Treatment

1

• Treatment
• Why not refer all BP?
• Cant (waiting lists)
• Wont go, or will get lost
• If all you have is a hammer, everything looks
  like a nail
• Most rewarding of all mental health diagnoses?
• Two medications to master
• Why these two? Who says?
• Low-dose lithium (blood level lt0.8) lithium
  primer
• lamotrigine
• (mechanism of action of lithium the biological
  clock )
• Non-medication component
• Therapist, up-trained CMA, health coach groups
• Substance-free (or almost) regular physical
  activity weight control diet
• Patient education
• Regular sleep (and darkness Dark Therapy, blue
  light, dawn simulators, amber lenses)

2

• Treatment
• Two medications to master
• Why these two? Who says?
• Low-dose lithium (blood level lt0.8) lithium
  primer
• lamotrigine
• (mechanism of action of lithium the biological
  clock )
• Non-medication component
• Who will do basics in house? (diet, ex, substance
  use)
• Patient education
• Regular 7-8 hour sleep in darkness
• (Chronotherapy)

3
Mood Stabilizers
lithium Eskalith valproate/divalproex Depakote
carbamazepine Tegretol, Carbatrol
oxcarbazepine Trileptal lamotrigine Lamictal olan
zapine Zyprexa quetiapine Seroquel omega-3
fatty acids fish oil aripiprazole Abilify (verapa
mil) --- risperidone Risperdal ziprasidone Geo
don
4
Mood Stabilizers
lithium Eskalith valproate/divalproex Depakote
carbamazepine Tegretol, Carbatrol
oxcarbazepine Trileptal lamotrigine Lamictal olan
zapine Zyprexa quetiapine Seroquel omega-3
fatty acids fish oil aripiprazole Abilify (verapa
mil) --- risperidone Risperdal ziprasidone Geo
don
5
BP Depression monotherapy guidelines
lithium lamotrigine quetiapine
2003 British Assn Psychopharmacology ? ? (valproate/antipsychotic)
2004 Australian/NZ College of Psychiatry ? ? -
2005 American Psychiatric Assn ? ? ?
2005 TMAP (Texas) ? ? ?
2006 NICE (European) ? (valproate) (antipsychotic)
2009 CANMAT (Canada) ? ? ?
TMAP Texas Medical Algorithm Project NICE
National Institute for Health and Clinical
Excellence CANMAT Canadian Network for
Mood/Anxiety Treatment
Adapted from Malhi et al. Bipolar Disorders,
2009 June
6
Ms. B.
Depression irritable, mild/moderate agitation -
no euphoria DIGFAST (middle insomnia) - family
Hx father suicide - 1st episode age 19,
relationship breakup gt5 - post-partum onset,
wax/wane over last year - 3 previous
antidepressants 1 loss of response Thyroid
status normal Current rx citalopram 30 mg
daily
7
Ms. B.
Depression irritable, mild/moderate agitation -
no euphoria DIGFAST (middle insomnia) - family
Hx father suicide - 1st episode age 19,
relationship breakup gt5 - post-partum onset,
wax/wane over last year - 3 previous
antidepressants 1 loss of response Thyroid
status normal Current rx citalopram 30 mg
daily
Unipolar or bipolar?
8
Ms. B.
Depression irritable, mild/moderate agitation -
no euphoria DIGFAST (middle insomnia) - family
Hx father suicide - 1st episode age 19,
relationship breakup gt5 - post-partum onset,
wax/wane over last year - 3 previous
antidepressants 1 loss of response Thyroid
status normal Current rx citalopram 30 mg
daily
Unipolar augmentation options?
9
Lithium augmentation
Bschor et al, Pharmacopsychiatry, 2003
10
Pros Cons
lithium lt0.8 Best known Fast Neurotrophic Low incidence of SEs Cheap 1-in-15 blahs stop Renal risk 10-year, high dose Toxicity antihypertensives, NSAIDS Thyroid monitor closely Tremor lower dose (B-blocker) Nausea try XR
11
Ms. B.
Depression irritable, mild/moderate agitation -
no euphoria DIGFAST (middle insomnia) - family
Hx father suicide - 1st episode age 19,
relationship breakup gt5 - post-partum onset,
wax/wane over last year - 3 previous
antidepressants 1 loss of response Thyroid
status normal Current rx citalopram 30 mg
daily
options?
12
Ms. B.
Depression irritable, mild/moderate agitation -
no euphoria DIGFAST (middle insomnia) - family
Hx father suicide - 1st episode age 19,
relationship breakup gt5 - post-partum onset,
wax/wane over last year - 3 previous
antidepressants 1 loss of response Thyroid
status normal
lamotrigine pros and cons?
13
Lamotrigine Rash Onset

364
378
392
0
14
28
42
56
70
84
98
112
126
140
154
168
182
196
210
224
238
252
266
280
294
308
322
336
350
Rash Onset Time in Days
6 weeks
Messenheimer J, et al. Drug Safety
199818(4)281-96
14
olanzapine/fluoxetine combination v. lamotrigine
Brown EB et al, J Clin Psychiatry, 2006
15
Lamotrigine Dosing
Week Standard Dose
1 and 2 25
3 and 4 50
5 100
6 200
7
8
16
Lamotrigine Dosing
Week Standard Dose Cautious Option
1 and 2 25 25
3 and 4 50 50
5 100 75
6 200 100
7 150
8 200
17
Lamotrigine Dosing
Week Standard Dose Cautious Option Freaked Out
1 and 2 25 25 up by 5 q 4 days
3 and 4 50 50 (then after 25 x 1 week)
5 100 75 Up by 12.5 q week
6 200 100
7 150
8 200
18
Lamotrigine Dosing
Week Standard Dose Cautious Option Freaked Out
1 and 2 25 25 up by 5 q 4 days
3 and 4 50 50 (then after 25 x 1 week)
5 100 75 Up by 12.5 q week
6 200 100
7 150
8 200
(divalproex)
19
Pros Cons
lithium lt0.8 Best known Fast Neurotrophic Low incidence of SEs Cheap 1-in-15 blahs stop Renal risk 10-year, high dose Toxicity antihypertensives, NSAIDS Thyroid monitor closely Tremor lower dose (B-blocker) Nausea try XR
lamotrigine No long term risks No weight gain 1/day, no labs No side effects 1-in-20 worsening Moderately complex titration Benign rash risk 1-in-10 SJS/TEN 1-in-1,000 (1-in-3,000?) (hair loss)
20

• Treatment
• Two medications to master
• Why these two? Who says?
• Low-dose lithium (blood level lt0.8) lithium
  primer
• lamotrigine
• (mechanism of action of lithium the biological
  clock )
• Non-medication component
• Therapist, up-trained CMA, health coach groups
• Substance-free (or almost) regular physical
  activity weight control diet
• Patient education
• Regular sleep (and darkness Dark Therapy, blue
  light, dawn simulators, amber lenses)

21
Colom , Vieta et al. Arch Gen Psych 2003
Psychoeducation
22
Colom et al Br J Psych 2009
5 years
23

PsychoEducationColom Vieta et al

• Introduction
• What is bipolar illness?
• Causal and triggering factors
• Symptoms (I) Mania and Hypomania
• Symptoms (II) Depression and mixed episodes
• Course and outcome
• Treatment (I) mood stabilizers
• Treatment (II) antimanic agents
• Treatment (III) antidepressants
• Serum levels lithium, carbamazepine, valproate
• Pregnancy and genetic counseling
• Psychopharmacology vs alternative therapies
• Risks associated with treatment withdrawal
• Alcohol and street drugs risks in bipolar
  illness
• Early detection of manic and hypomanic episodes
• Early detection of depressive and mixed episodes
• What to do when a new phase is detected?
• Regularity
• Stress management techniques

21 sessions Groups of 8-12 pts.
Manual de Psicoeducación en Trastornos
Bipolares The Psychoeducation Manual for Bipolar
Disorder
24
David Miklowitz, Ph.D.
One-Book EducationBipolar I

• the Bipolar Disorder Survival GuideWhat you and
  your family need to know

25
One-Source EducationBipolar II
www.PsychEducation.org
26
Youngsters
PAL Washingtons Partnership Access Line
MCPAP Massachusetts Child Psychiatry Access
Project
27
Youngsters
12-16 17-22 20-30
28
online cognitive behavioral therapy MoodGym moo
dgym.anu.edu
29

• Treatment
• Two medications to master
• Why these two? Who says?
• Low-dose lithium (blood level lt0.8) lithium
  primer
• lamotrigine
• (mechanism of action of lithium the biological
  clock )
• Non-medication component
• Therapist, up-trained CMA, health coach groups
• Substance-free (or almost) regular physical
  activity weight control diet
• Patient education
• Regular 7-8 hour sleep in darkness
• (Chronotherapy blue light, dawn simulators,
  amber lenses)

30
Social Rhythm Therapy
31
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32
(No Transcript)
33
Dark therapy
34
Implications 1. dark bedroom 2. regularity
35
Implications 1. dark bedroom 2.
regularity Problem (1) dawn
36
Dawn simulator
Lighten Up
37
Dawn simulator
Terman and Terman. Am J Psych, 2006
38
Implications 1. dark bedroom 2.
regularity Problem(2)
39

• Treatment
• Two medications to master
• Why these two? Who says?
• Low-dose lithium (blood level lt0.8) lithium
  primer
• lamotrigine
• (mechanism of action of lithium the biological
  clock )
• Non-medication component
• Therapist, up-trained CMA, health coach groups
• Substance-free (or almost) regular physical
  activity weight control diet
• Patient education
• Regular 7-8 hour sleep in darkness
• (Chronotherapy blue light, dawn simulators,
  amber lenses)

40
But Why are they small? Why are they blue?
41
A 3rd Photoreceptor
Evidence for a novel circadian photoreceptor.
rodsconescircadian photoreceptors
Glickman, Brainard et al. J Neurosci., 2001
42
(No Transcript)
43
450 nm 550 nm 600 nm
Cones blue green red
44
450 nm 550 nm 600 nm
Cones blue green red Circadian
photoreceptor?
45
450 nm 550 nm 600 nm
Cones blue green red Circadian
photoreceptor?
46
Why Blue Light?
446-477 nm as the most potent wavelength region
providing circadian input for regulating
melatonin secretion.
Glickman, Brainard et al. J Neurosci., 2001
47
(No Transcript)
48

• Limiting factor in Dark Therapy
• what is your patient doing between 8-10 pm?

Light, from a circadian point of view, is only
blue
49

• (have your darkness and eat it too)

50
Virtual Darkness filter out the blue
51
Physiologic Evidence
Kayumov et al. J Clin Endocrinol Metabolism, 2005
52
Physiologic Evidence
Kayumov et al. J Clin Endocrinol Metabolism, 2005
53
Virtual Darkness as Treatment

• - 20-pt case series, initial or middle insomnia
  (BP)
• 50 response shorter latency
• Phelps J. Med Hypotheses, 2008
• 20-pt randomized trial, initial or middle
  insomnia
• Burkhart and Phelps. Chronobiology
  Internat, 2009

54
N10 per group
Burhart and Phelps. Chronobiol Int. 2009 Dec
55
Virtual Darkness as Treatment

• Protocol
• glasses at 8 p.m. for bed at 10 p.m.
• remove when real darkness
• Where do you get them?
• website link Light and Darkness in Bipolar
  Disorder

56
Virtual Darkness as Treatment

• Protocol
• glasses at 8 p.m. for bed at 10 p.m.
• remove when real darkness
• no-blue nightlight if needed

25(lowbluelights.com)
57
Virtual Darkness as Treatment

• Protocol
• glasses at 8 p.m. for bed at 10 p.m.
• remove when real darkness
• no-blue nightlight if needed
• couple with a dawn simulator

58
Chronotherapeutics
Education biological clock (website dark
therapy, light therapy)
light box, 65-143 Lightphoria, Uplift
amber lenses, 7(website Light and Darkness)
dawn simulator, 30(website Light Therapy)
no-blue nightlight, 25(lowbluelights.com)
59

• DX
• Why care?
• 1 in 3-4 depressions has bipolarity
• Antidepressants can make bipolar disorder worse
• FDA Bipolar Screening requirement
• Outcomes
• Spectrum
• How many ADs to try before switching strategies?
  
• Placing patients on the spectrum
• Non-manic bipolar markers
• Harvard approach Bipolarity Index
• Operational
• MoodCheck
• Web-based patient education

60

• Rx
• Two medications to master
• lithium
• lamotrigine
• Non-medication component
• Who will do basics in house? (diet, ex, substance
  use)
• Patient education
• Regular 7-8 hour sleep in darkness
• Chronotherapy