Barriers to achieve remission and recovery in schizophrenia

Prof Köksal Alptekin MD Dept of Psychiatry

Dokuz Eylül University

School of Medicine

İzmir-TURKEY

GAMIAN-Europe Regional Seminar: Psychosocial Recovery, Budapest 2011

koksal.alptekin@deu.edu.tr

Barriers to achieve remission and Barriers to achieve remission and recovery in schizophreniarecovery in schizophrenia

Treatment effectiveness Treatment side effects and early death Combined antipsychotics use Treatment adherence Cognitive deficits and psychosocial

functioning

One-year follow up study of schizophrenia patients: a multicenter, naturalistic design

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Baseline 3th month 6th mont 9th month 12th month

Pos.Symp

Neg.Symp

Dep.Symp

BP

RS

scor

es

382 patients with DSM-IV schizophrenia 44 % patients were followed-up for a yearTotal BPRS: Baseline: 53.11, 12th Month: 42.11

Predictor Factors of Disability(Multiple Linear Regression Analysis)

B Std.Eror Beta t___

Negative symp. 0.391 0.155 0.302 2.304*

DUP 0.428 0.181 1.181 2.365* (Constant) 3.513 1.001 ----- 2.429__        

* p < 0.05 ( DUP : Duration of Untreated Psychosis) 

(Alptekin et al. 2005, Psychiatry Research)

Only 14 % met full recovery criteria for 2 years or longer.Better cognitive functioning was associated with full recovery (adequate social/vocational functioning, and symptom remission) Shorter duration of psychosis before study entry predicted both full recovery and symptom remission.

RRemission emission && recovery in schizophrenia recovery in schizophrenia

Duration of untreated psychosis Cognitive functions Negative symptoms

Discontinuation Rates

1. Lieberman JA et al. N Engl J Med 2005; 353: 1209–23. 2. Alptekin K et al. J Psych Res 2005; 135:101–11

Pat

ien

ts %

CATIE study1

56

44

All drugs

(n=382)2*

*Graph showing discontinuation rate for patients on various antipsychotic drug combinations for 12 month period; CATIE study shows discontinuation rate over 18 months

150 double-blind, mostly short-term studies,21 533 participantsFour of these drugs were better than FGAs for overall efficacy, with small to medium effect sizesAmisulpride: −0·31 [95% CI −0·44 to −0·19, p<0·0001]Clozapine: −0·52 [−0·75 to −0·29, p<0·0001]Olanzapine: −0·28 [−0·38 to −0·18, p<0·0001] Risperidone: −0·13 [−0·22 to −0·05, p=0·002])

CATIE CATIE Phase Phase 2 E2 Efficacyfficacy::Treatment DiscontinuationTreatment Discontinuation

Total p-value = 0.010*KLZ vs OLZ p=0.019 KET vs OLZ p=0.004 KLZ vs RIP p=0.003

McEvoy JP, et al. Am J Psychiatry 2006;163:600-610.

0

0.2

0.4

0.6

0.8

1

0 3 6 9 12 15 18

Klozapin (N=45)Olanzapin (N=17)

Ketiapin (N=14)Risperidon (N=14)

Tre

atm

ent

con

tin

uat

ion

rat

es

MONTHS

78 Randomized Double Blind Studies, 13558 patients(PANSS Total Scores)

(Leucht ve ark., Am J Psych 2008)

Clozapine (400 mgr/gün) ≥ Risperidone

0 0,1 0,2 0,3 0,4

Sertindole r = 0.34, N=1, n = 424Sertindole r = 0.34, N=1, n = 424

EPS – SGA & FGA

Amisulpride Amisulpride r = 0.25, N=12, n = 1599r = 0.25, N=12, n = 1599

Olanzapine r = 0.39, N=3, n = 2694Olanzapine r = 0.39, N=3, n = 2694

Quetiapine r = 0.32, N=2, n = 757Quetiapine r = 0.32, N=2, n = 757

Risperidone r = 0.14, N=12, n = 2421Risperidone r = 0.14, N=12, n = 2421

(r)

Leucht et al. Am J Psychiatry 2002

Antipsychotics & Cognitive Functions (Meta-analysis)

First & Second Generation antipsychotics *Between 1990-1998, 15 studies. 3 randomized double-blind and 12 open label.SGA BETTER Keefe 1999

FGA & Placebo (Effect Size:0.22) *FGA & SGA (14 studies) **Clozapine, Olanzapine, Quetipine, RisperidoneSGA BETTER (Effect Size: 0.24)* Mishara ve Goldberg, 2004, **Woodward ve ark. 2005

Verbal fluency, attention, executive functions, Learning and information processing speed Effect Size: 0.22 / 0.24Correlated to motor dysfunctions and EPS

One-year follow up study of schizophrenia patients: a multicenter, naturalistic design

Combined antipsychotics use “dirty little secret” (Stahl)

05

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Only Two Threeand

more

Antipsychotics

0

2

4

6

8

10

12

14

16

18

Baseline 6 Weeks

RisperidonePlacebo

PANSS Positive :

Time p 0.0001 Treatment group x time p 0.05

0

20

40

60

80

Baseline 6 Weeks

RisperidonePlacebo

Prolactine Levels :

Treatment group x time p 0.0001

Time p 0.0001

Treatment group 0.0001

Pro

lact

in le

vel (

ng/m

l) L

S M

eans

p0.0001

p =0.002

PA

NS

S P

OS

LS

Mea

ns

Anıl Yağcıoğlu ve ark., J Clin Psychiatry 2006

Colton CW, Manderscheid RW. Prev Chronic Dis [serial online] 2006 Apr [date cited]. Available Colton CW, Manderscheid RW. Prev Chronic Dis [serial online] 2006 Apr [date cited]. Available from: from: URL:http://www.cdc.gov/pcd/issues/2006/apr/05_0180.htm, (Newcomer J Clin Psych), (Newcomer J Clin Psych)

Compared to the general population, persons with major mental illness typically lose more than 25 years of normal life span

Physical Health: A Major Concern to Psychiatrists

and Patients

1. Saravane D et al. European Psychiatry 2007; S101–S220: Abstract # P130. 2. NICE Guidelines. 3. Hofer A et al. J Clin Psychiatry 2002; 63:49–53. 4. Angermeyer MC et al. Psychiatr Prax 2000.

Weight change

Metabolic

abnormalities

EPS

Sexual

dysfunction

Sedation

3,764 respondents, across 12 European countries (2006)10-question survey on aspects of physical health in schizophreniaPhysical health monitoring and the impact of antipsychotic therapyOnly 66 % reported that they were monitoring weight.

Psychiatrists report ¹

Schizophrenia Patients report 2-4 ?

Helbling J et al. BMC Psychiatry 2006;6:42

Doctors and lay people differ in their attitudes

towards weight gain

Patients may encounter negative public attitudes towards antipsychotics and strong pressure to stop medication in the event of side effects

Intolerable Side Effects Lay Persons GPsVisible movement disorder 62.8 48.5*

Marked tremor 58.9 33.7**

Risk of drug dependancy 55.2 22.7**

Continuous feeling of unrest 53.5 43.4 ns

Significant weight gain 35.9 9.3***

Continuous anhedonia 33.9 24.5*

Frequent sexual dysfunction 27.1 4.1**

Heavy sweating 26.1 3**

Unpleasant dry mouth 18.3 2**

*** p 0.001

Treatment NonadherenceTreatment Nonadherence

Increase relapse rates Frequent hospitalization Poor prognosis Impaired psychosocial functioning Poor quality of life

J Clin Psychiatry 2003;64:10–3

Insight Cognitive dysfunctions Patient’s feelings

J Clin Psychiatry 2004;65:1211–8

Side effects Efficacy

Doctor/patient relationship -a working therapeutic alliance

Nonadherence

ConclusionsConclusions.1 .1 ::

Clozapine seems quite better Dose is very relevant regarding remission of

symptoms However patients are still symptomatic. Far away from recovery issues mainly due to

inefficacy of available antipsychotics over cognitive dysfunctions

Treatment side effects, weight gain, early death issue

ConclusionsConclusions.2 .2 ::

Efficacy in remission of positive symptoms Less efficacy in improving negative symptoms and

especially cognitive dysfunctions Receptors underlying cognitive dysfunctions are not

clear New medicines are required to treat both psychosis

and cognitive dysfunctions or future treatment of schizophrenia may happen by combining SGAs and new medicines which improve cognitive dysfunctions.

koksal.alptekin@deu.edu.tr