journal psikiatri hehe.pptx

8/14/2019 journal psikiatri hehe.pptx

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Efficacy of second-generation

antipsychotics in patients at ultra-high risk

and those with first-episode or multi-episode schizophrenia

Neuropsychiatric Disease and

Treatment -

2013 Washida et al, publisher andlicense Dove Medical Press Ltd.

Supervisor : dr Sabar P Siregar, Sp KJ


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Introduction

Patients will have a better prognosis with a shorterperiod from the onset of illness to intervention andearly detection before disease progression may havea good influence on the prognosis.

Second-generation antipsychotics are effective forpreventing or delaying progression to psychosis

Their use is restrictedas first-linepharmacotherapy


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Aim: to examine the speed of response,

doses, and safety of treatmentwith second-generation antipsychotics (SGAs) in patients at

ultra-high risk (UHR) compared to those with

schizophrenia.

AIM


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Methods

A 12-week open-label, prospective study of SGAs was performed inUltra-High Risk(UHR)patientsand those with first-episodeschizophrenia(FES) and multi-episode schizophrenia(MES).

The subjects:

1430 years old; recruited @ Zikei Hospital, Okayama, Japan.

Observed:

December 1st, 2006 - December 1st, 2011.

The clinical rating scales:

Global Assessment of Functioning (GAF)

Positive and Negative Syndrome Scale (PANSS)

Clinical Global Impression-Severity scale (CGI-S).


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Subjects

Schizophrenia

First-episodeschizophrenia(FES)

Multi-episodeschizophrenia(MES)

Ultra-HighRisk (UHR)

Attenuated positive

symptom state Brief intermittent

psychotic state

Genetic risk anddeterioration state


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Subjects

Patients with UHR and FES had not been prescribed

any other antipsychotics for more than 2 weeks before

the start of the study.

No consent was obtained;

Pregnancy;

IQ under 70;

Neurological disorder and drugdependence;

Mood disorders;

Pervasive developmental disorders;

Personality disorders

Exclusion criteria


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Treatments

UHR

SGAs*

Antidepressants*

Benzodiazepines*

Anticholinergic(min. Dosages)

Supportivepsychotherapy

Occupationaltherapy

FES

SGAs*



Occupationaltherapy

MES

SGAs*



Occupationaltherapy

Clinical evaluation: after 4, 8, and 12 weeks of treatment.

If treatment was ended before 12 weeks, an evaluation was performed at the

end point.

* Note: Main Agent


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MEDICAL ETHICS

For patients whowere minors, theconsent of one ormore guardians

was alsoobtained.

Informed consentwas obtained

from eachpatient.

Approved by the

medical ethicscommittee ofZikei Hospital.


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Statistical Analysis

2 and Fishers exact test Differences in ratios among the three groups.

Friedman test Differences in data over time within groups.

KruskalWallis test Differences among the three groups at each time.

SteelDwass test Comparison among the three groups at each time.

MannWhitney U test Differences in the doses of antipsychotic drugs at

individual time points within groups.

P < 0.05 was considered to be significant in all analyses.


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BASELINE

CHARACTERISTICS

A total of 72 patients (48subjects were inpatients)were registered at Zikei

Hospital, but only 61(UHR = 17, FES = 23,MES = 21) wereincluded as subjects

because only casestreated with anantipsychotic drug as themain agent were eligiblefor this study.


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Results


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GAF score improved significantly in

the UHR, FES, and MES groupsafter 12 weeks

GAF score were higher in UHR at 4weeks after initiation of therapy .

The lowest improvement aftertherapy was in MES group

GAF


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PANSS

Significant improvements in all threegroups

Highest improvement shown in UHRgroup compared to the FES andMES group


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CGI - S

UHR patients clearly had significantly betterearly improvement compared with patients

with schizophrenia


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Dose of SGA

The modal doses in the UHR group

required for improvement was significantly

lower than that in two other groups

MES group received the highest doses

among three groups.


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Switching of SGAs and Adverse

Events

The rates for switching dueto poor efficacy

70% inthe

MES

70% inthe

FES

44% inthe

UHR


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70% inthe MES

50% in theFES

67% inthe UHRThe rates for

switching due to

adverse events


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Each group was prescribed anticholinergic

agentsthe FES group had a

significantly higher frequency of EPSs

compared with the other two groups.

Adverse events other than EPSs included somnolence and

fatigue in all three groups.


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Discussion

We examined response doses safety SGA

UHR Schizophrenia

UHR patients showed significantly fasterand greater improvement compared to those

with FES and MES

CAARMSUHR patients are defined as those with mild symptoms of

schizophrenia


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The CGI-S is a rating scale that can be used after

evaluation with GAF and PANSS.

The CGI-S result showed that UHR patients had already

reached a good level after 4 weeks with greater

improvement at this time point compared with the other

two groups

Thus, this is the first study to show faster improvement

of functions and global impressions in UHR patients

compared to those with FES and MES after treatment

with SGAs, based on the GAF and CGI-S


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SGAs as the main agent in

this study

UHR FES & MES

Minimun

recommended dose

Within the limits of the recommended

doses

Result = UHR patients have a faster response to

lower doses of SGAs compared to patients with

schizophrenia


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Switching of SGAs was

performed at a rate of almost

50% in all patients

UHR

Adverse events = 67%

Poor response = 44%

FES and MESAdverse events =

Poor response =

good response of

UHR patients to

SGAs

both a poor responseand adverse events

led to switching in

the FES and MES

groups


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SGAs can be administered safely in UHR patients by

proper choice of the dosage and use of anti cholinergic

agents

Anti cholinergic agents were permitted in the study,

including preventive prescription before appearance of

EPSs.

UHR group showed the most improvement of functions and

global impressions and the lowest incidence of EPSs


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SGAs caused less EPSs compared than f irst-generat ion

ant ipsy cho t ics (FGAs), and FGAs m ay increase the

incid ence of EPSs in UHRs patients .

EPSs occured in one

subject (6%) in th UHR

group during the 12-

week study period.

if UHR patients are prescribed

SGAs at higher doses that

necessary to improve symptoms

safety can be compromised

and adverse event may reach

level observed in the FES group.


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Based on age, MES group tended to be higherthan in the FES higher.

The sl igh t ly higher age in the MES group

may cause the s low imp rovement of

funct ions and g lobal impress ions.


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All SGAs have some inhibitory effects on

receptors relate to sedation, such as histamine

or 1 receptor

A meta-analysisshowed thatrisperidone,quetiapine,

olanzapine, andaripiprazole

frequently caused

somnolence as anadverse event.

Other adverseevents :

a. Somnolence

b. Fatigue


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In a double-blind

comparative study ofolanzapine and placebo

in UHR patients,McGlashan et al found a

significant

improvement in thosetreated with olanzapine

from 8 weeks and a fasterresponse to olanzapinecompared to placebo.

Similarly, SGAs have

been shown to besignificantly more

effective than placebo in

comparative studies in

UHR patients from 8 to12 weeks of treatment,

with no difference in

safety.

Thus, the short-term advantage of

SGAs in UHR patients is clear


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Antipsychotics areappropriate for use ifimmediateimprovement isneeded.

However, theefficacy and safety

of SGAs for falsepositive casesremains uncertain.


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Conclusion

The studies showedthat UHR patients hadhigher sensitivity anda faster response to a

lower dose of SGAs,compared to patients

with FES or MES.

We suggest that SGAscan be safely

prescribed to UHRpatientswith extremelymild positive symptomsbut with serious acting

out.

The efficacy and safetyof SGAs in these

patients was shown bygiving minimizing dose

and usinganticholinergic drugs.


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CRITICALAPPRAISAL

Journal

ID

Valid

Impo

rtant

Accept

abl

e

PICO


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Jo rnal


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Valid

Important

Accepta

ble

PIC

O

Journal

ID

Published by Dove Medical Press,

Neuropsychiatric Disease & Treatment

Section, on June 18th2013

Available at:

http://dx.doi.org./10.2147/NDT.S45697

Journal


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Valid

Important

Accepta

ble

PIC

O

Journal

ID Titles

Efficacy of second-generation antipsychotics in

patients at ultra-high risk and those with first-episode or multi-episode schizophrenia

Positive: Clearly shows that variables that were investigated

Bold written

There is no abbreviation

Negative: No location

No time Without a capital letter at the beginning of the word

More than 12 words (20 words)

Journal


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Valid

Important

Accepta

ble

PIC

O

Journal

ID

Consist of 5

sections

Aim

Methods

Results

Conclusion

Keywords

> 250 words


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Valid

Important

Accepta

ble

PIC

O

Journal ID

Positive:

Participant of study is clear, followed

by the inclusion and exclusioncriteria

Analysis tools mentioned clearly

Measurable outcomes are clear

Technique sampling is randomized

Negative:

None


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Valid

Important

Accepta

ble

PIC

O

Journal ID

Positive

Tables are presented in accordance withthe international journal writing format

(without the vertical and horizontal linesin a) with no serial number and table titleand description of the contents of thetable

- Negative: Theres no explanation about what

type of drug that used to switched toSGA

J l


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Valid

Important

Accepta

ble

PIC

O

Journal

ID

Positive

There are advantages of the mentioned research results

that have been achieved

There is an emphasis if the results of the research will beapplied

There are suggestions for future research

Negative:

There was no significant indicator to measure the response

of therapy (should be using three indicators)


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Valid

Accepta

ble

PICOPICO N LYSIS POPULATION

Patient aged 14 30 years olds whowere UHR group, first-episodeschizophrenia (FES) and multi-episode

schizophrenia (MES) who visited ZikeiHospital, Okayama, Japan fromDecember 1st, 2006 to December 1st,2011.

INTERVENTION Treatment by using SGAs as the main

agent for UHR, FES, and MES.


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Valid

Accepta

ble

PICO

COMPARATION The speed of response, the safety

of using SGAs in patient with UHR

and those with FES or MES in 12

weeks.

OUTCOME

The UHR group have a better and

safely response to SGAs in minimaldosage compare to patient with

schizophrenia.

V lid


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Valid

Acceptab

le

V LID EVIDENCEQUESTIONS

Is the allocation of patients in the study

randomized?

YES

Is patient observation done quite long and

complete?

YES

Are all patients in the randomized, analyzed? NO

Whether patients and physicians remain blind in

doing therapy, apart from the therapy being

tested?

NO

Accept


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Accept

able

QUESTIONS

Is there a difference in our

patients when compared

with that found in previous

studies so that the results

can not be applied to our

patients?

NO, because there is no previous

studies.

Whether such therapy may

be applied to our patients?

YES

Does the patient have a

potential beneficial or

detrimental treatment or

when the program

implemented?

Profitable

PPLIC BILITY OFTEST


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CONCLUSION

1

Clinical study is valid

2 Clinical study isapplicable


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Prodromal or Ultra-High Risk (UHR)

States

Attenuated positive symptom state: Non-psychotic,pre-delusional unusual thought content; pre-hallucinatory perceptual abnormalities; orsubthreshold disorganization of speech.

Brief intermittent psychotic state: Psychoticsymptoms emerging in the recent past that are toobrief to meet criteria for psychotic disorder.Symptoms present at least several minutes per dayat least once per month.

Genetic risk and deterioration state: Genetic risk forpsychosis (first degree relative with any psychoticdisorder, affective or nonaffective; and/or patient hasschizotypal personality disorder) plus a loss of socialor work capacity, or both, in past month.

journal psikiatri hehe.pptx

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