2.1. Procedure and study setting
The present study is a clinical trial with pre-post-test and follow -up stages. The statistical population included all patients with bipolar I disorder in Zanjan. A sample of 30 patients with bipolar disorder was selected by purposive sampling and randomly assigned in two groups. Random allocation was done by dividing the participants into the desired groups according to the Random Number Generator.v1.3 program. The ethics committee of the Zanjan University of Medical Sciences (ZUMS) approved the clinical trial of this study (Approval ID: IR.ZUMS.REC.1398.452). The trial was registered at the Iranian Registry of Clinical Trials (registration No. RCTID: IRCT20191229045931N1). Samples were referred according to the inclusion criteria by a psychiatrist and if they were not fulfill the exclusion criteria, they were included in the groups. The samples were outpatients of Suhrawardi Clinic of Shahid Beheshti Hospital in Zanjan. After obtaining informed consent to participate in the study, the Bart impulsivity scale was presented. Present clinical trial was a randomized WITH parallel-group study which conducted over a 5-week period in one of the psychiatric hospitals (Shahid Beheshti Psychiatric Hospital affiliated with Zanjan University of Medical Sciences). All activities of this trial from the beginning to the end have been approved by the ethics committee of the Zanjan University of Medical Sciences (ZUMS) (Approval ID: IR.ZUMS.REC.1398.452) and its identification code in Iranian Registry of Clinical Trials is IRCT20191229045931N1. Also, its process was accordant with the Declaration of Helsinki and its principles. Patients' symptoms were measured at the baseline time and weeks fifth and follow up (3 months after completion of trial). To conduct the study ethically, all the steps and objectives were described to the patients. Then, a written informed consent form was given to the patients. Moreover, all necessary explanation concerning the right to withdraw the study for any reason was provided to the patients.
The tDCS protocol was performed for 10 sessions of 20 minutes (anode on F3 and cathode on F4) for the experimental group. In the treatment of direct current cranial wall stimulation, two electrodes, one positive pole and the other negative pole, are placed on the head through a sponge pad soaked in a conductive solution. The electric current by these electrodes, after passing through different areas (scalp, skull, etc.), reaches the surface of the cerebral cortex. The current that reaches this area charges the neurons with electricity and creates a positive and negative pole, which leads to a change in the activity of that area. The pharmacotherapy group also received psychiatric medication plus tDCS. It should be noted that the sample was not from the inpatient department and went to the psychiatrist's office on an outpatient basis. There was no way for groups to be as homogeneous as possible. After the intervention, the Bart impulsivity Scale (BIS) was performed again and also 3 months after the intervention in order to follow up the results.
At the end of the treatment sessions, the collected information was analyzed using multivariate methods and SPSS 20 software (IBM Corporation, Armonk, NY). In data analysis, descriptive statistics were used to classify and display the data. To test the hypotheses from covariance analysis tests (univariate and multivariate) and to check the assumptions of the mentioned test, from Levin test (for homogeneity of variances), Kolmogorov Smirnov (for data normality), for homogeneity of groups from independent t-test were used. Also, FOR testing the research hypotheses, the analysis of variance test with repeated measures was used.
2.2. Determination of sample size
2.3. Participants
Recruitment process was performed from outpatient wards (including patients 18 to 50 years of age of both sexes). All of the patients met the necessary criteria for bipolar disorder type I diagnosis according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). Before any intervention, the psychiatrist diagnosed bipolar disorder type I based on the DSM-5 criteria for all participants and took a complete medical history. Besides, Inclusion criteria included diagnosis of bipolar disorder type I, tendency to participate in research, Age range minimum 18 and maximum 50 years old, Minimum high school education, No severe psychiatric disorders such as psychotic disorders and cognitive disorder, Lack of history of seizures and history of head injury, Not consuming drugs and alcohol and not receiving psychological and technological treatments at least one month before entering the research. Exclusion criteria included Absence for more than two sessions, Suicidal ideation during intervention sessions, no need to take ECT during intervention sessions, canceling continuation of intervention sessions, having a metal device or other electrical device in the head and pregnancy. Finally, 30(15 patients for every groups) patients assigned in two groups pf pharmacotherapy and combined pharmacotherapy with tDCS randomly.
2.4. Intervention
In order to random assignment, the sample were assigned into 2 parallel groups randomly. So, the first group only took mood stabilizers including 300 mg lithium, 200 mg sodium valproate, and 200 mg carbamazepine, two times per day. Moreover, for pharmacotherapy plus TDCS group, along the previous treatment, the TDCS (2 mA) was performed for 10 consecutive days, two sessions per day each for 20 minutes. To do so, two electrodes (positive Anode and negative Cathode) covered by a sponge soaked in saline were positioned in the subjects’ head over dorsolateral prefrontal cortex (DLPFC) with anode position over F3 and cathode over F4 according to the EEG 10–20 International System.
2.5. Instrument
Barratt Impulsivity Scale: Barratt Impulsivity Scale (BIS) has 31 questions that evaluate three factors including cognitive impulsivity, motor impulsivity and nonplanning. The questions are formulated in four options and the highest score that is obtained from the sum of three factors is equal to 120. Some authors have calculated the validity and reliability of Persian versions of the Barratt scale in determining risky behaviors and impulsive (21). Cronbach's alpha was calculated at 0.83. Also, the subscales showed a significant correlation with each other (R=0.4) (22).
TDCS: Transcranial Direct Current Stimuli (TDCS) device made in Canada that has FDA approval. The protocol included stimulation over the DLPFC for 10 sessions of 20 minutes for the combined group (stimulation over left Anode/ right Cathode) [F3, F4]. During TDCS, two electrodes, one positive pole and the other negative pole, are placed on the head through a sponge pad soaked in a conductive solution. Electric current by these electrodes after passing through different areas (scalp, skull, etc.), reaches the surface of the cerebral cortex. The current that reaches this area charges the neurons with electricity and causes a positive and a negative pole, which leads to a change in the activity of that area. Depending on the specific disorder, the following should be considered: current intensity, duration and direction, location of pads, size of pads, and number of sessions.
2.6. Safety
All participants were assured that they were free to withdraw from the trial. Also, sufficient information was provided to inform the members of the research team in case of any unexpected side effects. Over the course of 5 weeks, there was no dropout due to different side effects.
2.7. Data analysis
IBM SPSS Statistic (version 20) (IBM Corporation, Armonk, NY) was applied for analysis the data. Categorical variables (number of patients and percentage) were considered and mean – SD were counted as continuous variable (95%= CIs) was considered to report MD. For comparison of trend of change in Barratt Impulsivity Scale (BIS) during 5 weeks of treatments General Linear Model (GLM) repeated measure was used by analyzer. Between-subject factor and within-subject factor are counted for study groups and times of measurements, respectively. Greenhouse– Geisser correction was performed for reporting of degrees of freedom (DF) if Mauchly’s test of sphericity was significant statistically. Moreover, for evaluating effectiveness of each treatment in reducing symptoms, one-way analysis of variance was performed. T-test was also used to compare of changing the status of scores from baseline in the first and second group. Two statistical methods included Fisher’s exact and Chi-square for comparison categorical variables too. Also, in all stages of analysis the data a p-value <0.05 was considered as level of significance.