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Bipolar Disorders
2013
Ronald A. Remick, MD, FRCP(C)
Medical Director, Mood Disorder Association of British Columbia
Email : [email protected]
Sophia I. Zisman, Bsc Hons.
St. George’s University of London
Epidemiology
①
Lifetime prevalence :
•
•
②
③
bipolar I : 0.8%
bipolar II : 0.6% (Murphy, 2000)
Bipolar disorder is the 6th leading
cause of disability, in people aged
between 15-44, worldwide (depression
is 2nd!)
At any given point in time, 60% of
patients with bipolar disorder are not in
treatment
Mood Disorders and the
Workplace
Work related economic losses due to
depression are estimated to cost 6
billion dollars per year in Canada
Health Report, Statistics Canada, 2006
Mood Disorders and the
Workplace
Absenteeism vs. Presenteeism
•
•
Presenteeism (lost productivity while at work) – likely a
more significant problem with mood disorders than
previously recognized in Canada
Productivity loss from presenteeism due to depression is 4
hours/week while loss from absenteeism is but 1 hour/week
(between $6-60 billion loss per annum)!
Epidemiology
①
②
③
The course of bipolar I is 9-10 cycles
during a lifetime – often stabilizing
after 4-5 cycles
Without treatment the average
depressive episode is 10 weeks and
average manic episode is 5 weeks
60% of patients have an increase in
episode intensity/duration with age
What about the role of ‘stress’
in bipolar illness?
Disruption in sleep, but not ‘stress’ can lead to
a bipolar relapse.
Early childhood ‘trauma’ is NOT causative in
bipolar illness, however;
① sexual abuse – may increase risk of suicide
attempts
② physical abuse – may increase risk of
manic relapses
③ sexual/physical abuse – may lead to
earlier illness onset
Genetics of Bipolar Illness
•
•
•
Polygenic inheritance – fifty percent of
bipolar patients have a family history of
bipolar illness.
Linkage studies (in several studies) have
identified markers on chromosome 18 &
22.
New research is working to identify
individuals at risk which will possibly lead
to superior treatments in the future.
Evolving genetic concepts
①
②
Endophenotypes are gene intermediaries that
turn on or turn off a specific gene
‘Stress/adversity can influence
endophenotypes. That is, stress or adversity
can turn on or turn off certain genes that can
either trigger depression (vulnerability) or
protect from depression (resiliency)
STRESS and the BRAIN
CRF
ACTH
Adrenaline
cAMP
BDNF
Brain Cell Growth
STRESS and the BRAIN
CRF
ACTH
Adrenaline
cAMP
BDNF
Brain Cell Growth
Hypothalamus
CRF
STRESS
Hippocampal
Shrinkage
Limbic
System
Mood dysregulation
Memory impairment
Pituitary
ACTH
Adrenal
Cortex
Apoptosis/neuron death
Cortisol + Adrenaline
Diagnosing Bipolar
Disorders
Diagnosis of depression
①
②
A distinct mood change (depressed,
irritable, anxious, etc) for at least two
weeks
Four or more SIGECAPS
Sleep
Interest
Guilt
Energy
Concentration
Appetite
Psychomotor Activity
Suicide
Diagnosis of
Mania/Hypomania
①
②
A distinct mood change (elated,
irritable, expansive, etc) for > one
week (four days for hypomania)
Three or more GST RAID :
S leep(decreased)
A gitation Rapid thoughts
Grandiosity
T alkative
I mpaired judgement
Sleep
Agitation
D istractible
Talkative
Impaired judgment
Distractible
Diagnosing bipolar illness
①
②
③
Distinguish bipolar I (mania) from
bipolar II (hypomania)
Bipolar II is among the most frequently
missed diagnoses in psychiatry
The diagnosis of bipolar II disorder is
risky, at best, without collateral
information.
Diagnosis of Hypomania
Doctors often fail to ask key questions (of a family member and the
patient) that assist in the diagnosis of bipolar II disorder …
“ Has there been a period of time when you were
feeling so good or hyper that other people thought
you were not your normal self, or were so hyper you
got into trouble?”
“ What about a period of time when you were
so irritable that you would shout at people or
start fights or arguments?”
Treatment of Bipolar Disorders
Treatment of Bipolar Disorders
Bipolar disorder is a chronic illness:
 Expect exacerbations and remissions
 Long term chemotherapy is the rule
not the exception
It is risky, at best, to treat bipolar patients in a
vacuum i.e. without the involvement of
family/significant others
Treatment of Bipolar Illness
1
Psychological
Interventions
2
Biological
Interventions
Psychological Interventions
Psycho
education
Psychotherapy
• Mood Disorders Association of
British Columbia http www.mdabc.net
• Internet/ readings www.patient.co.uk, www.crestbd.ca
• Cognitive behavioural therapy(CBT)
for the depressive phase of the illness
• CBT to prevent manic relapse
Cognitive Behavioral Therapy
(CBT)
•
•
•
The evidence based psychotherapies are
AS EFFECTIVE as antidepressants in
mild/moderate MDD.
CBT is accessible in British Columbia.
CBT response rate(8-12 weekly sessions)
= 65%.
Cognitive Behavioral Therapy
Identify automatic
maladaptive thoughts
and distorted beliefs
that lead to
depressive moods
Use a systematic
approach to reinforce
positive coping
behaviors
Learn strategies to
modify these beliefs
and practice adaptive
thinking patterns
Accessibility
Private
Psychologist
Public
Resources
Online
• Not covered by medical insurance
• The majority of outpatient psychiatry
departments in hospitals offer group based
CBT which is covered by MSP funding.
Enquire at your local hospital or with your
doctor!
• www.carmha.ca/publications - ‘antidepressant skills workbook (free download)-an
outstanding self directed CBT workbook
• www.moodgym.anu.edu.au
Biological Treatments for bipolar
disorders
①
②
③
④
⑤
⑥
⑦
LITHIUM
VALPROIC ACID
CARBAMAZEPINE
LAMOTROGINE
ATYPICAL ANTIPSYCHOTICS
ANTIDEPRESSANTS
OTHER ANTICONVULSANTS
Lithium
Lithium
• Expect “two thirds” response to lithium:
- 33% complete response
- 33% significant mood attenuation
- 33% no response/intolerance
Complete response
No
response/intolerance
Significant mood attenuation
• “anti-suicide” effect of lithium
• Lithium remains the ‘GOLD STANDARD’ in treating bipolar
illness and is among the most effective and underutilized
treatments in all of psychiatry!
80
70
60
50
40
30
20
10
0
Suicide attempts before, during, one year,
and two years post lithium treatment
Valproic Acid
•
•
•
•
•
Valproic acid (divalproex; Depokoate; Epival) is an effective
antimanic agent
The evidence for the prophylactic efficacy of valproic is still not
clear (one short RCT, pharmaceutical company sponsored) 
Recommended as first line maintenance therapy (Dr. Remick)
Valproic is far superior as an anti manic rather than an
antidepressant preventative agent
Recommended to be used as a 1st line combination therapy
medication for the treatment of acute BD-1 depression
Serum levels appropriate (versus no defined therapeutic range
with carbamazepine)
Carbamazepine
•
•
•
•
•
Carbamazepine (Tegretol) is an effective antimanic agent (19
studies)
Carbamazepine is an effective prophylactic agent (10 RCTs), but
likely less effective than lithium (Davis et al, 1999)
Carbamazepine appears to be a forgotten (yet very effective)
treatment in bipolar illness
Oxcarbazepine (Trileptil) is being touted as a ‘similar’ but
‘superior’ medication to carbamazepine, but recent studies shed
some doubt
Recommended as 3rd line therapy in the treatment of depression
in bipolar disorder
Lamotrogine (Lamictal)
①
②
③
There is increasing evidence that lamotrogine is
an effective agent in treating both bipolar I and II
depression  currently recommended as a first
line agent in the treatment of depression.
There is very limited (but some) evidence that
lamotrogine is an effective anti-manic or
prophylactic agent.
Lamotrogine has a relatively benign (e.g. non
sedative, weight neutral) side effect profile.
Dose range not determined but likely 100300mg/day
Other anticonvulsants in
bipolar disorder
There is NO evidence that gabapentin
(Neurontin) or topiramate (Topramax)
has any benefit at all in the treatment of
bipolar depression, bipolar mania, and/or
the preventative/prophylactic treatment
of bipolar illness. They are not
recommended in the treatment of
bipolar disorder.
Typical/Atypical Antipsychotics
①
②
③
④
Quetiapine and Olanzepine show evidence of mood
stabilizing properties – both antidepressant and
antimanic.
Current guidelines suggest Quetiapine is preferable to
other antipsychotic agents due to its side effect profile.
Olanzapine is a 3rd line treatment due to its side effect
profile.
Side effects can included: weight gain, dyslipidemia, &
diabetes with atypicals; especially olanzapine(Zyprexa)
and clozapine(Clozaril) but also risperidone(Risperdol)
and quetiapine (Seroquel)
Lifestyle
•
The diet of individuals with SMI(Serious Mental Illness) has been
characterized as high fat, high in calories and high in simple
carbohydrates.
•
Patients with SMI are less active then those in the general
population and are more likely to walk as their sole form of
physical activity.
•
Smoking rates are elevated in the SMI and range between 32%
and 92% in schizophrenia samples.
“ Do not rashly use every new product of which the
peripatetic siren sings. Consider what surprising reactions
may occur in the laboratory from the careless mixing of
unknown substances. Be as considerate of your patient and
yourself as you are of the test tube.”
Sir William Osler
Bipolar Medications and
Pregnancy
①
②
③
Lithium – ensure careful monitoring during
pregnancy
Valproic Acid – proven to be harmful for fetuses, it
is recommended that new mothers switch to
another treatment
Carbamazepine – should only be used if it is the
only option
Always contact your physician if you are being treated for bipolar
disorder and are planning to fall pregnant.
Managing depressive
and manic relapses
“don’t throw out the baby with the
bathwater”
If the treatment has muted or attenuated the
illness consider adding a second treatment
rather than eliminating the treatment that is
offering partial efficacy.
Managing Depressive Relapse
①
②
Don’t throw out the baby with the
bathwater!
The risk of an antidepressant
induced manic switch in both bipolar
I/II is < 10% (SSRI’s & bupropion <
TCA and SNRI)
Managing Depressive Relapse
Treatment options:
a. second mood stabilizer (I) (lamotrogine)
b. antidepressant (II,I)/ lamotrogine
c. CBT(I,II)
d. ECT(I,II)
Managing Manic/Hypomanic
Relapse
1. Don’t throw out the baby with the bath water
2. Other treatment options:
a. hospital care (I)
b. no treatment intervention (II)
c. second mood stabilizer (I/II)
d. atypical /typical antipsychotic (I/II)
e. benzodiazepine (II)
f. ECT (I)
Prevention of future manic
relapses – Ulysses Agreement
①
②
Set it up BEFORE manic relapse
with doctors, family, employers, etc.
Put it in writing – outline the type of
treatment e.g. hospitalization,
antipsychotic medication, etc.
Factors associated with
relapse
•
•
•
•
•
•
•
•
medication adherence (70% to 30%)
presence of subsyndromal symptoms
baseline psychosocial stress
higher number of prior episode
BD-11 versus BD-I
female gender
substance abuse
Rapid cycling (>4 episodes per year)
“Grey zones” in bipolar
illness…(topics for future
presentations)
①
②
③
④
⑤
⑥
“Stressful life problems” versus mild depressive
relapse
The role of psychological “adversity” in bipolar illness
To treat or not treat hypomania
Social/family/vocational stigma
“Doctor should we have children?”
Bipolar illness and creativity
What’s the deal with childhood
bipolar illness?
①
②
③
④
⑤
The onset in bipolar illness can be in late adolescence,
particularly in children of bipolar parents.
The diagnosis of childhood bipolar illness (i.e. ages 5-15)is
very different in USA compared to Canada, where childhood
bipolar illness is virtually nonexistent.
In Canada, the onset of bipolar illness typically begins with a
lengthy depressive episode.
In the USA, children with mood lability/irritability, anxiety and
insomnia are often given a diagnosis of childhood bipolar
illness.
The USA position is not consistent with decades of age of
onset research, genetic studies, or current diagnostic criteria
for bipolar disorders.
“Doctor, should we have children?”
•
•
•
•
The risks are real, but small (2% versus 15%).
Illness severity is not related to the severity of the illness in
the family.
Illness onset is at least twenty years in the future with
extensive new developments and treatments on the way.
Bipolar illness, without any other risk factors, in a parent is
certainly not an exclusion to having and effectively parenting
children.
The relationship between
creativity and bipolar illness
①
②
③
④
⑤
Many studies have shown that between 20 and 35% of artists
(musicians, painters, writers, poets, etc ) develop bipolar
illness where the rate of bipolar illness in the population is
about 2%.
The higher rate of bipolar illness cannot be explained by
‘stressful’ life style, poverty, etc.
Severe manic and depressive episodes impair creative output.
Creativity and bipolar illness have a familial (i.e. genetic) link.
Touched with Fire : Manic Depressive Illness and the Artistic
Temperment. by Kay Redfield Jamieson (1993)