Prof. DR.

Joesoef Simbolon, SpKJ (K)

Dept. Psikiatri FK UISU
Medan
 The philosopher Martin Heidegger said,
that to be human means to be a question in
search of an answer

One of the most essential challenges that

faces us, is to ask,
who can I become and why should I say yes to
life?
He saw the world in a way no one could have imagined.

4
 Do you ever feel that others are against you?

Do you believe that others are influencing

your mind?

Do you believe that other people talk about

you?

Can you communicate with animals?

Do you ever feel that your professor / the
editor is against you?

Do you believe that drug companies are

influencing your mind?

Do members of your clinical / research team

gossip about you?

If you have a pet, can you tell what it is thinking?

 Decreases in
Overall grey matter (-2%)
Superior temporal gyrus (-
7%)
Amygdala, hippocampus (-
6%)
Parahippocampal (-6%)
Thalamus (-4%)
Frontal lobes (-2%)
Increases in
Globus pallidus (24%)
Putamen (6%)
Caudate (4%)
Wright IC et al. Am J Psychology. 2000;157:16-25.
Negative symptoms
& cognitive
impairment

Excess
Striatal DA

Hyperstimulation
D2 receptors

Positive
symptoms

Feedback effect on Frontal Function

 Stages of Illness
Premorbid Prodromal Onset/ Residual/Stable
Deterioration

Healthy


Worsening
severity
of
signs
and
symptoms

10 20 30 40 50
Gestation/birth Puberty
Years

Adapted from Lewis DA, Lieberman, JA. Neuron. 2000;28:325-334.

 WHAT ARE THE KEY CHALLENGES ?
Brain tissue loss

Social integration Functionality

Symptoms remission

Subjective well being

Treatment adherence

Treatment resistant
 Reducing mortality Promoting functional
rates recovery

Reducing the Challenges Improving

risk of relapse adherence to
and associated antipsychotic
brain tissue loss medication
Ongoing need for novel
treatments that offer
additional advantages,
eg neuroprotection
 Acute setting Long-term
treatment
Maintain remission and
Stabilise acute symptoms prevent relapse

Improve cognition, insight,

Improve negative symptoms role and social functioning

Achieve treatment adherence through

Improve mood symptoms good psychiatrist-patient relationship

Attain full
Optimise treatment
functional recovery

Arango & Bobes 2004; Kane 2007

Efficacy
Positive symptom relief Negative symptom relief
Hostility, aggression Improve mood and
Smooth IM to PO transition depressive symptoms
Cognitive improvement
Control
Behavior
(agitation) Relapse Prevention
1-3 days 7-14 days 6+ months
Acute dystonia EPS TD
Sedation Drug-drug interactions Hyperprolactinemia
Orthostasis QTc prolongation Weight gain
QTc prolongation Hyperglycemia
QTc prolongation

Safety
1970 Haloperidol Positive Symptoms
Clozapine
DSM III
1980 Risperidone
DSM III R
Sertindole Negative Symptoms
1990
Olanzapine Affective Symptoms
Amisulpride Cognitive Symptoms
DSM IV Quetiapine IR
2000 Ziprasidone
DSM IV TR Aripriprazole
Paliperidone ER
Quetiapine XR
 INVEGA/
CLOZARIL RISPERDAL ZYPREXA SEROQUEL GEODON ABILIFY

Low Blood Pressure +++ + +/0 ++ 0/+ 0/+

Dry mouth,
constipation +++ 0 +/++ 0 0 0
Tremors, stiffness,
endocrine problems
0 +/++ 0/+ 0 +/0 0
Sedation +++ +/- ++ +++ 0 0
Weight gain ++++ + ++++ ++ -/+ -/+
Lipids +++ + +++ ++ 0 0
Blood sugar +++ + +++ ++ 0 0

CLOZ = clozapine; RIS = risperidone; OLZ = olanzapine; QUET = quetiapine; ZIP = ziprasidone; ARIP =
aripiprazole; Adapted from: Nasrallah HA, Mulvihill T. Ann Clin Psychiatry. 2001(Dec);13(4):215-227
 Past Areas of Current Medical Realities
Concern
Diabetes TD

Weight Gain
Tardive Prolactin
Hyperlipidemia
Dyskinesia Insulin
Sedation
Weight Resistance
Gain
Insulin Hyper-
Resistance Sedation Coronary Heart
lipidemia
CHD Disease
Prolactin
Drug Weight Gain Risk for Worsening
Diabetes Lipid Profile

Clozapine (Clozaril) +++ ++ ++

Olanzapine (Zyprexa) +++ ++ ++

Risperidone (Risperdal) ++ +/- +/-

Paliperidone (Invega)
Quetiapine (Seroquel) ++ +/- +

Aripiprazole* (Abilify) +/- - -

Ziprasidone* (Geodon) +/- - -

+ = increase effect; - = no effect; D = discrepant

results. *Newer drugs with limited long-term data.
 Inquiry Measure Lab
Personal or family history: Height Fasting Glucose
Diabetes Weight Fasting Lipids
Hypertension Waist circumference
CHD (MI or Stroke) Blood Pressure
Cigarette smoking
Diet
Physical Activity

And - trying to use medications which have fewer

metabolic side effects!
ARIPIPRAZOLE IN THE
TREATMENT OF
SCHIZOPHRENIA
 Mood-stabilizing
Effective for properties
positive and negative Low EPS, TD
symptoms

Ideal
Cognitive
benefits
antipsychotic Affordable

Less change in No adverse

body weight long-term health
Improved consequences
function and
quality of life

22
 COMMUNITY TREATED SCHIZOPHRENIC PATIENTS
( naturalistic setting in daily psychiatric practice)

Schizophrenic patients
- whose clinical symptoms are not optimally controlled or
- who experience tolerability problems (weight-gain, prolactin,
somnolence,
cognition, energy, akathisia,
E.P.S., mood) randomized, open, comparative

Abilify 10-30 mg Standard of Care

(n=284) (n=271)
olanzapine:5-20 mg
quetiapine:100-800 mg
risperidone:2-8 mg
26 weeks
INVESTIGATORS ASSESSMENT QUESTIONAIRE
BODY-WEIGHT, DYSLIPIDEMIA, PROLACTINEMIA
QUALITY-OF-LIFE , IMPACT OF WEIGHT ON QUALITY-OF-LIFE
PROLACTINEMIA ASSOCIATED SEXUAL-DYSFUNCTION
PREFERENCE OF MEDICATION
4thEuropean Congress of Psychiatry Nice-France,2006 & A.P.A.,Toronto-Canada 2006
 BETTER QUALITY OF LIFE
ABILIFY Abilify 10-30mg (n=284) vs Standard of Care
(n=271)
(olanzapine:5-20mg / quetiapine:100-800mg / risperidone:2-8m

MEAN CHANGE IN SCORE

 STAR: 26 week Naturalistic Trial in Schizophrenia

NOT INDUCE WEIGHT -GAIN

ABILIFY
Abilify 10-30mg (n=284) vs Standard of Care
(n=271)
(olanzapine:5-20mg / quetiapine:100-800mg / risperidone:2-8mg

MEAN WEIGHT-CHANGE FROM BASELINE AT WEEK-26 (kg)

2.1 kg
Observed Case
Standard of Care
olanzapine:5-20mg
quetiapine:100-800mg
risperidone:2-8mg

1.3 kg
Abilify 10-30mg

26

Corey-Lisle.14thEuropean Congress of Psychiatry Nice-France,2006 & A.P.A.,Toronto-Canada 2006

 IMPROVES QUALITY OF LIFE
ABILIFY Abilify 10-30mg (n=284) vs Standard of Care (n=271)
(olanzapine:5
-20mg /quetiapine
:100-800mg / risperidone:2
-8mg)

CHANGE FROM BASELINE

IN IMPACT -OF -WEIGHT ON QUALITY -OF -LIFE AT WEEK -26

* :p:p << 0.001

0.01
** Abilify

Abilify Abilify
SoC Abilify

SoC Abilify
SoC SoC
SoC AbilifySoC
Total Physical Self Sexual Public Work
Score Function Esteem Life Distress
P.Corey-Lisle.14thEuropean Congress of Psychiatry Nice
-France,2006 & A.P.A.,Toronto
-Canada 2006
 STAR: 26 week Naturalistic Trial in Schizophrenia

NOT INDUCE HYPERPROLACTINEMIA

ABILIFY Abilify 10-30mg (n=284) vs Standard of Care
(olanzapine:5-20mg / quetiapine:100-800mg / risperidone:2-8
(n=271)
MEAN PROLACTINEMIA-CHANGE FROM BASELINE (mg/dL)

Standard of Care
(- 12.3mg/dL)

Abilify
(- 32.1 mg/dL)

Hanssens. 14thEuropean Congress Psychiatry, Nice-France 2006 & APA Toronto-Canada 200
 NOT INDUCE SEXUAL DYSFUNCTION
ABILIFY Abilify 10-30mg (n=284) vs Standard of Care
(n=271)
(olanzapine:5-20mg / quetiapine:100-800mg / risperidone:2-8m

IMPROVEMENT OF MEAN SCORE FROM BASELINE

IN ARIZONA SEXUAL EXPERIENCE SCALE
sex-drive, arousal, vaginal lubrication / penile erection,
ability to reach orgasm, satisfaction with orgasm

SoC
SoC SoC

p=0.025
p=0.005 p=0.012
Abilify
Abilify
Abilify

6 point-Likert scale: 1=better functioning ; 6=worse functioning L.O.C.F.

 NOT INDUCE DYSLIPIDEMIA
ABILIFY Abilify 10-30mg (n=284) vs Standard of Care
(n=271)
(olanzapine:5-20mg / quetiapine:100-800mg / risperidone:2-8m

TRIGLYCERIDES (mg/dL) TOTAL CHOLESTEROL (mg/dL)

Standard of Care
Standard of Care

Abilify

Abilify

HDL-CHOLESTEROL (mg/dL) LDL-CHOLESTEROL (mg/dL)

Abilify Standard of Care

Abilify
Standard of Care

.
R.Kerwin. 14thEuropean Congress of Psychiatry Nice-France,2006
 EVIDENT BASED EFFECTIVENESS
ABILIFY in daily psychiatric practice
Abilify 10-30mg (n=284) vs Standard of Care
(n=271) (olanzapine:5-20mg / quetiapine:100-800mg / risperidone

HIGH PREFERENCE OF MEDICATION

 Safety & Tolerability of Aripiprazole
Weight : Mean weight change of -1.26 kg in a 26-week trial1
1.05 kg in a 52-week
trial 2

Glucose : Comparable to placebo 1

Lipids : Comparable to placebo 1

QTc interval : No significant difference from placebo 3

Orthostatic hypotension : 1.9% vs placebo 1.0%

Somnolence : 11% vs placebo 8% 3

E.P.S. : 6.0% vs placebo 5.8% 3
Prolactinemia : 1.8% vs placebo 7.0%3
Constipation : 10.3% vs placebo 7.7%3
Discontinuation rate due to adverse events & all reasons :
1)Pigott.J Clin Psychiatry 2003; 2)Kasper.Int J
comparable to
placebo
Neuropsychopharmacol 2003;
3) Marder.Schizophr Res 2003
It isnt possible to
get values and
color. You cant be
at the pole and the
equator at the same
time. You must
choose your own
line, as I hope to
do, and it will
probably be color.
 Oleh:
Prof.dr.H.M.Joesoef Simbolon,
SpKJ(K)
 Informasi pasien
Usia : 18 tahun
Alamat : Jln. Gaperta Gg. Sekata No. 14, Medan
Status : belum menikah
16 Oktober 2009
Keluhan
Sering emosi, 2 bulan yang lalu melempar rumah tetangga
hingga kacanya pecah sehingga menimbulkan keributan. 1
bulan yang lalu keadaan terulang kembali
Halusinasi pendengaran, waham curiga
Sekolah terganggu, lebih sering mengurung diri di kamar, tidur
terganggu
Diagnosa sementara
Skizofrenia Paranoid
 Anjuran
Rawat inap, keluarga masih menolak minta rawat jalan
saja
Pasien diungsikan ke rumah kakeknya
Therapi
Abilify 10 mg 1 x 1 pagi
Heximer 2 mg 1 x 1 pagi
Iterax 1 x 1 malam
30 Oktober 2009
Keluhan
Agak membaik, bisa bermain dengan saudara sepupu.
Kadang-kadang halusinasi pendengaran dan waham
curiga masih ada
Ada ide bunuh diri
 Therapi
Abilify 10 mg 1 x 1 pagi
Heximer 2 mg 1 x 1 pagi
Iterax 1 x 1 malam
Iglodep 50 mg 1 x 1 pagi
Selanjutnya kontrol setiap 2 minggu dan keadaan
semakin membaik dan sudah sekolah kembali
3 Februari 2010
Kemauan belajar semakin baik bahkan sudah mau
mengikuti les di rumah karena ingin lulus dalam ujian
akhir
Obat diteruskan
 Informasi pasien
Usia : 25 tahun
Alamat : Jln. T.Cut Ali No. 186, Tapak Tuan
Status : belum menikah
10 September 2009
Keluhan
Terganggu tidur takut diguna-gunai orang lain, ada rasa sedih
karena sejak 10 bulan yang lalu putus dengan pacarnya karena
dinikahkan orang tuanya dengan orang lain
Rasa putus asa bahkan pernah berencana bunuh diri, tapi tidak
dilakukan karena masih takut berdosa
Mendengar suara-suara yang menuduhnya sebagai orang
bodoh
Pemeriksaan PD = tak
 Diagnosa sementara
Episoda Depresif dengan gejala psikotik
Therapi
Iglodep 50 mg 2 x 1
Abilify 5 mg 1 x 1 pagi
Heximer 2 mg 1 x 1 pagi
Iterax 1 x 1 malam
Psikoterapi
16 Oktober 2009
Ada kemajuan, mampu menerima hasil diskusi
Suara-suara di telinga kadang masih ada yang
menimbulkan rasa jengkel
Therapi dilanjutkan
 17 November 2009
Banyak kemajuan bahkan Os sudah ada. Mampu
menerima calon suami yang dijodohkan orang tua
Obat dilanjutkan
21 Desember 2009
Keadaan semakin membaik sudah mulai mampu
bicara banyak dan melupakan masa lalu yang tidak
mengenakkan
Obat dilanjutkan
20 Januari 2010
Tenang, pikiran cerah, bulan depan direncanakan
menikah
Obat dilanjutkan
 Informasi pasien
Usia : 11 tahun
Alamat : Jln. Pahlawan No. 9 Delitua
Status : belum menikah
18 Februari 2004
Keluhan
Belum bisa bicara, sosialisasi (-), emosional, tantrum
dan tidak suka mendengar suara genset
Therapi
Risperdal 0,200 mg
Artane tab
Sach. Lactis qs 2 x 1
Tab Aricepts 5 mg 1 x
Pasien selalu kontrol dengan teratur
 30 Juli 2007
Mulai bisa bicara
Tetapi tantrum masih ada
Badan semakin gemuk dan masih emosional
Kontrol teratur
26 Februari 2009
Mulai bisa membaca dan berhitung
Tantrum tetap ada
Badan bertambah gemuk
Emosional
29 Januari 2010
Risperdal 0,200 mg diganti Abilify 2,5 mg
Pengamatan seminggu emosi dan tantrum semakin
terkendali
 Informasi pasien
Usia : 28 tahun
Alamat : Simpang Naga Pane Tiga Runggu. Kecamatan
Purba
Status : menikah
25 Juni 2002
Keluhan
Banyak diam
Mau ketawa sendiri
Emosi meningkat
Sudah pernah berobat diSembada 4 tahun dan opname 2
minggu
Bicara ngawur
Mandi (-), suka mencari barang yang aneh-aneh
Memukul
Merokok
 Therapi
Zoloft 2 x 1
Clozaril 25 mg 1 x 1
13 April 2006
Keluhan
ketawa sendiri
Banyak diam
Emosi
Therapi
Risperdal 2 x 1
Cpz 2 x 1
Haloperidol 2 mg 2 x 1
 1 Juni 2006
Therapi
Abilify 10 mg 1 x 1
10 Juni 2006
Therapi
Abilify 10 mg 1 x 1
Clozaril 25 mg 1 x 1
5 Desember 2009
Therapi
Abilify 5 mg 1 x 1
Clozaril 25 mg 1 x 1
 Informasi pasien
Usia : 30 tahun
Alamat : Suka Maju, Sei Mencirim
Status : belum menikah
21 November 2009
Keluhan
Merasa kepalanya panas, pening
Tidur (-)
Bicara ngawur
Merasa dirinya dukun
Therapi
Abilify 10 mg 1 x 1
Iterax 1 x 1 (malam)
Iglodep 50 mg 1 x 1
 23 November 2009
Keluhan
Bicara ngawur
Tidur (-)
Therapi
Risperdal 2 mg 2 x 1
Cpz 100 mg 1 x 1
10 Desember 2009 6 Januari 2010
Therapi
Abilify 10 mg 1 x 1
Iterax 1 x 1
Iglodep 50 mg 1 x 1
Clopin 25 mg 1 x 1
 Informasi pasien
Usia : 30 tahun
Alamat : Jln. Seroja, Medan
Status : belum kawin
15 Oktober 2008
Keluhan
Merasa kedinginan
Pernah memakai narkoba (sabu-sabu)
Gelisah
Tidur (-)
Therapi
Haloperidol 2 mg 2 x 1
Ludiomil 25 mg 1 x 1
Trileptal 300 mg 2 x
 21 Januari 2009 4 Januari 2010
Therapi
Abilify 10 mg 1 x
Zoloft 1 x
Alganax 1 mg 2 x 1
Merlopam 2 mg 1 x 1
Depakote 500 mg 1 x 1
 Informasi pasien
Usia : 24 tahun
Alamat : Jln. Bahagia No.2 Tanjung Balai
Status : menikah
6 November 2007
Keluhan
Banyak menghayal
Gelisah
Bicara ngawur
Emosional
Tidur (-)
Therapi
Risperdal consta
Abilify 10 mg 1 x 1
 21 November 2007 12 Agustus 2009
Therapi
Abilify 10 mg 1 x 1
Luften 100 mg 1 x
10 November 2009
Keluhan
Bicara ngawur
Marah-marah
Senyum sendiri
Telanjang
Tidur (-)
Therapi
Risperdal 2 mg 2 x 1
Cpz 100 mg 1 x 1
2 Desember 2009 13 Januari 2010
Therapi
Abilify Os 1 x 10 ml
 Informasi pasien
Usia : 30 tahun
Alamat : Desa Surbakti, Kec. Simpang Empat, Kab.
Karo
Status : belum menikah
6 Januari 2007
Keluhan
Dengar-dengar suara
Marah-marah
Mengganggu orang lain
Therapi
Risperdal 2 mg 2 x 1
Cpz 100 mg 1 x 1
 28 Agustus 2007
Keluhan
Sering menguap
Emosi
Gelisah
Tidur (-)
Therapi
Risperdal 2 mg 2 x 1
Cpz 100 mg 1 x 1
17 September 2007 17 November 2009
Therapi
Risperdal 2 mg 2 x 1
Stelazine 5 mg 2 x 1
Sizoril 25 mg 1 x 1
6 November 2009 26 Desember 2009
Therapi
Abilify 5 mg 1 x 1
Stelazine 5 mg 2 x 1
Sizoril 25 mg 1 x 1
Tribestan 2 x 1
 Informasi pasien
Usia : 21 tahun
Alamat : Desa Pulou, Labuhan Batu
Status : belum menikah
12 Juli 2007
Keluhan
Bingung
Bicara sendiri
Tertawa sendiri
Halusinasi
Tidur (-)
Therapi
Risperdal 2 x 1
Cpz 100 mg 1 x 1
 8 Agustus 2007 23 Juli 2009
Therapi
Risperdal 2 mg 2 x 1
Sizoril 25 mg 1 x 1
5 Agustus 2009 14 Januari 2010
Therapi
Abilify 5 mg 1 x 1
Sizoril 25 mg 1 x 1
Trilestand 2 x 1
 Informasi pasien
Usia : 37 tahun
Alamat : Jln. Batu Tulis Petisah
Status : menikah
1 Januari 2000
Keluhan
Marah-marah seperti yang kesurupan
Menari-nari
Bicara ngawur
Therapi
Risperdal 2 mg 2 x 1
Cpz 100 mg 1 x 1
30 Oktober 2001
Keluhan
Marah-marah
Bicara sendiri
 Therapi
Risperdal 2 mg 2 x 1
Cpz 100 mg 1 x 1
13 Agustus 2002 20 Agustus 2009
Keluhan
Tenang
Therapi
Risperdal 2 mg 2 x 1
Cpz 100 mg 1 x 1
31 Agustus 2009 20 Januari 2010
Keluhan
Tenang
Therapi
Abilify 10 mg 1 x 1
Iterax 1 x 1
 Sekian
dan
Terima Kasih