Efficacy of an Early Antipsychotic Switch in Case of Poor Initial Response to the Treatment of Schizophrenia

The Switch Study - Efficacy of Early Antipsychotic Switch Versus Maintenance in Patients With Schizophrenia Poorly Responding to Two Weeks of Antipsychotic Treatment

The main aim of the trial is to study whether a change of medication in non-responders to a two-weeks antipsychotic drug trial is more effective than continued treatment with the same antipsychotic. Hypothesis: Non-responders who are switched at 2 weeks to another antipsychotic are more frequently in symptomatic remission at week 8 than non-responders who stay on the same antipsychotic

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder
• Intervention / Treatment: Drug: Olanzapine or amisulpride

Detailed Description

The patients will be randomised to a double-blind 2 week run in phase with fixed doses of either oral amisulpride 800 mg/day or olanzapine 20mg/day.

Those participants who have not responded to treatment at two weeks (PANSS improvement <25%) will be randomised to a 6 week double blind flexible dose phase:

1. Experimental intervention: switch to the other antipsychotic (oral olanzapine 5-20mg/d or oral amisulpride 200-800 mg/d)
2. Control intervention: continuation with the same drug as in the first 2 weeks in flexible dose ranges as above for another six weeks Those participants who have responded at week 2 (≥25% PANSS reduction) will continue on the same drug in flexible dose ranges as above Total duration of intervention per patient: 8 weeks

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munic, 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

Description

Inclusion Criteria:

• Inpatients with Diagnostic and Statistical Manual of Mental Disorders 4th Edition Text Revision (DSM-IV TR) diagnosis of schizophrenia, schizophreniform or schizoaffective disorder
• PANSS total score at baseline > 75, at least two PANSS psychosis items ≥ 4, Clinical Global Impression of severity score moderately ill or more (≥4)
• Increase in the level of care (outpatient care to day clinic or inpatient care)

Exclusion Criteria:

• contraindication to study drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: initial amisulpride	Drug: Olanzapine or amisulpride; Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding
Active Comparator: early responders	Drug: Olanzapine or amisulpride; Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding
Active Comparator: early non-responders switched	Drug: Olanzapine or amisulpride; Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding
Active Comparator: ealy non-responders non-switched	Drug: Olanzapine or amisulpride; Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding
Active Comparator: initial olanzapine	Drug: Olanzapine or amisulpride; Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients in Symptomatic Remission at Week 8 Comparing the "Switched" With the "Non Switched" Early Non-responders	Remission is defined as a maximum rating of 3 points (equals a severity rating of "mild") in each of all the following eight items of the PANSS (Kay et al.) rating scale: Delusions (P1), unusual thought content (G9), hallucinatory behavior (P3), conceptual disorganization (P2), mannerisms/posturing (G5), blunted affect (N1), social withdrawal (N4) and lack of spontaneity (N6); if one item is >3 the remission status is "no" (non-remission); all times have a rating from 1 to 7, so the min. rating is 8, the max. rating is 56. Remission is a dichotomous item (yes/no) without a specific min. or max. rating	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PANSS Total Score Change	The Positive and Negative Syndrome Scale (Kay SR, Fiszbein A, Opler LA: The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bull 1987; 13:261-276) is a 30- item inventory assessing the absence or severity of schizophrenia symptoms across three subscales: positive symptoms (items P1-P7, including hallucinatory behavior, delusions, and conceptual disorganization), negative symptoms (items N1-N7, including blunted affect, social and emotional withdrawal, and lack of spontaneity), and general psychopathology symptoms (items G1-G16, including mannerisms and posturing, unusual thought content, and lack of insight). Each item is scored on a scale ranging from 1 (absent) to 7 (extreme), with item ratings incorporating the presence, effects of symptoms on an individuum's thinking, feeling or behaving as well as their severity. The min. sum rating is 30, the max. sum rating is 210.	8 weeks

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Stefan Leucht, MD, Psychiatrische Klinik und Poliklinik fuer Psychiatrie und Psychotherapie der Technischen Universität München am Klinikum rechts der Isar

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: December 9, 2009
• First Submitted That Met QC Criteria: December 9, 2009
• First Posted (Estimated): December 10, 2009

Study Record Updates

• Last Update Posted (Actual): October 21, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; 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; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Dopamine Antagonists; Antidepressive Agents, Second-Generation; Selective Serotonin Reuptake Inhibitors; Olanzapine; Amisulpride
• Other Study ID Numbers: 01KG0910