The Treatment Efficacy of Combination Atypical Antipsychotics With Sertraline in Patients With Schizophrenia

Study Overview
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Brief Summary
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A randomized, double-blind trial of the treatment effect of dose-low antipsychotics combined with low-dose sertraline in 1640 schizophrenia patients

Detailed Description
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OBJECTIVE: This study aimed to evaluate the treatment effect of combination low-dose antipsychotics with low-dose sertraline in 1640 schizophrenia patients METHODS: atypical antipsychotics and dose: including four atypical antipsychotics to form eight treatment groups: 1) olanzapine (7.5-10mg/day) combined with sertraline (50-100mg/day) group 2) only olanzapine (12.5-20mg/day) group 3) risperidone (2-3.5mg/day) combined with sertraline (50-100mg/day) group 4) only risperidone (4-6mg/day) group 5) paliperidone (3-4.5mg/day) combined with sertraline (50-100mg/day) group 6) only paliperidone (6-9mg/day) group 7) ziprasidone (60-100mg/day) combined with sertraline (50-100mg/day) group 8) only ziprasidone (120-160mg/day) group blood biochemical examination: including blood routine examination, liver function, renal function, thyroid function, glucose and lipid level, prolactin, and related hormones and proteins electrophysiological examination: including electrocardiograph, electroencephalography (EEG), and brain evoked potential scale assessment: each patient was assessed by four clinical psychiatrists using the following scales: 1) psychopathology: positive and negative symptoms scale (PANSS) and clinical global impression scale (CGI-S) 2) emotional symptoms: Hamilton depression rating scale (HAMD) and Hamilton anxiety rating scale (HAMA) 3) social function: personal and social performance scale (PSP) 4) side-effect: treatment emergent side-effect scale (TESS) and rating sale for extrapyramidal side-effect (RESES) blood drug concentration assay: including the drug concentration of olanzapine, risperidone, paliperidone, ziprasidone and sertraline, respectively Weigh gain measurement: to measure height, weight for each patient The above measurement data were collected at baseline, week4, week8, week 12 and week24.

Official Title
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The Treatment Efficacy of Combination Atypical Antipsychotics With Sertraline in Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: olanzapine-sertraline combination
* Drug: only olanzapine
* Drug: risperidone-sertraline combination
* Drug: only risperidone
* Drug: paliperidone-sertraline combination
* Drug: only paliperidone
* Drug: ziprasidone-sertraline combination
* Drug: only ziprasidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia by two senior psychiatrists Between 18 and 60 years and Han Chinese Exclusion Criteria: A Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I diagnosis other than schizophrenia Documented disease of physical diseases including, but not limited to seizure, epilepsy, aneurysm brain tumor, and stroke, dementia, parkinson's disease, Huntington's disease, multiple sclerosis Acute, unstable and/or significant and untreated medical illness (e.g., infection, unstable diabetes, uncontrolled hypertension)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: olanzapine-sertraline combination<br>the patient was prescribed low-dose olanzapine (7.5-10mg/day) combined with low-dose sertraline (50-100mg/day) | Drug: olanzapine-sertraline combination<br>* the patient was prescribed low-dose olanzapine (7.5-10mg/day) combined with low-dose sertraline (50-100mg/day)<br>* Other names: olanzapine-sertraline;|
| Placebo Comparator: only olanzapine<br>the patient was prescribed moderate to severity dose of olanzapine (12.5-20mg/day) | Drug: only olanzapine<br>* the patient was prescribed moderate to severity dose of olanzapine (12.5-20mg/day)<br>|
| Experimental: risperidone-sertraline combination<br>the patient was prescribed low-dose risperidone (2-3.5mg/day) combined with low-dose sertraline (50-100mg/day) | Drug: risperidone-sertraline combination<br>* the patient was prescribed low-dose risperidone (2-3.5mg/day) combined with low-dose sertraline (50-100mg/day)<br>* Other names: risperidone-sertraline;|
| Placebo Comparator: only risperidone<br>the patient was prescribed moderate to severity dose of risperidone (4-6mg/day) | Drug: only risperidone<br>* the patient was prescribed moderate to severity dose of risperidone (4-6mg/day)<br>|
| Experimental: paliperidone-sertraline combination<br>the patient was prescribed low-dose paliperidone (3-4.5mg/day) combined with low-dose sertraline (50-100mg/day) | Drug: paliperidone-sertraline combination<br>* the patient was prescribed low-dose paliperidone (3-4.5mg/day) combined with low-dose sertraline (50-100mg/day)<br>* Other names: paliperidone-sertraline;|
| Placebo Comparator: only paliperidone<br>the patient was prescribed moderate to severity dose of paliperidone (6-9mg/day) | Drug: only paliperidone<br>* the patient was prescribed moderate to severity dose of paliperidone (6-9mg/day)<br>|
| Experimental: ziprasidone-sertraline combination<br>the patient was prescribed low-dose ziprasidone (60-100mg/day) combined with low-dose sertraline (50-100mg/day) | Drug: ziprasidone-sertraline combination<br>* the patient was prescribed low-dose ziprasidone (60-100mg/day) combined with low-dose sertraline (50-100mg/day)<br>* Other names: ziprasidone-sertraline;|
| Placebo Comparator: only ziprasidone<br>the patient was prescribed moderate to severity dose of ziprasidone (120-160mg/day) | Drug: only ziprasidone<br>* the patient was prescribed moderate to severity dose of ziprasidone (120-160mg/day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in psychopathology symptoms on PANSS during antipsychiatric treatment | The Positive and Negative Syndrome Scale (PANSS) is a well-characterized and widely applied dimensional assessment that reflects a balanced representation of positive and negative syndromes, their differential and general severity of illness. The scales not only measures positive and negative syndromes, but also suggests their differential and general severity of the illness. The items on the PANSS are defined with increasing levels from 1 to 7: 1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderate-severe, 6 = severe, and 7 = extreme. Then the PANSS score is totaled by sum up the ratings across different items, the potential range for positive and negative scales are from 7 to 49 whereas the General Psychopathology Scale is ranged between 16 to 112. | baseline, week 4, week 8, week 12, and week 24 | 
| changes in depressive symptoms on HAMD during antipsychiatric treatment | HAMD stands for Hamilton Rating Scale. It is the assessment that designed for examining the treatment significant of depression severity. The general format contains 17 items, 12 of them are scored from 0 to 4 while the rest of them ranges from 0 to 2. The items represented a variety of aspects: Depression mood, Feeling of guilt, Suicide, Insomnia early, Insomnia middle, Insomnia late, Work and activities, Motor retardation, Agitation, Psychic anxiety, Somatic anxiety, Somatic symptoms(gastrointestinal), somatic symptoms(general), Genital symptoms (sexual interest). Hypochondriasis, Weight loss and Insight. So A cut-off score less than or equal to 7 in the HAMD scale defines the symptomatic remission. | baseline, week 4, week 8, week 12, and week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in electroencephalography examination for brain activity during antipsychiatric treatment | electroencephalography, or EEG is the physiological method of choice to record the electrical activity generated by the brain via electrodes placed on the scalp surface. For faster application, electrodes are mounted in elastic caps similar to bathing caps, ensuring that the data can be collected from identical scalp positions across all respondents. By analysis of frequency and amplitude of five kind of brain waves(delta, theta, alpha, beta, gamma) , we could detect the synchronized activity of neurons within cortical areas even at sub-second timescales | baseline, week 4, week 8, week 12, and week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, sertraline, olanzapine, risperidone, paliperidone, ziprasidone