Clinical trial NCT04876521: Low Dose Amisulpride Vs Olanzapine-Fluoxetine Combination in Post-Schizophrenic Depression
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Post-Schizophrenic Depression
Keywords: Post-Schizophrenic Depression
Amisulpride
Olanzapine-Fluoxetine Combination
Post Psychotic Depression
Lead sponsor: All India Institute of Medical Sciences, Bhubaneswar
Sponsor class: OTHER
First posted: 2021-05-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, parallel-group, rater-blinded, clinical trial.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: 8 weeks
Secondary outcomes:
measure: Clinical Global Impression - Severity (CGI) Scale
timeFrame: 8 weeks
measure: Serum BDNF Levels
timeFrame: 8 weeks
measure: Correlation
timeFrame: 8 week
measure: Adverse Drug Reactions
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Bhubaneswar
country: India
facility: All India Institute of Medical Sciences
state: Orissa
Study officials:
affiliation: All India Institute of Medical Sciences, Bhubaneswar
name: Biswa R Mishra, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Rahim 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.
citation: Whitehead 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.
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citation: 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.
citation: 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.