Early Pharmacological and Psychological Intervention for Late Prodromal States of Psychosis

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Psychoses
• Intervention / Treatment: Behavioral: Supportive management; Drug: Amisulpride

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50924
      • Department of Psychiatry and Psycotherapy University of Cologne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 (APS)
   • Presence of at least one of the following symptoms: 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: Hallucinations, Delusions, Formal thought disorder, Gross disorganized or catatonic behavior

Exclusion Criteria:

• Diagnostic and Statistical Manual of Mental Disorders (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 psychotropic 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: supportive management; needs-focused, unspecific supportive management	Behavioral: Supportive management; The needs-focused intervention could include psychoeducation, crisis intervention, family counselling and assistance with education or work-related difficulties, according to need. Regular psychotherapy was not permitted.; Other Names: Clinical Management
Experimental: amisulpride; 24 months amisulpride 50 to 800 mg, needs-focused, unspecific supportive management.	Drug: Amisulpride; Daily doses could range from 50 to 800 mg, with increments of 50 mg at first step and 100 mg at further steps. As a guideline, it was suggested that the dosage be increased as long as attenuated or brief limited intermittent positive symptoms were present. The interval between such steps should be at least 14 days if brief limited symptoms were absent and the APS score had improved.; Other Names: Solian

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
improvement of risk related symptoms	Decrease of symptom scores; complete remission of risk related symptoms	3, 6, 12, 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global functioning	Increase of Global Assessment of Functioning (GAF) scores	3, 6, 12, 24 months

Collaborators and Investigators

• Sponsor: University of Cologne
• Collaborators: German Federal Ministry of Education and Research; Heinrich-Heine University, Duesseldorf; Ludwig-Maximilians - University of Munich; Sanofi-Synthelabo; German Research Network On Schizophrenia; Department of Psychiatry University of Bonn
• Investigators: Study Chair: Joachim Klosterkötter, Professor, Department of Psychiatry and Psycotherapy University of Cologne

Publications and helpful links

Helpful Links

• Click here for more information about this study: Early pharmacological and psychological intervention for late prodromal states of psychosis
• Homepage of co-ordinating center

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Primary Completion (Actual): June 1, 2005
• Study Completion (Actual): June 1, 2005

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Estimate): December 24, 2014
• Last Update Submitted That Met QC Criteria: December 23, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: schizophrenia; psychosis; early intervention; amisulpride; ultra high risk; prodromal state
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Prodromal Symptoms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Dopamine Agents; Dopamine Antagonists; Antidepressive Agents, Second-Generation; Amisulpride
• Other Study ID Numbers: 01 GI 9935 - P 1.1.3