Early Pharmacological and Psychological Intervention for Late Prodromal States of Psychosis

• improvement of prodromal symptoms (ERIRAOS-Scale, PANSS)
• social impairment

• social functioning (GAF)
• depression

The study will provide an empirical basis for a pharmacological treatment option. An open-label, randomized, multi-centre parallel group design is used. An intensified clinical management (CM), which allows needs-based psychological crisis intervention, is compared to a combination of such a CM and the atypical neuroleptic amisulpride. The central hypothesis is that the combination of a clinical management with an atypical neuroleptic is the superior treatment.

The first diagnosis of schizophrenia is preceded by a long lasting period comprising an untreated psychotic and a prodromal state. The duration of untreated psychosis correlates with a significant worsening of several outcome variables and persons fulfilling criteria of a prodromal state are already suffering from prodromal symptoms and from a significant deterioration of social and vocational functioning. However, a sufficient strategy for early intervention is still lacking. The study will provide an empirical basis for a pharmacological treatment option. An open-label, randomized, multi-centre parallel group design is used. An intensified clinical management (CM), which allows needs-based psychological crisis intervention, is compared to a combination of such a CM and the atypical neuroleptic amisulpride. For analysis 130 patients will be recruited within three years, the treatment period is two years.

• Schizophrenia
• Psychoses

• Behavioral: Clinical Management (CM)
• Drug: Amisulpride

Inclusion Criteria:

1. General criteria

   • Age between 14 and 36 years
   • male or female, in- or outpatients
   • written informed consent, for patients below 18 years also signed by parents

2. Special criteria (present within the last three months prior to the study)

   • Attenuated Positive Symptoms
   • Presence of at least one of the following symptoms (assessed by ERIraos):ideas of reference, odd beliefs or magical thinking, unusual perceptual experiences, odd thinking and speech, suspiciousness or paranoid ideation
   • Symptoms have to appear several times per week for a period of at least one week

AND / OR

• Brief Limited Intermittent Psychotic Symptoms (BLIPS)
• Duration of episode less than one week, interval between episodes at least one week
• Symptoms resolve spontaneously
• Presence of at least one of the following symptoms (assessed by ERIraos): Hallucinations, Delusions, Formal thought disorder, Gross disorganized or catatonic behavior

Exclusion Criteria:

• DSM-IV diagnosis of schizophrenia, schizophreniform,schizoaffective, delusional or bipolar disorder, at any time of life.
• DSM-IV diagnosis of brief psychotic episode with a duration of more than one week, at any time time of life, or BLIPS within one week before inclusion.
• DSM-IV diagnosis of delirium, dementia, amnestic and other cognitive disorders, mental retardation, mental disorders due to a general medical condition or mental disturbances due to psy-chotropic substances.
• Abuse of alcohol or drugs within the last three months prior to the study; exception: cannabis user have to be drug-free during four weeks prior to the study. In case of drug abuse, it has to be determined, whether present prodromal symptoms appeared before any drug abuse; If not, symptoms have to be still present after a drug-free period of 3 months (hallucinogens, amphetamines), or four weeks (cannabis).

• German Federal Ministry of Education and Research
• German Research Network On Schizophrenia
• Sanofi-Synthelabo
• Department of Psychiatry University of Bonn
• Heinrich-Heine University, Duesseldorf
• Ludwig-Maximilians - University of Munich