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Objectives: The Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale) is the most widely used clinical measure of lithium response phenotypes. We assess its performance against recommended psychometric and clinimetric standards. Methods: We used data from the Consortium for Lithium Genetics and a French study of lithium response phenotypes (combined sample >2500) to assess reproducibility, responsiveness, validity, and interpretability of the A scale (assessing change in illness activity), the B scale, and its items (assessing confounders of response) and the previously established response categories derived from the Total Score for the Alda scale. Results: The key findings are that the B scale is vulnerable to error measurement. For example, some items contribute little to overall performance of the Alda scale (eg, B2) and that the B scale does not reliably assess a single construct (uncertainty in response). Machine learning models indicate that it may be more useful to employ an algorithm for combining the ratings of individual B items in a sequence that clarifies the noise to signal ratio instead of using a composite score. Conclusions: This study highlights three important topics. First, empirical approaches can help determine which aspects of the performance of any scale can be improved. Second, the B scale of the Alda is best applied as a multidimensional index (identifying several independent confounders of the assessment of response). Third, an integrated science approach to precision psychiatry is vital, otherwise phenotypic misclassifications will undermine the reliability and validity of findings from genetics and biomarker studies. [ABSTRACT FROM AUTHOR]

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]

Background. Functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients. Method. A total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants' neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients. Results. Patients receiving functional remediation (n = 56) showed an improvement on delayed free recall when compared with the TAU (n = 63) and psychoeducation (n = 69) groups as shown by the group × time interaction at 6-month follow-up [F2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU (p = 0.04), but not with psychoeducation (p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome (F2,158 = 4.26, df = 2, p = 0.016). Conclusions. Functional remediation is effective at improving verbal memory and psychosocial functioning in a sample of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation. [ABSTRACT FROM AUTHOR]

Objective To study the prevalence of attention-deficit and hyperactivity disorder ( ADHD) in adult patients with bipolar disorder ( BD) and identify differential clinical features for a better diagnosis. Method A total of 163 euthymic bipolar out-patients were screened for ADHD with the ASRS.V1 and the WURS at a BD Unit. Patients with a positive screening were assessed with the CAADID, at an ADHD unit. Sociodemographic and clinical features of the groups with and without ADHD were compared. Results Lifetime prevalence of comorbid ADHD was 17.9% (10.5% for adult ADHD and 7.4% for childhood ADHD). The BD + ADHD group showed more suicidal behaviour although less severe. Comorbidity was also more common, especially regarding substance use disorders. Nevertheless, these patients did not show more affective episodes or hospitalizations and suffered more atypical but less melancholic depression. However, they required more treatment with psychotherapy and valproate. One-third of positive screenings at the ASRS were false; a severe course of BD was the hallmark of this subgroup. Conclusion Adult patients with BD and ADHD show differential clinical features, but not a more severe course of BD. Comorbidity with substance abuse is a big issue, deserving special clinical attention. Better screening tools are necessary to avoid overdiagnosis of comorbid ADHD in BD. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to analyze differences in clinical and socio-demographic characteristics between older and younger bipolar outpatients paying special attention to depressive symptoms in a large, naturalistic cohort. Method: Five hundred and ninety-three DSM-IV-TR bipolar outpatients were enrolled. Clinical characteristics were assessed according to DSM-IV-TR (SCID-I). Subjects were categorized into two groups according to current age (older OBD: age > 65 years; younger-YBD: age < 65 years). Results: About 80% of patients were younger (N = 470), and a fifth were older (N = 123), with a mean age of 77.30 years in OBD. Older patients were more likely to be married, not qualified, bipolar II, with depressive polarity of first episode, higher age at illness onset, higher age at first hospitalization. They were more likely to present with depressive predominant polarity, with lifetime history of catatonic, psychotic and melancholic features, age at illness onset >40 years, as well as suffering from more medical comorbidities when compared to younger bipolars. Conclusion: The clinical presentation of bipolar disorder in late life would be defined more frequently by melancholic depressive features and a predominantly depressive polarity. These results suggest that treatment strategies for elderly bipolar patients should focus in the prevention of depressive episodes. [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 This article reviews psychological therapies in the treatment of bipolar disorder, in particular psychoeducation, and how the inclusion of four fundamental principles - patient/therapist communication, flow of information, patient involvement and a trusting relationship - can improve patient outcomes. Method The content of this article is based on the proceedings of a 1-day standalone symposium in November 2011 exploring how to establish a bipolar clinic within the context of existing services in the UK's National Health Service. Results Certain psychological interventions have emerged as beneficial add-on treatments to pharmacotherapy in bipolar disorder and are associated with greater stabilisation of symptoms, fewer relapses and longer time to relapse. Psychoeducation is a simple approach to support prevention of future episodes by delivering behavioural training to improve illness insight, early symptom identification and development of coping strategies. Empowering patients to actively participate in their treatment provides independence, counteracts the current disconnect of therapist and patient, and increases awareness and understanding of the challenges of living with and treating bipolar disorder. Conclusion Psychoeducation enables patients to understand bipolar disorder, get actively involved in therapy planning, and be aware of methods for episode prevention, therefore effectively contributing to improved treatment outcomes and patient quality of life. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of psychoeducation in the symptomatic and functional recovery, and quality of life (QoL) in a sample of patients with bipolar disorder (BD). Method: The sample comprised 55 patients with BD I and II in remission (Young Mania Rating Scale ≤6 and Hamilton Depression Rating Scale ≤7). Out-patients were matched assigned to receive 16 sessions of psychoeducation [experimental group (EG)] or 16 sessions of placebo without psychoeducation [control group (CG)]. Groups were evaluated at study baseline, midpoint, endpoint, and at 6- and 12-month follow-ups. Results: No significant differences between the groups were found for the variables evaluated (mood symptoms, functioning and QoL), except for overall clinical improvement, subjectively perceived by EG subjects. Both groups showed a trend toward improved clinical global impression and QoL (environmental). No reduction in mood symptoms or improvement in psychosocial functioning was observed. Psychosocial treatment compliance was positively correlated with global functioning, social adjustment, sociability, and global clinical impression. Conclusion: Sixteen session psychoeducation seems to be ineffective to prevent mood episodes or improve functioning in a sample of bipolar patients. [ABSTRACT FROM AUTHOR]

Murru A, Pacchiarotti I, Nivoli AMA, Bonnin CM, Patrizi B, Amann B, Vieta E, Colom F. Rates and clinical correlates of treatment non-adherence in schizoaffective bipolar patients. Objective: To analyze demographical, clinical, and therapeutic variables that may be associated with pharmacological non-adherence in a sample of schizoaffective patients, bipolar type. Method: Adherence to treatment and its clinical correlates were assessed at the end of a 10-year follow-up in 76 patients meeting DSM-IV-TR diagnosis of schizoaffective disorder, bipolar type. Adherent and poorly adherent patients were compared regarding clinical and therapeutic variables. Results: The rate of poorly adherent patients was 32/76 (41.2%) of the sample. Adherent patients were more likely to have presented an affective episode at illness onset and to have fewer purely - non-affective - psychotic episodes. Demographic or other clinical variables were not found to be associated to treatment adherence. Family history for psychiatric disorders or suicide did not correlate either, and neither did any specific pharmacological agent. Conclusion: Rates of non-adherence in schizoaffective disorder are high. Adherence seems to be associated to a more affective course of illness (affective first episode and fewer purely psychotic episodes). Patients with more prominent schizophrenia-like characteristics could be at higher risk for poor adherence and need to be closely followed and monitored. Even when properly treated, schizoaffective disorder is a disabling and severe disorder with high risk for recurrences. [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]

Of all ethical issues in clinical trial designs, only placebo use is dealt with acrimony and unwarranted, rhetoric emphasis. Many misconceptions are biased and may hamper research in the mechanisms of healing and recovery if placebo is banned from clinical trials, as some influential ethicists propose. Current treatments in psychiatry are by no means optimal and may vary in their effect across studies, rendering difficult to find the best available therapeutic method with which to compare new drugs. Because drugs possess specific mechanisms, it is not possible to compare drugs with different mechanisms as to their relevance in the pathophysiology of a given disorder. Placebo acts through non-specific mechanisms and is the ideal control for any disorder whose pathophysiology is relatively unknown and its treatment is still suboptimal. Sticking to short-term patient benefit in a trial reflects an individualistically oriented thinking in contemporary ethics and is likely to limit further research and efforts to better understand the mechanisms of disease and drug action, but also those related to general body reactance and self-healing, which are enhanced by placebo administration. Because in history ethics are swinging between two opposed views, it is possible that in the near future, the balance will move towards communitarianism, which is more likely to better serve long-term patient needs. Ethicists should also consider some other aspects of human experimentation, such as the consistency of research lines and the trend to substitute older drugs with their metabolites or enantiomers. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper was to review the association of most commonly used psychopharmacological drugs with weight gain in bipolar disorder. Method: Information was retrieved from a PubMed/Medline literature search reviewing weight gain in pharmacological studies in bipolar disorder. Results: Obesity and overweight in bipolar disorder are partly related to prescribed drugs with a strong effect of clozapine and olanzapine. Lesser but still relevant weight gain is caused by quetiapine, risperidone, lithium, valproate, gabapentin and by some antidepressants. Ziprasidone, aripiprazole, carbamazepine and lamotrigine do not seem to cause significant overweight. Conclusion: Careful monitoring of weight changes in patients before and after drug prescription should be implemented in the clinical routine and drugs which potentially cause weight gain should be avoided in overweight patients with bipolar disorder. Furthermore, eating habits and daily activities should be targeted as they may also have a significant impact on overall health and weight-related issues. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND: More than 20% of bipolar patients may present with seasonal pattern (SP). Seasonality can alter the course of bipolar disorder. However, to date, long-term follow-up studies of bipolar patients presenting with SP are scarce. We present a 10-year follow-up study comparing clinical and demographic features of bipolar patients with and without SP.MethodThree hundred and twenty-five bipolar I and II patients were followed up for at least 10 years. SP was defined according to DSM-IV criteria. Clinical variables were obtained from structured interviews with the patients and their relatives. Patients with and without SP were compared regarding clinical and sociodemographic variables and a stepwise logistic regression was performed. RESULTS: Seventy-seven patients (25.5%) were classified as presenting with SP, while 225 (74.5%) were considered as presenting with no significant seasonal variation. Twenty-three patients (7%) were excluded from the study because it was unclear whether they had seasonality or not. There were no differences between groups regarding demographic variables. Patients with SP predominantly presented with bipolar II disorder, depressive onset, and depressive predominant polarity. The greater burden of depression did not correlate with indirect indicators of severity, such as suicidality, hospitalizations or psychotic symptoms. CONCLUSIONS: Our study links the presence of SP with both bipolar II disorder and predominant depressive component. However, we could not find any difference regarding functionality or hospitalization rates. Modifications in the criteria to define SP are suggested for a better understanding of bipolar disorder. [ABSTRACT FROM AUTHOR]

ABSTRACTBackgroundMore than 20% of bipolar patients may present with seasonal pattern (SP). Seasonality can alter the course of bipolar disorder. However, to date, long-term follow-up studies of bipolar patients presenting with SP are scarce. We present a 10-year follow-up study comparing clinical and demographic features of bipolar patients with and without SP.MethodThree hundred and twenty-five bipolar I and II patients were followed up for at least 10 years. SP was defined according to DSM-IV criteria. Clinical variables were obtained from structured interviews with the patients and their relatives. Patients with and without SP were compared regarding clinical and sociodemographic variables and a stepwise logistic regression was performed.ResultsSeventy-seven patients (25?5%) were classified as presenting with SP, while 225 (74?5%) were considered as presenting with no significant seasonal variation. Twenty-three patients (7%) were excluded from the study because it was unclear whether they had seasonality or not. There were no differences between groups regarding demographic variables. Patients with SP predominantly presented with bipolar II disorder, depressive onset, and depressive predominant polarity. The greater burden of depression did not correlate with indirect indicators of severity, such as suicidality, hospitalizations or psychotic symptoms.ConclusionsOur study links the presence of SP with both bipolar II disorder and predominant depressive component. However, we could not find any difference regarding functionality or hospitalization rates. Modifications in the criteria to define SP are suggested for a better understanding of bipolar disorder. [ABSTRACT FROM AUTHOR]

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Objectives: To review the definition of non-adherence, its clinical and economic impact and identify its role and impact in clinical practice. Methods: A selective review of the literature as conducted of articles and literature known to the authors. Results: There is a paucity of studies examining specifically treatment non-adherence and its consequences in bipolar disorder. Few studies have systematically examined ways in which treatment adherence can impact treatment and improve outcome. Conclusion: Non-adherence is common in the management of bipolar disorder. Clinicians and Researchers alike need to remain alert and be aware of issues related to non-adherence – in particular suicide. Like other course-modifiers non-adherence has to be considered, sought and addressed, and this is perhaps best done by including psychoeducation in routine clinical care. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect on the serum lithium levels of a psychoeducational program in patients with bipolar disorder. Method: This is a subanalysis of data obtained from a larger study on the efficacy of group psychoeducation in the prophylaxis of recurrences in bipolar disorders. Data on plasma lithium levels were obtained at five time points: baseline, 6, 12, 18 and 24 months. Serum lithium levels of patients who had received psychoeduction (psychoeducated) (N = 49) and non-psychoeducated patients (N = 44) were compared. Results: Mean serum lithium levels were significantly higher and more stable for the psychoeducation group. Conclusions: As changes in serum lithium level may be a powerful predictor of recurrence for bipolar patients, the addition of group psychoeducation to standard pharmacological treatment may be beneficial to optimize serum lithium levels and, thereby improve outcome. [ABSTRACT FROM AUTHOR]

Objective: 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. Method: 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. Results: 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. Conclusion: 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]

The authors reflect on the polarity in categorical diagnosis of bipolar disorders with its lack of biologic underpinning and alleged overinclusiveness. They state the review on the changes of diagnostic and statistical manual (DSM) IV of mental disorders in any specific subgroup of individuals. Also examined is the testing of different proposals for refining or redefining diagnosis of bipolar disorders such as Barcelona proposal and Harvard index.

Colom F. The mechanism of action of psychotherapy. Bipolar Disord 2002: 4(Suppl. 1): 102. © Blackwell Munksgaard, 2002. [ABSTRACT FROM AUTHOR]