Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics in Schizophrenic Patients

Study Overview
=================
Brief Summary
-----------------
The main objective of the trial is to evaluate, how long an antipsychotic relapse-prevention should be continued and to which time a patient with schizophrenia is protected enough, so that a withdrawal or reduction of the medication seems appropriate. Relapse is defined as primary outcome.

Detailed Description
-----------------
The main objective of the trial is to evaluate for the first time, how long an antipsychotic relapse-prevention should be continued and to which time a patient is protected enough, so that a guided withdrawal or reduction of the medication seems appropriate. Relapse is defined as primary outcome. We include patients with schizophrenia or schizoaffective disorder in remission for at least 3 years under a stable antipsychotic medication.

Official Title
-----------------
Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics for the Prevention of Relapse in Long-term Stabilized Schizophrenic Patients: a Randomized, Single-blind, Longitudinal Trial

Conditions
-----------------
Schizophrenia, Schizophrenia and Disorders With Psychotic Features, Schizoaffective Disorders

Intervention / Treatment
-----------------
* Drug: Olanzapine
* Drug: Amisulpride
* Drug: Risperidone
* Drug: Haloperidol
* Drug: Quetiapine
* Drug: Perphenazine
* Drug: Sulpiride
* Drug: bromperidol
* Drug: Zuclopenthixol
* Drug: Thioridazine
* Drug: Paliperidone
* Drug: Ziprasidone
* Drug: Benperidol
* Drug: Fluspirilene
* Drug: Pimozide
* Drug: Perazine
* Drug: Fluphenazine
* Drug: Flupentixole
* Drug: Sertindole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of schizophrenia or schizoaffective disorder The participants have to be in remission for at least 3 years (i.e. no psychiatric hospitalisation) under a stable antipsychotic medication. Remission will be measured using the remission criteria by Andreasen et al. (2005) Score ≤3 for the items concerning psychosis of the Positive and Negative Syndrom Scale (PANSS; Kay et al., 1987): Delusions (P1), Conceptual disorganisation (P2), Halluzinations (P3), Mannerisms and posturing (G5) and Unusual thought content (G9) and a score ≤3 on the Clinical Global Impression Severity Scale (CGI-S; Guy, 1976) Able to give informed consent Exclusion Criteria: Actively suicidal Serious medical illnesses Known non-complience concerning the medication Medication with clozapin Medication with antidepressants and mood stabilisors that were initiated during the last 6 weeks before study enrollment Patients with substance dependence other than nicotine or caffeine within 6 months prior to baseline Unability to give informed consent Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intervention group: guided discontinuation or dose-reduction of the current antipsychotic medication. The antipsychotic drug used before study start will be discontinued gradually under medical surveillance. The process of discontinuation depends on the physicians judgement und should be guided be the participants needs and clinical status. This approach was already used before in another study (gradual discontinuation, Wunderink et al., 2007). We assume that the dose can be reduced by approximately 1/6 of the starting dose every two weeks. If long acting antipsychotics are applied, there is no need for a gradual discontinuation due to their long half life. | Drug: Olanzapine<br> <br> Drug: Amisulpride<br> <br> Drug: Risperidone<br> <br> Drug: Haloperidol<br> <br> Drug: Quetiapine<br> <br> Drug: Perphenazine<br> <br> Drug: Sulpiride<br> <br> Drug: bromperidol<br> <br> Drug: Zuclopenthixol<br> <br> Drug: Thioridazine<br> <br> Drug: Paliperidone<br> <br> Drug: Ziprasidone<br> <br> Drug: Benperidol<br> <br> Drug: Fluspirilene<br> <br> Drug: Pimozide<br> <br> Drug: Perazine<br> <br> Drug: Fluphenazine<br> <br> Drug: Flupentixole<br> <br> Drug: Sertindole<br> <br> |
| Active Comparator: Control<br>The participants receive the same antipsychotic drugs, they have received before the start of the study, without changing the dose or the application form. Study medication is, with exception of Clozapin, every oral or depot neuroleptic drug approved for the treatment of schizophrenia in Germany. | Drug: Olanzapine<br> <br> Drug: Amisulpride<br> <br> Drug: Risperidone<br> <br> Drug: Haloperidol<br> <br> Drug: Quetiapine<br> <br> Drug: Perphenazine<br> <br> Drug: Sulpiride<br> <br> Drug: bromperidol<br> <br> Drug: Zuclopenthixol<br> <br> Drug: Thioridazine<br> <br> Drug: Paliperidone<br> <br> Drug: Ziprasidone<br> <br> Drug: Benperidol<br> <br> Drug: Fluspirilene<br> <br> Drug: Pimozide<br> <br> Drug: Perazine<br> <br> Drug: Fluphenazine<br> <br> Drug: Flupentixole<br> <br> Drug: Sertindole<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse | The criterion is measured at every visit (every two weeks) two weeks with two criteria, both have to be fullfilled: Score ≥4 (moderate) for at least two of the following PANSS-items : Delusions (P1), Conceptual disorganisation (P2), Halluzinations (P3), Mannerisms and posturing (G5) and Unusual thought content (G9) (PANSS; Kay et al., 1987) Score ≥4 on the Clinical Global Impression Severity Scale (CGI-S; Guy, 1976b) | Every 2 weeks up to 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychiatric rehospitalisation |  | Every 2 weeks up to 26 weeks | 
| Totalscore of Positive and Negative Syndrome Scale (PANSS) | PANSS-Scale | Baseline, then every 4 weeks up to 26 weeks | 
| Occurence of specific adverse effects (open interview) |  | Baseline,then every 4 weeks up to 26 weeks | 
| Clinical Global Impression - Severity Scale (CGI-S) | CGI-I Scale | Baseline, then every 4 weeks up to 26 weeks | 
| Quality of life measured by the questionnaire Subjective well-being under neuroleptics scale (SW-N) | SW-N-Scale | Baseline, and after 12 and 26 weeks | 
| Status of occupation |  | Baseline, and after 12 and 26 weeks | 
| Personal and Social Performance (Personal and Social Performance Scale [PSP]) | PSP-Scale | Baseline, and after 12 and 26 weeks | 
| Adherence/Attitude of patients towards medication (Medication Adherence Rating Scale [MARS]) | MARS-Scale | Baseline, and after 12 and 26 weeks | 
| Drop-outs total and due to specific reasons |  | Every 2 weeks up to 26 weeks | 
| Movement disorders (Abnormal Involuntary Movement Scale [AIMS]) | AIMS-Scale | Baseline, and after 12 and 26 weeks | 
| Weight change |  | Baseline, and after 12 and 26 weeks |