Phases Of Bipolar Disorder Research Articles

Cross-sectional study of neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in mood disorders

ObjectiveNeutrophil-lymphocyte, monocyte-lymphocyte and platelet-lymphocyte ratio are inexpensive and reproducible biomarkers of inflammation found to be elevated in mood disorders. This study aimed to compare inflammatory ratios between bipolar disorder and major depressive disorder and between bipolar disorder manic episodes and bipolar disorder depressive episodes. MethodWe included 142 Caucasian patients (major depressive disorder: n = 36; bipolar disorder manic episode: n = 66; bipolar disorder depressive episode: n = 40). We measured white blood cells, neutrophils, lymphocytes, monocytes, platelets, glucose, and total cholesterol. Neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, and platelet-lymphocyte ratio were calculated. ResultsNeutrophil-lymphocyte ratio and monocyte-lymphocyte ratio were significantly higher in bipolar disorder manic episodes when compared to bipolar disorder depressive episodes and major depressive disorder episodes after adjustment for age, sex, body mass index, and smoking. ConclusionTo our knowledge, our study is the first one to compare inflammatory ratios between different bipolar disorder phases and major depressive disorder episodes. In accord with previous studies on other inflammatory mediators, we found higher neutrophil-lymphocyte and monocyte-lymphocyte ratios in bipolar manic episodes, suggesting that inflammatory changes occur especially during acute episodes of mania.

Thiol/disulphide homeostasis in manic episode and remission phases of bipolar disorder

Purpose: Bipolar disorder (BD) is a chronical psychiatric disorder of which pathophysiology was demonstrated to be related with oxidative stress. Thiol–disulphide homeostasis is an indicator of oxidative balance. This study aims to investigate thiol–disulphide homeostasis in BD.Materials and methods: 27 patients in manic episode (MA), 29 patients in remission (RE) and 60 healthy participants (HC) were included to the study. Serum native thiol and total thiol levels were measured with a novel colorimetric, automated method. The disulphide levels and disulphide/native thiol ratios were also calculated from these measured parameters.Results: Native thiol levels and total thiol levels of both MA and RE groups were lower than HC. No significant difference detected between MA and RE in terms of native thiol levels and total thiol levels. Disulphide levels and disulphide/native thiol ratio was detected statistically similar between three groups.Conclusion: Our results support the oxidative imbalance theory in pathophysiology of BD. Further studies with larger sample sizes are needed for being able to understand these pathways in detail and use them as a target of treatment.

Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder: systematic review and meta-analyses.

A reliable biomarker signature for bipolar disorder sensitive to illness phase would be of considerable clinical benefit. Among circulating blood-derived markers there has been a significant amount of research into inflammatory markers, neurotrophins and oxidative stress markers.AimsTo synthesise and interpret existing evidence of inflammatory markers, neurotrophins and oxidative stress markers in bipolar disorder focusing on the mood phase of illness. Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a systematic review was conducted for studies investigating peripheral biomarkers in bipolar disorder compared with healthy controls. We searched Medline, Embase, PsycINFO, SciELO and Web of Science, and separated studies by bipolar mood phase (mania, depression and euthymia). Extracted data on each biomarker in separate mood phases were synthesised using random-effects model meta-analyses. In total, 53 studies were included, comprising 2467 cases and 2360 controls. Fourteen biomarkers were identified from meta-analyses of three or more studies. No biomarker differentiated mood phase in bipolar disorder individually. Biomarker meta-analyses suggest a combination of high-sensitivity C-reactive protein/interleukin-6, brain derived neurotrophic factor/tumour necrosis factor (TNF)-α and soluble TNF-α receptor 1 can differentiate specific mood phase in bipolar disorder. Several other biomarkers of interest were identified. Combining biomarker results could differentiate individuals with bipolar disorder from healthy controls and indicate a specific mood-phase signature. Future research should seek to test these combinations of biomarkers in longitudinal studies.Declaration of interestNone.

Randomized Controlled Trials of Psychoeducation Modalities in the Management of Bipolar Disorder: A Systematic Review.

This review sought to summarize the extant literature on the efficacy of 4 modalities of psychoeducation (individual, group, family, internet- based) in the management of patients with bipolar disorder. We searched the digital databases (Science Direct, Scopus, PubMed/MEDLINE) for relevant randomized controlled trials (RCTs) pertaining to psychoeducation in bipolar disorder from inception to February 2017. Keywords and combinations used included psychoeducation, bipolar disorder, individual, family, group, and internet. Reference lists of review articles were also used for retrieval of relevant articles. We retrieved 48 studies and ultimately reviewed 40 RCTs meeting inclusion criteria. Studies were included if they were in English, were RCTs of different psychoeducation modalities managing patients with bipolar disorder, and used standardized assessment of outcomes of psychoeducation. We examined each of the selected publications for relevant data. The majority of psychoeducation RCTs (28 of 40 studies, 70.0%) focused on group and family psychoeducation, with positive benefits reported in clinical outcomes, treatment, and functioning measures. Group psychoeducation was associated with reduced illness recurrences, decreased number and duration of hospitalizations, increased time to illness relapse, better treatment adherence, higher therapeutic lithium levels, and reduced stigma. Family psychoeducation was associated with reductions in illness recurrence, hospitalization rates, and better illness trajectory as well as increased caregiver knowledge, skills, support, and sense of well-being and reduced caregiver burden. There are fewer RCTs on individual and internet-based psychoeducation, with findings being inconsistent or negative. Future studies may include direct comparisons of different psychoeducation modalities to elucidate specific benefits of unique psychoeducation interventions at different phases of bipolar disorder.

Cognitive performance in patients with acute phase of bipolar disorder

Cognitive performance in patients with acute phase of bipolar disorder

White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: Combined DTI and immunological investigation in the different phases of bipolar disorder

BackgroundWhite matter (WM) microstructural abnormalities and, independently, signs of immunological activation were consistently demonstrated in bipolar disorder (BD). However, the relationship between WM and immunological alterations as well as their occurrence in the various phases of BD remain unclear. MethodIn 60 type I BD patients – 20 in manic, 20 in depressive, 20 in euthymic phases – and 20 controls we investigated: (i) diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) using a tract-based spatial statistics (TBSS) approach; (ii) circulating T cell subpopulations frequencies, as well as plasma levels of different cytokines; (iii) potential relationships between WM and immunological data. ResultsWe found: (i) a significant widespread combined FA-RD alteration mainly in mania, with involvement of the body of corpus callosum (BCC) and superior corona radiata (SCR); (ii) significant increase in CD4+ T cells as well as significant decrease in CD8+ T cells and their subpopulations effector memory (CD8+ CD28-CD45RA-), terminal effector memory (CD8+ CD28-CD45RA+) and CD8+ IFNγ+ in mania; (iii) a significant relationship between WM and immunological alterations in the whole cohort, and a significant correlation of FA-RD abnormalities in the BCC and SCR with reduced frequencies of CD8+ terminal effector memory and CD8+ IFNγ+ T cells in mania only. ConclusionsOur data show a combined occurrence of WM and immunological alterations in mania. WM abnormalities highly correlated with reduction in circulating CD8+ T cell subpopulations that are terminally differentiated effector cells prone to tissue migration, suggesting that these T cells could play a role in WM alteration in BD.

Mood Stabilizers: Implementing Combined Treatment Regimens in Bipolar Disorder

Patients with bipolar disorders spend a greater proportion of their illness in a depressed or mixed state rather than experiencing either mania or hypomania. Over the past 20 years, most major pharmaceutical companies have either reduced or abandoned the research and development of novel psychiatric drugs, exiting the development of new, safe, efficacious, and tolerable treatment regimens for bipolar disorder. Therefore, optimizing the current treatments available is critical. We review studies of the last 15 years that provide guidance relevant to managing the maintenance phase of bipolar disorders. Based on these data, we provide recommendations for effective treatment planning and implementation, principally for the maintenance phase care of persons with bipolar disorder. We also discuss strategies for implementing medication regimens, differentiating strategies for maintenance phase treatment from those of acute phase treatment. Assessing key symptoms that are sensitive to change is critical for longitudinal assessments and treatment planning for patients with bipolar disorders. In most studies, only a subset of rating scale items differentiate patients with good responses from those without. Identified symptoms include racing thoughts, less need for sleep, hyperactivity, increased activity, and increased energy. We developed a procedure for using Multistate Outcome Analysis of Treatment (MOAT) in bipolar disorders. MOAT integrates efficacy and tolerability data during studies to provide information about the quantity and quality of time spent in distinct mood states. The protocol developed will be useful for assessing treatment strategies in bipolar disorder. This review contains 4 figures, 7 tables and 32 references Key words: bipolar, depression, lithium, mania, mixed, mood stabilizer, survival analysis, symptom domains, valproate

Pharmacological Treatment Strategies for Acute Bipolar Depression

Of the different phases of bipolar disorder, bipolar depression is more prevailing and is more difficult to treat. However, there is a deficit in...

Efficacy of vestibular stimulation treatment in the depressive phase of bipolar disorder: study protocol for a randomized, double-blind, controlled trial

Background and objectives: Bipolar disorder (BD) is a neuropsychiatric disorder characterized by the oscillation of mood states between hypoactive/pessimistic (depressive phase) and hyperactive/optimistic states (manic/hypomanic phase). Previous studies evidenced that a particular technique of neuro-vestibular stimulation is an effective treatment for major depression. This study will investigate the efficacy of the said vestibular stimulation technique in the depressive phase of BD, and will compare it with sham vestibular stimulation. Design: A double-blind, randomized controlled study. Methods: One hundred and twenty patients with bipolar type I or II, currently undergoing a depressive phase, will be randomized into the experimental group (n = 60) or control group (n = 60), receiving three sessions of real/sham vestibular stimulation. Outcome measures: The primary outcome is the change in Montgomery Asberg Depression Rating Scale scores from baseline to post 4 and 12 weeks. The secondary outcome is the vestibular activity assessed at baseline, post 4 and 2 weeks. Discussion: Currently, no treatment has proved efficacy for bipolar depression. Studies have demonstrated that lateralized neuro-vestibular stimulation is an effective treatment for mayor depression but has not been studied in the depressive phase of bipolar disorder. This investigation will give the first evidence supporting or denying the use of vestibular stimulation treatment in BD depression. Ethics and dissemination: This study protocol was approved by the Ethics Committee of SSMO (Servicio de Salud Metropolitano Oriente) in Santiago, Chile (approval No. 08032016) on March 8, 2016. The results of the study will be published in scientific journals and other media. Trial registration: ClinicalTrials.gov Identifier: NCT02778256.

Pharmacologic Treatment Options for Bipolar Disorder in Children and Adolescents

Purpose of review Bipolar disorder is a chronic and disabling condition that often presents in adolescence and leads to significant functional impairment, especially in the areas of emotional, cognitive, and social development. Pharmacotherapy is a vital component of the complex treatment of this disorder.The purpose of this review is to provide an overview of the available data on the management of bipolar disorder and the most common comorbid conditions in youth. Recent findings Several medications such as lithium and second-generation antipsychotics (risperidone, aripiprazole, olanzapine, quetiapine, and asenapine) are currently approved by the FDA for the management of acute mixed or manic phases of pediatric bipolar disorder. Very limited data are available on continuation treatment and management of depressive phases of bipolar disorder. There is some evidence that supports the use of a combination of an antipsychotic with lithium or an anticonvulsant for treatment of resistant cases. Summary Monotherapy with an atypical antipsychotic or lithium is the preferable initial treatment of acute manic or mixed episodes. The available evidence supports the use of an olanzapine/fluoxetine combination for the treatment of bipolar depression, which has also been approved by the FDA for this purpose. Additional studies are needed to evaluate safety and efficacy of psychopharmacological interventions, especially focusing on treatment of the depressive and maintenance phases of bipolar disorder.

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder. A Randomized, Double-Blind, Placebo-Controlled Clinical Trial: Erratum

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder. A Randomized, Double-Blind, Placebo-Controlled Clinical Trial: Erratum

Correlation between alterations of inflammatory markers and treatment with atypical antipsychotics in patients diagnosed with bipolar affective disorder

IntroductionClinical evidences suggests that cerebral inflammatory processes are involved in the development of major affective disorders [1].Obvious correlations exist between changes of inflammatory markers such as acute-phase protein C (PCR) and VES, in patients with bipolar spectrum diagnosis [2].ObjectivesOur aim is demonstrating the correlations between changes of PCR and VES and pharmacological treatment with atypical antipsychotics in patients with acute bipolar disorder, highlighting a trend.MethodTwenty patients with bipolar disorder were assessed at the entrance (T0), after three weeks (T1) and after six weeks (T2) of hospitalization using specific rating scales and blood tests routines include PCR and VES.ResultsIs possible to appreciate a correlation between the affective phase of bipolar disorder and inflammatory markers with a proportional trend (Table 1).Discussion and conclusionThe scores obtained seem to confirm the effect of antipsychotic in both sense of psychiatric symptomatology reduction and in anti-inflammatory action.A confirmation of a correlation between the resolution of affective disorders and normalization of inflammatory markers confirm the intrinsic anti-inflammatory activity of such drug compounds [3].Disclosure of interestThe authors have not supplied their declaration of competing interest.

A pilot study to determine whether combinations of objectively measured activity parameters can be used to differentiate between mixed states, mania, and bipolar depression

BackgroundUntil recently, actigraphy studies in bipolar disorders focused on sleep rather than daytime activity in mania or depression, and have failed to analyse mixed episodes separately. Furthermore, even those studies that assessed activity parameters reported only mean levels rather than complexity or predictability of activity. We identified cases presenting in one of three acute phases of bipolar disorder and examined whether the application of non-linear dynamic models to the description of objectively measured activity can be used to predict case classification.MethodsThe sample comprised 34 adults who were hospitalized with an acute episode of mania (n = 16), bipolar depression (n = 12), or a mixed state (n = 6), who agreed to wear an actiwatch for a continuous period of 24 h. Mean level, variability, regularity, entropy, and predictability of activity were recorded for a defined 64-min active morning and active evening period. Discriminant function analysis was used to determine the combination of variables that best classified cases based on phase of illness.ResultsThe model identified two discriminant functions: the first was statistically significant and correlated with intra-individual fluctuation in activity and regularity of activity (sample entropy) in the active morning period; the second correlated with several measures of activity from the evening period (e.g. Fourier analysis, autocorrelation, sample entropy). A classification table generated from both functions correctly classified 79% of all cases based on phase of illness (χ2 = 36.21; df 4; p = 0.001). However, 42% of bipolar depression cases were misclassified as being in manic phase.ConclusionsThe findings should be treated with caution as this was a small-scale pilot study and we did not control for prescribed treatments, medication adherence, etc. However, the insights gained should encourage more widespread adoption of statistical approaches to the classification of cases alongside the application of more sophisticated modelling of activity patterns. The difficulty of accurately classifying cases of bipolar depression requires further research, as it is unclear whether the lower prediction rate reflects weaknesses in a model based only on actigraphy data, or if it reflects clinical reality i.e. the possibility that there may be more than one subtype of bipolar depression.

Pharmacological Treatment of Bipolar Disorder in the Elderly

Due to the early age of onset, bipolar disorder is most commonly studied in younger adults, among whom the prevalence is 3.9% in adults aged 18–30 years. Unfortunately, relatively less attention has been paid to the unique needs of older adults with bipolar disorder (OABD), despite clinical complexities that include medical comorbidity, polypharmacy, cognitive decline, and phase of life losses of occupation and social identity. Furthermore, impaired cognitive performance in some older adults may limit the ability to stabilize mood episodes and interfere with the individual’s engagement in multi-modal treatment. Many OABD may also struggle with impairments in their independent activities of daily living (IADLs) which can lead to greater psychiatric, medical, psychological, financial, or social sequelae of mood episodes. Further complicating this picture is the fact that most OABD are treated by general psychiatrists or family practitioners due to a worldwide shortage of geriatric psychiatrists. This will become increasingly common as the mean life expectancy continues to increase. It is therefore incumbent on all general practitioners to understand the phases of bipolar disorder and the associated treatment options throughout the lifespan. Treatment of manic or depressive episodes focuses on symptomatic remission primarily through pharmacotherapy and neurotherapeutics. Management of the maintenance phase focuses on optimizing pharmacotherapy while reducing subclinical symptoms, treating comorbid illness, preventing relapse, and restoring psychosocial functioning and intacts identity through multimodal approaches including psychopharmacology, psychotherapy, diet, and lifestyle modifications. Comprehensive care for OABD is best achieved through close collaboration with the affected individual, the family physician, pharmacist, family members, and social supports.

A vestibular biomarker of manic and depressive phase in bipolar disorder

Background and objectives: Bipolar disorder (BD) is a neuropsychiatric disorder characterized by cyclic changes in mood between hypoactive, pessimistic (depressive phase) and hyperactive, optimistic (manic/hypomanic phase). Prior studies in major depression patients show that the right side of the vestibular system (inner ear's equilibrium system) is less active compared to the left. It suggests a relationship between mood and abnormal lateralization of the vestibular activity. This exploratory investigation analyzes the right and left vestibular activity in different mood phases of BD and healthy controls. Design: A transversal cross-sectional study. Methods: We will study and compare the lateralization of the vestibular activity of BD I or II patients, who match the selection criteria for different mood phases: depression, mania/hypomania, euthymia and healthy controls (6 patients each group). Outcome measures: For vestibular evaluation, we will use rotary chair technique and electronystagmography. The primary outcome measure is the per- and post-rotatory asymmetry. The secondary outcome measures are the slow phase velocity of the nystagmus, the rhythmicity of nystagmus, and the type of slow ocular tracking. Discussion: This study addresses the relationship between mood states and abnormal right-left side lateralization of the vestibular activity in BD patients. Ethics and dissemination: The study protocol was approved by the ethics committee of Servicio de Salud Metropolitano Oriente, in Santiago, Chile on June 21st, 2016. Participants will provide written informed consent prior to participation in the trial. Trial registration: ClinicalTrials.gov identifier: NCT02827045 on July 6th, 2016.

The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm.

Background:The current paper includes a systematic search of the literature, a detailed presentation of the results, and a grading of treatment options in terms of efficacy and tolerability/safety.Material and Methods:The PRISMA method was used in the literature search with the combination of the words ‘bipolar,’ ‘manic,’ ‘mania,’ ‘manic depression,’ and ‘manic depressive’ with ‘randomized,’ and ‘algorithms’ with ‘mania,’ ‘manic,’ ‘bipolar,’ ‘manic-depressive,’ or ‘manic depression.’ Relevant web pages and review articles were also reviewed.Results:The current report is based on the analysis of 57 guideline papers and 531 published papers related to RCTs, reviews, posthoc, or meta-analysis papers to March 25, 2016. The specific treatment options for acute mania, mixed episodes, acute bipolar depression, maintenance phase, psychotic and mixed features, anxiety, and rapid cycling were evaluated with regards to efficacy. Existing treatment guidelines were also reviewed. Finally, Tables reflecting efficacy and recommendation levels were created that led to the development of a precise algorithm that still has to prove its feasibility in everyday clinical practice.Conclusions:A systematic literature search was conducted on the pharmacological treatment of bipolar disorder to identify all relevant random controlled trials pertaining to all aspects of bipolar disorder and graded the data according to a predetermined method to develop a precise treatment algorithm for management of various phases of bipolar disorder. It is important to note that the some of the recommendations in the treatment algorithm were based on the secondary outcome data from posthoc analyses.

The Sexuality of Male Patients with Affective Disorders - Demographic and Clinical Features

Objective: Aim: The aim of this study was to explore sexuality (frequency and willingness to initiate sexual contact, opinions on sexual life and possible sexual dysfunctions) among Polish male patients treated in psychiatric clinics with a diagnosis of affective disorder. Design and Method: Method: 62 men aged 23-61 years with diagnosed affective disorder according to ICD-10 criteria were included. Participants were asked to complete the Kratochvil Sexual Function of Man (SFM/K) Questionnaire and the Alcohol Use Disorder Identification Test (AUDIT). Obtained data was complemented by socio-medical history, including type of affective disorder, duration of the disease, drug abuse, and somatic comorbidities. Results: Results: 52% of participants were diagnosed with bipolar disorder, the second most common diagnosis was recurrent depressive disorder. Bipolar men reported more often sexual contacts, more frequently had a good feeling after sexual intercourse. 61% of respondents reported at least one sexual dysfunction. Most common psychological factor was fear of failing as sexual partner. Statistically significant influences on the average SFM/K total score were: age at the onset of illness, duration of affective disorders and its treatment, number of hospitalizations. Conclusions: Averaged total score of SFM/K, for all examined men was found to range moderate results. Recurrent depression seem to be more strongly correlated with lower scores, so global as well as within each response, rather than affective phase in bipolar disorder. Greater differentiation relates to “duration of intercourse” and “problems with premature ejaculation”.

Abnormal functional-structural cingulum connectivity in mania: combined functional magnetic resonance imaging-diffusion tensor imaging investigation in different phases of bipolar disorder.

The objective of the study was to investigate the relationship between structural connectivity (SC) and functional connectivity (FC) in the cingulum in bipolar disorder (BD) and its various phases. We combined resting-state functional magnetic resonance imaging and probabilistic tractographic diffusion tensor imaging to investigate FC and SC of the cingulum and its portions, the SC-FC relationship, and their correlations with clinical and neurocognitive measures on sustained attention in manic (n = 21), depressed (n = 20), and euthymic (n = 20) bipolar patients and healthy controls (HC) (n = 42). First, we found decreased FC between the anterior and posterior parts of the cingulum in manic patients when compared to depressed patients and HC. Second, we observed decreased SC of the cingulum bundle, particularly in its anterior part, in manic patients when compared to HC. Finally, alterations in the cingulum FC (but not SC) correlated with clinical severity scores while changes in the cingulum SC (but not FC) were related with neurocognitive deficits in sustained attention in BD. We demonstrate for the first time a reduction in FC and concomitantly in SC of the cingulum in mania, which correlated with psychopathological and neurocognitive parameters, respectively, in BD. This supports the central role of cingulum connectivity specifically in mania.

The Treatment of Adult Bipolar Disorder with Aripiprazole: A Systematic Review

Bipolar disorder is characterized by exacerbations of opposite mood polarity, ranging from manic to major depressive episodes. In the current nosological system of the Diagnostic and Statistical Manual – 5th edition (DSM-5), it is conceptualized as a spectrum disorder consisting of bipolar disorder type I, bipolar disorder type II, cyclothymic disorder, and bipolar disorder not otherwise specified. Treatment of all phases of this disorder is primarily with mood stabilizers, but many patients either show resistance to the conventional mood stabilizing medications or are intolerant to their side-effects. In this setting, second-generation antipsychotics have gained prominence as many bipolar subjects who are otherwise treatment refractory show response to these agents. Aripiprazole is a novel antipsychotic initially approved for the treatment of schizophrenia but soon found to be effective in bipolar disorder. This drug is well studied, as randomized controlled trials have been conducted in various phases of bipolar disorders. Aripiprazole exhibits the pharmacodynamic properties of partial agonism, functional selectivity, and serotonin-dopamine activity modulation – the new exemplars in the treatment of major psychiatric disorders. It is the first among a new series of psychotropic medications, which now also include brexpiprazole and cariprazine. The current review summarizes the data from controlled trials regarding the efficacy and safety of aripiprazole in adult bipolar patients. On the basis of this evidence, aripiprazole is found to be efficacious in the treatment and prophylaxis of manic and mixed episodes but has no effectiveness in acute and recurrent bipolar depression.

Subthreshold symptoms in bipolar disorder

Introduction Bipolar disorder is a severe mental illness characterized by intermittent episodes of mania, depression and mixed states. The presence of residual symptoms, seems to be the common factor in many studies assessing functioning in BD patients. Objective To evaluate the prevalence of residual symptoms (both depressive and manic) in euthymic patients with bipolar disorder and seek for associated factors. Methodology A total of 30 patients with bipolar disorder were enrolled for this study. They were in remission for at least two months. The patients answered the Hamilton Depression Rating Scale and the Disorder Questionnaire Mood Hirschfeld (the MDQ scale). Results The average age of our patients was 43±13 years. Most patients were from a rural area (70%), married (60%) and did not go beyond secondary school level (93.3%). Forty percent (40%) had organic personal history. Social dysfunction was found in 40% of cases, and professional difficulties in 30% of patients. Depressive residual symptoms were found in 33.3% in cases and hypomaniac ones in 26.6%. Residual depressive symptoms were significantly more frequent among married patients and having organic personal history ( P =0.025). The professional difficulties were associated with male gender ( P =0.025) and the poor quality of free interval ( P =0.03). Conclusion These results illustrate that the intercritical phase in bipolar disorder is not really euthymic. These findings are in favour of developing interventions to manage subthreshold symptoms to reduce their impact on social and professional functioning.