Post-Schizophrenic DepressionPhase 4PSD-AOFCNCT04876521
Low Dose Amisulpride Vs Olanzapine-Fluoxetine Combination in Post-Schizophrenic Depression
A Phase 4 study testing Amisulpride and Olanzapine-Fluoxetine Combination in people with Post-Schizophrenic Depression, run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Post-Schizophrenic Depression
- What is being tested?
- Amisulpride and Olanzapine-Fluoxetine Combination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteIndia
- Study dates
- 14 Oct 2019to 30 Jun 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
India1 site
All India Institute of Medical Sciences
Bhubaneswar, Odisha, DR BISWA RANJAN MISHRA
About this study
Official title: Comparative Efficacy and Safety of Low Dose Amisulpride Vs Olanzapine-Fluoxetine Combination in the Treatment of Post Schizophrenic Depression: A Randomized Controlled Trial
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.
Read the 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
- Being tested
- Amisulpride, Olanzapine-Fluoxetine Combination
- Keywords
- Post-Schizophrenic Depression, Amisulpride, Olanzapine-Fluoxetine Combination, Post Psychotic Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmisulprideDrug
Also called Sulpitac, Amazeo, Soltus
low dose of Amisulpride at 100-300 mg/day
Olanzapine-Fluoxetine CombinationDrug
Also called Oleanz Fort, Oleanz Plus
Olanzapine (5-10 mg/day) and Fluoxetine (20 mg/day)
| Study group | Role | What they receive |
|---|---|---|
| Amisulpride Group | Experimental | The patients will receive low dose Amisulpride at 100-300 mg/day. Receives: Drug: Amisulpride |
| Olanzapine-Fluoxetine Group | Active comparator | the patients will receive Olanzapine-Fluoxetine Combinations at 5/10 + 20 mg/day. Receives: Drug: Olanzapine-Fluoxetine Combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Calgary Depression Scale for Schizophrenia (CDSS)
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.
Measured: 8 weeks
Secondary outcomes (4)
Clinical Global Impression - Severity (CGI) Scale
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.
Measured: 8 weeks
Serum BDNF Levels
The change in serum BDNF levels in the study groups at 8 weeks (in pg/mL)
Measured: 8 weeks
Correlation
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].
Measured: 8 week
Adverse Drug Reactions
Detect adverse drug reactions (if any) and grading their severity
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2021
- Study start14 Oct 2019
- Primary completion9 Jun 2021
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Post-Schizophrenic DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, parallel-group, rater-blinded, clinical trial.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences, Bhubaneswar
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, BISWA RANJAN MISHRA, All India Institute of Medical Sciences, Bhubaneswar
- Investigators
- Biswa R Mishra, MD, Principal investigator, All India Institute of Medical Sciences, Bhubaneswar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04876521
- Sponsor's protocol ID
- AIIMS BBSR/PGThesis/2019-21
- Acronym
- PSD-AOFC
- Status last verified
- Sep 2024
- First submitted
- 3 May 2021
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: To maintain the confidentiality of the participants.
Publications
Berrios GE, Bulbena A. Post psychotic depression: the Fulbourn cohort. Acta Psychiatr Scand. 1987 Jul;76(1):89-93. doi: 10.1111/j.1600-0447.1987.tb02866.x.
PubMed 3630758Stern MJ, Pillsbury JA, Sonnenberg SM. Postpsychotic depression in schizophrenics. Compr Psychiatry. 1972 Nov-Dec;13(6):591-8. doi: 10.1016/0010-440x(72)90060-0. No abstract available.
PubMed 4637572Rahim T, Rashid R. Comparison of depression symptoms between primary depression and secondary-to-schizophrenia depression. Int J Psychiatry Clin Pract. 2017 Nov;21(4):314-317. doi: 10.1080/13651501.2017.1324036. Epub 2017 May 15.
PubMed 28503978Whitehead C, Moss S, Cardno A, Lewis G. Antidepressants for the treatment of depression in people with schizophrenia: a systematic review. Psychol Med. 2003 May;33(4):589-99. doi: 10.1017/s0033291703007645.
PubMed 12785461Addington D, Addington J, Schissel B. A depression rating scale for schizophrenics. Schizophr Res. 1990 Jul-Aug;3(4):247-51. doi: 10.1016/0920-9964(90)90005-r.
PubMed 2278986Moller 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.
PubMed 14642970Bocchio-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.
PubMed 20334574Biswas 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.
PubMed 38560960
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Efficacy and Safety of Low Dose Amisulpride Vs Olanzapine-Fluoxetine Combination in the Treatment of Post Schizophrenic Depression: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04876521
- Acronym / sponsor ID
- PSD-AOFC / AIIMS BBSR/PGThesis/2019-21
- Conditions
- Post-Schizophrenic Depression
- Keywords
- Post-Schizophrenic Depression, Amisulpride, Olanzapine-Fluoxetine Combination, Post Psychotic Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- All India Institute of Medical Sciences, BhubaneswarUniversity, hospital or other
- Study start
- 14 Oct 2019 (actual)
- Primary completion
- 9 Jun 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 6 May 2021 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, parallel-group, rater-blinded, clinical trial.
| Arm | Type | Receives |
|---|---|---|
| Amisulpride Group | Experimental | Drug: AmisulprideThe patients will receive low dose Amisulpride at 100-300 mg/day. |
| Olanzapine-Fluoxetine Group | Active comparator | Drug: Olanzapine-Fluoxetine Combinationthe patients will receive Olanzapine-Fluoxetine Combinations at 5/10 + 20 mg/day. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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]
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmisulprideAlso: Sulpitac, Amazeo, Soltuslow dose of Amisulpride at 100-300 mg/day | Drug | Amisulpride Group |
| Olanzapine-Fluoxetine CombinationAlso: Oleanz Fort, Oleanz PlusOlanzapine (5-10 mg/day) and Fluoxetine (20 mg/day) | Drug | Olanzapine-Fluoxetine Group |
Primary outcome
Calgary Depression Scale for Schizophrenia (CDSS)
Time frame: 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.
4 secondary outcomes
Clinical Global Impression - Severity (CGI) Scale
Time frame: 8 weeks
Serum BDNF Levels
Time frame: 8 weeks
Correlation
Time frame: 8 week
Adverse Drug Reactions
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 3630758Berrios GE, Bulbena A. Post psychotic depression: the Fulbourn cohort. Acta Psychiatr Scand. 1987 Jul;76(1):89-93. doi: 10.1111/j.1600-0447.1987.tb02866.x.
- Background: PubMed 4637572Stern MJ, Pillsbury JA, Sonnenberg SM. Postpsychotic depression in schizophrenics. Compr Psychiatry. 1972 Nov-Dec;13(6):591-8. doi: 10.1016/0010-440x(72)90060-0. No abstract available.
- Background: PubMed 28503978Rahim T, Rashid R. Comparison of depression symptoms between primary depression and secondary-to-schizophrenia depression. Int J Psychiatry Clin Pract. 2017 Nov;21(4):314-317. doi: 10.1080/13651501.2017.1324036. Epub 2017 May 15.
- Background: PubMed 12785461Whitehead C, Moss S, Cardno A, Lewis G. Antidepressants for the treatment of depression in people with schizophrenia: a systematic review. Psychol Med. 2003 May;33(4):589-99. doi: 10.1017/s0033291703007645.
- Background: PubMed 2278986Addington D, Addington J, Schissel B. A depression rating scale for schizophrenics. Schizophr Res. 1990 Jul-Aug;3(4):247-51. doi: 10.1016/0920-9964(90)90005-r.
- Background: PubMed 14642970Moller 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.
- Background: PubMed 20334574Bocchio-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.
- Derived from this study: PubMed 38560960Biswas 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.
- Individual participant dataSharing planned: No. To maintain the confidentiality of the participants.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Biswa R Mishra, MD principal investigator
All India Institute of Medical Sciences, Bhubaneswar
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Amisulpride and Olanzapine-Fluoxetine Combination in people with Post-Schizophrenic Depression, run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Calgary Depression Scale for Schizophrenia (CDSS) (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04876521, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.