SCHIZOPHRENIA

Around 0,3 % population , 60 % mental hospital

in-patients

ETIOLOGY:
I. -Heredoconstitutional factor:
the possibility of schizophrenia:
-one parent (+) , children 7-16 % (+)
-all parent (+) , children 40 %
-monozygotic twin ----85,8 %
-dizygotic twin -------14 %
II. -Psychogenic factor
III. -Exogenic factor
SYMPTOMATOLOGY

-Attention and initiative markedly decrease

-Lazy, lack of self care
-Psychical contact limited,monosyllable, poker face
-Flat affect , emotion difficult to feel, no empaty
-Concentration decrease, discriminative insight disturbed,
but no dementia

-Thought process: association disorders--incoherence,often

with delusion and hallucination. Dereistic thinking, neologisme,
hemmung & sperrung.Sometimes there are depersonalization &
derealization.

-Behavioural symptoms: abulia or hypobulia and also often

impulsivity.
 Usually there's pre-schizophrenic periode around
2 years, e.g
-emotional withdrawl, appearing faraway , apathy,
feeling unwelcome, lack of social contacts,
begining lack of nuance feeling, and finally
went to poor emotional life & dysharmonious
so it finally become unfelt and inapropriate.

The symptoms above are similar with the residual type

which there's remission with sequelle.
THE MAIN CLINICAL FEATURES

-a certain psychotic characteristic during the

active phase,
-multiple specific psychological symptoms,
-deterioration,
-onset before 45 years,
-minimal 3-6 months (PPDGJ-II),
-not because of affective /organic mental
disorders
PRODORMAL OR RESIDUAL SYMPTOMS

-isolation,social impairment, bizzare behavior,lack of self care,

flat affect,blunted or inapropriate, unusual ideas or magical
thought,unusual perception e.g ilusion.

During the phase of the illness minimal there's one of the

following symtoms:
-bizzare delusion,controlled,broadcast/insertion/withdrawl,with
-somatic,megalomania,nihilistic delusions,
-delusion of persecution or jealousy with hallucination,
-auditoric hallucination-comment or dialogue
-auditoric hallucination not related to depression or euphoria
-incoherence
SUBTYPES OF SCHIZOPHRENIA

It's better to look the longitudinal history of the illness.

The classical subtypes of schizophrenia are:

-hebephrenia, catatonia and paranoid type (Kraepelin),
-simplex/simple type ( Bleurer).
Simple type
-slowly beginning, hallucination not frequent/rare,
-limited thought, inability to absstract thought,
-association disorders rare,
-bizzare behavior ass. with emotion,attention & activity.
Hebephrenic type
-rapid disintegration, very disturbed association, a lot of
incoherence, neologisme.
-bizzare delusions, frequent cheerfull hallucinations,
-severe regression, frequent mannerism, deep autism.
Catatonic type
-frequently as stupor or furor catatonic ,
-catalepsy symptoms or flexibilitas cerea.
Paranoid type
-predominant delusions with hallucinations

Schizophreiform disorder
-premorbid tends to normal,
-acute, during 2 weeks untill 6 months
-hazy conciousness,oneroid, double book-keeping
symptom

Schizoaffective type,
-dominant affective symptoms,

Laten type
-unclear symptoms, hide/silent

Residual type
-remission with residual symptoms
DIAGNOSIS

1.Eugen Bleurer: 4 As
Primary symptoms:-association disorders,
-affect disorders,
-autism,
-ambivalence.
Secondary symptoms:-delusions,hallucinations etc.

2.Kurt Schneider:
First rank symptoms:
-halucinations;audible thought, dialogue,commentary
-somatic passivity experience,
-thought process:
-interruption/thought withdrawl,thought broadcast,
-delusional peceptions,
-changing desire-
3.PPDGJ (according to ICD & DSM )
In PPDGJ III schizophrenia is in Group II
Hierarchi of Mental Illness Block Diagnosis
( F20-F29 ) where more completely ass.with
schizotypal disorder , acute & transient
psychotic disorders which can be followed
by schizophrenic symptoms and also
schizophrenic-like type ,and post
schizophrenic depression.
DIFFERENTIAL DIAGNOSIS
-Mental organic disorders
-Other functional psychosis
-Hysteria/Dissociative dsisorders
-Beliefs, tradition, religious
TREATMENTS / MANAGEMENT THERAPY OF SCHIZOPHRENIA

I.Hospitalization

II.Somatic treatments/biological therapies

-pharmacotherapy:
usually using major tranquillizers (antipsychotic/neuroleptic drugs),
first choice is the classic typical antipsychotic and if no progress use
the newer generation of drugs it's the atypical antipsychotic drugs
-other drugs : lithium,anticonvulsants,benzodiazepines
-other biological therapies
-ECT as the last choice if there's no progress in drugs therapy

III.Psychosocial therapies
-Social skills training
-Family-oriented therapies
- Case management
-Assertive community treatment(ACT)
-Group therapy
-Cognitive behavioral therapy
-Individual psychotherapy
-Vocational therapy
PROGNOSIS-I
-40% remission-social recovery,60% deteriorated.
-Less than one year 30% full remission,30% social recovery &
30% will be long stay in mental hospital

-Bad prognosis:
flat affect, lack of initiative,depersonalization & derealization,
bad premorbid personality,gradual symptoms too high perso
nal aspiration,signs of hypochondriasis,persistent hallucination,
recovery more than one year, deep regression.

-Good prognosis:
acute,clear affective ..elements, clear anxiety or emotional
signs, cyclothymic premorbid personality, self-accused hallucination,
longer interval of remission.

-Robin & Guze :

Good :good premorbid personality,clear precitating factor,negative
family hystory or affective elements,clouding conciousness, acute
onset, no flatness of affect, paranoid symptoms.
PROGNOSIS-II (Kaplan & Sadock’s)
To evaluate the prognosis it's better to look up the longitudinal history of illness
begins with the family hystory and at last how about the support system.

Features weighting towards good to poor pronosis in schizophrenia

-Good prognosis
-Family history of mood disorders
-Good premorbid social,sexual & work hystories
-Late onset
-Married
-Acute onset
-Obvious precipitating factors
-Mood disorder symptoms (especially depressive disorders)
-Positive symptoms
-Good support systems
-Poor prognosis
-Family history of schizoprenia
-History of perinatal trauma
-Young onset
-Poor premorbid social,sexual & works histories
-Single,divorced or widowed
-Insidious onset
-No precipitating factors
-Neurological signs & symptoms
-Withdrawn,autistic behavior
-Negative symptoms
-No remmission in 3 years
-Many relapses
-History of assaultiveness
-Poor support systems
F 20. SCHIZOPHRENIA----PPDGJ III / ICD-10
*Schizophrenia and schizotypal --starting almost
similar.

*In schizophrenia:
-distortion of thought & perception
-hallucination & perception changes,
---confusion,elliptical & unclear thought,
-motility--interrupted & interpolation,
-thought insertion,
-inappropriate & blunted affect,
---shallow,capricious,incongruous,
-ambivalency & desire -disorders (volition ):
-inertia,negativism,stupor catatonia,
- the course of illness:
-acute onset or gradual-silent,
-later becomes broader variation,
-not always chronic or become worse
DIGNOSTIC GUIDELINES

Minimal one month at- least one of the following symptoms:

a.thought echo/insertion/withdrawl/broadcast,
b.delusion of control/influence-passivity,
c.comment/dialogue/discussion hallucinations or from the
organs of the body,
d.bizzare delusion
or at least two of the following symptoms:
e.persistent hallucination/delusion/overvalued ideas,
f.interrupted motility thought/insertion-incoherence/neologisme
g.catatonic behavior:excitement,posturing,mutism,negativism
flexibilitas cerea,stupor.
h.negative symptoms :apathy, paucity speech,blunting/
incongruity emotional response,resulting in social withdrawl/
lowering social performance and all of these causing:
i.a significant and consistent change in the overall quality of
some aspect of personal behavior manifest as loss of interest,
aimlessness,idleness,a self absorbed attitude and social
withdrawl
Retrospective:
-prodormal phase/non psychotic:
-loss of interest in works,social activities and personal
appearance and hygiene together with generalized anxiety
and mild depression and preoccupation,before the psychotic
symptoms for some weeks/month

Pattern of course:
-continuosly,
-episodic with progressive deterioration,
-episodic with stable deficit,
-episodic remittent,
-with incomplete remission or
-complete remission.
-other,
-periode of observation less then one year.

Criteria of time for residual schizophenia minimal 1 year and for

schizotypal disorder 2 years, if the psychotic phase not yet 1
month, the preliminary diagnosis is Acute Schizophrenic-like
Disorder.
Subtypes of schizophrenia

F 20.0 Paranoid schizophrenia

The general criteria for a diagnosis of schizopheni must be satisfied.In addition,
hallucinations and/or delusions must be prominent,and disturbances of affect,
volition and speech,and catatonic symptoms must be relatively inconspicious.
Delusions can be of almost any kind but delusions of control,influence,or passivity,
and persecutory belief of various kinds are the most characteristic.,

F20.1 Hebephrenic schizophrenia

A form of schizopohrenia in which affective changes are prominent,delusions and
hallucinatons fleeting and fragmentary,behaviour irresponsible and unpredictable,
and mannerisms common.The mood is shallow and inappropriate and often
accompanied by giggling or self-satisfied,self-absorbed smiling,or by a lofty
manner, grimaces, mannerisms,pranks,hypochondriacal complaints,and reiterated
phrases. Thought is disorganized and speech rambling and incoherent.There's a
tendency to remain solitary, and behaviour seems empty of purpose and feeling.
Usually starts between the age of 15 and 25 years and gendss to have a poor
prognosis because of the rapid development of negative symptoms,particularly
flattening of affect and loss of volition.
F20.2 Catatonic schizophrenia
Prominent psychomotor disturbances are essential and dominant features and may
alternate between extremes such as hyprkinesis ands stupor,or automatic obedience
and negativism.Constraineds attitude and postures maybe maintained for long
periods. Episodes of violent excitement maybe a striking feature of the condition.

F 20.3 Undifferentiated schizophrenia

Condition meeting the general dignostic criteria for schizophrenia,but not conforming
to any of the above subtypes,or exhibiting the features of more than one of them
without a clear of predominance of a particular set of diagnostic characteristic.

F 20.5 Residual schizophrenia

A chronic stage in the development of a schizophrenic disorders in which there has
been a clear progression from an early stage comprising one or more episodes of
exacerbation to a later stage.

F 20.6 Simple schizophrenia

Slowly progressive develpment of the characteristic negative symptoms of residual
Schizophrenia without any history of hallucinations,delusions or other manifestations
of earlier psychotic episode,and with significant changes in personal behaviour,
manifest as a marked loss of interesr,idleness,and social withdrawal.
F 25 Schizoaffective disorders
These are episodic disorders in which both affective and schizophrenic symptoms are
prominent within the same episode of illness,preferably simultanously,but at least
within a few days of each other.

F 25.0 Schizoaffective disorder,manic type

There must be a prominent elevation of mood,or a less obvious elevation of mood
combined with increased irritability or excitement.Within the same episode,at least one
and preferably two typically schizophrenic symptoms should be clearly present.

F 25.1 schizoaffective disorder,depressive type.

A disorder in which schizophrenic and depressive symptoms are both prominent in the
same episodes of ilness.Depression of mood is usually accompanied by several
characteristic depressive symptomsor behavioural abnormalities such as retardation ,
insomnia, lost of energy, appetite or weight reduction of normal interests,impairment
of concentration guilt,feelings of hopelessness,and suicidal thoughts.At the same time
or within the same episode,other more typically schizophrenic symptoms are present.
This subtype usually less florid and alarming than manic type,but they tends to last
longer and the prognosis is less favourable.Although the majority of patients recover
completely,some eventually develop a schizophrenic defect.

F 25.2 Schizoaffective disorder,mixed type

Disorders in which symptoms of schizophrenia coexist with those of a mixed bipolar
affective disorder.
 PARANOID DISORDERS
A group of severe mental diorders with the main symptoms
is a variety of delusions, often systematic with or without
hallucinations.
The psychotic symptoms often very clear & sometimes
only delusions which is dominant.

Since Hippocrates,paranoia means "sanity",used again by

Vogel, and more confirmed by Kahlbaum (1863).

Kraepelin: introduce the term paraphrenia and there're 4

type: systematic,expansive,confabulative and fantastic.

Freud: paraphrenia is identically the same as paranoid

schizophrenia.
EPIDEMIOOGY
Prevalence (USA) 0.025-0.03% ( Schizophrenia 0.1 %
and affective disorders 0.5%).Women twice than men
and usually single and suspected with homosexual
orientation and chronic prejudice.

Age:average 40 years,when the delusions cannot be

tolerated anymore, the agression drive will invite
counter agression from the environment and so
make it easier to develope delusion of persecution,
nihilistic etc.,resulting abandoned by friends, feeling
isolated/unwelcome and inferior, finally become
more paranoid.
 SYMPTOMS
The main symptoms:delusions,logic,sistimatic,complex,sometimes
looks like isolated /apart from the personality,so the personality seems
intact, and disturbed when the delusions being touch.

-Persecuted delusions:feels being hatred- by relatives,want to be

unmistakeable, the misintepretation & misunderstanding resulting in
persecuted delusions.

-Delusion of reference if there's a feeling that someone is talking or

commenting obout him/her

-Litygious type: feeling of being treated unfair,feeling of being right and

superior.

-Exaltase type:delusions of grandeur,megalomania,often appear long

time after persecuted delusions, often feels as God‘s mission

-Erotic type:feeling the celebrities fall in love with him/her.

Often appear as suicidal homocidal action.
ETIOLOGY

-Psychogenic cause: frustated ambition drive

-Freud :homosexual fixation
-sadistic experiences during early childhood
( anal sadistic phase)

-Genuine paranoid rarely seen,usually an extension of

paranoid premorbid personality.
-more often in the form of paranoid reaction,
-the defence mechanism which is used: denial &
projection

-Heriditary / constitutional e.g:

-low threshold for frustation,
-rigid in relationship,
-hypersensitivity etc.
Premorbid usually paranoid personality e.g
blame on others easily,many prejudice,
uneasy to confess wrong,often irritable
easily hurt, angry, egocentric and easily
paranoid/ suspicious.

Prognosis:
Not so good in genuine paranoia with
paranoid personality back ground which
begins gradually or if there's a picture of
schizophrenic symptoms because of rarely
full remission.
In PPDGJ II these disorders includes:
-paranoia
-shared paranoid disorders,
-paraphrenia,
-unspecified paranoid disorders

In PPPDGJ III
-F22 Persistent delusional diorders
-F 23.3 Other acute predominantly delusional
psychotic disorder.
-F 24 Induced delusional disorder
SHARED PARANOID DISORDER (Folie a Deux / Trois)

1877: Laseque & Falret: induced psychosis with symptom

of delusions,in close relatives, the induced person
which is submissive,suggestibel, dependent and
emotionally depends on the first.
The used defence mchanism is identification.
INVOLUTIONAL PARAPHRENIA

Rarely genuine,often mixed wirth melancholia

Premorbid full of defence mechanism projection,
inferior,critical,tends to blame others,jealous,
cannot forgive,suspicious.

Symptoms:-organized persecutory delusion,

annoyed, feeling of hostility.

Prognosis:-worse than involutional melancholia

DELUSIONAL DISORDER IN PPDGJ III/ICD-10
-Having uncertain relation with schizophrenia

-Specifically:persistent single/systematic delusions,

sometimes all life ---long.
-Often delusions of persecutory,hypochondriac,grandiose or
which is related with court,jealousy,abormal body,feels
that the body has bad smell or homosexual.
-Depression symptoms can be found intermittently.
-Maybe there're olfactoric and tactil hallucinatios
-Auditoric hallucination appears temporaly & generally in
old age.
-Usually in midslife age ,except in abnormal body delusion
which often in young age
-Often related with environtmental situation,persecutrory
delusion frequently in minority group.

-Apart from the behavior & attitude related with delusions, the
affect, talking & behaviour still normal.
Other persistent delusional disorder

-Delusional disorder with persistent

hallucination or schizophrenic
symptoms which not enough for
schizophrenic criteria and minimally 3
months duration.

-Includes here: delusional dysmorphobia

& involutional paranoid state.
OTHER NON-ORGANIC PSYCHOSIS

Includes here are depressive type psychosis

or excitation, reactive confusional state,
acute or psychogenic paranoid disorders,
brief reactive psychosis and unspecified
psychosis.

Usually there's a real stressor in

interpersonal relatioship problems or
environmental problems which are very
stressfull and generally last during 2weeks
until 6 months and the prognosis usually
good enough
G0LONGAN OBAT ANTIPSIKOTIK / NEUROLEPTIK

I.OBAT ANTI PSIKOTIK TIPIKAL

-phenothiazine: -chlorpromazine: tablet 25mg; 100mg

-levomepromazine: tablet 25 mg; 100 mg
-perphenazine : tablet 4 mg; 8 mg
-trifluoperazine: tablet 5 mg
-thioridazine: 10 mg; 100 mg

-butyrophenone:
-haloperidol: tablet 0,5mg;1,5mg;2mg;5mg

-diphenyl-butyl-piperidine:
-pimozide : tablet 2mg; 4 mg
 TYPICAL NEUROLEPTICS
HYPNOGENIC EFFECT
Levomepromazine

Thioridazine
Reserpin

Chlorpromazine

Haloperidol
Perphenazine
Fluphenazine

Pimozide

ANTIPSYCHOTIC
II.OBAT ANTI PSIKOTIK ATIPIKAL

-benzamide:
-sulpiride :tablet 50mg; 200mg

-dibenzodiazepine:
-clozapine:tablet 25mg; 100mg
-olanzapine:tablet 5mg; 10 mg
-quetiapine: tablet 25mg; 100mg; 200mg
-zotepine:tablet 25mg; 50mg
-aripiprazole; tablet 10mg; 15 mg

-benzisoxazole:
-risperidone: tablet 1mg; 2mg; 3 mg
-paliperidone : kapsul 3mg; 6 mg ;9mg
GOLONGAN ANTIDEPRESAN

1.Golongan ikatan trisiklik

-amitriptyline : tablet 25 mg
-imipramine: tablet 10 mg; 25 mg
-tianeptine: tablet 12,5 mg
2.Golongan ikatan tetrasiklik
-maprotiline : tablet 25 mg; 50mg
-mianserine: tablet 10 mg; 30 mg
-amoxapine: tablet 100 mg
3.Golongan Mono Amine Oxidase Inhibitor (MAOI)Reversible
-moclobemide: 150 mg
4.Golongan Selective Serotonin Reuptake Inhibitor (SSRI)
-sertraline: tablet 50 mg
-fluoxetine: tablet 20 mg
-paroxetine : tablet 20 mg
-fluvoxamine: tablet 50 mg
-citalopram : tablet 20 mg
5.Golongan antidepresan atipikal
-mirtazapine: tablet 15mg; 30mg; 45 mg
-duloxetine: tablet 60mg; 120mg
-venlafaxine Hcl: tablet 75mg; 150mg; 225mg
 OBAT ANTIMANIK

1.Mania akut:
-haloperidol:tab 0,5mg; 1,5mg; 2mg; 5mg
-carbamazepine: tablet 200mg
-valproic: tablet 200mg
-lithium carbonate: tablet 200 mg

2.Profilaksis: -lithium carbonate tablet 200mg

 MEDIKASI ANTIPSIKOTIK

Pada medikasi antipsikotik hendaknya pilihan

berdasar
efikasi obat untuk mengurangi:
1.simptom positif seperti delusi,halusinasi dan
gangguan proses pikir,
2.simptom negatif seperti afek datar, hilangnya
kehendak dan energi serta disintergrasi sosial,
3.simptom kognitif seperti gangguan daya
ingat,kurang
perhatian dan kesulitan pada cara berpikir
abstrak,
4.simptom afektif seperti dysforia,depresi
&suisidalitas.
Dalam hal ini antipsikotik tipikal kurang memenuhi
syarat dan jenis atipikal ternyata lebih baik
 ANTIPSYCHOTICS CLASSIFICATION

First Generation Antipsychotics ( FGA “Conventional”)

1. Low Potency/High Dose: Chlorpromazine
2. High Potency/Low Dose: Haloperidol

Second Generation Antipsychotics (SGA “New atypical”)

1. Serotonin-Dopamine Antagonists ( SDA ) :
Risperidone, Ziprasidone, (Sertindiole)

2. Multi-Acting Receptor Targeted Agents ( MARTA ):

Clozapine, Olanzapine, Quetiapine, Zotepine

Third Generation Antipsychotics ( TGA )

Dopamine System Stabilizers ( DSS ):
Aripiprazole
 PERAN DOPAMIN
Kalau dopamin terlalu sedikit akan mengakibatkan
hipoaktivitas, depresi, simptom negatif serta
perlambatan kognitif.
Bila terlalu banyak dopamin akan menyebabkan
hiperaktivitas, mania, simptom positif serta
akselerasi kognitif.

Dopamin akan meningkatkan sekresi prolaktin,

sedang
serotonin dan histamin akan meningkatkan
sekresi dari prolactin-releasing factor
 THE SEROTONIN-DOPAMINE ( S/D )
THEORY, Meltzer (1995)
Atipikalitas suatu obat antipsikitik dapat diprediksi dari
ratio yang lebih tinggi dari afinitas obat untuk reseptor
serotonin 5HT2a relatif terhadap afinitas reseptor
dopamin D2c

*Afinitas D1/D2:
efikasi thd simptom positif dan kurangnya EPS
*Afinitas 5HT2a:
efikasi pd bidang afektif,simptom negatif, aktivitas
antidepresi dan kurangnya EPS
*Afinitas 5HT6:
kurangnya parkinsonism
*Afinitas NA transporter:
efikasi pada kognitif dan aktivitas anti depresi
Keterbatasan dari Anti-psikotik Tipikal /
Konvensional (generasi pertama)

• Mekanisme kerja
– Antagonis Dopamine D2
• Efektivitas
– Kurang efektif untuk mengatasi gejala negatif
dan kognitif, bisa memperburuk (neuroleptic-
induced deficit syndrome)
• Keamanan dan tolerabilias
– Antagonis reseptor dopamine D2 terkait
dengan efek samping yang menonjol antara
lain EPS, tardive dyskinesia dan
hyperprolactinemia
 Keterbatasan Anti-psikotik Atipikal
(generasi kedua)
• Mekanisme kerja
– Antagonis Dopamine D2 dan
– Antagonis serotonin 5-HT2A
• Efektivitas
– Respon untuk gejala negatif dan gejala kognitif
lebih baik, meskipun masih kurang adekuat
• Keamanan dan tolerabilitas
– Efek samping yang pervasif (berat-badan
meningkat, diabetes, dyslipidemia, efek
anticholinergik, hypotensi, sedasi, dsb.)
 Antipsikotik Konvensional dan
Fungsi Kognitif
Antipsikotik Konvensional
khususnya hanya mengatasi
gejala positif skizofrenia
Antipsikotik Konvensional
tidak memberi dampak
Positif pada fungsi kognitif

Penggunaan antikolinergik
Antipsikotik konvensional dan
untuk terapi EPS
beberapa antipsikotik atipik
dapat memberatkan
dapat menimbulkan EPS
disfungsi kognitif
 Efficacy of atypicals extends beyond
positive symptoms of disease

+ –
Positive Negative Cognitive Affective

Conventional
antipsychotics

Atypical
antipsychotics
 KHASIAT SAMPINGAN
NEUROLEPTIKA ATIPIK
• BERAT TUBUH BERTAMBAH
(Olanzapine,Risperidone, Quetiapine, Zyprasidone,
Aripiprazole)
• DISFUNGSI SEXUAL
• AMBANG RANGSANG KEJANG TURUN
• HIPOTENSI/HIPERTENSI
• RESPIRATORY AKATHISIA (Risperidone,Quetipine )
• AGRANULOSITOSIS ( Clozapine)
• HIPERPROLAKTINEMIA (Antipsikotik tipikal)
• HIPERGLIKEMIA, DM, KETOACIDOSIS, KOMA
(Olanzapine, Risperidone, Quetiapine, Clozapine,
Aripiprazole)
 KHASIAT SAMPINGAN
NEUROLEPTIK ATIPIK-2
• PERPANJANGAN PR & QTc, QRS, DEPR. ST
FLATTENING/NOTCHING T-WAVES, EMERGENCE
OF U-WAVES ( Ziprazidone, Olanzapine, Risperidone)
• KREATIN FOSFOKINASE MENINGKAT
• DYSLIPIDEMIA (Cholesterol, Triglyceride)
• SOMNOLEN ( Clozapine) / INSOMNIA(Aripiprazole)
• NYERI KEPALA/AGITASI
• MULUT KERING
• ALT & AST MENINGKAT
 Risiko EPS rendah: ciri AP Atipik

Meningkatkan
Kepatuhan
Tak memberatkan Risiko TD
Gejala Negatif rendah

Keuntungan
EPS rendah
Tak mengganggu Efek samping
Kognisi Motorik ringan
Risiko
Dysphoria
kurang

December 3, 2007
Jibson & Tandon 1998
Konsekuensi yang merugikan
peningkatan prolaktin
Disfungsi Kanker
Sexual Payudara

Osteoporosis Ginecomastia
Prolaktin
meningkat
Fertilitas
Galactorrhoea
menurun

Gangguan
Amenorrhoea
Kardiovaskuler

Halbreich et al 2003
 PENINGKATAN BERAT BADAN
PADA PEMAKAIAN ANTIPSIKOTIK ATIPIKAL

BB naik disertai DM & dyslipidemia:

*tertinggi : clozapine, olanzapine
*sedang : risperidone, quetiapine
*sedikit : aripiprazole, ziprasidone,
zotepine
*hampir ideal –- asenapine --------?
*Anjuran : kerjasama dengan disiplin lain ,
minimal Bagian Penyakit Dalam diperlukan.
 KOMPARASI BEBERAPA AP ATIPIKAL
*Risperidone: -banyak prolaktinemia & EPS
AE:-mengantuk, menstruasi tak teratur,berat badan
meningkat
*Clozapine: -banyak DM/sering mengiduksi
*Olanzapine:-banyak sindrom metabolik & obesitas / DM
sedikit prolaktinemia
AE:-mengantuk, berat badan naik, insomnia
*Quetiapine:-dosis awal tinggi-hypotensi postural, pada
pada manula kurangi dosis
AE:-mengantuk, jam tidur meningkat, berat badan
meningkat
*Aripiprazole:-kenaikan berat badan kurang, efek pada
agitasi dan kondisi depresi kurang
 KOMPARASI -2
*Zotepine :prolaktinemia / DM kurang, low EPS &
seizurogenic potential,efek proarritmia
kurang,
juga kurang dysfungsi seksual /
amenorrhoea /
galactorrhoea/ peningkatan triglycerida
AE:-mengantuk, sempoyongan, sakit kepala,
mulut kering, berat badan naik

-Kelebihan: -efek sedasi kuat, efektif pada simptom

positif / negatif, harga relatif murah dan aman.
-Kelemahan:-oversedasi pada awal,terutama pria,
berat badan naik (relatif sedikit).
 BEBERAPA CATATAN
• Efektivitas, keamanan, kenyamanan antipsikotik
atipikal menjadi hal yang penting, khususnya
karena umumnya obat-obat tersebut ditargetkan
untuk pemakaian jangka panjang.
• Kepatuhan dalam penggunaan obat juga menjadi
hal yang penting, disamping biaya pengobatan.
• Hal tersebut makin menjadi tuntutan dengan makin
luasnya indikasi (Skizofrenia dan gangguan mental
lainnya: bipolar, dsb) yang menjadi sasaran dari
pengobatan AP Atipikal
• Dari paparan profil berbagai obat AP tadi, dapat
kiranya dijadikan pertimbangan klinis pemilihan
obat mana yang sesuai dengan tujuan atau sasaran
terapi.
 PENGGUNAAN AP ATIPIKAL
*Khusus untuk neuroleptik atipikal ada beberapa
indikasi yang telah lama dikenal, meskipun sudah lebih
baik dari jenis tipikal tetapi harus diingat bahwa pada
jenis obat neuroleptik satupun tak ada yang
sempurna, jadi cenderung ada ke arah polifarmasi.
*Neuroleptik tipikal meskipun sering menimbulkan efek
samping, tetapi justru hal ini dapat dipakai untuk
penentuan dosis optimal melalui gejala EPS yang timbul
*Bila pada awal tak ada masalah dalam pemberian
neuroleptik atipikal,maka biasanya terapi dapat
dilanjutkan untuk pemakaian jangka panjang, dan
tentunya tetap dengan pengawasan
*Saat ini ada beberapa indikasi lain yang sedang giat diteliti khususnya
juga untuk gangguan bipolar dan demensia

*Ada beberapa indikasi lain yang mungkin nantinya akan dapat

dikembangkan selain untuk kondisi psikotik a.l. untuk gangguan
anxietas dan gangguan kepribadian serta masalah NAPZA
 INDIKASI PEMBERIAN
NEUROLEPTIKA ATIPIK
• TERAPI TERDEPAN untuk ANEKA
GANGGUAN SKIZOFRENIK dan
GANGGUAN PSIKOTIK LAINNYA
• SKIZOFRENIA yang RESISTEN terhadap
OBAT & BERHENDAYA
• MEREDAM GEJALA POSITIF
• MEMPERBAIKI GEJALA NEGATIF
• MENCEGAH KECENDERUNGAN BUNUH
DIRI pada SKIZOFRENIA
 INDIKASI PEMBERIAN
NEUROLEPTIKA ATIPIK-2

• GG. PSIKOTIK dengan UNSUR AFEKTIF,

DEPRESIF / MANIK
• GANGGUAN PSIKOTIK ORGANIK
• GANGGUAN PSIKOTIK dengan
GANGGUAN KOGNITIF
• GANGGUAN SPEKTRUM AUTISTIK
• GANGGUAN OBSESIF KOMPULSIF
• FOBIA SEKOLAH pada ANAK
BEBERAPA KENDALA :
*ketidak-patuhan makan obat
*mahalnya neuroleptik atipikal yang
belum ada generiknya
*jenis yang murah/terutama gol.tipikal
biasanya ada ketidak-nyamanan
*skizofrenia & gangguan bipolar
kadang sulit dibedakan sehingga sulit
untuk menentukan jenis obat
*atipikal-mahal, lebih nyaman
*tipikal-murah, sering tak-nyaman
 Sindrom Metabolik

• Definisi: Satu kelompok faktor-faktor

risiko terkena CVD pada seseorang:
-Obesitas sentral
-Dysglicemia
-Dyslipidemia
-Hypertensi
-Mikroalbuminuria
-Faktor-faktor prothrombotik lain
Risk factors/profile for the development
of cardiovascular & metabolic disorders

*Medical factors:
-obesity,dyslipidemia,hypertension, smoking,
hyperglycemia, diabetes.
*Behavioral factors:
-poor diet, smoking, physical inactivity,
high stress.
*Genetic factors:
-ethnicity, family history of metabolic or
cardiovascular disease.
 AHA/NHLBI: The Metabolic Syndrome
Diagnosis is established when >3 of these risk
factors are present
Risk factors Defining level
Waist circumference*
Men >102 cm (>90 cm for Asian men)
women >88 cm (>85 cm for Asian women)
Triglyceride** >150 mg/dL (>1.7 mmol/L)
HDL-Cholesterol**
men <40 mg/dL (<1.0 mmol/L)
women <50 mg/dL (<1.2 mmol/L)
Blood pressure** >130 or >85 mm Hg
Fasting blood glucose** >100 mg/dL (>6.1 mmol/L)
* Some US adults of non-Asian origin with marginal ** or on drug therapy for
increases should benefit from lifestyle changes. the risk factor

Grundy et al., Circulation 2005; 112: 2735-52

 Beberapa Faktor Risiko yang
Masih Dapat Dimodifikasi Akibat
Penggunaan Psikotropik

*Overweight / Obesity
*Insulin resistance
*Diabetes/dysglycemia
*Dyslipidemia
 Insulin Resistance

“Inadequate” Compensatory
Insulin Response Hyperinsulinemia

Insulin Resistance
Type 2 Diabetes
Syndrome

Cardio- Hypertension
vascular Polycystic Ovarian
Retinopathy Disease Syndrome
Nephropathy (CVD) Non-Alcoholic Fatty
Liver Disease
Neuropathy
Cancer
Sleep Breathing Disorder
Steinberg HO, Baron AD. Diabetologia. 2002;45:623-634.
Caballero AE. Obesity Res. 2003;11:1278-1289.
Reaven GM. Diabetes. 1988;37:1595-1607.
 Beberapa Anjuran
• Kesehatan fisik harus diperhatikan
dan dicatat adanya:
 Gangguan endokrine ( Diabetes,
Hyper-

prolaktinemia )
 Faktor risiko CV ( TD, Kadar
bbrp.Lipid )
 Efek samping medikasi
 Faktor gaya hidup ( Merokok dsb )
 Beberapa Anjuran-2

• Bila pada pemakaian antipsikotik

atipik  BB naik terus/ ada diabetes,
maka pasien haruslah dipantau dan/
atau diubah jenisnya (atipikal/tipikal)
• Selalu dipantau/catat ( respon klinik,
efek samping, kepuasan si pemakai)
• Bila pasien puas dengan medikasi
yang diberikan, tak perlu diubah lagi
 SIMPULAN-1
*Sebelum pemakaian SGA waspadai akan adanya gangguan
metabolik dan faktor risiko
*Pada pemilihan SGA haruslah pertimbangkan risiko metabolik
dari obat & juga profil pasien
*Sebaiknya memakai SGA dengan risiko paling rendah dan
ekonomis
*Prediabetes,diabetes,hyperlipidemia dan obesitas
harus sering dipantau pada beberapa bulan pada
awal pemberian, bila ada harus diatasi segera,
penanganan selanjutnya adalah merubah obat
dengan risiko lebih rendah
*Diperlukan informasi ke pasien /keluarga dan
kerjasama dengan Bagian Penyakit Dalam
Pada wanita perlu perhatian lebih khusus.
 Atipikal Psikotik

High
Potential
Risk of
Metabolic
SyNDRO
ME

Here is a look at the conclusions of the American Diabetes Association (published in a joint statement
with the American Psychiatric Association) regarding weight gain (Wt Gn), diabetes risk, and worsening cholesterol levels:
 TERAPI SKIZOFRENIA
I.Terapi somatik
~ -Psikofarmakologi: antipsikotik /
neuroleptik
-ECT,ICT,
-Psychosurgery
II.Manipulasi lingkungan ( Milieu therapy )
-T.Okupasional,aktivitas sosial,open wards,
terapi keluarga dll.
III.Psikoterapi
-Individual dan kelompok.

*Saat ini yang terpenting ----medikasi dg

antipsikotik/neuroleptik.
 TERAPI SKIZOFRENIA
PSIKO
TERAPI

TERAPI
.LINGKUNGAN

TERAPI SOMATIK
NE UR O L E P T I K
ECT, ICT
PSYCHOSURGERY

.
AWAL TERAPI TERBAIK : DENGAN NEUROLEPTIK
 SEJARAH PERKEMBANGAN
TERAPI SIMPTOM SKIZOFRENIA
• 1952 mengatasi gejala/simptom positif
• 1980 memperbaiki gejala/simptom negatif
• 1990 memperbaiki disfungsi kognitif
• 1995 mencegah gangguan afektif
• 1997 memilih obat yang enak / nyaman
tanpa gejala sampingan
• 2000 mempertahankan / meningkatkan
kualitas hidup
 Perkembangan Terapi Medik untuk
Gangguan Psikotik

’30s ’40s ’50s ’60s ’70s ’80s ’90s ’00 ’02 ’06 (?)

ICT Haloperidol Clozapine Aripiprazole

ECT Fluphenazine Zotepine
Thioridazine Risperidone Paliperidone
Reserpine Loxapine Olanzapine
Perphenazine Quetiapine
Ziprasidone
Chlorpromazine

Anti-psikotik Anti-psikotik Generasi

Generasi Pertama Generasi Kedua berikutnya?
ECT = electroconvulsive therapy.
Kapur and Remington. Ann Rev Med. 2001;52:503.
Worrel et al. Am J Health Syst Pharm. 2000;57:238. (modified)
 Perkembangan Terapi Medik untuk
Gangguan Psikotik

’30s ’40s ’50s ’60s ’70s ’80s ’90s ’ 00 ’04 ‘06 (?) ‘09-’11

ICT Haloperidol Clozapine* Aripiprazole ILOPERIDONE

ECT Fluphenazine Zotepine* ASENAPINE
Thioridazine Risperidone LURASIDONE
Reserpine Trifluoperazine Olanzapine* Paliperidone
Perphenazine Quetiapine*
Ziprasidone
Chlorpromazine

Anti-psikotik Anti-psikotik
Generasi Pertama Generasi Kedua Generasi
FGA SGA: SDA & MARTA* berikutnya?

ECT = electro convulsive therapy.

Kapur and Remington. Ann Rev Med. 2001;52:503.
Worrel et al. Am J Health Syst Pharm. 2000;57:238. (modified)
 Gejala negatif
Gejala kognitif
Target Gejala afektif
Terapi Gejala positif Gejala efek samping
Hidup Berkualitas

’30s ’40s ’50s ’60s ’70s ’80s ’90s ’ 00 ’04 ‘06 (?) ‘09-’11

ICT Haloperidol Clozapine* Aripiprazole ILOPERIDONE

ECT Fluphenazine Zotepine* ASENAPINE
Thioridazine Risperidone LURASIDONE
Reserpine Trifluoperazine Olanzapine* Paliperidone
Perphenazine Quetiapine*
Ziprasidone
Chlorpromazine

Anti-psikotik Anti-psikotik
Generasi Pertama Generasi Kedua Generasi
FGA SGA: SDA & MARTA* berikutnya?

ECT = electro convulsive therapy.

Kapur and Remington. Ann Rev Med. 2001;52:503.
Worrel et al. Am J Health Syst Pharm. 2000;57:238. (modified)
 MEDIKASI ANTIPSIKOTIK

Saat ini terapi obat berdasarkan efikasi terhadap:

1.simptom positif seperti delusi,halusinasi dan

gangguan proses pikir,
2.simptom negatif seperti afek datar, hilangnya
kehendak dan energi serta disintergrasi
sosial,
3.simptom kognitif seperti gg. daya ingat,
kurang
perhatian dan kesulitan cara berpikir
abstrak,
4.simptom afektif seperti dysforia, depresi serta
suisidalitas.
Dalam hal ini antipsikotik tipikal (FGA) kurang baik
dan jenis atipikal (SGA) dan obat generasi III (TGA)
ternyata lebih baik
 EFEK SAMPING NEUROLEPTIKA ATIPIK

1.BB naik…………………..Olan.,Risp., Quet.,Zipra.,Arip.

2.Disf.Seksual
3.Risiko Kejang naik
4.Hipo/hipertensi
5.Resp. Akathisia ………….Risp.,Quet.
6.Agranulositosis.……….....Clozapine
7.Hiperprolaktinemia……....Antipsikotik tipikal umumnya
8.Hiperglikemia, DM,
Ketoasidosis ,Koma………Olan.,Risp.,Quet.,Cloz.,Arip.
 EFEK SAMPING ( lanjutan )
9.Perpanjangan PR&QTc,QRS,
Dep.ST, Flattening/ Notching
T-Waves, Emerg.of U-Waves …..........Zipr.,Olan.,Risp.
10.Kreatin Fosfokinase Naik
11.Dyslipidem (Chol., Trigl.)
12.Somnolen…………………………….Clozapine
13.Insomnia……………………………...Aripiprazole
14.Nyeri / Agitasi
15.Mulut Kering
16.ALT & AST Naik
Extract from J. Švestka’s Lecture
• Risperidone and Amisulpride should not be
used for Female patient
• Prolactin Elevation is harmful not only for
sexual disfunction and menstrual disorder,
but also osteoporosis and osteopenia. It is
also suspected inducing breast cancer. It
induces much more severe disorders.
Typical / First Generation
Antipsychotic
( F GA )

* Antagonis D2
* Efek samping kuat:
-EPS
-Tardive Dyskinesia -Typical
-Hyperprolactinemia Antipsychotic
(FGA)

D2
 C0MPARATIVE RECEPTOR PROFILE

Asenapine Risperidone
11 11
9
D2 9
D2
p 7 p 7
5
Ki 5 Ki

Clozapine Aripiprazole
11 11
9
D2 9 D2
p 7 p 7
5
Ki Ki 5

Olanzapine Haloperidol
11 11
9 D2 9 D2
p 7 p 7
Ki 5 Ki 5

Quetiapine
11 Dashed line=respective affinity of each agent for D2 receptor;
9
p 7 D2 pKi, a measure of binding affinity
Ki 5

77
Shahid et al. J Psychopharmacol 2009;23:65-73
 Beyond the SDA concept

5HT2A
5HT2A
M1
H1
5HT1D α1
Atypical Atypical α2
Antipsychotic 5HT2C
Antipsychotic NRI
( SDA ) 5HT3 ( MARTA ) D1
D2 5HT6 D2
5HT7 D4 D3
Stephen M.Stahl; Psychopharmacology of Antipsychotics, 1999
 PROFIL RESEPTOR
FGA & SGA

5HT2A
M1
H1
5HT2A
5HT1D α1
Atypical α2
Typical Atypical 5HT2C
Antipsychotic Antipsychotic Antipsychotic NRI
( FGA ) ( SDA ) 5HT3 ( MARTA ) D1
D2 D2 5HT6 D2
FGA
5HT7 D4 D3
S G A
Stephen M.Stahl; Psychopharmacology of Antipsychotics, 1999
 5HT2A
Risperidone:
α1
( SDA )
-banyak prolaktinemia α2
-EPS bila dosis naik
-kadar lipid diperburuk.
-AE:-mengantuk,
-menstruasi tak teratur. D2
5HT7

Stephen M.Stahl; Psychopharmacology of Antipsychotics, 1999

 Clozapine:
( MARTA )
-
-BB cepat naik dan sering
5HT2A menginduksi DM.
M1 -Bahaya agranusitosis !
H1
-Risiko potensi kejang tinggi.
α1 -Kadar lipid sering meninggi.
ά2 ----------------------------------------
5HT2C
Clozapine
-Untuk kasus resisten
D1 -Indeks Keamanan Kehamilan
5HT3 Kategori B
5HT6 D2 -Risiko EPS rendah.
5HT7 D4 D3 -Mengurangi risiko bunuh diri
Stephen M.Stahl; Psychopharmacology of Antipsychotics, 1999
 C L O Z A P I N E
( MAR TA)
5 HT1A
M1
5HT2A
NEGATIF: H1
POSITIF:
*BB cepat naik ά1
*Induksi DM ά2
•Potensi kejang 5HT2C
Clozapine *Skizofrenia yang
resisten
meningkat D1 *EPS risiko kecil
*Lipid naik 5H3 *Index keamanan
*Agranulositosis Kehamilan B
5HT6
5HT7 D3D2 *Risiko bunuh diri
D4 mengecil
Olanzapine :
(MARTA)
-banyak sindrome
metabolik,obesitas 5HT2A M1
H1
dan DM,
α1
-sedikit prolaktinemia.
AE: 5HT2C
-mengantuk, D1
-berat badan naik, 5HT3
-insomnia. 5HT6 D2
D4 D3
Quetiapine :
(MARTA)
-tendensi hipotensi
postural pada dosis 5HT2A
awal tinggi, H1
-kurangi dosis pada α1
manula . α2
AE:
-mengantuk, jam tidur
meningkat, 5HT6 D2
-berat badan naik 5HT7

Stephen M.Stahl; Psychopharmacology of Antipsychotics, 1999

 Zotepine receptor profile
Zotepine:
(MARTA)
-efek sedasi kuat, 5HT2A
H1---efek SEDASI
-efektif untuk
simptom negatif α1
AA
dan positif, NRI ---efek AD
-potensi risiko 5HT2C
D1
kejang seperti
gol. tipikal. 5HT6 D2
5HT7 D3
D4
Stephen M.Stahl; Psychopharmacology of Antipsychotics, 1999
BEBERAPA ANTIPSIKOTIK GENERASI TERBARU
*Aripiprazole:
-kenaikan BB kurang,
-efek agitasi dan kondisi depresi kurang,
-harga mahal.
-partial agonist pd D2 & 5HT1A ,
antagonist pd 5HT2a
*Paliperidone
-lebih baik dari risperidone , harga mahal.
*Iloperidone, asenapine, lurasidone
-gol. atipikal terbaru,data terbatas.
 ASENAPINE

5HT2A
5HT2A M1

5HT2B
Serotonin
5HT2C
Dopamine
Antagonist

D2 5HT6 D2
5HT7
Stephen M.Stahl; Psychopharmacology of Antipsychotics, 1999
 INDIKASI PEMBERIAN
NEUROLEPTIKA ATIPIK
1.TERAPI TERDEPAN untuk aneka GG
SKIZOFRENIK dan PSIKOTIK LAIN
2.SKIZOFRENIA RESISTEN , HENDAYA
BERAT, SIMPTOM POSITIF & NEGATIF
TENDENSI BUNUH DIRI
3.GANGGUAN PSIKOTIK dg UNSUR-UNSUR
AFEK TIF (MANIK/DEPRESIF), ORGANIK,
GG.KOGNITIF,OBSESIF KOMPULSIF.
4,ANAK : GG SPEKTRUM AUTISTIK, FOBIA
SEKOLAH.
 PERKEMBANGAN LANJUT

*Saat ini sedang diteliti khusus untuk

gangguan bipolar dan demensia

*Indikasi lain dikembangkan untuk

gangguan anxietas , gangguan
kepribadian serta masalah NAPZA
(Hasil dari Final Faculty Discussion Zotepine Workshop in
Amsterdam, October 21st 2005 )

Soestiantoro.D November 2007

 PENGELOLAAN-Catatan
*Efektif, aman,nyaman,murah dan o.s.patuh
penting, karena untuk jangka panjang.
*Pertimbangan klinis pemilihan obat sesuai
dg
tujuan atau sasaran terapi.
*Tendensi polifarmasi ada.
* Terapi diteruskan bila awal tak ada
masalah

*Gol.tipikal , penetapan dosis optimal

lebih
mudah ( ada EPS )
 The optimal treatment for…?
- GOOD EFFICACY - BEST PRICE
- LACK OF ADVERSE REACTION - GOOD COMPLIANCE

Good Sedative Action

Doctors wondering
Refractory

SDA ?
Stable patients
 Long Term Treatment

*Well efficacy & prevent relaps

*Improve clinical global impression
*Well tolerability & lack of
adverse reaction incidencies
 Anjuran Pemakaian Atipikal
Sebelumnya, perhatikan :
-GG. endokrine(Diabetes, Hiper-
prolaktinemia)
-Faktor risiko CV ( TD, Kadar bbrp.Lipid )
-Efek samping medikasi
-Faktor gaya hidup ( Merokok dsb )
Sesudahnya:
*BB naik terus/ada diabetes, ganti obat.
*Catat respon klinik pasien.
SIMPULAN
-Terapi dan pengelolaan skizofrenia saat
ini:
*terpenting medikasi neuroleptik,
*umumnya atipikal lebih baik,
*hati-hati polifarmasi,
*lihat profil pasien,
*waspadai gangguan/risiko metabolik,
*gunakan SGA risiko terkecil, nyaman,
murah
-Perlu kerjasama minimal Bagian Penyakit Dalam.
Olanzapin
-Have sometimes severe
hyperlipidemia side effects
-Represent a significant
increase weight.
Risperidone
-Have EPS side effects in
increased dosage.
-Have significant hyper
prolactinemia compare to
other antipsychotics.
Quetiapine
-Significant weight gain.
Ziprasidone Zotepine
-Have QTc prolongation
profile
Amisulpiride
-Have significant hyperpro-
lactinemia compare to other
antipsychotics.
Clozapine
-Around 5% (?) of agranulo-
cytosis incidence rate.
-Seizure risk at least as
frequent as conventional one.
-Represent a significant
increase weight.
-Have seizure risk at least as
frequent as conventional one
PENGELOLAAN
*Efektivitas, keamanan, kenyamanan,kepatuhan dan
biaya menjadi penting,karena umumnya untuk
pemakaian jangka panjang.
*Dengan meluasnya indikasi / sasaran AP atipikal
(Skizofrenia dan gangguan mental lain seperti
gangguan bipolar, dsb) hal diatas semakin penting.
*Pertimbangan klinis pemilihan obat agar disesuaikan
dengan tujuan atau sasaran terapi.
Meskipun atipikal sudah lebih baik tetapi tidak ada
satupun yang sempurna, ada tendensi polifarmasi.
* Bila awal tak ada masalah penggunaan atipikal dapat
dilanjutkan/jangka panjang dan tetap diawasi.
*Gejala EPS yang timbul pada neuroleptik tipikal dapat
dipakai sebagai indikator penentuan dosis optimal.