Schizoaffective Disorder, Schizophrenia, Schizophreniform Disorder
Conditions
Brief summary
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
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
Interventions
DRUGOlanzapine or amisulpride
Oral olanzapine 5mg to 20mg/d OR oral amisulpride 200mg to 800mg/d; both preferably once daily, both encapsulated for blinding
Sponsors
Technical University of Munich
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients in Symptomatic Remission at Week 8 Comparing the Switched With the Non Switched Early Non-responders | 8 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PANSS Total Score Change | 8 weeks | 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. |
Countries
Germany
Participant flow
Pre-assignment details
The enrollment at baseline comprises the periods initial olanzapine and initial amisulpride; a re-randomisation was performed after 2 weeks of treatment; the patient numbers in the second phase of the trial must not be added to the overall participant number at baseline (other three groups all formed in phase II of the trial); NOTE that the groups early responders, early non-responders switched, early non-responders non-switched become active only in phase II of the trial, not before!!
Participants by arm
| Arm | Count |
|---|---|
| Period 1: Initital 2-week Treatment - Amisulpride Baseline assessment of period 1 of all patients randomised to amisulpride flexible 200-800 mg/d double blind treatment | 163 |
| Period 1: Initital 2-week Treatment - Olanzapine Baseline assessment of period 1 of all patients randomised to olanzapine flexible 5-20 mg/d double blind treatment | 164 |
| Total | 327 |
Baseline characteristics
| Characteristic | Period 1: Initital 2-week Treatment - Olanzapine | Total | Period 1: Initital 2-week Treatment - Amisulpride |
|---|---|---|---|
| Age, Continuous | 39.3 years STANDARD_DEVIATION 10.9 | 39.8 years STANDARD_DEVIATION 11.5 | 40.3 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 164 Participants | 327 Participants | 163 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Germany | 75 Participants | 150 Participants | 75 Participants |
| Region of Enrollment Romania | 89 Participants | 177 Participants | 88 Participants |
| Sex: Female, Male Female | 79 Participants | 154 Participants | 75 Participants |
| Sex: Female, Male Male | 85 Participants | 173 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 163 | 1 / 164 | 1 / 140 | 0 / 70 | 0 / 72 |
| other Total, other adverse events | 36 / 163 | 33 / 164 | 32 / 140 | 21 / 70 | 7 / 72 |
| serious Total, serious adverse events | 3 / 163 | 3 / 164 | 7 / 140 | 5 / 70 | 4 / 72 |
Outcome results
Primary
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
Time frame: 8 weeks
Population: please note that all patients, regardless of the medication received, were combined in these groups for the primary endpoint analysis solely depending on whether they have met the criteria for early non-response at the end of phase I of the trial; so the statistical analysis does not follow the treatment arms in phase I of the trial (patients received alternatively olanzapine or amisulpride, but both types of treatment appear in one and the same analysis group!)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early Non-responders Switched | Number of Patients in Symptomatic Remission at Week 8 Comparing the Switched With the Non Switched Early Non-responders | 41 Participants |
| Early Non-responders Non-switched | Number of Patients in Symptomatic Remission at Week 8 Comparing the Switched With the Non Switched Early Non-responders | 25 Participants |
Comparison: Irrespective of the initially assigned antipsychotic treatment in period 1 of the trial (2-week-phase), the patients showing little improvement over the two weeks of treatment in period 1 now switched from the initial treatment in period 2 of the trial (6-week-phase) were grouped together as well as the patients non-switched from their initial treatment.p-value: =0.01Regression, Logistic
Secondary
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.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early Non-responders Switched | PANSS Total Score Change | -22.8 units on a scale | Standard Deviation 19.9 |
| Early Non-responders Non-switched | PANSS Total Score Change | -17.3 units on a scale | Standard Deviation 15.1 |