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

Phase 4

• Conditions: Post-Schizophrenic Depression
• Interventions: Drug: Amisulpride; Drug: Olanzapine-Fluoxetine Combination

• Registration Number: NCT04876521
• Lead Sponsor: All India Institute of Medical Sciences, Bhubaneswar

Brief Summary

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

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.

Study Timeline

• Status Verified: 2021-05
• Study First Submitted: 2021-05-03
• Study First Submitted QC: 2021-05-03
• Study Start: 2021-05-04
• Study First Posted: 2021-05-06
• Last Update Submitted: 2021-05-29
• Last Update Posted: 2021-06-03
• Primary Completion: 2022-04-04
• Study Completion: 2022-05-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Patients with Post Schizophrenic Depression according to ICD10-DCR (International Classification of Diseases 10- Diagnostic Criteria for Research).
2. Aged between 18 to 60 years of either sex
3. Patients with a positive score of less than 29 on the Positive and Negative Syndrome Scale (PANSS) [88]
4. Patients with a score of more than 6 on the Montgomery-Asberg Depression Rating Scale (MADRS) [89-90]
5. Patients without Extrapyramidal symptoms: a score of less than 3 on the Simpson-Angus Scale [91]
6. With Informed consent from the Legally Authorised Relative

Exclusion Criteria

1. Patients with a medical or neurological disorder
2. Patients with a history of substance dependence
3. Patients with high suicidality
4. Patients with a past history of primary depression
5. Patients already on Olanzapine-Fluoxetine combination or Amisulpride

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Amisulpride Group	Amisulpride	The patients will receive low dose Amisulpride at 100-300 mg/day.
Olanzapine-Fluoxetine Group	Olanzapine-Fluoxetine Combination	the patients will receive Olanzapine-Fluoxetine Combinations at 5/10 + 20 mg/day.

Primary Outcome Measures

Name	Time	Method
Calgary Depression Scale for Schizophrenia (CDSS)	8 weeks	Calgary Depression Scale for Schizophrenia (CDSS) scores is used to measure the severity of depressive symptoms in the study groups. The total score ranges from 0 - 36. Higher scores represent a higher severity of depression.

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impression - Severity (CGI) Scale	8 weeks	The Clinical Global Impression - Severity (CGI-S) is a 7-point scale used to measure the severity of the illness in the study groups \[minimum: 1 and maximum 7\]: Higher scores mean higher severity of disease.
Serum BDNF Levels	8 weeks	The change in serum BDNF levels in the study groups at 8 weeks (in pg/mL)
Correlation	8 week	Determine the correlation (if any) between the changes in CDSS scores and serum BDNF levels. The correlation coefficient is represented as r, with values from -1 to +1 \[where +/- 1 mean strongest correlation and 0 mean no correlation\].
Adverse Drug Reactions	8 weeks	Detect adverse drug reactions (if any) and grading their severity

Trial Locations

Locations (1)

All India Institute of Medical Sciences; 🇮🇳 Bhubaneswar, Orissa, India