Background
Overall functional impact of current treatments is modest:
1. Many patients do not respond sufficiently
2. Responders often discontinue and relapse
3. Responders who continue still suffer from substantial deficits
Little guidance on some simple & fundamental questions:
Is there a rational basis for choosing the first antipsychotic?
Can I predict how well the patient will do?
If the patient fails to respond to the first antipsychotic how long do I wait?
Do I continue for some more time or do I switch to another antipsychotic?
If so, which one?
Study objectives
Overall objectives:
1. Optimising current treatments in schizophrenia
2. Explore novel therapeutic options for schizophrenia
Study is divided into several work packages:
 WP1: Imaging (MRI)
 WP2: Pharmacotherapy
 WP3: Psychosocial intervention (PSI)
 WP5: Biological markers (incl. MRS)
Study objectives
1. Optimising current treatments in schizophrenia
WP1: To use MRI to optimise treatment outcome through the
exclusion of “organic’ psychoses and to facilitate prediction of
response to treatment.
WP2: To provide a rational basis for antipsychotic choices in
the treatment of first episode schizophrenia or
schizophreniform disorder.
WP3: To improve functional outcome and reduce drug
discontinuation by means of psychosocial interventions.
Study objectives
2. Explore novel therapeutic options for schizophrenia
WP5: To use theoretically driven neurochemical imaging (MRS) and
empirically driven genetic/genomic markers as predictors of
response to treatment.
WP4: To explore the potential of cannabidiol CBD, a modulator of
endocannabinoid functioning, as an alternative to D2 based
antipsychotics
Study flow pharmacotherapy (WP2)
500
first episode patients
Screening
Informed consent, MRI/MRS,
MINI, physical examinations,
ECG, etc
Phase I
4 week open label amisulpride treatment
After 4 weeks of treatment, remission criteria are assessed
Study flow pharmacotherapy (WP2)
In remission:
Go to Psychosocial
Intervention
Not in remission: start phase II
6 weeks double blind treatment with
amisulpride or olanzapine (randomized)
After 6 weeks of treatment, remission criteria are assessed
In remission:
Go to Psychosocial
Intervention
Not in remission: start phase III
12 weeks open label treatment with
clozapine
Study flow pharmacotherapy (WP2)
End of 12 week clozapine treatment:
remission criteria are assessed
In remission:
Go to Psychosocial
Intervention
Not in remission:
Start of pharmacotherapeutical
treatment outside the trial.
Patient may participate in
Psychosocial Intervention.
Please note: f/u after 6 months
Study flow Psychosocial Intervention (WP3)
Starts at the end of phase I, II or III*
Randomization to PSI or no PSI
Psychosocial Intervention:
1. Motivational interview (6)
2. SMS reminders & support
3. Psychoeducational website
Follow-up at 8-9 set times
up to 12 months
Treatment as usual:
Follow-up at 3-4 set times
up to 12 months
* Drop outs and non-remitted patients after phase III can also participate!
Study flow biological markers (WP5)
The biological marker component (WP5) is woven into the
pharmacotherapy component of the study.
Blood samples required at
 baseline
 the end of phase I, II and III (pharmacotherapy component)
Inclusion criteria
1. Diagnosis of schizophrenia, schizophreniform or schizoaffective
disorder as defined by DSM-IV on the basis of the Mini
International Neuropsychiatric Interview Plus.
2. Age 18-40 years.
3. Written informed consent.
Exclusion criteria
1. A time interval between the onset of psychosis and study entry
> 2 years.
2. Prior use of antipsychotic medication longer than two weeks in
the previous year and/or 6 weeks lifetime.
3. Intolerance to one of the drugs in this study.
4. Patients who are coercively treated at a psychiatric ward
(based on a judicial ruling).
5. Patients who are represented by a legal ward or under legal
custody.
6. Presence of one or more of the contraindications against any
of the study drugs as mentioned in the IB texts.
7. Pregnancy (determined through pregnancy test) or lactation.