Mood Stabilizers of First and Second Generation.

The topic of this narrative review is mood stabilizers. First, the author's definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology of their introduction into the psychiatric armamentarium. First-generation mood stabilizers (FGMSs), such as lithium, valproates, and carbamazepine, were introduced in the 1960s and 1970s. Second-generation mood stabilizers (SGMSs) started in 1995, with a discovery of the mood-stabilizing properties of clozapine. The SGMSs include atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, and risperidone, as well as a new anticonvulsant drug, lamotrigine. Recently, as a candidate for SGMSs, a novel antipsychotic, lurasidone, has been suggested. Several other atypical antipsychotics, anticonvulsants, and memantine showed some usefulness in the treatment and prophylaxis of bipolar disorder; however, they do not fully meet the author's criteria for mood stabilizers. The article presents clinical experiences with mood stabilizers of the first and second generations and with "insufficient" ones. Further, current suggestions for their use in preventing recurrences of bipolar mood disorder are provided.

Application of Antipsychotic Drugs in Mood Disorders.

Since their first application in psychiatry seventy years ago, antipsychotic drugs, besides schizophrenia, have been widely used in the treatment of mood disorders. Such an application of antipsychotics is the subject of this narrative review. Antipsychotic drugs can be arbitrarily classified into three generations. First-generation antipsychotics (FGAs), such as phenothiazines and haloperidol, were mainly applied for the treatment of acute mania, as well as psychotic depression when combined with antidepressants. The second-generation, so-called atypical antipsychotics (SGAs), such as clozapine, risperidone, olanzapine, and quetiapine, have antimanic activity and are also effective for the maintenance treatment of bipolar disorder. Additionally, quetiapine exerts therapeutic action in bipolar depression. Third-generation antipsychotics (TGAs) started with aripiprazole, a partial dopamine D2 receptor agonist, followed by brexpiprazole, lurasidone, cariprazine, and lumateperone. Out of these drugs, aripiprazole and cariprazine have antimanic activity, lurasidone, cariprazine, and lumateperone exert a significant antidepressant effect on bipolar depression, while there is evidence for the efficacy of aripiprazole and lurasidone in the prevention of recurrence in bipolar disorder. Therefore, successive generations of antipsychotic drugs present a diverse spectrum for application in mood disorders. Such a pharmacological overlap in the treatment of schizophrenia and bipolar illness stands in contrast to the dichotomous Kraepelinian division of schizophrenia and mood disorders.

Impact of COVID-19 pandemic on relapse of individuals with severe mental illness and their caregiver's burden.

Background: The implementation of quarantine and social distancing measures to control the COVID-19 pandemic led to restrictions at the community level and most of in-person psychiatric services were discontinued. This situation could affect the psychopathology of the patients and the burden of their caregivers. The aim of this study was to investigate the effects of COVID-19 pandemic on people with severe mental illnesses (SMIs) and their caregivers' burden. Method: The study sample consisted of 86 patients with severe mental illness and 86 caregivers. The mental status, relapse rate, and rehospitalization rate of the patients and the general health status and burden of caregivers were investigated in three waves, including before and 3 and 6 months after the COVID-19 pandemic. Results: The relapse rate of the patients was 14%, 33.7%, and 43% (p = 0.000) and the rehospitalization rate was 4.7%, 7%, and 10.5% in waves 0, 1, and 2, respectively (p = 0.000). Most of the psychopathological scales increased in three waves (p = 0.000). The caregivers' burden and health condition worsened during the nine months of the study as well (p = 0.000). Conclusion: The COVID-19 pandemic led to the exacerbation of symptoms and increased the relapse rate in people with SMIs. It also worsened the caregivers' condition. People with severe mental illnesses (SMIs) and their caregivers are one of the most vulnerable groups on which the COVID-19 pandemic had a marked negative effect.

Caregiver-Reported Burden in RE-KINECT: Data From a Prospective Real-World Tardive Dyskinesia Screening Study.

BACKGROUND: RE-KINECT (NCT03062033), a real-world study of possible tardive dyskinesia (TD) in antipsychotic-treated patients, included a questionnaire to assess the effects of patients' abnormal involuntary movements on caregivers. AIMS: To capture the experiences of caregivers who assisted individuals with abnormal involuntary movements that were confirmed by clinicians as being consistent with TD. METHODS: Qualified (nonpaid) caregivers were invited to complete a questionnaire that included the following: caregivers' sociodemographic characteristics, their perceptions about the impact of abnormal involuntary movements on patients, and the impact of these movements on themselves (caregivers). RESULTS: Of the 41 participating caregivers, 25 (61.0%) were women, 20 (48.8%) were employed full time or part time, and 35 (85.4%) were family members or friends. Based on responses from caregivers who noticed patients' abnormal involuntary movements and were caring for individuals who also noticed those movements, 48.0% of patients had "a lot" of severity in ≥1 body region and 76.0% had abnormal involuntary movements in ≥2 regions. Caregiver ratings were significantly correlated with patient ratings (but not with clinician ratings) for maximum severity of abnormal involuntary movements and the number of affected regions (both p <.05). Based on their own judgments and perceptions, caregivers reported that the patient's movements had "some" or "a lot" of impact on their (caregiver's) ability to continue usual activities (50.0%), be productive (58.3%), socialize (55.6%), or take care of self (50.0%). CONCLUSIONS: Caregivers as well as patients are negatively affected by TD, and the impact of TD on caregivers' lives should be considered when determining treatment options.

Top-Up Clozapine for Risperidone LAI-Related Acute Dystonia and TR Bipolar in an Adolescent with ID-Putting the Cart before the Horse?

Objectives: Young patients with intellectual disability (ID) have both diagnostic and therapeutic challenges. These include, inter alia, diagnostic overshadowing, diagnostic slippage and heightened vulnerability to adverse drug reactions. These would portent a generally poor prognostication. Methods: This is a case-study of an adolescent with intellectual disability long-hospitalized for co-morbid treatment-resistant bipolar mood disorder that failed to respond to ECT. Patient partially responded to LAI risperidone with repeated ADRs. Top-up with low-dose clozapine (100 mg/d) was pursued. Results: Low-dose clozapine top-up complemented therapeutic response (mood lability and paranoia) and strikingly safeguarded effectively against risperidone-related extrapyramidal side effects. Conclusions: Add-on clozapine remains a viable option, albeit off-label, in young patients with ID and treatment-resistant affective/schizophreniform psychoses. Clozapine has an edge over other agents in the setting of dyskinesias.

Bipolar disorder treatment according to illness trajectory: a systematic review of clinical trials.

The current bipolar disorder treatment guidelines focus mainly on the prevention of recurrence and stabilization of acute mood episodes while neglecting outcomes related to the longitudinal course of illness. We systematically reviewed studies that assess the impact of disease progression in the treatment of patients with bipolar disorder. We searched PubMed, Embase, and Web of Science for clinical trials that moderated treatment effects by number of previous episodes, disease length, or a clinical staging model. We retrieved 6,156 potential abstracts. After deduplication, 5,376 were screened and eight studies met inclusion criteria. Seven trials moderated results by number of prior episodes, and one of those also used a measure of disease length. One trial used a clinical staging model and yielded informing results. Only three studies evaluated pharmacological interventions, the other five assessing psychotherapeutic modalities. Most of the studies were post-hoc analysis of clinical trials not primarily aimed at studying variables associated with illness trajectory. Overall, a loss of efficacy was found according to clinical progression, which supports early intervention. Tailored recommendations according to disease stages cannot be made. Furthermore, we identified methodological weaknesses and strengths in this subfield of research, suggesting the use of clinical staging models for future studies.

Case report: Bipolar disorder in 48,XXYY syndrome.

48,XXYY syndrome is a rare condition. The presentations of impulsive and aggressive behavior have been reported in several case reports among patients with 48,XXYY syndrome. The management of the psychological impact and neuropsychiatric sequela of this condition is a significant issue faced by families, carers, and healthcare professionals. We report a patient, 21-year-old Malay male, with underlying 48,XXYY syndrome with attention deficit hyperactivity disorder (ADHD) and intellectual disability, diagnosed later in adulthood with a bipolar mood disorder and benefited after being started on lithium. We describe the key clinical features and diagnostic workouts that allowed the arrival of the correct psychiatric diagnosis. Challenges in psychopharmacotherapy, including the risks of metabolic syndrome and deep vein thrombosis associated with 48,XXYY syndrome, are also considered. We suggest that for patients with 48,XXYY syndrome, routine psychological screening for mood symptoms such as mania and depression should be done by healthcare professionals with early involvement of psychiatrist in the multidisciplinary team due to the challenges in the management of these patients.

A quality assessment of clinical practice guidelines with recommendations for family involvement in the care of individuals diagnosed with schizophrenia, bipolar mood disorder, and major depressive disorder: Critical appraisal utilizing AGREE II.

Introduction: Evidence suggests that family-center collaborative care is useful for individuals identified with chronic mental illness. Clinical practice guidelines offer specific recommendations primarily based on to be had studies and are beneficial in informing evidence-based practice and guiding destiny studies. Objective: Identify current scientific practice guidelines including family-center collaborative care suggestions for individuals with Bipolar Mood Disorder, Schizophrenia, and Major Depressive Disorder and analyze the selection of guidelines for their methodological quality. Methods: A systematic search was conducted on seven electronic databases (G-I-N), (NICE), (MOH), (SIGN), (WHO), (NIH) and (APA) and additional sources. Three referees independently reviewed articles and selected guidelines for inclusion criteria. Subsequently, 18 trained appraisers independently assessed all 15 guidelines using AGREE II. Results: The mean scores for domains and overall quality were computed. For the overall assessment of the guidelines, 60% reached the quality threshold with domain scores of 60%. The overall average quality rating for these guidelines was 58/29%. Conclusion: The applicability of the guidelines needs to be improved in order to improve their relevance and clinical utilization. As individuals with chronic mental illnesses progress through their disease course, families and health care providers play a crucial role in helping them. The analysis of research knowledge on effective rehabilitation techniques, including the involvement of families in treatment, can be enhanced by using well-developed and appropriate methods.

High Frequency of Bipolar Disorder Comorbidity in Medical Inpatients.

Objective: Bipolar disorder is a severe, disabling, and recurring disorder. Some studies have shown that the frequency of bipolar disorder in patients with medical diseases is higher than healthy controls. The aim of this study was to investigate the frequency of bipolar disorders in medically ill patients hospitalized in Iranian general hospitals. Method : In this cross sectional study, 697 inpatients (342 men, 49.1%) from different wards of 3 general hospitals, with the mean age of 39.3+-10, were enrolled in the study using nonprobability sampling. Demographic questionnaire, Mood Disorder Questionnaire (MDQ) and Bipolar Spectrum Diagnostic Scale (BSDS) were used. Inclusion criteria were as follow: informed consent, age 18-65 years, ability to speak Persian, and having at least middle school education. Results: The frequency of bipolar disorder was 12.1% and 20.8% based on BSDS and MDQ, respectively. The results of both tests were positive in 7.9% of hospitalized patients. The frequency of bipolar mood disorder was significantly higher in single patients and in those with comorbidity of alcohol and substance use disorders. Conclusion: Considering the high frequency of bipolar mood disorders in hospitalized medically ill patients and its probable effects on compliance and prognosis, early screening, diagnosis, and treatment of bipolar mood disorders is important in these patients.

Assessment of Behavioral Approach and Behavioral Inhibition Systems in Mood Disorders.

INTRODUCTION: Psychiatric disorders could be evaluated in terms of behavioral activation and inhibition systems. Dysregulation of these systems may lead to development of manic or depressive episodes in patients with mood disorders. This study aimed to identify Behavioral Approach System (BAS) and Behavioral Inhibition System (BIS) hypersensitivity as the functional brain system behaviors in patients with major depressive disorder and bipolar mood disorder I, compared to healthy individuals. METHODS: This case-control study was conducted in Razi Psychiatric Hospital, a mental health referral center in Northwest of Iran. The study consisted of two groups of patients, one with major depressive and the other with bipolar mood disorders and one healthy group. Each group had 40 patients (20 men and 20 women). The study data were collected through BIS and BAS questionnaire, Beck Depression Inventory (BDI-II), Young Mania Rating Scale (YMRS). The obtained data were analyzed by SPSS version 18. RESULTS: The findings showed a significant negative correlation between BIS, BAS and BAS subscales with the severity of depression and positive correlation with mania symptoms (P<0.05). CONCLUSION: BAS and BIS dysregulations may predispose people to mood disorder symptoms. BAS is hyperactive during manic phase and may predict the symptom severity of bipolar mood disorder.

Efficacy of Group Cognitive-behavioral Therapy in Maintenance Treatment and Relapse Prevention for Bipolar Adolescents.

BACKGROUND: Despite conducting wide-ranging of pharmacotherapy for bipolar adolescents, many of them are showing a deficit in functioning with high relapse rate. The aim of the current study was to develop a manual and investigate the efficacy of group cognitive-behavioral therapy (G-CBT) for female bipolar adolescents. MATERIALS AND METHODS: During the first qualitative phase of a mixed-methods study, a manual of G-CBT was developed. Then, 32 female bipolar adolescents aged 12-19 years old, receiving usual maintenance medications (UMM), were selected. Participants were randomized to the control (UMM) and intervention group (5, 2 h weekly sessions based on G-CBT manual with UMM). The parents in intervention group participated in three parallel sessions. All participants filled the following questionnaires before 1, 3, and 6 months after the initiation of the study: Young Mania Rating Scale, Children Depression Inventory and Global Assessment of Functioning. The results were analyzed using SPSS 21 software. The concurrent qualitative phase was analyzed through thematic analysis. RESULTS: The results showed no significant differences in all questionnaires' scores through intervention and follow-up sessions (P > 0.05). However, using cutoff point of CDI, G-CBT was effective for intervention group (relapse rate: 25% vs. 44.4%). Two themes were extracted from the second qualitative phase: emotion recognition and emotion regulation, especially in anger control. CONCLUSIONS: The results showed that the addition of G-CBT to UMM leads to decrease in the depressive scores but has no effect on manic symptoms and relapse rate.

[The facets of creativity in the light of bipolar mood alterations]. / A kreativitás arculatai a bipoláris hangulatzavar tükrében.

The link between creativity, as the highest expression form of human achievement, and bipolar disorder came into focus of scientific investigations and research. Accomplished writers, composers and visual artists show a substantially higher rate of affective disorders, prodominantly bipolar mood disorders, comparing to the general population. Then again, patients afflicted with bipolar II subtype (hypomania and depression), as well as persons presenting the mildest form of bipolar mood swings (cyclothymia) possess higher creative skills. It evokes therefore that certain forms and mood states of bipolar disorder, notably hypomania might convey cognitive, emotional/affective, and motivational benefits to creativity. The aim of this paper is to display expression forms of creativity (writing, visual art, scientific work) as well as productivity (literary and scientific work output, number of artworks and exhibitions, awards) in the light of clinically diagnosed mood states at an eminent creative individual, treated for bipolar II disorder. Analysing the affective states, we found a striking relation between hypomanic episodes and visual artistic creativity and achievement, as well as scientific performance, whereas mild-moderate depressed mood promoted literary work. Severe depression and mixed states were not associated with creative activities, and intriguingly, long-term stabilised euthymic mood, exempted from marked affective lability, is disadvantageous regarding creativity. It seems, thereby, that mood functions as a sluice of creativity. Nevertheless, it is likely that there is a complex interaction between bipolar mood disorder spectrum and psychological factors promoting creativity, influenced also by individual variability due to medication, comorbid conditions, and course of disorder.

Informal Caregivers' Learning Experiences With Self-Management Support of Individuals Living With Bipolar Disorder: A Phenomenological Study.

BACKGROUND: The degree of informal caregiver involvement influences the self-management of individuals living with bipolar disorder (BD). OBJECTIVE: This article aims to provide a description of informal caregivers' learning experiences in self-management support of BD in order to guide professionals in tailoring future psychosocial and psychoeducational interventions. DESIGN: In-depth open interviews with 10 informal caregivers of patients with BD who followed treatment in the context of specialized outpatient bipolar care were conducted. RESULTS: Four learning phases emerged from the phenomenological analysis describing the informal caregivers learning process: (1) understanding BD, (2) overcoming the dilemmas in self-management support for individuals living with BD, (3) dividing tasks and responsibilities, and (4) acquiring a personal definition of self-management support for individuals living with BD. CONCLUSION: By grasping the concept of BD, informal caregivers gradually learn how to overcome dilemmas resulting from living with someone with BD, and how to control the expression of emotions. They learn to reflect on the nature of conflicts and how to share the responsibilities of illness management with individuals living with BD and professionals. Mastering these skills eventually allows them to define and delimit their supporting informal caregiver role in the self-management of BD. PRACTICE IMPLICATIONS: Our findings provide information regarding the educational needs of informal caregivers to tailor counseling, and psychosocial and psychoeducational interventions in specialized outpatient care for individuals living with BD.

Sodium Valproate-Induced Bilateral Pitting Pedal Edema - A Case Report.

Bilateral pitting edema is rare adverse drug reaction observed in the psychiatry department. Drug related pedal edema is most commonly seen with ACE inhibitors, non-steroidal antiinflammatory drug, and calcium channel blockers. But pitting edema with Sodium valproate is very rare. Here, we report two cases of Sodium valproate-induced bilateral pitting edema.

Comparing the Profile of Temperament and Character Dimensions in Patients with Major Depressive Disorder and Bipolar Mood Disorder with a Control Group.

Objective: This study was conducted to compare the profile of temperament and character dimensions in patients with major depressive disorder and bipolar mood disorder with a control group. Method: In this causal-comparative study, the population consisted of 2 clinical groups (major depressive disorder and bipolar mood disorder) and a non-clinical group. The sample was 193 individuals (77 patients with major depressive disorder, 86 patients with bipolar mood disorder, and 30 controls), with an age range of 18 to 65 years and the mean age of 40.1. They were selected from Roozbeh psychiatric hospital using available sampling method. Tools used in this research included Temperament and Character Inventory-140 and General Health Questionnaire-28. Collected data were analyzed by independent t test and one-way analysis of variance using Statistical Package for the Social Sciences-22 software. Results: The results revealed a significant difference among groups in dimensions of novelty seeking, harm avoidance, persistence, self-directedness, and cooperativeness (P <0.05). The results showed that the mean was different in males and females only in the novelty seeking dimension (P <0.05). Conclusion: In general, our results revealed that patients with major depressive disorder and bipolar mood disorder have different personality profiles in some dimensions of temperament and character compared with the control group.

Psychiatric conditions as predictors of rehospitalization among African American patients hospitalized with heart failure.

INTRODUCTION: African Americans (AAs) have the highest risk of developing heart failure (HF) among all ethnicities in the United States and are associated with higher rates of readmissions and mortality. This study aims to determine the prevalence and relationship of common psychiatric conditions to outcomes of patients hospitalized with HF. HYPOTHESIS: Psychiatric conditions lead to worse outcomes in HF patients. METHODS: This single-center retrospective study enrolled 611 AA patients admitted to an urban teaching community hospital for HF from 2010 to 2013. Patient demographics, clinical variables, and history of psychiatric disorders were obtained. Cox proportional hazards regression was used to assess impact of psychiatric disorders on readmission rates and mortality. RESULTS: The mean age was 66 ± 15 years; 53% were men. Median follow-up time from index admission for HF was 3.2 years. Ninety-seven patients had a psychiatric condition: 46 had depression, 11 had bipolar mood disorder (BMD), and 40 had schizophrenia. After adjustment of known risk factors and clinical metrics, our study showed that AA HF patients with a psychiatric illness were 3.84× more likely to be admitted within 30 days for HF, compared with those without (P < 0.001). Individually, adjusted Cox multivariable logistic regression analysis also showed that, for 30-day readmission, schizophrenia had a hazard ratio (HR) of 4.92 (P < 0.001); BMD, an HR of 3.44 (P = 0.02); and depression, an HR 3.15 (P = 0.001). No associations were found with mortality. CONCLUSIONS: Psychiatric conditions of schizophrenia, BMD, and depression were significantly associated with a higher 30-day and overall readmission rate for HF among AA patients.

A Case Study of Negative Affixes in Sadegh Hedayat's Letters: The Effect of Bipolar Mood Disorder.

This research studies the morphological features found in Sadegh Hedayat's letters, who, based on linguistic and psychological studies, may have had bipolar disorder. It aims to assess the impact of various types of moods on the frequency of negative affixes through qualitative analysis of the letters' text. The letters are written in Persian, and include six negative derivational affixes. As bipolar disorder includes four episodes, all letters are analyzed on the basis of six negative affixes concerning the episodes using SPSS. The results indicate that each episode shows totally different characteristics in using negative affixes. In fact, Hedayat mostly used negative affixes in depression, confirming psychological studies, and it is revealed that he mostly used negative affixes in hypomania when he experienced an irritated mood. Moreover, the frequency of negative affixes in mixed episode shows a combination of hypomania and depression, which is in agreement with previous studies. Additionally, euthymia shows few negative affixes.

Delayed Stevens-Johnson Syndrome Secondary to the Use of Lamotrigine in Bipolar Mood Disorder.

Lamotrigine is a mood-stabilizing drug used in maintenance treatment of bipolar I disease. There are adverse effects with lamotrigine such as a headache, blurred vision, diplopia, somnolence, ataxia, dizziness, rash, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis. SJS is a life-threatening, blistering mucocutaneous disease. SJS is characterized by the presence of flat, diffuse erythematous maculopapular rashes with the involvement of <10% of the body surface area. Standard trigger is drugs including anticonvulsants, antibiotics, and Mycoplasma pneumoniae infection. We report a case where a patient developed SJS secondary to delayed-type hypersensitivity reaction after 6 months of the use of lamotrigine, while his initial response during the first 6 months did not show any sign of SJS.

A Magnetic Resonance Spectroscopy Study of Lovastatin for Treating Bipolar Mood Disorder: A 4-Week Randomized Double-Blind, Placebo- Controlled Clinical Trial.

BACKGROUND: No trial has examined the effect of lovastatin on the brain metabolites in patients with bipolar mood disorder. OBJECTIVES: Current medications for treating bipolar disorders cause metabolic syndrome. It is supposed that lovastatin not only decreases the rate of metabolic syndrome but also impacts some brain metabolites and their ratio like common treatments that are measured by Magnetic Resonance Spectroscopy. METHODS: 27 Manic phase patients were randomly allocated into two groups, lovastatin and placebo as their adjuant medication. Clinical symptoms were assessed at baseline, weeks 2, 4. The brain metabolites were measured at baseline and week 4. RESULT: Regarding the change of clinical symptoms, no significant difference was found between two groups. However, lovastatin significantly increased the level of NAA in cingulate gyrus in comparison to the placebo group. Moreover, lovastatin more than placebo increased creatine in the left basal ganglia. Furthermore, choline/ creatine showed a significant decrease in the left basal ganglia in lovastatin group. CONCLUSION: Using MRS after treating with lovastatin showed lovastatin increases NAA in cingulate gyrus, indicating the possible effect of NAA for increasing the reduced viable neuron. Moreover, the increment of Cr by lovastatin in the left basal ganglia suggests the role of lovastatin for maintaining energy homeostasis, anti-apoptotic activity and ATP production in bipolar disorder. Some patents using lovastatin as an adjuant therapy for treating bipolar patients and depression in MDD patients are also outlined. This trial was registered in the Iranian Clinical Trials Registry (http://www.irct.ir/) (IRCT201302203930N18).

The Effect of Family-Centered Psycho-Education on Mental Health and Quality of Life of Families of Adolescents with Bipolar Mood Disorder: A Randomized Controlled Clinical Trial.

BACKGROUND: Bipolar Mood Disorder (BMD) is a type of mood disorder which is associated with various disabilities. The family members of the patients with BMD experience many difficulties and pressures during the periods of treatment, rehabilitation and recovery and their quality of life (QOL) is threatened. In the present study, we aimed to evaluate the effect of family-centered education on mental health and QOL of families with adolescents suffering from BMD. METHODS: In this randomized controlled clinical trial performed on 40 families which were mostly mothers of the adolescents with BMD referred to the psychiatric clinics affiliated to Shiraz University of Medical Sciences during 2012-13. They were randomly assigned to intervention and control groups. RESULTS: The results of single factor multivariate ANOVA/single-factor multivariate analysis of variance and Bonferroni post hoc tests showed that the interaction between the variables of group and time was significant (P<0.001). The mean of QOL and mental health scores increased in the intervention group, but it decreased in the control group at three measurement time points. CONCLUSION: The study findings confirmed the effectiveness of family-centered psychoeducation program on Mental Health and Quality of life of the families of adolescents with Bipolar Mood Disorder. TRIAL REGISTRATION NUMBER: IRCT201304202812N15.