Bagian/SMF Psikiatri

Fakultas Kedokteran Universitas Udayana

RSUP Sanglah Denpasar

Antipsychotic polypharmacy
in clozapine resistent
schizophrenia: a randomized
controlled trial of tapering
antipsychotic co-treatment
Presented by : dr. I Putu Diatmika
Mentored by : dr. Ni Ketut Putri A Sp.KJ

Introduction
Treatment resistance and inadequate
response
to
antipsychotic
(AP)
medication are significant clinical
problems.
Treatment
resistant
patients
represent 20-30 % of people with
schizophrenia.

Introduction
Patients are comonly trated with clozapine
Atypical Antipsychotic Monotherapies at
therapeutic doses have been suggested to
be the best pharmacological treatmant of
schizophrenia.
In spite of recommendations, these patients
often have added on polypharmacy with
several APs.
This augmentation has been questioned in
several studies.

introduction
From the results of four randomized con-trolled
trials (RCTs), Paton et al. 6 suggested that
augmentation of clozapine with another AP
cannot be recommended but it is worth of a
long enough clinical trial.
After reviewing 19 RCTs, Correll et al.7
suggested that antipsychotic co-treatment may
be superior to monotherapy in certain clinical
situations.
However, it was not possible to derive firm
clinical recommendations from these results

Introduction

AIM
The aim of the present study was to
determine if clozapine monotherapy
is
as
effective
as
clozapineolanzapine therapy for treatment
resistant
schizophrenia
in
a
randomized double-blind setting.

MATERIALS AND METHODS

PATIENTS
In 2009, 30 schizophrenic patients in
the Niuvanniemi State Mental Hospital
received clozapine-olanzapine therapy
for severe psychotic symptoms after
only partially responding to clozapine
alone.

Patient flowchart.

Methods
The criteria inclusion;
An age of at least 18 years, competence to understand the meaning of the
study and give informed consent,
Insufficient response to clozapineolanzapine therapy,
Unchanged psychotropic medication
during the last two months and
No concurrent pregnancy

Ethical considerations
Every pastien in this study signed the
informed consent.

Primary outcome measures

Methods

Results

Conclusions
The clinical state of seriously ill
schizophrenic patients who were on
olanzapine-clozapine therapy was not
affected
by
discontinuation
of
olanzapine.
The natural fluctuating course of
schizophrenia is often represented by
worsening of psychotic symptoms
which may lead to longlasting and
unnecessary AP polypharmacy

KAJIAN KRITIS KEDOKTERAN

BERBASIS BUKTI

APAKAH BUKTI TENTANG

PROGNOSIS INI PENTING ?
Seberapa besar kemungkinan
kesudahan ini terjadi untuk jangka
waktu yang lebih panjang ? Peneliti
tidak menjelaskan tentang
kemungkinan jangka panjangnya.
Seberapa persisi estimasi prognosis ?
Tidak dijelaskan detail
---- PENELITIAN INI PERLU DI TINJAU
ULANG

Apakah hasil ini dapat kita

terapkan ?
Apakah kondisi dalam penelitian ini
mirip (serupa) dengan kondisi kita ? YA
Apakah bukti ini akan mempunyai
pengaruh yang penting secara klinis
terhadap kesimpulan kita tentang apa
yang perlu dilakukan ? Ya dapat di
gunakan dalam kombinasi pengobatan
------------------- DAPAT DI TERAPKAN

Supporting Journal

Supporting journal

THANK YOU
TERIMA KASIH

CGI

PREVALENSI
PREVALESI RESISTENSI 20%-45% DARI
ORANG DENGAN SKIZOFRENIA DENGAN
DURASI LEBIH DARI DUA TAHUN HANYA
SEBAGIAN YANG RESPONSIF TERHADAP
ANTIPSIKOTIK DAN 5%-10% TIDAK
MENDAPATKAN MANFAAT SAMA SEKALI.
PADA PENGOBATAN TIPIKAL AP (FGA)
Pantelis C, lambert TJ. Managing patients
with treatmant resistant schoziphrenia
Med J Aust 2003

IPAP (international
psychopharmacology algorithm project)
CRITERIA OF TREATMENT RESISTANT
SCHIZOPHRENIA

No period of good functioning in previous 5

years.
Prior non response to at least 2 antipsychotic
drugs of 2 different chemical classes for at least
4-6 weeks each at dosages equivalent to >400
mg/d of chlorpromazine or 5 mg/d of
risperidone
Moderate to severe psychopathology, especially
positive symptoms: conceptual disorganization,
suspiciousness, delutions, or hallucinatory
behaviors

Kane creteria for treatment-resistant

schizophrenia (BPRS brief psychiatric rating
scale, CGI clinical global impression)
Treatment resistant
(TR)

creteria

History of TR

At lest 3 treatments with typical

antipsychotic from at least 2 defferent
chemical classes with dosages equivalent to
1000mg/d of chlorpromazine for a period of
6 weeks without significant relief of
symptoms, no period of good function within
the preceding 5 years

Severity of symptoms

A score of at least 45 in the BPRS (1-7

severity degree) with scores of at least 4 in 2
of the following items : conceptual
disorgenization, suspiciousness,
hallucinatory behavior, or unusual thought
content

Current TR

No improvemeny after 6 weeks of treatment

with haloperidol (60mg/d or higher) :
improvement is defined as a 20 % reduction