Table Of ContentChronotherapeutics for Affective Disorders
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II
Anna Wirz-Justice
Francesco Benedetti
Michael Terman
Chronotherapeutics for
Affective Disorders
A Clinician’s Manual for Light and Wake Therapy
33 figures, 21 in color, 10 tables, 2009
Basel • Freiburg • Paris • London • New York • Bangalore •
Bangkok • Shanghai • Singapore • Tokyo • Sydney
III
Anna Wirz-Justice A project of the
Centre for Chronobiology
Center for Environmental Therapeutics
Psychiatric University Clinics
www.cet.org
Basel, Switzerland
An independent, non-profit
Francesco Benedetti professional agency dedicated to education and
Department of Clinical Neurosciences research on the new environmental therapies.
Scientific Institute and
Board of Directors:
University Vita-Salute San Raffaele
Michael Terman, PhD (president)
Milano, Italy
Gustave Manasse, PhD
Dan Oren, MD
Michael Terman
Elaine Tricamo, RN
Department of Psychiatry
Anna Wirz-Justice, PhD
Columbia University
New York, N.Y., USA
Library of Congress Cataloging-in-Publication Data
Wirz-Justice, Anna.
Chronotherapeutics for affective disorders : a clinician‘s manual for
light and wake therapy / Anna Wirz-Justice, Francesco Benedetti, Michael
Terman.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-3-8055-9120-1 (pbk. : alk. paper)
1. Affective disorders--Alternative treatment. 2. Clinical chronobiology.
3. Circadian rhythms--Therapeutic use. 4. Sleep deprivation--Therapeutic
use. 5. Light--Therapeutic use. I. Benedetti, Francesco, 1966- II. Terman,
Michael. III. Title.
[DNLM: 1. Mood Disorders--therapy. 2. Chronotherapy--methods. 3.
Phototherapy--methods. 4. Sleep Disorders--therapy. WM 171 W799c 2009]
RC537.W575 2009
616.85‘2706--dc22
2009000805
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ISBN 978–3–8055–9120–1
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IV
Contents
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IX
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XI
List of Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XII
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Unmet Needs in the Treatment of Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Role of Biological Rhythms in Psychiatry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3 Principles of Circadian Timing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.4 Principles of Sleep Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.5 Mood Level Varies with Time of Day and Duration of Wakefulness . . . . . . . . . . . . . . . . . . . . 8
1.6 Sleep Deprivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.7 How It All Began: Light Therapy for Seasonal Affective Disorder . . . . . . . . . . . . . . . . . . . . . . . 10
1.8 Light Therapy – Beyond SAD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.9 What Is Chronotherapeutics? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2 Individual Chronotherapeutic Elements: Light, Wake Therapy and
Sleep Phase Advance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2.1 Efficacy of Bright Light Therapy for SAD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2.2 Timing of Bright Light Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.3 Dawn (and Dusk) Simulation Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.4 Efficacy of Bright Light Therapy for Non-Seasonal Depression . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.5 Dark Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.6 Wake Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.7 Phase Advance of the Sleep-Wake Cycle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
2.8 Negative Air Ionisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3 Integrative Chronotherapeutics: Combinations of Light, Wake Therapy
and Sleep Phase Advance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.1 A Note on Diagnostic Differences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.2 Bright Light Augmentation of Antidepressant Drug Treatment . . . . . . . . . . . . . . . . . . . . . . . . 26
d
n
3.3 Wake Therapy Added to Medication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 u
o
3.4 Wake and Light Therapy Added to Antidepressant Drugs or Mood Stabilisers . . . . . . . . . 29 r
g
k
3.5 Wake, Light, and Sleep Phase Advance Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 c
a
3.6 Repeated Wake Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 B
V
4 Inpatient Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
4.1 Response Assessment and Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
4.2 Light Therapy Timing and Duration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
4.3 Exceptions to the Early Morning Light Rule for Bipolar 1 Disorder . . . . . . . . . . . . . . . . . . . . . 35
4.4 Beginning with Light Therapy (± Medication) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
4.5 Wake Therapy + Light Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
4.6 Wake Therapy + Light Therapy + Sleep Phase Advance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
4.7 Three Alternate Nights of Wake Therapy + Light Therapy + Freely Chosen Sleep
Phase Advance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
4.8 Variations on the Theme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
4.9 Maintenance Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
4.10 Drug Tapering to Discontinuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
5 Practical Details for Wake Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
5.1 Which Patients Are Suitable? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
5.2 Predictors of Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
5.3 Medication Allowances and Contraindications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
5.4 What to Tell Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
5.5 Setting and Structure for the Night Awake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
5.6 Staff Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
5.7 Nurses on the Night Shift . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
5.8 Nurses on the Day Shift after Wake Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
5.9 Structure of the Day After . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
5.10 Phase Advance of Sleep following Wake Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
5.11 The Doctor’s Tasks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
5.12 Is One-Time Wake Therapy Enough? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
5.13 Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
5.14 Special Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
5.15 If There Is No Response. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
5.16 At the End of One Week of Chronotherapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
5.17 In Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
6 Practical Details for Light Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
6.1 Criteria for Light Box Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
6.2 Using the Light Box . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
6.3 Side Effects of Light Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
6.4 Cautionary Notes about Bright Light Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
6.5 Before Beginning Light Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
6.6 In Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
s
d
7 Outpatient Treatment Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 o
h
7.1 Light Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 t
e
M
7.2 Wake Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
VI
8 Range of Chronotherapeutic Indications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
8.1 Antepartum Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
8.2 Premenstrual Dysphoric Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
8.3 Bulimia Nervosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
8.4 Attention Deficit/Hyperactivity Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
8.5 Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
8.6 Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
8.7 Shift Work and Jet Lag Disturbance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
9 Light Therapy for Children and Adolescents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
s
n
o
10 Light and Wake Therapy for Older Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 ti
a
c
di
n
11 The Visually Impaired: More Sleep Disturbances, More Depression . . . . . . . . . . . 65 I
12 Endogenous and Exogenous Melatonin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
12.1 The Physiological Effects of Melatonin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
12.2 Melatonin in Circadian Sleep-Wake Cycle Disturbances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
12.3 Melatonin for Depression? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
y
13 Drugs That Affect Rhythms (Chronobiotics) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 g
o
13.1 Melatonin Agonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 ol
c
a
13.2 Chronobiology of Lithium and Antidepressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 m
r
13.3 Clock Genes in Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 a
h
13.4 Caffeine, Modafinil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 P
14 Social Rhythm Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 s
t
c
e
p
15 Chronobiology in Everyday Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 os
r
15.1 Know Your Chronotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 P
e
15.2 Timing of School and Work Schedules versus Sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 ur
t
15.3 Light and the Built Environment: Implications for Architecture . . . . . . . . . . . . . . . . . . . . . . . . 79 u
F
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
VII
Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
1 Morningness-Eveningness self-assessment questionnaire (chronotype), with
scoring and interpretation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
2 Personal Inventory for Depression and SAD (diagnostic status), with scoring and
interpretation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
3 25-item expanded Hamilton Depression Scale with atypical symptoms (current level
of depression), self assessment questionnaire with scoring and interpretation . . . . . . . . . 102
4 6-item Hamilton Depression Scale, core symptoms (for monitoring
short-term changes) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
5 Daily sleep and medication logs, and mood and energy ratings . . . . . . . . . . . . . . . . . . . . . . 111 x
di
6 Chronotherapeutics information to outpatients and clinicians following n
e
hospital discharge . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 p
p
7 Center for Environmental Therapeutics clinical assessment tools . . . . . . . . . . . . . . . . . . . . . . 114 A
Authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
VIII
Foreword
Sun worship has existed since the beginning of yond the core depressive disorders, we consider
human life on earth. Light is our source of energy, a broader range of current and potential appli-
of warmth, of spiritual and emotional sustenance. cations (Indications), introduce melatonin and
Light is the major synchroniser of the biological drugs that affect rhythms (Pharmacology), end-
clock. It is no surprise to see light enter psychia- ing with a discussion of social issues that impinge
try as a practical treatment. Sleep deprivation has on rhythmic structure and everyday well-being
been investigated for three decades: the instanta- (Future Prospects).
neous, overnight remission of severe depression Outpatients with affective disorders can learn
remains one of the most striking phenomena in to use light therapy – and even wake therapy – at
psychiatry. Sleep deprivation did not enter the home, but they must have directive coaching by
therapeutic armamentarium because patients the clinician. The current mode – ‘Go buy/try a
usually relapse after recovery sleep, or even a nap. light box, see if it works. (Period.)’ – is a formula
Now we have learned how to sustain the effect for disappointment, and discredits the solid clin-
with morning light therapy, sleep phase advances ical research of more than 20 years. Clinicians
and a variety of medications. Practical experi- need to learn the timing principles of the circa-
ence shows that major depression can indeed re- dian clock’s response to light, and carefully dose
mit quickly and remain remitted even in other- the treatment as they would a medication.
wise refractory cases. Not to give up medication, though: the combi-
Here, we combine the elements of chronother- nation of light therapy with antidepressants can
apeutics in a new synthesis. We hope that the provide a potent enhancement over either one
methods will be widely explored on inpatient alone. The lucky minority – as we have seen in
units, with the prospect of higher success rates, seasonal depression – will be able to taper drugs
real remissions without ominous residual symp- to discontinuation and remain euthymic under
toms, and shorter hospital stays. maintenance light monotherapy.
We designed this manual as a source book for A new therapeutic paradigm often seeks a new
clinicians. Readers can choose which category generation of clinicians, and we especially encour-
to read. We begin by presenting the insights of age psychiatric residents to get these principles un-
chronobiology and sleep research that provide der their belt – to help the field identify limitations
the scientific basis, followed by an overview of and refinements, and to view each case as an im-
the clinical literature, which justifies the treat- portant learning experience for all of us. As we
ments (Background). We then describe the prin- emphasize in the Manual, there are significant
cipal therapeutic procedures with practical de- loose ends that can and should be resolved before
tails for both inpatients and outpatients, and for we contemplate a second, revised edition. Feed-
younger and older individuals (Methods). Be- back from the field is now our priority.
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