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

NCT ID: NCT04876521

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-14
• Study Completion Date: 2021-06-30

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.

Conditions

Post-Schizophrenic Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Amisulpride Group

The patients will receive low dose Amisulpride at 100-300 mg/day.

Group Type: EXPERIMENTAL

Amisulpride

Intervention Type: DRUG

low dose of Amisulpride at 100-300 mg/day

Olanzapine-Fluoxetine Group

the patients will receive Olanzapine-Fluoxetine Combinations at 5/10 + 20 mg/day.

Group Type: ACTIVE_COMPARATOR

Olanzapine-Fluoxetine Combination

Intervention Type: DRUG

Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)

Interventions

Amisulpride

low dose of Amisulpride at 100-300 mg/day

Intervention Type: DRUG

Olanzapine-Fluoxetine Combination

Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)

Intervention Type: DRUG

Other Intervention Names

Sulpitac; Amazeo; Soltus; Oleanz Fort; Oleanz Plus

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

All India Institute of Medical Sciences, Bhubaneswar

OTHER

Sponsor Role: lead

Responsible Party

BISWA RANJAN MISHRA

Additional Professor, Department of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Biswa R Mishra, MD

Role: PRINCIPAL_INVESTIGATOR

All India Institute of Medical Sciences, Bhubaneswar

Locations

All India Institute of Medical Sciences

Bhubaneswar, Odisha, India

Countries

India

References

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Reference Type: BACKGROUND

PMID: 3630758 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 4637572 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 2278986 (View on PubMed)

Moller HJ. Amisulpride: limbic specificity and the mechanism of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1101-11. doi: 10.1016/j.pnpbp.2003.09.006.

Reference Type: BACKGROUND

PMID: 14642970 (View on PubMed)

Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, Giovannini C, Rillosi L, Ventriglia M, Riva MA, Gennarelli M. Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry. 2010 Sep;11(6):763-73. doi: 10.3109/15622971003611319.

Reference Type: BACKGROUND

PMID: 20334574 (View on PubMed)

Biswas T, Mishra BR, Maiti R, Padhy SK, Mishra A. Efficacy and safety of low-dose amisulpride versus olanzapine-fluoxetine combination in post-schizophrenic depression: A randomized controlled trial. J Psychiatr Res. 2024 May;173:302-308. doi: 10.1016/j.jpsychires.2024.03.048. Epub 2024 Mar 28.

Reference Type: DERIVED

PMID: 38560960 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

AIIMS BBSR/PGThesis/2019-21

Identifier Type: -

Identifier Source: org_study_id