Schizophrenia - dr. Waskita

SCHIZOPHRENIA

Dr. W.M ROAN, DPM(Lond.), SpKJ(K)

PERSPECTIVE HISTORY OF THE DISCOVERY OF SCHIZOPHRENIA

MOREL(1860) : DÉMENCE PRÉCOCE EMIL KRAEPELIN(1899) : DEMENTIA PRAECOX: DETERIORASI KEPRIBADIAN (personality deterioration)

HECKER(1871): HEBEFRENIA (Silly Deter.) KAHLBAUM(1874): KATATONIA (catatonia)

JASPERS(1910): TAK DPT DI-EMPATI (cannot be empathized)

HISTORY (1)

EUGEN BLEULER(1911): SCHIZOPHRENIE

• GEJALA KARDINAL (Cardinal symptoms)

• GEJALA AKSESORIS (accessory symptoms) ADOLPH MEYER(1920): REAKSI ORANG THD

KEGAGALAN MENGATASI MASALAH HIDUP (human reactions towards failures in coping with life)

Bleuler’s Concept of schizophrenia (1)

Cardinal SymptomenDer Autismus (autism)Die Aufmerksamkeit (attention)Der Wille (volition)Die Person (The person)Die Schizophrene Demenz (dementia schiz)

Bleuler’s Concept (2)

Akzessorischen symptomen (accessory symptoms)Wahrnehmung (perception of the 5 senses)Wahnideen (delusions)Gedächtnisstorungan (disturbances of thought)Depersonalisation (depersonalization)Sprache und Schrift (speech & language)Körperliche Symptome (bodily symptoms)Die Katatone Symptome (catatonia)Akut Syndrome (acute syndrome)

HISTORY (2)

RÜMKE(1935): PRAECOX GEVOEL• Barrier between doctor – pt relationship

KURT SCHNEIDER(1939): FIRST RANK SYMPTOMS

• SPECIFIC HALLUCINATIONS– ECHO DE LA PANSÉE (THOUGHT-ECHO, -

SONORIZATION, GEDANKENLAUTWERDEN, AUDIBLE THOUGHT)

– PT BEING COMMENTED IN THE THIRD PERSON

– PASSING COMMENTARIES ON PT'S BEHAVIORS

HISTORY (3)

• DISTURBANCE OF EGO BOUNDARY– SOMATIC PASSIVITY FEELINGS– THOUGHT WITHDRAWAL / INSERTION / BROADCAST– MADE FEELINGS– MADE IMPULSES– MADE VOLITIONAL ACTS– DELUSIONAL PERCEPTION (PRIMARY DELUS.)

KUSUMANTO SETYONEGORO(1966)• 6 A: DISTURBANCES OF ATTENTION,

AFFECT, AUTISM, ASSOCIATION, AMBIVALENCE, ABULIA

SEJARAH (Sambungan IV)

LAING (1960s): ANTIPSYCHIATRY AGAINST

• THE LABELLING OF SCHIZOPHRENIA• ECT• HOSPITALIZATION• CHILDREN BEING DRUGGED

PATIENTS ARE NORMAL, THE SOCIETY IS ILL

PTS, STAFF & DOCTORS ARE EQUAL

WHO ICD-10DIAGNOSTIC CRITERIA

WHO ICD-10 = PPDGJ-III THOUGHT ECHO , THOUGHT-INSERTION,-WITHDRAWAL,

-BROADCASTS DILUSION OF CONTROL HALLUCINATORY VOICES WAHAM MENETAP HALUSINASI MENETAP THOUGHT BLOCKING CATATONIA NEGATIVE SYMPTOMS PERSONALITY CHANGE

SCHIZOPHRENIAPERSPECTIVE & PRACTICAL REVIEW

POSITIVE SYMPTOMSNEGATIVE SYMPTOMSCOGNITIVE FUNCTION DISTURBANCES AFFECTIVE LIFE DISTURBANCES PSYCHOMOTOR DISTURBANCES

EXTRAPYRAMIDAL SYMPTOMS (-)

VEGETATIVE FUNCTIONS: SLEEP, EAT, SEX

QUALITY OF LIFE

POSITIVE SYMPTOMS OF POSITIVE SYMPTOMS OF SCHIZOPHRENIASCHIZOPHRENIA

Gg bentuk pikir, asosiasi longgar (Gg bentuk pikir, asosiasi longgar (loosening of loosening of associationassociation))

Tingkah laku kacau, keluyuran (Tingkah laku kacau, keluyuran (disorganized & disorganized & erratic behaviour, vagabondageerratic behaviour, vagabondage))

Afek tak serasi, bermusuhan (Afek tak serasi, bermusuhan (incongruent affect, incongruent affect, hostilehostile))

Waham, megalomania, w.-kejar (Waham, megalomania, w.-kejar (delusion, delusion, megalomania, persecutory d.megalomania, persecutory d.))

Halusinasi & perilaku penyerta (Halusinasi & perilaku penyerta (hallucinations & hallucinations & subsequent behaviourssubsequent behaviours))

NEGATIVE SYMPTOMS OF NEGATIVE SYMPTOMS OF SCHIZOPHRENIASCHIZOPHRENIA

Tuna/Miskin pikir & wicara (Tuna/Miskin pikir & wicara (Poverty of Poverty of thought and speechthought and speech))

Gg kehendak (Gg kehendak (impaired volition, apathyimpaired volition, apathy))Afek tumpul (Afek tumpul (blunt affect & anhedoniablunt affect & anhedonia))Penarikan diri (Penarikan diri (Social withdrawalSocial withdrawal))Hubungan dr-ps kurang hangat (Hubungan dr-ps kurang hangat (Poor rapportPoor rapport)) Sulit berpikir abstrak & stereotipi (Sulit berpikir abstrak & stereotipi (Abstract Abstract

thinking & stereotipythinking & stereotipy))

Cognitive Functions

daya perhatian (attention)daya ingat (memory)daya tanggap (perception)daya cakap & bahasa (speech & language)daya belajar & pembelajaran (learning)daya komunikasi (communication)fungsi exekutif (executive functions)

EXECUTIVE FUNCTIONS

MEMORI & PERSEPSI (memory & perceptions) MENYIMPAN, MENGATUR, PERBARUI, MENGGUNAKAN

INFORMASI (retention, organization, update, information) MEMILIH RESPONS YG TEPAT, MEREDAM YG TIDAK

TEPAT (select the appropriate & discard the useless response) MEMBUAT RENCANA, MENYELESAIKAN MASALAH

(planning, executing) DEFISIT (Deficits):

GEJALA NEGATIF: TAK ADA SPONTANITAS, KURANG MOTIVASI, ASOSIAL (Negative symptoms: lack initiatives, unmotivated, asocial)

POOR SELECTIVE ATTENTION OR FILTERING HALLUCINATIONS, IDEAS OF REFERENCE

Gejala afektif skizofrenia Gejala afektif skizofrenia (Affective symptoms of schizophrenia)(Affective symptoms of schizophrenia)

Fase skizofrenik (schizophrenic phase): depresi / mania (depression / mania) cemas / panik, (anxiety / panic) obsesi / kompulsi, (obsession / compulsion) histerik, (hysterical) fobia akibat halusinasi atau waham (phobia due to

hallucinations / delusions) Fase kronik (chronic phase)

gejala negatif, menarik diri, autistik, malas, tak mau ganti pakaian, kotor (negative symptoms: withdrawn, autistic, lack of initiatives, avoid bathing, unkempt, no change of clothing)

04/19/23 Stress pasca trauma/Roan 26





PSYCHOMOTOR DISTURBANCES

EXTRAPYRAMIDAL DISTURBANCES AKINESIA, BRADYKINESIA (Akinesia, bradykinesia) AKATHISIA (Akathisia) TREMOR, RABBIT TREMOR PARKINSONISM OCULOGIRIC CRISIS (Oculogyric crisis) DISTONIA, HEMIBALISMUS, SINDROM PISA (dystonia,

hemibalism, pisa syndr) CHOREO-ATHETOSIS (choreo-athetotic movement dist.) TARDIVE DYSKINESIA (Tardive dyskinesia)

TARDIVE DYSKINESIA

DEVELOPMENTAL HISTORY OF SCHIZOPHRENIA THERAPY

1952 OVERCOME POSITIVE SYMPTOMS1952 OVERCOME POSITIVE SYMPTOMS 1980 ALLEVIATE NEGATIVE SYMPTOMS1980 ALLEVIATE NEGATIVE SYMPTOMS 1990 IMPROVE COGNITIVE DYSFUNCTIONS1990 IMPROVE COGNITIVE DYSFUNCTIONS 1995 PREVENT AFFECTIVE DISTURBANCES 1995 PREVENT AFFECTIVE DISTURBANCES 1997 THE CHOICE OF DRUGS, COMFORTABLE 1997 THE CHOICE OF DRUGS, COMFORTABLE

NO SIDE EFFECTSNO SIDE EFFECTS 2000 MAINTAIN & IMPROVE QUALITY OF 2000 MAINTAIN & IMPROVE QUALITY OF

LIFELIFE

1952 OVERCOME POSITIVE SYMPTOMS1952 OVERCOME POSITIVE SYMPTOMS 1980 ALLEVIATE NEGATIVE SYMPTOMS1980 ALLEVIATE NEGATIVE SYMPTOMS 1990 IMPROVE COGNITIVE DYSFUNCTIONS1990 IMPROVE COGNITIVE DYSFUNCTIONS 1995 PREVENT AFFECTIVE DISTURBANCES 1995 PREVENT AFFECTIVE DISTURBANCES 1997 THE CHOICE OF DRUGS, COMFORTABLE 1997 THE CHOICE OF DRUGS, COMFORTABLE

NO SIDE EFFECTSNO SIDE EFFECTS 2000 MAINTAIN & IMPROVE QUALITY OF 2000 MAINTAIN & IMPROVE QUALITY OF

LIFELIFE

ATYPICAL ANTIPSYCHOTIC DRUGS

DRUG Receptor profile* Recommended dose Pharmaceut. Co(Waddington) (mg/day)**Amisulpride D2/3, D1, D2 200 - 800 (50 - 1200) Sanofi - SynthelaboClozapine 5HT2, D, M, H1 200 - 450 (50 - 900) NovartisOlanzapine 5HT2, D, M, H 10 (5 - 20) Ely LillyQuetiapine 5HT2, D2, H1 150 - 750 Astra ZenecaRisperidone 5HT2, D, H1 4 - 6 (1 - 16) JanssensSertindole 5HT, D, 12 - 20 (4 - 24) LundbeckZiprasidone 5HT2, D2, 5HT1A, M1, 40 - 160 PfizerZotepine 5HT2, D1,2 H1, M 100 - 300 (50 - 450) Rhone - Poulenc RorerD : Dopamin, adrenergik, M : Muscarinic, H : Histamine, 5HT : Serotonin* ) Listed in order of descending affinity**) Doses in general correspond to the recommendations of the manufacturer.Doses listed in parentheses represent extremes sometimes justified in individual patients.

N O V E L A N T I P S Y CH O T I CS

Chemical Structures of Olanzapine and OtherChemical Structures of Olanzapine and OtherAntipsychotic AgentsAntipsychotic Agents

Clozapine

N

N

CCll

N

N

CH

3

H

Olanzapine

N

N

N

N

CH3

HS CH3

Seroqel

N

S

N

N

O

OH

Risperidone Haloperidol

N

HO

Cl O

F

O

N

N

N

N

O

F

CH3

SertindoleN

NN

N

Cl

F

O

H

H

1. Multi-Acting Receptor Targeted Antipsychotics (MARTA)

2. Serotonin: Dopamine Antagonists (SDA)3. Dopamine - 2 Antagonist

• Olanzapine has eliminated the halogen (Cl) from the clozapine molecule, a potentially reactive metabolite

Receptor pharmacology of atypical antipsychotics

D1D2D45HT2A5HT2CMusc12H1

Haloperidol Clozapine

Risperidone

Quetiapine

Sertindole Ziprasidone Zotepine

Olanzapine

INDICATIONS OF NEUROLEPTIC ADMINISTRATION

FIRST LINE TREATMENT FOR VARIOUS SCHIZOPHRENIA & OTHER PSYCHOTIC CONDITIONS

RESISTENT SCHIZOPHRENIA TOWARDS DRUGS & HANDICAPPED

PSYCHOTIC DITURBANCES WITH AFFECTIVE ELEMENTS DEPRESSIVE / MANIC

ORGANIC PSYCHOTIC DISORDERS PSYCHOTIC DISORDERS WITH COGNITIVE

DYSFUNCTIONS OVERCOME POSITIVE SYMPTOMS IMPROVE NEGATIVE SYMPTOMS AUTISTIC SPECTRUM DISORDERS OBSESSIVE COMPULSIVE DISORDERS SCHOOL PHOBIA IN CHILDREN

SIDE EFFECTS OF ATYPICALS

WEIGHT GAINSEXUAL DYSFUNCTIONSLOWERED CONVULSIVE THRESHOLDHYPOTENSION / HYPERTENSIONAGRANULOCYTOSIS (ESP. CLOZAPINE)HIPERPROLACTINEMIA, AMENORRHOEAHYPERGLYCEMIA, DM, KETOACIDOSIS,

COMA

(CON’T)

PR & QTc, QRS, PROLONGATION, ST FLATTENING/NOTCHING T-WAVES, EMERGENCE OF U-WAVES (FOR ZYPRASIDONE, OLANZ, RISP.)

INCREASE CREATININ PHOSPHOKINASESOMNOLENT (FOR CLOZAPINE) /

INSOMNIASEVERE HEADACHE / AGITATEDDRY MOUTH INCREASED ALT & AST

SIDE EFFECTS DIFFERENCES AMONG NEUROLEPTICS

EXTRAPYRAMIDAL SIDE EFFECTS: RISP > ZIPRA/OLAN > QUET

PROLACTINEMIA, AMENORRHOEA: RISP > ZIPRA/OLAN > QUET

WEIGHT GAIN: OLAN > QUET/RISP > ZIPRA

GENETICS & DISEASESSingle-gene mutations & rare diseases(Mendelian inheritance)Rare inheritance (high penetrance)

Cystic fibrosis (CFTR gene)• Inheritance: autosomal recessive

• Location: chromosome 7 (7q31)

• Mutation: deletion of 3 bp at codon 508 accounts to 70% of mutations

Huntington’s disease• Inheritance: autosomal dominant

• Location: Chromosome 4 (4p16.3)

• Mutation: cytosine/adenine/guanine repeat>35x

Gene polymorphisms and common disease susceptibility - some examples(polygenic; complex inheritance)

Common late-onset Alzheimer's disease• Susceptibility gene (ApoE) on chromosome 19(19q13)

• Susceptibility gene locus on chromosome 12(12q)

Migraine• Susceptibility gene loci on chromosome 19(19p13); X(Xq24)

Non-insulin-dependent diabetes mellitus• Susceptibility gene loci on chromosome 12(12q); 2(2q)

Psoriasis• Susceptibility gene locus on chromosome 3(3q21)

GENETICS OF SCHIZOFRENIA

Since December 1996 genome scans were conducted among hundreds of families & they found that there exists linkage from ½ of all chromosomes 3, 4, 6, 8, 9, 11, 13, 14, 15, 17, 20, & 22

MODE OF INHERITANCE): Non-Mendelian, reduced penetrance Oligogenic of moderate effect Polygenic of small effect

GENETIC DEFECTS THAT COULD CAUSE THE INCIDENCE OF SCHIZOPHRENIA IS AT THE TIME OF EMBRYONAL DEVELOPMENT, GROWTH AND PLASTICITY, DURING NEURONAL MIGRATION TO THE CORTEX, DURING ADOLESCENCE WHEN NEURONAL PRUNING & DENDRITIC REBRANCHING OCCUR, AND WHEN THE NORMAL PROCESS OF AGEING & THE REDUCTION OF THE NUMBERS AND SIZES OF CORTICAL NEURONS IS HAPPENING.

THANK YOU

FOR YOUR ATTENTION

FARMAKO-GENETIKA

ILMU YG MEMEPELAJARI PENGARUH GENETIK THD RESPONS OBAT YANG BERBEDA PD PASIEN

DG ILMU INI KITA DPT MENYUSUN VARIASI PROFIL ANTAR DNA ORANG DEMI MERAMALKAN RESPONS OBAT

BISA DITENTUKAN KHASIAT & EFEK SAMPINGAN LB DULU

KEPENTINGAN MEDIK & NILAI EKONOMIK EFFICACY & SAFETY PENGEMBANGAN OBAT YG SELARAS DG PENY.

MENINGKATKAN MUTU HIDUP

KESEHATANPENDIDIKANPEKERJAANEKONOMI / KEUANGANPERUMAHANMOBILITAS

MENINGKATKAN MUTU HIDUP

RASA SEJAHTERA SUBJEKTIFKEPUASANKEBUDAYAANPOLITIK / KEWARGANEGARAANHOBBY / PENGGUNAAN WAKTU

SENGGANG


Clozapine in other conditionsClozapine in other conditionsAdjunct treatment for better sleep Adjunct treatment for better sleep

pattern in drug abuse and dependent pattern in drug abuse and dependent patients esp. opiates, amphetamine, patients esp. opiates, amphetamine, methamphetamine methamphetamine

induce a better employment for chronic induce a better employment for chronic disabled patientdisabled patient

improve longstanding thought loosening improve longstanding thought loosening of association in chronic patientsof association in chronic patients

continuedameliorate disgusting behavior ameliorate disgusting behavior

(coprophagy) & improve patients’ QoL(coprophagy) & improve patients’ QoLprevent upsurgence of post-prevent upsurgence of post-

schizophrenic depressionschizophrenic depressionprevent relapse and reduce re-admissionprevent relapse and reduce re-admissionre-establish physical / emotional growthre-establish physical / emotional growthno extrapyramidal symptomsno extrapyramidal symptomsbetter prognosisbetter prognosis

TERAPI BOLEH DICAMPUR

Dg neuroleptika tipik spt chlorpromazine, haloperidol, perphenazine, trifluoperazine, fluphenazine utk kasus akut gelisah & refrakter

dg methylphenidate(Ritalin) utk perilaku yg eratik pd gg. spektrum autistik dg/tanpa gg hiperaktif

dg donepezil(Aricept) utk demensia insipien yg bicara kotor & perilaku agresif

dg antidepresiva spt TCAs, SSRIs, Mianserine Mirtazapine(Remeron)

HARAPAN DAN TANTANGAN MASA DEPAN PENANGANAN SKIZOFRENIA

NEW OPPORTUNITIES AND CHALLENGES IN THE TREATMENT OF SCHIZOPHRENIA

TINJAUAN PERSPEKTIF DISAJIKAN PADA PERTEMUAN NASIONAL KE-2

TENTANG SKIZOFRENIA

DR. W.M. ROAN, DPM(Lond.)PSIKIATER

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Schizophrenia - dr. Waskita