Francesc Colom

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

OBJECTIVE The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. METHOD An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. RESULTS There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. CONCLUSIONS Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Validity and reliability of the Functioning Assessment Short Test (FAST) in bipolar disorder

BackgroundNumerous studies have documented high rates of functional impairment among bipolar disorder (BD) patients, even during phases of remission. However, the majority of the available instruments used to assess functioning have focused on global measures of functional recovery rather than specific domains of psychosocial functioning. In this context, the Functioning Assessment Short Test (FAST) is a brief instrument designed to assess the main functioning problems experienced by psychiatric patients, particularly bipolar patients. It comprises 24 items that assess impairment or disability in six specific areas of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships and leisure time.Methods101 patients with DSM-IV TR bipolar disorder and 61 healthy controls were assessed in the Bipolar Disorder Program, Hospital Clinic of Barcelona. The psychometric properties of FAST (feasibility, internal consistency, concurrent validity, discriminant validity (euthymic vs acute patients), factorial analyses, and test-retest reliability) were analysed.ResultsThe internal consistency obtained was very high with a Cronbachs alpha of 0.909. A highly significant negative correlation with GAF was obtained (r = -0.903; p < 0.001) pointing to a reasonable degree of concurrent validity. Test-retest reliability analysis showed a strong correlation between the two measures carried out one week apart (ICC = 0.98; p < 0.001). The total FAST scores were lower in euthymic (18.55 ± 13.19; F = 35.43; p < 0.001) patients, as compared with manic (40.44 ± 9.15) and depressive patients (43.21 ± 13.34).ConclusionThe FAST showed strong psychometrics properties and was able to detect differences between euthymic and acute BD patients. In addition, it is a short (6 minutes) simple interview-administered instrument, which is easy to apply and requires only a short period of time for its application.

The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders.

OBJECTIVES Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. METHODS Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. RESULTS Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. CONCLUSION Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature.

Cognitive dysfunctions in bipolar disorder: evidence of neuropsychological disturbances.

Although cognitive dysfunctions in psychosis have classically been associated with schizophrenia, there is clinical evidence that some bipolar patients show cognitive disturbances either during acute phases or in remission periods. The authors critically review the data on cognitive impairment in bipolar disorder. The main computerized databases (Medline, Psychological Abstracts, Current Contents) have been consulted crossing the terms ‘cognitive deficits’, ‘neuropsychology’, ‘intellectual impairment’, ‘mania’, ‘depression’ and ‘bipolar disorder’. Changes in the fluency of thought and speech, learning and memory impairment, and disturbances in associational patterns and attentional processes are as fundamental to depression and mania as are changes in mood and behavior. Moreover, a significant number of bipolar patients show persistent cognitive deficits during remission from affective symptoms. However, there are several methodological pitfalls in most studies such as unclear remission criteria, diagnostic heterogeneity, small sample sizes, absence of longitudinal assessment, practice effect and poor control of the influence of pharmacological treatment. Most studies point at the presence of diffuse cognitive dysfunction during the acute phases of bipolar illness. Most of these deficits seem to remit during periods of euthymia, but some of them may persist in approximately one third of bipolar patients. Methodological limitations warrant further research in order to clear up the relationship between neuropsychological functioning and clinical, demographic and treatment variables in bipolar disorder.

A meta-analysis of relapse rates with adjunctive psychological therapies compared to usual psychiatric treatment for bipolar disorders

This paper reviews published randomized controlled treatment trials of psychological therapies added to standard psychiatric treatment vs. standard psychiatric treatment alone to explore whether adjunctive psychotherapy reduces relapse rates in individuals with bipolar disorders. Core components and characteristics of effective psychological therapies were identified from descriptions in the literature. Relapse rates were calculated for selected treatment trials and then pooled odds ratios were calculated using meta-analytical techniques that explored differences in outcome according to therapy model, type of relapse experienced and whether the subject was euthymic at entry to the study. The different therapy models have a number of similar components. A meta-analysis of eight recent studies demonstrates a significant reduction in relapse rates (of about 40%) compared to standard treatment alone. Therapies were most effective in preventing relapses in subjects who were euthymic when recruited into the treatment trial, and may be less effective in those with a high number of previous episodes (previous relapses >12). Efficacy studies demonstrate that adjunctive psychological treatments for individuals with bipolar disorders reduce relapse risk, but there is a need to undertake pragmatic effectiveness studies to determine which individuals with bipolar disorders are most likely to benefit from such interventions.

Executive Function in Patients with Remitted Bipolar Disorder and Schizophrenia and Its Relationship with Functional Outcome

Background: Recent studies have reported that differences in cognitive performance between schizophrenic and bipolar patients seem to be smaller than expected. Patients with schizophrenia have consistently shown frontal executive dysfunctions, but studies regarding executive abilities in bipolar patients are scarce and discrepant. As executive function has been associated with psychosocial functioning in schizophrenia, we wanted to investigate if such a relationship is also present in bipolar disorder and the differences between the two groups. Methods: Executive function was assessed in 49 euthymic (at least 6 months in remission, Hamilton Depression Rating Scale ≤8 and Young Mania Rating Scale ≤6) bipolar and in 49 schizophrenic, residual-type (with at least 1 year without acute exacerbation and predominant negative symptomatology) patients, by the Wisconsin Card Sorting Test (WCST), FAS Test (COWAT) and Trail Making Test. Baseline clinical and psychosocial variables were controlled and psychopathology evaluated by means of the Positive and Negative Syndrome Scale (PANSS). Results: The two groups showed a similar pattern of cognitive deficits in tests of executive function, except for the number of categories achieved in the WCST, which was significantly lower in the schizophrenic group (F = 7.26; p = 0.009). Functional outcome was predicted by the negative syndrome (PANSSN) and perseverative errors (WCST) in schizophrenic patients, and general psychopathology (PANSSG) was the best predictor of functional outcome in the bipolar group. Conclusion: Executive function was a good predictor of functional outcome in the schizophrenic group, whereas clinical variables were more predictive of the bipolar one. Patterns of cognitive disturbances in tasks of executive function are similar in both groups but quantitatively more marked in schizophrenia.

Clinical implications of a staging model for bipolar disorders

A model of staging in the field of bipolar disorder (BD) should offer a means for clinicians to predict response to treatment and more general outcome measures, such as the level of functioning and autonomy. The present staging model emphasizes the assessment of patients in the interepisodic period and includes: latent phase: individuals who present mood and anxiety symptoms and increased risk for developing threshold BD; Stage I – patients with BD who present well established periods of euthymia and absence of overt psychiatric morbidity between episodes; Stage II – patients who present rapid cycling or current axis I or II comorbidities; Stage III – patients who present a clinically relevant pattern of cognitive and functioning deterioration, as well as altered biomarkers; and Stage IV – patients who are unable to live autonomously and present altered brain scans and biomarkers. Such a model implies a longitudinal appraisal of clinical variables, as well as assessment of neurocognition and biomarkers in the interepisodic period. Staging facilitates understanding of the mechanisms underlying progression of the disorder, assists in treatment planning and prognosis and, finally, underscores the imperative for early intervention.

Efficacy of Functional Remediation in Bipolar Disorder: A Multicenter Randomized Controlled Study

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukeys post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Impact of caregiver group psychoeducation on the course and outcome of bipolar patients in remission: a randomized controlled trial

OBJECTIVE Although there are some randomized controlled trials that highlight the positive role of family-focused treatment added to pharmacotherapy in bipolar disorder, no trials using contemporary methodologies have analyzed the specific effect of working with caregiver-only groups. The aim of this study was to assess the efficacy of a psychoeducational group intervention focused on caregivers of euthymic bipolar patients. METHOD A total of 113 medicated euthymic bipolar outpatients who lived with their caregivers were randomized into an experimental and a control group. Caregivers in the experimental group received twelve 90-min group psychoeducation sessions focused on knowledge of bipolar disorder and training in coping skills. The patients did not attend the groups. Caregivers assigned to the control group did not receive any specific intervention. Patients were assessed monthly during both the intervention and the 12 months of follow-up. The primary outcome was time to any mood recurrence. RESULTS Psychoeducation group intervention focused on the caregivers of bipolar patients carried a reduction of the percentage of patients with any mood recurrence (chi2 = 6.53; p = 0.011) and longer relapse-free intervals (log-rank chi(2) = 4.04; p = 0.044). When different types of episodes were analyzed separately, the effect was significant for both the number of patients who experienced a hypomanic/manic recurrence (chi2 = 5.65; p = 0.017) and the time to such an episode (log-rank chi2 = 5.84; p = 0.015). The differences in preventing depressive and mixed episodes were not significant. CONCLUSIONS A psychoeducation group intervention for the caregivers of bipolar patients is a useful adjunct to usual treatment for the patients in reducing the risk of recurrences, particularly mania and hypomania, in bipolar disorder.

Mental imagery as an emotional amplifier: Application to bipolar disorder

Cognitions in the form of mental images have a more powerful impact on emotion than their verbal counterparts. This review synthesizes the cognitive science of imagery and emotion with transdiagnostic clinical research, yielding novel predictions for the basis of emotional volatility in bipolar disorder. Anxiety is extremely common in patients with bipolar disorder and is associated with increased dysfunction and suicidality, yet it is poorly understood and rarely treated. Mental imagery is a neglected aspect of bipolar anxiety although in anxiety disorders such as posttraumatic stress disorder and social phobia focusing on imagery has been crucial for the development of cognitive behavior therapy (CBT). In this review we present a cognitive model of imagery and emotion applied to bipolar disorder. Within this model mental imagery amplifies emotion, drawing on Clarks cyclical panic model [(1986). A cognitive approach to panic. Behaviour Research and Therapy, 24, 461-470]. We (1) emphasise imagerys amplification of anxiety (cycle one); (2) suggest that imagery amplifies the defining (hypo-) mania of bipolar disorder (cycle two), whereby the overly positive misinterpretation of triggers leads to mood elevation (escalated by imagery), increasing associated beliefs, goals, and action likelihood (all strengthened by imagery). Imagery suggests a unifying explanation for key unexplained features of bipolar disorder: ubiquitous anxiety, mood instability and creativity. Introducing imagery has novel implications for bipolar treatment innovation--an area where CBT improvements are much-needed.