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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04876521

Acronym

PSD-AOFC

Enrollment

Registered

2021-05-06

Start date

2019-10-14

Completion date

2021-06-30

Last updated

2024-09-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Post-Schizophrenic Depression

Keywords

Post-Schizophrenic Depression, Amisulpride, Olanzapine-Fluoxetine Combination, Post Psychotic Depression

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.

Interventions

DRUGAmisulpride

low dose of Amisulpride at 100-300 mg/day

DRUGOlanzapine-Fluoxetine Combination

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Masking description

The proposed study will be rater-blinded. The ratings would be done by a psychiatrist who would be blinded to the nature of the intervention provided

Intervention model description

Randomized, parallel-group, rater-blinded, clinical trial.

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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

Countries

India

Participant flow

Participants by arm

Arm	Count
Amisulpride Group Received Amisulpride at 100-300 mg/day	30
Olanzapine-Fluoxetine Group Received Olanzapine-Fluoxetine Combination: Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)	30
Total	60

Baseline characteristics

Characteristic	Amisulpride Group	Olanzapine-Fluoxetine Group	Total
Age, Continuous	35.2 years STANDARD_DEVIATION 10.1	35.4 years STANDARD_DEVIATION 9.8	35.3 years STANDARD_DEVIATION 9.9
MADRS score	23.17 score on a scale STANDARD_DEVIATION 6.49	23.73 score on a scale STANDARD_DEVIATION 6.82	23.45 score on a scale STANDARD_DEVIATION 6.61
PANSS-P score	13.70 score on a scale STANDARD_DEVIATION 4.44	13.80 score on a scale STANDARD_DEVIATION 4.22	13.75 score on a scale STANDARD_DEVIATION 4.29
Race and Ethnicity Not Collected	—	—	0 Participants
Sex: Female, Male Female	13 Participants	12 Participants	25 Participants
Sex: Female, Male Male	17 Participants	18 Participants	35 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 30	0 / 30
other Total, other adverse events	0 / 30	0 / 30
serious Total, serious adverse events	0 / 30	0 / 30

Arm	Measure	Value (MEAN)	Dispersion
Amisulpride Group	Serum BDNF Levels	1453.59 picograms per milliliter	Standard Error 44.62
Olanzapine-Fluoxetine Group	Serum BDNF Levels	1471.19 picograms per milliliter	Standard Error 48.22

Source: ClinicalTrials.gov · Data processed: Feb 8, 2026