Transcript 10-15 mg/day 10-15 mg/day 30 mg/day

The research questions that need to be
answered for
atypical antipsychotics to be utilized as primary
treatment option
Chau-Shoun LEE, M.D., Ph.D.
Senior psychiatrist and assistant professor
Department of Psychiatry, Mackay Memorial Hospital, Taipei
Kainan university, Taoyuan, Taiwan
Prevalence of depression and anxiety symptoms
in Taiwan and the trends over the past 20 years
Time trends in probable CMDs and suicide rates in Taiwan, 19902010 CMDs=common mental disorders, including anxiety and depression.
Tiffany Szu-Ting Fu* , Chau-Shoun Lee* , David Gunnell , Wen-Chung Lee , Andrew Tai-Ann Cheng *1st authors
Changing trends in the prevalence of common mental disorders in Taiwan: a 20-year repeated cross-sectional survey
The Lancet Volume 381, Issue 9862 2013 235 - 241
http://dx.doi.org/10.1016/S0140-6736(12)61264-1
Ten-year cumulative survival curve by bipolar depression, major
depressive disorders (MDD) and other types of depression without MDD.
Jung-Chen Chang , Hsiu-Hsi Chen , Amy Ming-Fang Yen , Sam Li-Sheng Chen , Chau-Shoun Lee* * correspondence author
Survival of bipolar depression, other type of depression and comorbid ailments: Ten-year longitudinal follow-up of 10,922
Taiwanese patients with depressive disorders (KCIS no. PSY1)
Journal of Psychiatric Research Volume 46, Issue 11 2012 1442 - 1448
http://dx.doi.org/10.1016/j.jpsychires.2012.07.014
The first question is what is the current
status of treatment in mood disorders.
Can we go further in the future?
Stressful Life Events as a “Trigger” for Depression
Progressively Declines
10
“Kindling” Phenomenon
Risk
8
Risk (%) of depression
onset per month
6
With increasing
depressive episodes:
Risk of depression
Association with
stressful life events
4
2
Likelihood of recent life stress*
Likelihood of recent life stress*
0
0
1
2
3
4
5
6
7-8
9-11
No. of previous depressive episodes
*Odds ratio for depression given at least one stressful life event.
Kendler KS, et al. Am J Psychiatry. 2000;157:1243-1251.
Risk (%) of depression onset per month
STAR*D Results: Remission Rates
for Each Treatment Level
Decreasing Remission Rates
Patients in Remission* (%)
100
80
60
40
36.8
30.6
20
13.2
13.0
Level 3
Level 4
0
Level 1
Level 2
*Remission was defined by QIDS-SR16 ≤5 at exit from indicated treatment step.
Rush AJ et al. Am J Psychiatry. 2006;163:1905-1917.
STAR*D Results:
Improved Outcomes With Earlier Treatment Success
Increasing Relapse Rates
Patients Relapsing (%)
100
80
71.1
64.6
55.3
60
40.1
40
20
0
Level 1
Level 2
Rush AJ et al. Am J Psychiatry. 2006;163:1905-1917.
Level 3
Level 4
The SFBN: risk factors for suicide attempt and
consecutive course of illness
Mania
Severe
Moderate
Depression
Mild
Suicide attempts
Increased number of
Family history of
medical comorbidites
• Drug abuse
Eating disorder
• Suicide or serious
suicide attempt (past & current)
Age
(years)
Mild
5
10
15
20
25
30
35
40
Moderate
Severe
Physical Sexual
abuse abuse
Early onset
first symptoms
Loss of social support
632 patients | Age of onset: 19.4 years | First treatment: 29.2 years | Suicide attempt: 28.7%
Chien-Hsiun Chen*, Chau-Shoun Lee*, Ming-Ta Michael Lee* et al., in review, N Eng J Med, *1st authors
METHODS
A GWAS was carried out on 294 BPI patients receiving lithium treatment.
The top SNPs identified were then examined in a replication sample of 100
patients and further tested in a prospective follow-up cohort of 24 patients.
Re-sequencing of the identified candidate gene was then carried out.
RESULTS
Two SNPs in high linkage disequilibrium showed the most significant
associations in GWAS (P = 5.50 X10-37 and 2.52 X 10-37), replication (P=9.19
X10-15 for both) and combined samples (P = 1.66 X 10-49 and 7.07 X 10-50).
These two SNPs reached a high sensitivity of 0.930 for predicting lithium
response. They also successfully differentiated between the good and poor
responders in the follow-up cohort. Re-sequencing of the gene identified a
novel variant which is in complete linkage disequilibrium and is predicted to
affect splicing.
CONCLUSIONS
We report here the first GWAS in the Han Chinese population to identify
genes for response to lithium prophylaxis treatment for BPI. The genetic
variants identified from this study could serve as biomarkers for predicting
lithium response to improve treatment for BPI.
Early detection, prompt effective intervention
with satisfied remission rate, and maintenance
treatment with good adherence
are essential for long term management in
mood disorders
The second question is how to differentiate
the diagnostic categories among the wide
mood spectrum
Two-dimensional mood/affective spectrum (does not include
schizoaffective disorder, as a transition to the schizophrenic spectrum)
Angst J BJP 2007;190:189-191
©2007 by The Royal College of Psychiatrists
The third question is what the most
important phase at the drug therapy for
a episodic chronic disorder,
acute or maintenance.
Maintenance treatment is the most important
at the Continuum of Care
Desired Clinical Outcome: Efficacy
Symptom
Control
15 Days
Minimize Side Effects
Treatment
Alliance
15 Weeks
Education
Treatment
Adherence
15 Months
Relapse
Prevention
15 Years
Clinician
Rehabilitation
Pharmacology
Diagnosis
Dosing
Drug Choice
Side Effects
Motivation
Polypharmacy
Obstacles to Achievement
Glenda M. MacQueen, MD, PhD, FRCPC Associate Professor McMaster University
Trevor Young, MD, FRCPC Psychiatrist Centre for Addiction and Mental Health-Clarke Site
Cost Concerns
Social Issues
The fourth question is whether the drug
therapy plays a role on the adherence to
maintenance treatment in mood disorders.
Minding the Other and empathy:
Simulation Theory and Social Neuroscience
• Mirror Neuron
– 鏡像神經元
• http://www.youtube.com/w
atch?v=XzMqPYfeA-s
• How many persons do
you need to empathize at
interview?
– 舉杯邀明月，對影成三人
Antipsychotic medications disrupt a mother rat's tendency to retrieve her pups. (Adapted from
Nelson RJ. An introduction to behavioral endocrinology, 3rd ed. Sunderland, MA: Sinauer; 2005
and Li M, Davidson P, Budin R, et al. Effects of typical and atypical antipsychotic drugs on
maternal behavior in postpartum female rats. Schizophr Res. 2004;70[1]:69–80.)
The relation between BOLD response and self–other discrepancy for
subregions of the MPFC: serotonergic v.s. dopaminergic therapy
Tamir D I , Mitchell J P PNAS 2010;107:10827-10832
©2010 by National Academy of Sciences
The final question is a dopamine partial
agonist is really able to resolve those
complex clinic issues.
Otsuka ABILIFY : the range of therapeutic dosages
Patient types
Indications
Initial dosage
Therapeutic
dosage
Maximal
dosage
Schizophrenia
10-15
mg/day
10-15
mg/day
30 mg/day
Bipolar Acute- Monotherapy
15 mg/day
15 mg/day
30 mg/day
Bipolar Acute and
Maintenance- Adjunctive
to lithium or valproate
10-15 mg/day 15 mg/day
30 mg/day
MDD add-on
2-5 mg/day mg/day
15 mg/day
adolescent
Schizophrenia
(13 - 17 y/o)
Bipolar AcuteMonotherapy
child
Bipolar Acute and
(10 - 17 y/o)
Maintenance- Adjunctive
to lithium or valproate
2 mg/day
10 mg/day
30 mg/day
child
Autism Disorder
(6 - •17
y/o) (agitation and irritability)
一天一次，不需配合進餐服用。
2 mg/day
5-10
mg/day
15 mg/day
Adult
5-10
• 服用ABILIFY無需要劑量調整 (年齡、性別、種族、抽煙情形、肝功能或腎功能)
李商隱的無題詩
•昨夜星辰昨夜風，畫樓西畔桂堂東。
•身無綵鳯雙飛翼，心有靈犀一點通。
•隔坐送鈎春酒暖，分曹射覆蠟燈紅。
•嗟余聽鼓應官去，走馬蘭臺類轉蓬。