Low Dose Amisulpride Vs Olanzapine-Fluoxetine Combination in Post-Schizophrenic Depression

Study Overview
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Brief Summary
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Post-Schizophrenic Depression (PSD) increases the morbidity and mortality of Schizophrenic patients. Hence, it warrants early assessment and intervention. But, clinical trials on PSD are very few. However, an Antipsychotic with an adjunctive Antidepressant (like Olanzapine-Fluoxetine Combination) is the commonly prescribed treatment in PSD. Low dose Amisulpride (<400 mg/day) which is effective against the negative symptoms of Schizophrenia has also proved efficacious in treating depression in non-psychotic conditions, but its antidepressant property has never been studied in PSD. This is an 8-week, randomized, parallel-group study that will explore the efficacy and safety of low-dose Amisulpride versus Olanzapine-Fluoxetine Combination in the treatment of PSD. Our hypothesis is that low dose Amisulpride has better efficacy and safety versus Olanzapine-Fluoxetine Combination in PSD, after 8-weeks.

Detailed Description
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The proposed study would be an 8-week, randomized, controlled, parallel-group, clinical trial which will be conducted at the Inpatient and Outpatient settings of the Department of Psychiatry, AIIMS, Bhubaneswar. Patients with the diagnosis of Post Schizophrenic Depression according to the ICD 10 (DCR) and meeting all the Inclusion and Exclusion Criteria would be selected for the study. At first, the patients and their family members/ guardians would be explained about the study procedure along with its possible risks and benefits using a Patient Information Sheet (in their local language). After obtaining a written Informed Consent from the Legally Authorised Relative, the patients would be finally recruited for the study. All recruited patients would be randomized using computer-generated random numbers into two treatment groups with an allocation ratio of 1:1. The sociodemographic and clinical data of the patients would be collected as per the designed sheets. Then at baseline, the CDSS and CGI ratings would be assessed, and the serum BDNF would be tested for each patient. The study would be rater-blinded. The experimental group would receive Amisulpride at a low dosage of 100-300 mg/day and the control group would receive a combination of Olanzapine at 5mg or 10 mg/day and Fluoxetine at 20mg/day. The two groups would be followed for 8 weeks, at the completion of which all the patients would be reassessed. The follow-up assessment would involve a re-evaluation of the CDSS and the CGI scores and the Serum BDNF levels to see for any change. The data thus collected would be analyzed, compared within and in between the study groups and statistical tests would be applied for drawing conclusions. The missing values will be analyzed by an intention-to-treat protocol.

Official Title
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Comparative Efficacy and Safety of Low Dose Amisulpride Vs Olanzapine-Fluoxetine Combination in the Treatment of Post Schizophrenic Depression: A Randomized Controlled Trial

Conditions
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Post-Schizophrenic Depression

Intervention / Treatment
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* Drug: Amisulpride
* Drug: Olanzapine-Fluoxetine Combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Post Schizophrenic Depression according to ICD10-DCR (International Classification of Diseases 10- Diagnostic Criteria for Research). Aged between 18 to 60 years of either sex Patients with a positive score of less than 29 on the Positive and Negative Syndrome Scale (PANSS) [88] Patients with a score of more than 6 on the Montgomery-Asberg Depression Rating Scale (MADRS) [89-90] Patients without Extrapyramidal symptoms: a score of less than 3 on the Simpson-Angus Scale [91] With Informed consent from the Legally Authorised Relative Exclusion Criteria: Patients with a medical or neurological disorder Patients with a history of substance dependence Patients with high suicidality Patients with a past history of primary depression Patients already on Olanzapine-Fluoxetine combination or Amisulpride

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
Interventional Model Description: Randomized, parallel-group, rater-blinded, clinical trial.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amisulpride Group<br>The patients will receive low dose Amisulpride at 100-300 mg/day. | Drug: Amisulpride<br>* low dose of Amisulpride at 100-300 mg/day<br>* Other names: Soltus;|
| Active Comparator: Olanzapine-Fluoxetine Group<br>the patients will receive Olanzapine-Fluoxetine Combinations at 5/10-5/20 mg/day. | Drug: Olanzapine-Fluoxetine Combination<br>* Olanzapine (5 mg/day) and Fluoxetine (10-20 mg/day)<br>* Other names: Oleanz Plus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calgary Depression Scale for Schizophrenia (CDSS) | Calgary Depression Scale for Schizophrenia (CDSS) scores will be used to measure the change in the severity of depressive symptoms in the study groups from baseline over 8 weeks. the total score ranges from 0 - 36. Higher scores represent higher severity of depression. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression (CGI) | Clinical Global Impression (CGI) scores will be used to measure the change in illness severity, global functioning and improvement in the study groups from baseline over 8 weeks. The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale [minimum: 1 and maximum 7]: Higher scores means higher severity of disease. The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale [minimum: 1 and maximum 7]: Higher scores means more clinical improvement. | 8 weeks | 
| Serum BDNF levels | The change in serum BDNF levels in the study groups over 8 weeks | 8 weeks | 
| Correlation | Determine the correlation (if any) between the between changes in CDSS scores, CGI scores and serum BDNF levels | 8 week | 
| Adverse drug reactions | Detect adverse drug reactions (if any) and grading their severity | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-Schizophrenic Depression, Amisulpride, Olanzapine-Fluoxetine Combination, Post Psychotic Depression