Symptomatik der Angstneurose nach Freud 1895

1
AEP Conference Stockholm, May 8, 2002 Symposium
on Early Psychosis and psychosis transitions
epidemiology and intervention A differential
approach to intervention in early psychosis M.
Hambrecht, S. Ruhrmann, M. Wagner, A. Wieneke, A.
Bechdolf, W. Maier J. Klosterkötter
2
Intervention in prodromal stages
why ? for whom ? when ? how ?
3
DUI
Häfner et al. 1993
DUP
4
First symptoms perceived by patients (ABC
Schizophrenia Study)
Restlessness, depressed mood, anxiety,
worrying Social withdrawal, lack of
self-confidence, lack of energy Cognitive
impairment, poor work performance
5
NEUROCOGNITIVE PROFILE
3,0
2,5
2,0
Z - SCORES (Z2)
1,5
1,0
0,5
0,0
p lt 0,10 p lt0,05 p 0,01
6
Prior to psychotic symptoms ...

• ... high prevalence of depression
• ... subjective and objective cognitive deficits
• ... high prevalence of substance misuse
• ... onset of social stagnation and decline

Interventions are justified.
7
Aims of early intervention
1. Improvement of presenting
symptomatology 2. Avoidance of an
unfavourable social course 3. Suppression or
delay of progression to psychosis
8
Methods available from relapse prevention

• Biological strategies
• Neuroleptics, tranquilizers, antidepressants,
  Avoidance of substance misuse
• Psychological strategies
• Psychoeducation, Stress management, CBT, IPT,
  and other interventions
• Social strategies
• Family information and -interventions, specific
  support at school, work, leisure etc.

9

Early intervention in analogy to relapse
prevention

• Strategies seem to work
• Integration of different modalities beneficial
• Problems with compliance
• But Lack of studies comparing first episodes and
  relapses

10

Current models of early intervention

• PACE, Melbourne
• RAP, Long Island
• PRIME, Yale U.
• EDIE, Manchester
• German Schizophrenia Research Network
• (Harvard Cases)

11
PACE- Clinic Melbourne Randomised controlled
trial(6 months intervention 6 months
follow-up) Inclusion criteria

• Brief limited intermittent psychotic symptoms
  (BLIPS)
• or attenuated psychotic symptoms
• or genetic/obstetric risk impaired
  functioning (GAF minus 30)

(McGorry et al.)
12
PACE- Clinic MelbourneTransition rates

• Control group 36
• Intervention group (combination of CBT, Social
  Support and up to 2mg Risperidon)
• with complete cooperation 10
• without complete cooperation 22

13
RAP- Programme, Long IslandRecognition And
PreventionNaturalistic (6-24 months) Follow-up
Study(Cornblatt et al. 2001)

• 77 adolescents (age 12-22) form 3 groups
• attenuated negative symptoms antidepressants as
  beneficial as neuroleptics
• combination of attenuated negative and
  attentuated positive symptoms antidepressants as
  beneficial as neuroleptics
• schizophrenia-like psychosisatypical
  neuroleptics33 transition to schizophrenia

14

Early Intervention in the German Schizophrenia
Research Network A differential approach
Depending on the stage of the prodrome a
manualized psychological treatment ora
pharmacological intervention
15
Defining two stages / risk groups

• Early prodromal stage Late prodromal stage
• - predictive BASIC SYMPTOMS - BLIPS
• or or
• - genetic/obstetric RISK plus - ATTENUATED
  PSYCHOTIC DECLINE in functioning symptoms
• Psychological Pharmacological
  Intervention Intervention

16
Definition of the Early prodromal stage

• Predictive basic symptoms
• Interference, blocking or pressure of thought
• Disturbances of receptive speech
• Disturbances of discrimination between ideas and
  perceptions, fantasy and memory contents
• Tendency to delusion of reference
  ('subject-centrism')
• or Genetic/obstetric risk GAF-score minus 30

17
Psychological Intervention in the Early prodromal
stage

• Individual therapy (25 sessions)
  Psychoeducation work on individual problems
• Small group therapy (16 sessions) Positive
  activities, training of social skills and
  problem solving
• Computerized cognitive training (16 sessions)
• Family information and counseling (3 sessions)

18
Definition of the Late prodromal stage

• BLIPS Or Attenuated psychotic symptoms
• more than twice, I. Hallucinations (PANSS
  P3 ? 4)
• less than one week, II. Delusions (PANSS
  P1, P5 oder P6 ? 4)
• spontaneous remission III. Formal thought
  disorder (PANSS P2 ? 4)
• I. Ideas of reference
• II. Unusal thoughts, magical ideation
• III. Unusual perceptions
• IV. Odd thinking or speech
• V. Suspicion or paranoid ideation

19
Pharmacological intervention in the late
prodromal stage

• careful assessment of inclusion and exclusion
  criteria
• randomization
• slow increase of amisulpiride in 100 mg
  intervals (intially 50mg)
• increase dosage until response
• decrease dosage if side effects, maximum dose
  800 mg
• duration of the intervention 2 years
• 2 outcome criteria remission of symptoms
  transition to psychosis

20
1.1.3 Study design
Open, controlled, randomised multicenter study
comparing Psychologically advanced Clinical
Management versus Psychologically advanced
Clinical Management Amisulpride Study
duration 5 years Treatment phase 2 years N
260 (minimum 130, adjusted for an expected drop
out rate of 50)
21
Preliminary Midterm Results
Start of inclusion Spring 2000 End of
inclusion Inclusions until March 2002
22
Characteristics at inclusion(analysed samples of
Mar 02)
23
Direct treatment outcome (early)(pre-post-compari
son of 10 completers Wilcoxon signed rank test)
24
Recruitment process
Checklist
Case numbers of Nov 13th, 2001
500
410
90
Checklist
Checklist -
No Inclusion Criteria Checklist
379
Inclusion Criteria Checklist
31
Inclusion Criteria Checklist -
Inclusion Criteria Checklist
180
199
87
93
Late prodromal stage
Early prodromal stage
Psychological intervention 1.1.2
Pharmacological intervention 1.1.3
42
35
25
Reasons for Drop out (Late)
Total number 13 of 36 Transition to
Psychosis 3 Non-compliance 4 Side
effects 2 Lack of response 2 Lost to
follow-up 2 Decision of patient to
discontinue because of good remission
26
Late Group Improvement of Attenuated Positive
Symptoms Descriptive interim analysis (Baseline ?
Week 8)
N 23
39.4
72.8
100 87 mg
27
Late GroupImprovement of Attenuated Positive
SymptomsDescriptive interim analysis (Baseline ?
Week 12)
28
Late GroupImprovement of Attenuated Positive
SymptomsDescriptive interim analysis (Baseline ?
Week 12)
29
Ethical Issues

• Stigma
• Self-fulfilling prophecy
• False-positive predictions
• Side effects

30
Answers to ethical questions

• Patients and families seek help themselves
• They suffer from symptoms
• Adequate setting
• Empathy in information and education
• Intervention taylored to individual symptoms
• Supportive psychological interventions
• Narrow indikation for medication

31
Conclusions

• Prevention requires prediction
• Pragmatic, symptom-oriented, individualized,
  multi-modal strategy
• Based on the vulnerability-stress-coping paradigm
• Analogy to relapse prevention
• Concern for ethical questions
• More data, i.e., systematic research needed
  (RCTs)