Anabel Martínez-Arán

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.

Functioning and Disability in Bipolar Disorder: An Extensive Review

Background: Bipolar disorder has generally been regarded as having a better functional outcome than schizophrenia. However, studies have suggested low functioning in bipolar patients even when they are in clinical remission. Our aim was to determine the degree of functioning and disability in bipolar patients. Secondly, we reviewed factors potentially associated with the low functioning of bipolar patients. Method: The authors conducted an extensive Medline and Pubmed search of the published literature from 1980 up to December 2007, using a variety of search terms to find relevant articles. Bibliographies of retrieved papers were further analysed for publications of interest. Articles that reported clinically significant findings on functioning and disability, and research reports were reviewed in detail. Results: From these articles, we determined that bipolar disorder is associated with significant impairment in work, family and social life, beyond the acute phases of the illness. The aspects that appear to increase the risk of low functioning and disability in bipolar patients are mainly subsyndromal symptoms and neurocognitive impairment, among others. Conclusions: Suitable pharmacological and psychological interventions may improve the level of functioning and reduce the disability in bipolar patients. Potential targets to be considered for intervention should be residual symptoms, comorbid conditions and neurocognitive deficits. Further research is required to better identify the factors that best predict functioning in bipolar patients.

Group psychoeducation for stabilised bipolar disorders: 5-year outcome of a randomised clinical trial

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.

Neurocognitive and clinical predictors of functional outcome in patients with schizophrenia and bipolar I disorder at one-year follow-up.

OBJECTIVE Many studies have reported that cognitive ability may be predictive of the functional outcome for patients with schizophrenia. However, no study has prospectively examined these aspects in schizophrenia and bipolar disorders simultaneously. The present study attempted to analyze if neurocognition and clinical status predicts the real-life functioning for patients with schizophrenia or bipolar I disorder, using a longitudinal design. METHOD Forty-seven schizophrenic and 43 bipolar I outpatients were assessed twice with a neurocognitive battery (Executive Functions, Working Memory, Verbal Memory, Visual Memory, Visual-Motor Processing, Vigilance, Vocabulary and Motor Speed tasks), clinical scales (the Positive and Negative Symptom Scale, the Hamilton Rating Scale for Depression and the Clinician Administered Rating Scale for Mania) and functional outcome measures (the Global Assessment of Functioning Scale, the WHOs Disability Assessment Scale and occupational adaptation level) over a one-year follow-up period. The cognitive performance of the patients was compared, at baseline and one year later, with that of 25 healthy subjects. RESULTS In schizophrenia patients, global functioning one year later was predicted by a composite neurocognitive score and three specific domain (verbal memory, motor speed, vocabulary). Symptoms appeared to explain less of the variance in functioning. In bipolar I patients, changes in the composite neurocognitive score over one year, deficits in the visual/motor processing domain, severity of symptoms (psychotic, excitatory and affective symptoms) and premorbid adjustment at the first assessment were the variables that better predicted functioning or disability changes over follow-up period. CONCLUSIONS Although the relationships between cognition, symptoms and functional capacity differ for schizophrenia or bipolar I patients, neuropsychological performance seems to be a principal longitudinal predictor of functioning in both disorders. Baseline neurocognition and cognitive changes over 12 months predicted changes in functioning over the same period, but only in bipolar I patients. These cognitive domains could be potential neurocognitive endophenotypes (endophenocognitypes) with regard to bipolar I disorder.

Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta‐analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view.

Clinical and neurocognitive predictors of functional outcome in bipolar euthymic patients: A long-term, follow-up study

OBJECTIVE To identify clinical and neurocognitive predictors of long-term functional outcome in patients with bipolar disorder METHODS A total of 32 subjects who met criteria for bipolar I or II disorder were recruited from the Barcelona Bipolar Disorder Program and were assessed clinically and neuropsychologically at baseline. After an average 4-year follow-up, they were interviewed with the Functioning Assessment Short Test (FAST) to assess functional outcome. Multivariate analyses were applied to identify clinical and neurocognitive predictors of functional outcome. RESULTS The main regression model for predictors of overall psychosocial functioning identified subclinical depressive symptoms (beta=0.516, t=3.51, p=0.002), and free delayed recall in a verbal memory task (beta=-0.314, t=-2.144, p=0.041), accounting for 36% of the variance. Specific predictors of occupational functioning were, again, subthreshold depression (beta=0.435, t=2.8, p=0.009) and a measure of executive function, digits backwards (beta=-0.347, t=-2.23, p=0.034). This model explained around 28% of the variance (corrected R(2)=0.28; F=6.38, gl=2, p=0.004). CONCLUSIONS Subdepressive symptomatology together with neurocognitive impairments related to verbal memory and executive functions are predictor variables of long-term functional outcome in bipolar disorder.

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.

Neurocognitive endophenotypes (Endophenocognitypes) from studies of relatives of bipolar disorder subjects: A systematic review

BACKGROUND There is growing interest to research neurocognition as a putative endophenotype for subjects with bipolar disorders (BD). The authors sought to review the available literature focused on relatives of subjects with bipolar disorder (BD-Rels) and identify suitable cognitive candidates to endophenotypes or endophenocognitypes. METHOD A systematic review was conducted in Medline, EMBASE and PsycINFO databases (1980-July 2007), supplemented with a manual search of reference lists. RESULTS Twenty-three cross-sectional papers of discordant twins (4 studies), genetic high-risk subjects (7), and different BD-Rel groups (12) met the inclusion criteria and evaluated 532 BD-Rels. Impairments on the broad domain of verbal learning/memory were found in 6 out of 11 studies (54%), as well as in 3 of 9 reports (33%) of working memory. Moreover, BD-Rels showed deficits in visual-spatial learning and memory (1/6 reports; 17%), alternating attention (1/8; 12.5%), psychomotor speed (2/10; 20%), and abstraction/cognitive flexibility, sustained attention and selective attention (2/8 each; 25%). Scores of general intelligence were lower than those of controls in 2/16 (12.5%) reports, but fell well within the average range in all studies. No study that assessed immediate memory or verbal fluency (6 each) reported impairments in BD-Rels. Finally, language, social cognition, and motor and planning skills are neglected areas of research. CONCLUSIONS Overall, the neurocognitive profile in BD-Rels is still unclear, and the evidence in support of the presence of cognitive deficits seems quite sparse. Verbal learning/memory and verbal working memory seem to be the most suitable endophenocognitypes for BD. Conversely, healthy family members would have an intact performance on immediate memory, verbal fluency, and probably on general intelligence. The possibility that BD-Rels show less cognitive efficiency compared to healthy controls also on other functions must be addressed by future studies with larger samples, comprehensive neuropsychological assessments, and, ideally, longitudinal designs.

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.