This study is a double-blind clinical trial performed during 1396 − 1395. Initially, 78 patients aged 18 to 50 years old diagnosed with bipolar mood disorder, based on DSM 5 criteria, And according to the inclusion criteria of current study, were participated in this study.
Inclusion criteria:
- The age of the subjects was 18 to 59 years old
- Diagnosis of bipolar-1 disorder with recent episode mania based on DSM-5 diagnostic criteria by Semi-structured interview done by a psychiatrist and diagnostic confirmation with a score of at least 20 of Young mania score (YMRS) (20)
- The absence of the diagnosis of schizophrenia, delirium, bulimia nervosa, anorexia nervosa, mental retardation, autism, substance abuse (at least 3 months ago), ADHD.
- No history of admission to the psychiatric ward during the past three months
- No history of seizure or epilepsy
- the absence of suicidal or homicidal risk during the psychiatric interview
- Women suspected to be pregnant will undergo a pregnancy test and, if positive, be excluded from the study.
- Lack of a history of susceptibility to sodium valproate or any herbal medicines.
- Patients who have received other medications during the last two weeks prior to study or during the study, including mood stabilizer treatments that cannot stop them. The washout period will be considered based on the medication's half-life for patients receiving drugs with a long half-life.
A full interview was conducted for each patient by a psychiatric resident (based on inclusion and exclusion criteria) and diagnostic suspicion cases were excluded from the study. The informed consent was obtained from eligible patients. (Or their legal guardians)
Patients who agreed to participate in our trial were randomly assigned into two groups using randomized number table. Patients in the intervention group besides receiving sodium valproate (starting at a dose of 600 mg / day and administrate up to 20 mg / kg / day or the highest dosage of the patient's tolerance), received curcumin drug while control group received placebo in addition to sodium valproate .
Placebo soft gels were made by the same manufacturer of soft curcumin gels, having the same size, color and smell. Soft curcumin gel has 40 mg Nanomycesel, absorbed as equivalent to 500 mg curcumin tablets.
Cases were evaluated at baseline, 1 week, 2weeks and 4 weeks after the prescription of the drugs using the clinical global impression (CGI) and young mania rating scale (YMRS).(20–22) MMSM (mini mental state examination) have been performed for cases at the end of the first and fourth weeks of treatment.
It should be noted that due to the lipophil nature of curcumin, the oral absorption of curcumin in common oral forms (powder, capsule and pill) is very low. In this study, soft gelatin capsules containing curcumin nanomicelles with the brand name Sina Curcumin was used. In the Sina Curcumin product, all curcumin is blocked in the hydrophobic section of curcumin nannies. These spherical nanomicelle particles have a particle size of about 10 nm and increase water solubility of curcumin. After oral administration, soft gel capsules containing curcumin nannies are disintegrate in the stomach acidic environment in less than 15 minutes. These nanomicelles remain for at least 6 hours in the acidic environment of stomach and do not eliminate and get to the small intestine intact.
Upon reaching the small intestine, nanomicelles facilitates the transfer of curcumin from the inert surficial water layer of the intestinal epithelial cells; which inhibits the absorption of lipid soluble compounds and increases the oral absorption of curcumin.
The side effects of drugs in each visit have been evaluated by psychiatric resident using a checklist and if necessary, the essential laboratory tests have been done under the psychiatrist’s vision.
For describing the data, descriptive statistics including frequency tables, diagrams, and statistical indicators were used, and data analysis was done using SPSS software version 11.5.
To analyze the data, Kolmogorov-Smirnov test, Mann Whitney test, independent T-test, Fisher's exact test and chi-square were applied. A p-value less than 0.05 were taken as mean statistical significance. To control and determine the effect of confounding variables in case of heterogeneity between two groups, appropriate statistical tests such as covariance or logistic regression were used.
Since this research was conducted for the first time and no similar research to ours has been done yet, with regard to the goals mentioned so far, sample size calculations cannot be used by statistical formulas. Therefore, this study was done as a preliminary study with a sample size of 20 people in each group, that is, a total of 40 cases.