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Objective We examined the relationship between biological rhythms and severity of depressive symptoms in subjects with bipolar disorder and the effects of biological rhythms alterations on functional impairment. Method Bipolar patients ( n = 260) and healthy controls ( n = 191) were recruited from mood disorders programs in three sites (Spain, Brazil, and Canada). Parameters of biological rhythms were measured using the Biological Rhythms Assessment in Neuropsychiatry ( BRIAN), an interviewer administered questionnaire that assesses disruptions in sleep, eating patterns, social rhythms, and general activity. Results Multivariate analyses of covariance showed significant intergroup differences after controlling for potential confounders (Pillai's F = 49.367; df = 2, P < 0.001). Depressed patients had the greatest biological rhythms disturbance, followed by patients with subsyndromal symptoms, euthymic patients, and healthy controls. Biological rhythms and HAMD scores were independent predictors of poor functioning ( F = 12.841, df = 6, P < 0.001, R2 = 0.443). Conclusion Our study shows a dose-dependent association between the severity of depressive symptoms and degree of biological rhythms disturbance. Biological rhythms disturbance was also an independent predictor of functional impairment. Although the directionality of this relationship remains unknown, our results suggest that stability of biological rhythms should be an important target of acute and long-term management of bipolar disorder and may aid in the improvement of functioning. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to identify psychopathological factors associated with long-term functional outcome in euthymic bipolar disorder patients and to test new measures of mood instability and symptoms intensity. Method Fifty-five patients with more than 12 months of follow-up were included. In addition to traditional clinical variables, the time spent ill was documented using a modified life-charting technique based on NIHM life-charting method. New measures, Mood Instability Factor, and Mood Intensity Factor were defined and assessed. Functioning Assessment Short Test ( FAST) was used to assess disability. Results The follow-up period was 3.00 ± 1.51 years. Weeks with subsyndromal depressive symptoms (β = 0.133, t = 2.556, P = 0.014), weeks with mild manic symptoms (β = 1.441, t = 3.10, P = 0.003), and the Mood Instability Factor (β = 0.105, t = 3.593, P = 0.001) contributed to approximately 46% of the FAST total score variance. Conclusion New methodologies including subsyndromal symptoms and mood instability parameters might contribute to understand the worse long-term functional outcome that affects a considerable percentage of BD patients even after episode remission. Concerns about therapeutic approaches are discussed. [ABSTRACT FROM AUTHOR]

Objective: To summarize the conceptual and operational definitions of treatment-resistant bipolar depression and to review the evidence-based therapeutic options. Method: Structured searches of PubMed, Index Medicus, Excerpta Medica and Psyclit conducted in December 2008. Results: Criteria for treatment resistance in bipolar depression are commonly based on concepts stemming from treatment resistance as defined for unipolar depression, an approach that proved to be inadequate. In fact, the addition of an ad hoc criterion based on lithium and other mood stabilizer unresponsiveness after reaching adequate plasma levels appears to be a patch that attempts to take into account the uniqueness of bipolar depression but fails to become operational. Recent data from randomized clinical trials of new anticonvulsants and second-generation antipsychotics should lead to the development of a modern definition of treatment-resistant bipolar depression, and specific therapeutic algorithms. Conclusion: We suggest a redefinition of resistant bipolar I and II depression. We propose different degrees of severity within bipolar depression in a stepwise manner. [ABSTRACT FROM AUTHOR]

Objective: There is a dearth of research focusing on factors associated with suicide attempts. High rates of atypical depression have been reported in studies including unipolar and bipolar II patients. In this study, the association between suicide attempt and atypical depression, in addition to other major risk factors, was evaluated in 390 bipolar I and II out-patients. Method: Variables were defined according to DSM-IV criteria, and assessed with a Structured Interview for DSM-IV (axis I and II). History of suicide attempt was obtained through interviews with patients and relatives. Attempters and non-attempters were compared using univariate and multivariate analysis. Results: Attempters showed significantly higher rates of atypical depression, family history of completed suicide, depression at index episode and cluster B personality disorder. Conclusion: Our results highlight the relevance of atypical depression in bipolar disorder. A more accurate identification of potential attempters may contribute to the development of effective preventive treatment strategies. [ABSTRACT FROM AUTHOR]

Background: The long-term efficacy of psychological interventions for bipolar disorders has not been tested.Aims: This study assessed the efficacy of group psychoeducation to prevent recurrences and to reduce time spent ill for people with bipolar disorders.Method: A randomised controlled trial with masked outcome assessment comparing group psychoeducation and non-structured group intervention during 5-year follow-up. One hundred and twenty people with bipolar disorders were included in the study and 99 completed 5-year follow-up. Time to any recurrence, number of recurrences, total number of days spent ill, frequency and length of hospitalisations were the main outcome measures.Results: At the 5-year follow-up, time to any recurrence was longer for the psychoeducation group (log rank=9.953, P<0.002). The psychoeducation group had fewer recurrences (3.86 v. 8.37, F=23.6, P<0.0001) of any type and they spent less time acutely ill (154 v. 586 days, F=31.66, P=0.0001). The median number of days of hospitalisation per hospitalised participant was also lower for the psychoeducation group (45 v. 30, F=4.26, P=0.047).Conclusions: Six-month group psychoeducation has long-lasting prophylactic effects in individuals with bipolar disorders. Group psychoeducation is the first psychological intervention showing such a long-term maintained efficacy in people with bipolar disorders. [ABSTRACT FROM AUTHOR]

Abstract: Background: To determine the clinical and therapeutic relevance of longitudinally predominant polarity for bipolar disorders long-term outcome. Method: Two hundred twenty-four patients (n =224) were enrolled for the study in the Bipolar Disorders Program of Barcelona, which provides integrated care for difficult-to-treat bipolar patients derived from all over Spain, but also provides clinical care to all bipolar patients coming from a specific catchment area (Eixample Esquerre) in Barcelona. Data collection regarding predominant polarity started on October 1994 and lasted for the following ten years. Patients were divided according to the predominance of depressive or manic/hypomanic episodes. The two groups were compared regarding clinical and sociodemographic variables. Results: 135 patients (60.3%) were classified as Depressive Polarity, whilst 89 (39.7%) were considered as Manic Polarity. Manic Polarity was more prevalent amongst bipolar I patients than bipolar II. Depressive Polarity was strongly associated with depressive onset of bipolar disorder. Lifetime history of attempted suicide was strongly associated with Depressive Polarity, who also had a higher mean number of suicide attempts. As for therapeutic issues, acute and maintenance use of atypical antipsychotics and conventional neuroleptics were more common amongst Manic Polarity whilst antidepressants and lamotrigine use was highly prevalent amongst Depressive Polarity. Conclusions: Prevention of depression is crucial for the maintenance treatment of bipolar II patients, whilst prevention of mania and depression would be equally important in the case of bipolar I patients. Predominant polarity is a valid prognostic parameter with therapeutic implications. [Copyright &y& Elsevier]

Vieta E, Colom F. Psychological interventions in bipolar disorder: From wishful thinking to an evidence-based approach Acta Psychiatr Scand 2004: 110 (Suppl. 422): 34–38. © Blackwell Munksgaard 2004. We aimed to examine the historical and current relevance of psychosocial approaches to bipolar illness by conducting a systematic review of prospective studies assessing the effectiveness of psychological interventions for bipolar disorder. A systematic literature search was conducted using EMBASE, MedLine and PsychLIT and reference sections of papers were scrutinized for further relevant reports. Only four trials met the criteria of a prospective study and achieved the necessary methodological standards. The studies showed benefits for patients in terms of relapse prevention and the reduction of hospitalization rates. Psychoeducation (delivered in groups or as part of a family intervention) and cognitive behavioural therapy were also found to be effective prophylactic treatments for bipolar disorder in medicated patients. Other interventions do not appear to be supported by sufficient evidence. Psychological approaches, and particularly psychoeducation and cognitive-behavioural therapies, are evidence-based prophylactic therapies for bipolar patients receiving pharmacotherapy. They should be used as adjuncts to medication where possible in the prevention of bipolar disorder. [ABSTRACT FROM AUTHOR]

Objective: Cognitive impairment in bipolar disorder may be a stable characteristic of the illness, although discrepancies have emerged with regard to what dysfunctions remain during remission periods. The aim of this study was to ascertain whether euthymic bipolar patients would show impairment in verbal learning and memory and in executive functions compared with healthy controls. Secondly, to establish if there was a relationship between clinical data and neuropsychological performance. Methods: Forty euthymic bipolar patients were compared with 30 healthy controls through a battery of neuropsychological tests assessing estimated premorbid IQ, attention, verbal learning and memory, and frontal executive functioning. The effect of subsyndromal symptomatology was controlled. Results: Remitted bipolar patients performed worse than controls in several measures of memory and executive function, after controlling for the effect of subclinical symptomatology, age and premorbid IQ. Verbal memory impairment was related to global assessment of function scores, as well as to a longer duration of illness, a higher number of manic episodes, and prior psychotic symptoms. Conclusions: Results provide evidence of neuropsychological impairment in euthymic bipolar patients, after controlling for the effect of subsyndromal depressive symptoms, suggesting verbal memory and executive dysfunctions. Cognitive impairment seems to be related to a worse clinical course and poor functional outcome. [ABSTRACT FROM AUTHOR]

Abstract: Background: Identifying and modifying burdensome aspects might reduce the level of burden and their negative effects both on caregivers and patients'' outcome. Most studies evaluate acutely ill patients, whereas the most relevant problems may be related to subthreshold symptoms and long-term outcome. The aims of the present study were to assess caregiver''s subjective burden, to analyse which were the most burdensome aspects for caregivers and to study which variables could explain the caregiver''s subjective burden. Methods: Caregivers of 86 euthymic bipolar patients completed the subjective burden subscale from an adapted version of the Social Behaviour Assessment Schedule. Results: Caregivers showed a moderate level of subjective burden. The highest levels of distress were reported regarding the patient''s behaviour; the most distressing behaviours were hyperactivity, irritability, sadness and withdrawal. Regarding the patient''s role performance, the most worrying aspects were those associated with the patient''s work or study and social relationships. Regarding adverse effects on others, caregivers were especially distressed by the way the illness had affected their emotional health and their life in general. Poorer social and occupational functioning, an episode in the last 2years, history of rapid cycling and the caregiver being responsible for medication intake explained a quarter of the variance of the caregiver''s subjective burden. Limitations: This was a cross-sectional study focused only on primary caregivers, there was no control group of non-bipolar patients. Conclusions: This study provides relevant data concerning the burden of caregivers of stable bipolar patients, pointing at potential targets for psychosocial interventions. [Copyright &y& Elsevier]

Abstract: Schizoaffective disorder (SAD) is a chronic, severe and disabling illness consisting on the concurrent presentation of symptoms of schizophrenia and affective disorders (depression and/or mania). Evidence for the treatment of SAD mostly derives from studies based on mixed samples (i.e. schizophrenic and schizoaffective patients) or on extrapolations from studies on schizophrenia or bipolar disorder. The objective of the present review is to systematically consider and summarize the best evidence-based approaches to the treatment of SAD and extensively point out the gap between treatment research and clinical practice of this disorder. The complex problem of controlling the pleomorphic presentation of SAD''s syndromic construct is reflected in the lack of evidence on key topics, including: diagnostic consistency, pharmacological approaches (mood stabilizers, antidepressants, both in acute and maintenance treatment as well as their possible combination), and the adjunctive role of psychosocial and biophysical interventions. Finally, treatment strategies for SAD, both unipolar and bipolar type, are proposed. [Copyright &y& Elsevier]

Abstract: Introduction: We hypothesized that predominant episode-polarity would predict response to treatment of depressive episodes in bipolar I disorder (BPD) patients with treatment in a placebo-controlled trial, in the sense that patients with manic predominant polarity (PM) would respond better than patients with depressive predominant polarity (PD). Method: This post-hoc analysis of a published trial examined outcomes of 788 depressed (MADRS score ≥20) adult BPD patients with baseline and follow-up assessments, according to their predominant polarity based on previous recurrences of mania-hypomania vs. depression in ≥2:1 excess. Patients (total=833) were randomized to an 8-week trial of treatment with placebo (n =377), olanzapine (5–20 mg/day; n =370), or olanzapine/fluoxetine combination (OFC; 6/25, 6/50, or 12/50 mg/day; n =86). Treatment response was based on improvement in Clinical Global Impression of depression severity (CGI-D). We analyzed for associations of this outcome with predominant lifetime illness-polarity, based on retrospective SCID-based assessment of individual clinical history. Results: Predominant polarity could be demonstrated in 367/788 patients (46.6%), showing a 2.7-fold excess of predominant depressive over manic past-illnesses (34.1%/12.4%), with similar distribution by sex and among treatment-arms. Moreover, based on least-square change in CGI-D severity (based on a mixed model of repeated measures [MMRM]), predominant polarity has different impact in the treatment outcome for each gender. Men with predominantly manic polarity had statistically significant better improvement than men with predominantly depressive polarity. Such difference was not observed in the female population. Other outcome measures yielded similar conclusions. Conclusions: Predominant previous depressive>manic episodes selectively yielded poorer responses of BPD to treatment for acute BP depression, particularly in men. [Copyright &y& Elsevier]

Abstract: Background: It has been reported that patients with bipolar disorder (BD) remain about 10 years symptomatic before the correct diagnosis is made. This fact is particularly important for patients with predominantly depressed polarity who tend to be diagnosed as suffering from unipolar major depressive disorder and treated with antidepressants. The present study was carried out to assess clinical differences between predominantly manic and depressed BD patients with a special focus on the time that patients remained undiagnosed. Methods: Clinical and socio-demographic characteristics were obtained from a sample of 149 euthymic bipolar outpatients. Patients were divided into depressive or manic predominance of polarity. Clinical features, number of years undiagnosed (NYU) and occupational functioning were assessed in the two groups. Results: Forty-five patients were classified as a “Depressive Polarity” whilst forty-seven were considered as “Manic Polarity”. Depressive Polarity was associated with a longer delay to be diagnosed (F=14.43, df=89, p=0.001). The predominantly depressive patients tended to present a depressive onset of illness, earlier age of onset, longer duration of illness and higher number of suicide attempts than manic polarity patients. Conclusion: There was a marked clinical difference between predominantly manic and depressive bipolar patients. Predominantly depressive polarity is associated with a longer delay in receiving a correct diagnosis and effective treatment which has an important impact on the management of the illness. [Copyright &y& Elsevier]