Bipolar disorder (BD), also known as manic depressive illness, is a common and complicated, recurring chronic emotional disorder, characterized by episodes of mania, hypomania, and alternating or intertwining episodes of depression. Bipolar disorder is a major cause of disability in young adults and can lead to cognitive and emotional disorders, which in severe cases can lead to suicide and increase mortality in the population. It is estimated that one percent of the world's population has bipolar disorder, regardless of nationality, race or socioeconomic status.
Despite extensive research into bipolar disorder and drugs, but we have not found a targeted drug for the treatment of BD. And the second-generation neuroleptics are still the first choice for the treatment of bipolar disorder before targeted drugs are used in clinical practice.
Case Study
This 4-month double-blind placebo-controlled randomized clinical trial examined the efficacy and safety of topiramate for treating the patients with bipolar disorder. Through this trial, we come to the conclusion that topiramate had a significant effect than placebo on improvement of the patients with bipolar disorder, and it seems to be without serious adverse effects.
In this trial, statistical analysis is a key challenge. We use SPSS 16.0 statistical software to process the statistical analyses of this trial. Considering the small sample size and lack of normal distribution, non-parametric tests were employed. The categorical variables were compared using Chi-square test. P values less than 0.05 were considered as statistically significant. The intention-to treat with at least one assessment after the baseline assessment was performed to handle missing data.
Another challenge is determining the standard cut-off point for Yale Brown Obsessive Compulsive Behavior Scale (YBOCS). After exploratory analyses of the data, we conduct that the decrease of over 34% in total YBOCS score was the response to treatment.
Design:
A randomized double blind placebo controlled clinical trial.
Participants:
The 39 patients in this study were from psychiatric hospital affiliated to Shiraz University of Medical Sciences, all of whom were diagnosed as BD type I-manic phase and had obsessive-compulsive disorder (OCD) symptoms (Figure 1). All recruited patients had the performance as follows:
- They were the inpatients in this hospital.
- They were diagnosed with BD type I-manic phase according to DSM-IV-TR.
- They were between 18 and 60 years old.
- They can take a pill.
- They had YBOC scores over 417.
Exclusion Criteria Were as Follows:
- The patients had any serious medical conditions such as hypothyroidism, active substance dependency, contraindication for taking topiramate, hypersensitivity to medications.
- Women of childbearing age did not have effective contraception.
Figure 1. Flowchart for the clinical trial of topiramate versus placebo group.
Length of Enrollment Period:
16 weeks
Interventions:
Participants (n=39) were randomized to receive topiramate (n=20) or placebo (n=19) as the adjuvant medications for 16 weeks. Both groups received lithium+ olanzapine+ clonazepam (placebo group: lithium 800mg, olanzapine: 7.5mg, clonazepam: 0.5mg; topiramate group: lithium: 825mg, olanzapine: 7.5mg, clonazepam: 0.75mg). The doses of lithium, olanzapine, and clonazepam were adjusted as recommended by the treating psychiatrist considering the clinical symptoms.
Main Outcomes:
- Yale Brown Obsessive Compulsive Behavior Scale (YBOCS) - Primary Outcome
- Adverse Effects
Results:
Participants who received topiramate treatment showed significant improvement in primary outcomes compared with placebo treatment.
The two groups’ means of YBOCS total score are displayed in Table 1. The mean score decreased from 24.2(4.8) to 17.6(8.7) in the topiramate group (P= 0.003) and from 20.9(2.9) to 9.6(3.5) in the placebo group (P=0.0001). The results indicated a significant difference between the two groups regarding the number of patients with a decrease of over 34% in total YBOCS score. Overall, 9 out of the 17 (52.9%) patients in the topiramate group and 2 out of the 16 (12.5%) patients in the placebo group showed more than 34% decrease in YBOCS score. This ratio of improvement was statistically different between the two groups (X2= 6.0, df= 1, P<= 0.01).
Table 1. The characteristics of the patients in the two groups
In adverse effects, four patients in the topiramate group experienced decrease of libido. One patient in the placebo group experienced nausea leading to dropout. Another patient dropped out due to skin rash in the placebo group. The rates of adverse effects are presented in Table 2.
Table 2. The rate of adverse effects in the two groups during the trial.
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References:
1. Sahraian A, Bigdeli M, Ghanizadeh A, et al. (2014) ‘Topiramate as an adjuvant treatment for obsessive compulsive symptoms in patients with bipolar disorder: a randomized double blind placebo controlled clinical trial’, Journal of Affective Disorders, 166(6):201-205.
2. Fagiolini A, Coluccia A, Maina G, et al. (2015) Diagnosis, Epidemiology and Management of Mixed States in Bipolar Disorder’, Cns Drugs, 29(9):1-16.