battery		at T0, T1 and T2	No
Secondary	fMRI (encoding task, recognition task, N-Back)		at T0 and T1	No
Secondary	structural MRI scanning (brain and volumetry of adrenals)		at T0 and T1	No
Secondary	MADRS		at T0, T1 and t2	No
Secondary	Adverse effects inventarisation		3-5 times during treatment	Yes