bipolar disorder – case studytsad2015 · treatment of bipolar disorders: aims achieve functional...
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Bipolar disorder Case studyBipolar disorder – Case study
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Treatment of bipolar disorders: aimsTreatment of bipolar disorders: aims
Achieve functional recovery, not just Address subthresholdy, j
treat or control mood episodes
symptoms and their drivers
Improve physical healthImprove physical healthAugment personal
autonomy, and well-b i t i litbeing to improve quality
of lifeReduce stigma and social exclusion
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Strategy and time course
AcuteAcute ContinuationContinuation MaintenanceMaintenance
0-8 wks 1-6 months Indefinite
SyndromalRecovery
FunctionalRecovery
Maximize function;StabilityRecovery
Maximize mood stabilizers;
Recovery
Optimize tolerability; Taper adjunctive
Stability
Optimize efficacyAnd tolerability;stabilizers;
adjunctive treatmentTaper adjunctive
Medications when Possible
And tolerability;Anticipate prodromes
Support/structure; Education; involve
family
Cognitive behavioralsystems;
Strategies toOptimize adaptation
And remissionfamily And remission
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PharmacotherapyPharmacotherapy
• Bipolar disorder pharmacotherapy depends on Illness
Subtypes PhaseClinical featuresyp features
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US FDA‐approved treatments for Bipolar disorderUS FDA approved treatments for Bipolar disorder
Acute Mania Acute Depression Long‐term treatment
Year Drug Year Drug Year DrugYear Drug Year Drug Year Drug
19701973
LithiumChlorpromazine
20032006
OLZ + fluoxetineQuetipine, XR
19742003
LithiumLamotrigine
199420002003
pDivalproexOlanzapine*Risperidone*
2013
p ,(2008)Lurasidone
200420062008
gOlanzapineAripiprazoleQuetiapine,2003
200420042004
RisperidoneQuetiapine*ZiprosidoneAripiprazole*
2008
20092009
Quetiapine, XR(adjunct)Risperidone LAI*Ziprasidone2004
20042009
AripiprazoleCarbamazepineAsenapine*
2009 Ziprasidone
* Adjunctive and monotherapy
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Psychosocial treatment targetsPsychosocial treatment targets
Responses to stressful
event High expressed emotion and
negative familynegative family interactions
Drug Adherence Sleep and
i dicircadian regulation
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Adjunctive Psychosocial therapy: NNT for Relapse/Recurrence prevention
l / lN Relapse/Recurrence
Rate%
NNT VS comparator
Sample, Source
Psychoeducation
d h
60 66.7 4 After 6+ months of remission
l31 91 7Nonstructured therapy Colom 200331 91.7
F il f d th 70 35 5 6 Aft tFamily focused therapy 70 35.5 6 After acute episode.
Miklowitz 2003Crisis management 48 54 3Crisis management 48 54.3
Cognitive therapy 48 43.8 4 When euthymic/ subsyndromalh h subsyndromal
2003No psychotherapy 48 75.0
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ผปวยหญง ค 30 ป มาดวย กงวลมาก มความคดอยากตายผปวยหญง ค 30 ป มาดวย กงวลมาก มความคดอยากตาย
2 เดอนกอน เรมซมเศรา หงดหงดงาย ออนเพลย ไมคอยมแรงทาอะไรเหมอนปกต กนอาหารมากกวาปกต นาหนกขน 5 กโลกรม และนอน
มากกวากวาปกต ไปพบแพทยทคลนกแหงหนง
Major depressive disorder
Fluoxitine 40 mg/day
j p
Fluoxitine 40 mg/day
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1 เดอนหลงจากได fluoxetine ผปวยรสกเศรา1 เดอนหลงจากได fluoxetine ผปวยรสกเศรามากขน หงดหงดงายขน และเหนอยงายขน บางครงม
การสลบกบความรสกมเรยวแรงมากกวาปกต ความการสลบกบความรสกมเรยวแรงมากกวาปกต ความ
ตองการนอนนอยลง ความคดเรวขน และมอาการ
panic attack และมความคดอยากทารายตวเอง panic attack และมความคดอยากทารายตวเอง
ในชวง 2 สปดาหสามของผปวยเลาวาผปวยม
พฤตกรรมเปลยนไป เชน เรมคยกบเพอนพฤตกรรมเปลยนไป เชน เรมคยกบเพอน
ชายหลายคนทาง internet มากขน
ผปวยไมสามารถไปทางานได และบางครงผปวยไมสามารถไปทางานได และบางครง
ลกชายพดวา "กลวแม” สามและผปวยยนยน
วาไมเคยดมเหลา หรอใชยา สารเสพตดใด ๆ วาไมเคยดมเหลา หรอใชยา สารเสพตดใด ๆ
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พอของผปวยทเสยชวตไปแลว มประวตเปนโรค พอของผปวยทเสยชวตไปแลว มประวตเปนโรค
bipolar และตอบสนองดตอการรกษาดวย lithium
Physical examination : within normal limit
MSE: ผปวยหญงแตงกายไมเหมาะสม ใสเสอผาสฉดฉาด แตงหนาเขม ทาปาก
แดง ขณะสมภาษณผปวยพดถงอารมณเศรา วตกกงวล และมความคดอยากทารายตวเอง
Labile Affect
Denied hallucination and delusionsDenied hallucination and delusions
Alert, orientated to time, person
Memory – intact
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ทานจะทาอยางไรตอไป
A. ซกประวตเพมเตมเกยวกบอาการทางจตเวช
จากผปวย และสาม
B. สงตรวจ urine drug screen
C. consult neurologist เพอ workup หา organic causes อน ๆ
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Beginning to address diagnostic challenges in Bipolar disorder
• Routine use of collateral information: family member, significant others: family member, significant others
• Skillful use of the DSM‐IV‐TR diagnosticSkillful use of the DSM IV TR diagnostic system including the use of diagnostic screening instrument g
• Use of additional (non DSM‐IV‐TR)• Use of additional (non DSM‐IV‐TR) information.
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Bipolar I depression more likely Unipolar depression more likely p p y
if ≥ 5
p p yif ≥ 4
Symptomatology
Hypersomnia Insomnia
Hyperphagia Decreased appetite
P h t t d ti P h t it tiPsychomotor retardation Psychomotor agitation
Other “atypical” symptoms
Psychosis and/or pathological guilt Somatic complaintPsychosis and/or pathological guilt Somatic complaintMood lability or manic symptoms
Course of IllnessCourse of Illness
Earlier onset (< 25 yrs) Later onset ( > 25 yrs)
Multiple depression (≥ 5 episodes) Long current depressionMultiple depression (≥ 5 episodes) Long current depression
(> 6 mo)Family history y y
Bipolar disorder No bipolar disorderAdapted from Mithell et al. 2008
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สามผปวยใหประวตเพมเตมวาสามผปวยใหประวตเพมเตมวา
เมอ 3 ปกอน หลงคลอดลกประมาณ 1 สปดาห ผปวยมอาการหงดหงดงายกวาปกต พดเรวขน และพดมากขน บอกอาการหงดหงดงายกวาปกต พดเรวขน และพดมากขน บอก
วาอยากทาโนนทาน นอนนอยลง ดมนใจในตวเองมากขน
แตอาการเปนอย 3‐4 วนกหายไปแตอาการเปนอย 3‐4 วนกหายไป
ในชวง 2 สปดาหทผามา ผปวยดอารมณ ดกวาปกต หงดหงดกวาปกต วอกแวกงาย
และนอนแควนละ 2‐3 ชวโมง แตผปวยบอกวาไมเคยรสกวามชวงทมความสข
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ทานจะวนจฉยโรค
A. Bipolar depression with mixed featurefeature
B. Bipolar mania with mixedB. Bipolar mania with mixed feature
C. Bipolar hypomania with mixed featurefeature
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Mixed featuresMixed features
W lik l t i i d• Women are more likely to experience mixed episodes
• Men are more likely to have unipolar mania and earlier onset and longer duration of manicearlier onset and longer duration of manic episodes, while women are more likely to have major depressive episodes.
• Anxiety symptoms, including panic attacks, are very i i d i d d b thcommon in mixed episodes and can be the
presenting complaint.
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ทานจะทาอยางไรตอไป
A. Add antimanic agent
B. Stop fluoxetine + add antimanicagentagent
C. Add benzodiazepineC. Add benzodiazepine
D. Increase dose of fluoxetineD. Increase dose of fluoxetine
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Treatment of maniaTreatment of mania
• Differences in both efficacy and tolerability between
Lithium, y
agents
Antips chotic dr gs seem
Chloropromanize
• Antipsychotic drugs seem to be better than lithium and anticonvulsantsAntiepileptics
• Olanzapine, risperidone and haloperidol seem toand haloperidol seem to have the best profile of available agent
Second-generation antipsychotics
Cipriani A. et al., Lancet. 2011;378:1306‐15
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• Indirect data suggest valproate may be more• Indirect data suggest valproate may be more effective than lithium for mixed mania.
• Valproate is associated with weight gain, birth defects and possibly polycystic ovariandefects, and possibly polycystic ovarian syndrome.
• Mixed mania can respond to lithium and good prophylactic lithium response runs in families.prophylactic lithium response runs in families.
• Antidepressants are not used to treat mixedAntidepressants are not used to treat mixed mania. There are no randomized, placebo‐controlled trials that show that antidepressants preduce depressive symptoms in mixed mania
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Off Fluoxetine Start Lithium 900 mg/day
1 li hi l l ไ 1 0 E /L1 เดอนถดมา ตรวจ lithium level ได 1.0 mEq/L
อาการ panic, หงดหงด และความคดอยากฆาตวตายหายไป สามบอก
ไมมชวงอารมรณดผดปกตอก แตยงรสกเศรามาก ไมคอยมเรยวแรงเวลาทาอะไร รสกกงวลกบเรองตาง ๆ และเครยดงาย นอนมากกวาปกต
(10‐12 ชวโมงตอวน) นาหนกเพมขนมาก (7 kgs) ผปวยอยากหยดกน lithium และกลบไปกน fluoxetine เหมอนเดม เพราะชอบ
ตวเองตอนกน fluoxetine มากกวา
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ทานจะทาอยางไรตอไป
A Off lithiumA. Off lithium
B Off lithium and add quetiapineB. Off lithium and add quetiapine
C. Off lithium and add lamotrigineC. Off lithium and add lamotrigine
D. ให lithium + quetiapineD. ให lithium + quetiapine
E. ให lithium + lamotrigineE. ให lithium + lamotrigine
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US FDA‐approved treatments for Bipolar disorderUS FDA approved treatments for Bipolar disorder
Acute Mania Acute Depression Long‐term treatment
Year Drug Year Drug Year DrugYear Drug Year Drug Year Drug
19701973
LithiumChlorpromazine
20032006
OLZ + fluoxetineQuetipine, XR
19742003
LithiumLamotrigine
199420002003
pDivalproexOlanzapine*Risperidone*
2013
p ,(2008)Lurasidone
200420062008
gOlanzapineAripiprazoleQuetiapine,2003
200420042004
RisperidoneQuetiapine*ZiprosidoneAripiprazole*
2008
20092009
Quetiapine, XR(adjunct)Risperidone LAI*Ziprasidone2004
20042009
AripiprazoleCarbamazepineAsenapine*
2009 Ziprasidone
* Adjunctive and monotherapy
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Taper of Lithium Start quetiapine XR และคอย ๆ เพม dose ถง 300 mg/day
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ผลขางเคยงของ
i i ไป quetiapine ตอไปนทตองการการตดตาม
A FatigueA. Fatigue
B. Hypotension
C. Rash
D. SedationD. Sedation
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What adverse effects are seen with quetiapine ?
• Central nervous system
(tremor, sedation*, headache, memory problems, akathisia, EPS)
• Gastrointestinal (nausea, vomiting, diarrhea, constipation)
• Dry mount
• Sexual dysfunction
• Increased appetitepp
• Weight gain
Ketter TA, et al. J Psychiatric Res 2010; 44: 921‐929
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Overview of Monotherapy Bipolar Preventive StudiesNumbers Needed to Treat for Relapse/Recurrence Prevention, Rates
NNT 639 4 47 4
Contemporary Registration Studies Other Studies8 14
p ,
NNT 6Aripiprazole
vsPlacebo
3Olanzapine
vsPlacebo
9Lamotrigine
vsPlacebo
4Risperidone
vsPlacebo
4Quetiapine
vsPlacebo
7Lithium
vsPlacebo
4Lithium
vsPlacebo
8Divalproex
vsPlacebo
14Lithium
vsPlacebo
70
80
rren
ce 80%
33%
***
*
Quetiapineunapproved for
maintenancemonotherapy
****
Divalproexunapproved for
maintenancemonotherapy
* p < 0.05, *** p < 0.001, **** p < 0.0001 vs. PBO.
50
60
se/R
ecur
*
33%
47%
11%
50%
*61%
56%****
52%26%
****16%
********
30
40
t Rel
aps
43%19%
47% 26%
30%
29%45% 26%
26%
38%14%
*8%
31%
10
20
Perc
ent
83
24.3mg/d77
25%
136
12.5mg/d225 = N
245mg/d223 188 135 404
1.8mg/d140
546mg/d404
23%
0.7mEq/L164
26%
0.6mEg/L36494
85ug/mL187
24%31%
1.0mEq/L
91
Ketter TA (ed). Handbook of Diagnosis and Treatment of Bipolar Disorder, Am Psych Pub, Inc.,
0 PBO83
Keck 06ARI77
PBO136
Tohen 06OLZ
225 = N
LTG223
PBO188
Goodwin 04 Quiroz 10PBO135
PBO404
Weisler 11RSP
140
QTP404
Li
164
Li364
PBO94
Bowden 00DVPX
187
Li91
Approved maintenance treatments generally have single-digit NNTs.
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ผปวยหญงคอาย 30 ป พนกงานบญช ผปวยหญงคอาย 30 ป พนกงานบญช
สามพามาตรวจ และใหประวตวา 2
สปดาหกอนผปวย หลงจากทะเลาะกบ
เจานายททางานผปวย เรมมพฤตกรรม
ผดปกต พดเสยงดง และเรวขน อารมณด
ครกครนมากกวาปกต มความมนใจใน
ตวเองมากขน ใชจายเงนมากขน บอกวา
ตวเองเปนพระเจากลบชาตมาเกด คนอน
โง นอน 2-3 ชวโมงตอวน
ไมเคยมประวตความเจบปวยทางจตเวช
และปฏเสธการใชยาสารเสพตดใด ๆ
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Hospitalization for 2 weeksHospitalization for 2 weeks
Manic episode with psychotic features OLZ 20 /h L 2 /hOLZ 20 mg/hs , Lorazepam 2 mg/hs
นด F/U OPD 2 สปดาห /
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Overview of 22 Acute Mania Registration Studies5 Combination
Therapy Studies17 Monotherapy
Studies
g
NNT 5 6Monotherapy vs Placebo Combination vs Monotherapy
rs crea
se)
5059.4%
60
18.1%
********
spon
der
atin
g de
c
40 41.3%49.9%
20.0%
erce
nt re
man
ia ra
20
3029.9%
Pe(≥
50%
m
10N = 2258 N = 862 N = 646N = 1798
0Li/DVPX/CBZ/SGA
N = 2258
SGA + Li/DVPX
N = 862
Li/DVPX
N = 646
Placebo
N = 1798
Ketter TA (ed). Handbook of Diagnosis and Treatment of Bipolar Disorder, Am Psych Pub, Inc., W hi t DC 2010
Montherapy vs. Placebo, Combination therapy vs. Monotherapy increase Response Rate %
****p < 0.0001.
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Acute Mania Monotherapy Registration Studies
NNT 4 47 5 7 5 855Somnolence / Sedation
27 67 6 5 9NNH 695Somnolence / Sedation
Weight Gain
)
609NNH ?723 71 -1281713 17
Weight Gain
onde
rsg
decr
ease
40
50
ent R
espo
ania
ratin
g
20
30
Perc
e(≥
50%
m
10
20
707mg/d
2778mg/d
1950mg/d
586mg/d
121mg/d
28mg/d
18mg/d
4.6mg/d
15mg/d
Adapted from:Ketter TA (ed). Handbook of Diagnosis and Treatment of Bipolar Disorder, Am Psych Pub, Inc.,
0N=1938
Placebo(pooled)
Carbamazepine
gN=223
Divalproex
gN=261
Lithium
gN=134
Quetiapine
gN=357
Ziprasidone
gN=268
Aripiprazole
gN=260
Asenapine
gN=357
Risperidone
gN=434
Olanzapine
gN=124
Weight gain > Somnolence / Sedation > Antimanic variability.
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ชวงหลงออกจาก รพ มอารมณเศราตลอด
กนจขน หวบอย นาหนกตวเพมขน 3 kgs โ
อารมณเศราดขนบาง แตยงรสกออนเพลย
ไมอยากทาอะไร และไมคอยมสมาธ นาหนก
นอนวนละ 10 ชวโมง
Mood ‐ depressed
เพมขน 2 kgs นอนวนละ 10 ชวโมง
Anhedonia, fatigue, Decreased concentration, psychomotor retardation
Mood ‐ depressedDrowsinesspsychomotor retardation
2wks 4 wks
Olanzapine 10 mg/hs10 mg/hs
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A. ลดขนาด olanzapine
B เปลยนยาเปน lamotrigineB. เปลยนยาเปน lamotrigine
C. เปลยนยาเปน lithium or divalproexdivalproex
D ป ป i idD. เปลยนยาเปน risperidone
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Lamotrigine maintenance studyLamotrigine maintenance study
• Lamotrigine and lithium were superior to placebowere superior to placebo in time to intervention for any mood episodey p
• Lamotrigine was superiorLamotrigine was superior to placebo for time to intervention for depression
Mean LTG dose was 245 mg/day,
Goodwin et al. 2004
mean serum LI level was 0.7 mEq/L
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Overview of Monotherapy Bipolar Preventive StudiesNumbers Needed to Treat for Relapse/Recurrence Prevention, Rates
NNT 639 4 47 4
Contemporary Registration Studies Other Studies8 14
p ,
NNT 6Aripiprazole
vsPlacebo
3Olanzapine
vsPlacebo
9Lamotrigine
vsPlacebo
4Risperidone
vsPlacebo
4Quetiapine
vsPlacebo
7Lithium
vsPlacebo
4Lithium
vsPlacebo
8Divalproex
vsPlacebo
14Lithium
vsPlacebo
70
80
rren
ce 80%
33%
***
*
Quetiapineunapproved for
maintenancemonotherapy
****
Divalproexunapproved for
maintenancemonotherapy
* p < 0.05, *** p < 0.001, **** p < 0.0001 vs. PBO.
50
60
se/R
ecur
*
33%
47%
11%
50%
*61%
56%****
52%26%
****16%
********
30
40
t Rel
aps
43%19%
47% 26%
30%
29%45% 26%
26%
38%14%
*8%
31%
10
20
Perc
ent
83
24.3mg/d77
25%
136
12.5mg/d225 = N
245mg/d223 188 135 404
1.8mg/d140
546mg/d404
23%
0.7mEq/L164
26%
0.6mEg/L36494
85ug/mL187
24%31%
1.0mEq/L
91
Ketter TA (ed). Handbook of Diagnosis and Treatment of Bipolar Disorder, Am Psych Pub, Inc.,
0 PBO83
Keck 06ARI77
PBO136
Tohen 06OLZ
225 = N
LTG223
PBO188
Goodwin 04 Quiroz 10PBO135
PBO404
Weisler 11RSP
140
QTP404
Li
164
Li364
PBO94
Bowden 00DVPX
187
Li91
Approved maintenance treatments generally have single-digit NNTs.
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