Bipolar Disorder
Conditions
Keywords
Oxcarbazepine, Brain Derived Neurotrophic Factor, Bipolar disorder, Neuroprotection
Brief summary
The present study has been designed to evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar disorder and to explore the possibility of its neuroprotective effect.
Detailed description
Bipolar disorder (BD) is a chronic psychiatric illness of partially unknown pathophysiology. BD likely involves, at a molecular and cellular level, dysfunctions of critical neurotrophic, cellular plasticity and resilience pathways and neuroprotective processes. Abnormalities of neurotrophins (NTs) and other trophic factors orchestrate important alterations which could be implicated in the etiology of BD. As consistently reported in post-mortem studies, these modifications are generally associated with the disruption of distinct subregions and functions of the brain, one of which is the deregulation of neurotrophins. NTs are capable of signaling neurons, glial cells and other cellular systems to enable survival, differentiation and growth. BDNF is one of the most studied and abundant NTs in the brain, which plays an important role in a variety of neural processes during the development of both animals and humans. Initially, BDNF is important for neurogenesis, neuronal survival, and normal maturation of neural development pathways. In the adult, BDNF is not only important for synaptic plasticity and dendritic growth, but also for long-term memory consolidation. Several studies have proved that BDNF is significantly reduced in manic, hypomanic or depressive stages of BD, whereas euthymic patients exhibit BDNF levels similar to healthy controls. Rafael T. de Sousa et al have observed a significant increase in serum BDNF levels after 28 days of lithium monotherapy in patients with BD and suggested neuroprotective role of lithium due to its direct regulatory effect on BDNF. Oxcarbazepine is a commonly used mood stabilizer which has demonstrated comparable efficacy to divalproate sodium and better tolerability profile but till date there is no study on its effect on BDNF. The aim of the present study is to evaluate the change in serum BDNF level with oxcarbazepine monotherapy in bipolar disorder and to explore the possibility of its neuroprotective effect.
Interventions
DRUGOxcarbazepine
After baseline assessments, patients in test group will be prescribed Tab. Oxcarbazepine (600mg/daily in two divided dose for 1 week followed by 900mg/daily in two divided dose for next 3 weeks).
Sponsors
All India Institute of Medical Sciences, Bhubaneswar
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* All patients with the diagnosis of bipolar affective disorder (by ICD-10 DCR) current episode mania without psychotic symptoms * Patients aged 18-45 years, of either sex. * Patients with baseline score \> 20 on the Young Mania Rating Scale (YMRS). * Patients who had not taken any treatment for at least 4 weeks before inclusion.
Exclusion criteria
* Patients with bipolar disorder (by ICD-10 DCR) presenting during depressive/euthymic/mixed episode. * Patients who are already under treatment for the presenting conditions. * Rapid cycling in the past 12 months. * Previous history of refractoriness to carbazepine or oxcarbazepine. * Patients with comorbid substance abuse or history of organicity * Pregnant and nursing women, patients with history of major medical or neurological illness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Brain Derived Neurotrophic Factor (BDNF) | Baseline and 4 weeks | Serum BDNF was estimated by ELISA using human BDNF ELISA kit from Boster Biological Technology Co. Ltd., Pleasanton, CA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Young Mania Rating Scale (YMRS) and Serum Brain Derived Neurotrophic Factor (BDNF) | At baseline | The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania. Spearman's rank correlation coefficient (Spearman's ρ) was calculated for measuring correlation between YMRS score and serum BDNF. |
Countries
India
Participant flow
Recruitment details
June 2015 to December 2015 Psychiatry outpatient department
Pre-assignment details
Out of 40 bipolar mania patients screened, 12 patients were excluded as they did not meet the inclusion criteria and another three patients declined to participate. For recruitment of healthy controls, 35 subjects were screened and after exclusion of 10 subjects, 25 were included in the study.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Control Twenty five (25) age and sex matched healthy individuals served as the control group. | 25 |
| Oxcarbazepine Twenty five (25) patients of bipolar mania will be prescribed oxcarbazepine for 4 weeks.
Oxcarbazepine: After baseline assessments, patients in test group will be prescribed Tab. Oxcarbazepine (600mg/daily in two divided dose for 1 week followed by 900mg/daily in two divided dose for next 3 weeks). | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Healthy Control | Oxcarbazepine | Total |
|---|---|---|---|
| Age, Continuous | 34.44 years STANDARD_DEVIATION 9.53 | 34.16 years STANDARD_DEVIATION 9.89 | 34.3 years STANDARD_DEVIATION 9.6 |
| Region of Enrollment India | 25 Participants | 25 Participants | 50 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 0 / 25 | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Change in Serum Brain Derived Neurotrophic Factor (BDNF)
Serum BDNF was estimated by ELISA using human BDNF ELISA kit from Boster Biological Technology Co. Ltd., Pleasanton, CA.
Time frame: Baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Control | Change in Serum Brain Derived Neurotrophic Factor (BDNF) | 23.1 pg/ml | Standard Deviation 92.7 |
| Oxcarbazepine | Change in Serum Brain Derived Neurotrophic Factor (BDNF) | 90.7 pg/ml | Standard Deviation 85 |
Secondary
Correlation Between Young Mania Rating Scale (YMRS) and Serum Brain Derived Neurotrophic Factor (BDNF)
The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania. Spearman's rank correlation coefficient (Spearman's ρ) was calculated for measuring correlation between YMRS score and serum BDNF.
Time frame: At baseline
Population: At baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Control | Correlation Between Young Mania Rating Scale (YMRS) and Serum Brain Derived Neurotrophic Factor (BDNF) | -0.59 Spearman's ρ |
| Oxcarbazepine | Correlation Between Young Mania Rating Scale (YMRS) and Serum Brain Derived Neurotrophic Factor (BDNF) | -0.59 Spearman's ρ |