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

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorders; Schizophrenia and Disorders With Psychotic Features
• Intervention / Treatment: Drug: Olanzapine; Drug: Ziprasidone; Drug: Risperidone; Drug: Quetiapine; Drug: Haloperidol; Drug: Amisulpride; Drug: Fluphenazine; Drug: Perphenazine; Drug: Perazine; Drug: Thioridazine; Drug: Benperidol; Drug: Sertindole; Drug: Zuclopenthixol; Drug: Fluspirilene; Drug: Pimozide; Drug: Sulpiride; Drug: Paliperidone; Drug: bromperidol; Drug: Flupentixole

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • Psychiatrische Klinik und Poliklinik fuer Psychiatrie und Psychotherapie der Technischen Universitaet Muenchen am Klinikum rechts der Isar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; 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; Drug: Ziprasidone; Drug: Risperidone; Drug: Quetiapine; Drug: Haloperidol; Drug: Amisulpride; Drug: Fluphenazine; Drug: Perphenazine; Drug: Perazine; Drug: Thioridazine; Drug: Benperidol; Drug: Sertindole; Drug: Zuclopenthixol; Drug: Fluspirilene; Drug: Pimozide; Drug: Sulpiride; Drug: Paliperidone; Drug: bromperidol; Drug: Flupentixole
Active Comparator: Control; 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; Drug: Ziprasidone; Drug: Risperidone; Drug: Quetiapine; Drug: Haloperidol; Drug: Amisulpride; Drug: Fluphenazine; Drug: Perphenazine; Drug: Perazine; Drug: Thioridazine; Drug: Benperidol; Drug: Sertindole; Drug: Zuclopenthixol; Drug: Fluspirilene; Drug: Pimozide; Drug: Sulpiride; Drug: Paliperidone; Drug: bromperidol; Drug: Flupentixole

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

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Stefan Leucht, Professor, Klinikum Rechts der Isar; Principal Investigator: Markus Dold, MD, Klinikum Rechts der Isar

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): June 22, 2016
• Study Completion (Actual): June 22, 2016

Study Registration Dates

• First Submitted: November 24, 2014
• First Submitted That Met QC Criteria: December 1, 2014
• First Posted (Estimate): December 4, 2014

Study Record Updates

• Last Update Posted (Actual): October 11, 2018
• Last Update Submitted That Met QC Criteria: October 10, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Schizophrenia; Disease; Psychotic Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Antidepressive Agents, Second-Generation; Anti-Dyskinesia Agents; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Risperidone; Ziprasidone; Amisulpride; Haloperidol; Perphenazine; Sertindole; Sulpiride; Pimozide; Fluphenazine; Fluphenazine depot; Fluphenazine enanthate; Thioridazine; Clopenthixol; Fluspirilene; Benperidol; Bromperidol; Perazine
• Other Study ID Numbers: 1723/1-1; 2013-000338-37 (EudraCT Number); DO 1723/1-1 (Other Grant/Funding Number: DFG (Deutsche Forschungs Gesellschaft)); DRKS00006878 (Other Identifier: Deutsches Register Klinischer Studien)