Doubled risk of Depression in Diabetes Prevalence: 10-20%

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Asher Wheeler
5 years ago
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Brouwer, PhD-student Marijke Bremmer, Psychiatrist Frank Snoek, Medical Psychologist

1 Bright Light Treatment for better Mood and Metabolic control: a Randomised Controlled Trial in patients with Type-2- Diabetes and Major Depressive Disorder Project group: Annelies Brouwer, PhD-student Marijke Bremmer, Psychiatrist Frank Snoek, Medical Psychologist Aartjan Beekman, Psychiatrist Annette Moll, Ophthalmologist Eus van Someren, Biologist, neurophycisist

2 Doubled risk of Depression in Diabetes Prevalence: 10-20%

3 Depression predicts Diabetes complications de Groot et al Psychosom Med 2001; 63:

4 Depression predicts Mortality in Women with DM Pan, A. et al. Arch Gen Psychiatry 2011;68:42-50.

5 Health Behaviour -- Non-compliance Somatic factors -- Sleep -- Cortisol -- Inflammation -- Obesity

6 Treating depression in Diabetes Co-morbid depression is more persistent and treatment resistant (Fisher,2008; Peyrot, 1999) Metabolic side effects of SSRIs (Harvey, 2000) Patients preference Medical outcome

7 Lustman 1998 Huang 2002 Simson 2008 Lu 2005 Li 2003 Echeverry 2009 Paile-Hyvarinen 2007 Lustman 1997 Xue 2004 Paile-Hyvarinen 2003 Treating depression: effectsize CBT Drugs Lustman 2000 Williams 2004 Ell 2009 Katon 2004 Collaborative Overall van der Feltz-Cornelis et al Genl Hosp Psychiatr 2010 Overall Effect Size:

8 Effect on glycaemic control: small Lustman 1998 Huang 2002 Li 2003 CBT Xue 2004, Par Lu 2005 Lustman 2000, Flu Paile-Hyvarinen 2003, Par Drugs Paile-Hyvarinen 2007 Par Echeverry 2009 Ser Williams 2004 Katon 2004 Ell 2009 Collaborative Overall Overall Effect Size: van der Feltz-Cornelis et al Gen Hosp Psychiatr

9 Integrated / Tailormade treatment aim: to improve both psychiatric and medical outcomes Collaborative care approach (Katon, 2012; Johnson, BMC,2012) Internet therapies E-health (van Bastelaar, 2011, 2012) Neurobiological approach

10 The many ( ) faces of depression

11 The many ( ) faces of depression DSM-IV waste-bin

12 One-size fits all? 6.8 million prescriptions a year (2008) Anti-depressant use in the Netherlands

13 Insomnia, hypersomnia and depression 80% of patients with MDD experience sleepproblems Early morning awakening Difficulty falling asleep Hypersomnia After depression remission: 25% chronic insomnia (J. van Mill, 2010) Insomnia is an important risk factor for recurrence

14 Metabolic effects of sleepdisorders Short sleep duration in healthy persons: Increased risk of hypertension, abdominal obesity, hyperglycaemia (Knutson, 2009, Spiegel, 2009) Short sleep duration in T2D 23% increased fasting glucose, 82% increased insulin resistance (Knutson,2011) Experiments (Van Cauter 2011, Donga, 2010) in both diabetes and healthy personons using clamps

15 The biological clock / Suprachiasmatic nucleus Part of the hypothalamus, located directly above the optic chiasm. Functions as the pacemaker of the circadian timing system of the rain. Receives input a.o. through retinal ganglion cells. The SCN, through several ways, reglates diurnal variations in sleep-wakefulness, basal energy expediture, glucoregulation, insulin sensitivity and Cortisol diurnal variability. Post-mortem evidence for SCN dysfunction in MDD (Zhou, 2001)

17 Circadian misalignment in depression Reduced diurnal variability in depression Bremmer et al; 2009

18 Hypothesis: Mediation by circadian misalignment Insomnia / Circadian misaligment Depression Insulin Sensitivity

19 Chronotherapy as a tailormade treatment Bright-Light Treatment for MDD in T2D

20 Bright-Light Treatment BLT is: Patient-friendly, home-treatment Well-tolerated Effective, also for non-seasonal depression BLT restores sleep-wake pattern BLT restores diurnal cortisol variability BLT may lead to increased insulin sensitivity

21 Zeitgeber

22 BLT in ( ) elderly with NON-seasonal depression Lieverse, R. et al. Arch Gen Psychiatry 2011;68:61-70.

23 Efects on Cortisol and sleep Sleep advancing get-up time after final awakening (p<.001) increased sleep efficiency (p=.01)

24 Hypothesis: Mediation by circadian misalignment Insomnia / Circadian misaligment Depression Insulin Sensitivity

25 Bright Light Treatment for better Mood and Metabolic control: a randomised double-blind placebo-controlled clinical trial in patients with Type 2 Diabetes Mellitus and Major Depressive Disorder Hypothesis treatment with BLT will improve depressive symptoms and insulin sensitivity, possibly by resetting the biological clock. The aim is to investigate: (1) the efficacy of BLT in patients with T2D and co-morbid Major Depressive Disorder (MDD), and (2) whether BLT leads to improved insulin sensitivity and (3) whether effects on mood and metabolic control are mediated by restoration of circadian rhythmicity as measured by a normalized greater amplitude of salivary cortisol and improved subjective and objective measures of sleep-duration and sleep quality.

26 T-1 T0 T1 T2 T3 T6 Randomized double-blind placebo-controlled clinical trial, 2x70 participants with T2D and MDD (DSM-IV criteria) 3 weeks, 1 hour early-morning bright-white light ( Lux) or dim red light (50 lux) exposure. Euglycaemic hyperinsulinaemic clamp in 2x 30 subjects before and after the intervention

27 Thank you Discussion

29 Primary Outcome measure Mean decline in IDS-SR scores from T0 to T3 in the active versus placebo condition Secondary Outcome measures Depression remission rates at T6 Temporal changes in IDS-SR scores at T0,T1, T2, T3, T6 Delta Clamp-derived M-value, (T0-T3) Delta HbA1C (T0-T6) Mediation of treatment effect by endocrine measures of the circadian rhythm: Diurnal cortisol variability Actigraphic measures of sleep efficiency, and measures of subjective sleepquality ANS balance

Index. sleep.theclinics.com. Note: Page numbers of article titles are in boldface type.

Index. sleep.theclinics.com. Note: Page numbers of article titles are in boldface type. Note: Page numbers of article titles are in boldface type. A Accidents, at work, effect of shift work disorder on, 263 264 Acetylcholine, in circadian rhythms, 100 105 Acrophase, definition of, 301 Actigraphy,