M. Mur

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.

Persistence of cognitive impairment and its negative impact on psychosocial functioning in lithium-treated, euthymic bipolar patients: a 6-year follow-up study

BACKGROUND Previous cross-sectional studies report that cognitive impairment is associated with poor psychosocial functioning in euthymic bipolar patients. There is a lack of long-term studies to determine the course of cognitive impairment and its impact on functional outcome. Method A total of 54 subjects were assessed at baseline and 6 years later; 28 had DSM-IV TR bipolar I or II disorder (recruited, at baseline, from a Lithium Clinic Program) and 26 were healthy matched controls. They were all assessed with a cognitive battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory) twice over a 6-year follow-up period. All patients were euthymic (Hamilton Rating Scale for Depression score lower than 8 and Young mania rating scale score lower than 6) for at least 3 months before both evaluations. At the end of follow-up, psychosocial functioning was also evaluated by means of the Functioning Assessment Short Test. RESULTS Repeated-measures multivariate analysis of covariance showed that there were main effects of group in the executive domain, in the inhibition domain, in the processing speed domain, and in the verbal memory domain (p<0.04). Among the clinical factors, only longer illness duration was significantly related to slow processing (p=0.01), whereas strong relationships were observed between impoverished cognition along time and poorer psychosocial functioning (p<0.05). CONCLUSIONS Executive functioning, inhibition, processing speed and verbal memory were impaired in euthymic bipolar out-patients. Although cognitive deficits remained stable on average throughout the follow-up, they had enduring negative effects on psychosocial adaptation of patients.

Influence of Clinical and Neuropsychological Variables on the Psychosocial and Occupational Outcome of Remitted Bipolar Patients

Objective: To measure the impact of the clinical course, the residual mood symptoms and the cognitive variables on the psychosocial and occupational functioning in bipolar disorder patients in remission. Method: Forty-four euthymic DSM-IV-TR bipolar lithium-treated outpatients were assessed with a clinical interview and neuropsychological testing. To assess psychosocial function, some psychometric scales were administered (Global Assessment of Functioning Scale and World Health Organization Disability Assessment Schedule), and to evaluate occupational function, the sample was divided according to the current work status (active vs. inactive). Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory). Results: Measures of psychosocial functioning were significantly correlated with cognition (processing speed, p = 0.004), clinical severity (p = 0.03) and residual depressive symptoms (p = 0.05). Occupational functioning showed a significant effect with a cognitive domain (visual memory, p = 0.006) and a clinical variable (chronicity, p = 0.04) but not with residual mood symptoms (p > 0.2). Conclusions: Remission in bipolar disorder is not synonymous with recovering in psychosocial and occupational functioning. Cognitive deficits, clinical course and persistent subsyndromal symptoms may compromise psychosocial functioning, and neurocognitive symptoms and chronicity may particularly affect occupational functioning.

The influence of cognitive reserve on psychosocial and neuropsychological functioning in bipolar disorder.

Cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain pathology in order to minimize symptomatology. CR was initially investigated in dementia and acute brain damage, but it is being applied to other neuropsychiatric conditions. The present study aims at examining the fit of this concept to a sample of euthymic bipolar patients compared with healthy controls in order to investigate the role of CR in predicting psychosocial and cognitive outcome in bipolar disorder (BD). The sample included 101 subjects: 52 patients meeting DSM-IV-TR criteria for BD type I or II and 49 healthy controls (HC) matched for age and gender. They were all assessed with a cognitive battery tapping into executive and memory functioning. CR was obtained using three different proxies: education-occupation, leisure activities and premorbid IQ. Psychosocial functioning was evaluated by means of the Functioning Assessment Short Test (FAST). MANCOVAs were performed to determine differences in cognitive and functioning variables. Linear regression analyses were carried out to predict neuropsychological and psychosocial outcomes. Euthymic bipolar patients showed worse neuropsychological performance and psychosocial functioning than HC. The linear regression models revealed that CR was significantly predictive of FAST score (β = -0.47, p < 0.0001), Executive Index (β = 0.62, p < 0.0001) and Visual Memory Index (β = 0.44, p = 0.0004), indicating that CR is a significant predictor of cognitive and psychosocial functioning in euthymic bipolar outpatients. Therefore, CR may contribute to functional outcome in BD and may be applied in research and clinical interventions to prevent cognitive and functional impairment.

Neuropsychological profile in bipolar disorder: a preliminary study of monotherapy lithium‐treated euthymic bipolar patients evaluated at a 2‐year interval

Objective:  To investigate the cognitive impairment of a sample of euthymic bipolar patients treated with lithium monotherapy at baseline in a 2‐year longitudinal study.

Making sense of DSM-5 mania with depressive features

Objective: The assessment of the depressive component during mania has become critical for the accurate diagnosis of mixed states, which were defined very narrowly in the past classification systems before Diagnostic and Statistical Manual of Mental Disorders (5th ed.). The aim of this study was to compare socio-demographic, clinical and therapeutic characteristics, as well as clinical and functional outcomes, between manic patients with and without mixed features to validate the relevance of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) mixed specifier. Methods: This is a subanalysis of a multicentre naturalistic study MANía Aguda y COnsumo de Recursos (acute mania and health resource consumption [MANACOR]) on the burden of mania in bipolar patients from four hospitals in Catalonia (Spain). The sample consisted of 169 adult patients presenting a manic episode and systematically assessed during a 6-month period. Results: A total of 27% (n = 46/169) of manic patients showed mixed features. Total number of episodes (p = 0.027), particularly depressive and mixed, was greater in manic patients with mixed features, as well as depressive onset (p = 0.018), suicide ideation (p = 0.036), rapid cycling (p = 0.035) and personality disorders (p = 0.071). In contrast, a higher percentage of pure manic subjects were inpatients (p = 0.035), started the illness with mania (p = 0.018) and showed family history of bipolar disorder (p = 0.037), congruent psychotic symptoms (p = 0.001) and cannabis use (p = 0.006). At baseline, pure manic patients received more risperidone (p = 0.028), while mixed patients received more valproate (p = 0.049) and antidepressants (p = 0.005). No differences were found in syndromic recovery at the end of the study. However, depressive change was higher in the mixed group (p = 0.010), while manic change was higher in the pure manic group (p = 0.029). At the end of follow-up, the group with mixed features showed a significant trend towards higher psychosocial dysfunction. Conclusion: A total of 27% of manic patients showed mixed features. Groups differed regarding clinical characteristics, course of illness, psychosocial functioning, prescribed treatment and symptom progress. Depressive symptoms in mania should be routinely assessed and considered to guide treatment.

Los costos y consumo de recursos sanitarios asociados a episodios maníacos en la práctica clínica diaria: el estudio MANACOR

INTRODUCTION Bipolar disorder is a relapsing-remitting condition affecting approximately 1-2% of the population. Even when the treatments available are effective, relapses are still very frequent. Therefore, the burden and cost associated to every new episode of the disorder have relevant implications in public health. The main objective of this study was to estimate the associated health resource consumption and direct costs of manic episodes in a real world clinical setting, taking into consideration clinical variables. METHODS Bipolar I disorder patients who recently presented an acute manic episode based on DSM-IV criteria were consecutively included. Sociodemographic variables were retrospectively collected and during the 6 following months clinical variables were prospectively assessed (YMRS,HDRS-17,FAST and CGI-BP-M). The health resource consumption and associate cost were estimated based on hospitalization days, pharmacological treatment, emergency department and outpatient consultations. RESULTS One hundred sixty-nine patients patients from 4 different university hospitals in Catalonia (Spain) were included. The mean direct cost of the manic episodes was €4,771. The 77% (€3,651) was attributable to hospitalization costs while 14% (€684) was related to pharmacological treatment, 8% (€386) to outpatient visits and only 1% (€50) to emergency room visits. The hospitalization days were the main cost driver. An initial FAST score>41 significantly predicted a higher direct cost. CONCLUSIONS Our results show the high cost and burden associated with BD and the need to design more cost-efficient strategies in the prevention and management of manic relapses in order to avoid hospital admissions. Poor baseline functioning predicted high costs, indicating the importance of functional assessment in bipolar disorder.

Asenapine prescribing patterns in the treatment of manic in- and outpatients: Results from the MANACOR study.

BACKGROUND Asenapine is the most recent compound that has been FDA- and EMA-approved for treatment of mania. Its efficacy and safety have been assessed in placebo-controlled trials, but little is known about its performance in routine clinical conditions. In this study, we compared features of patients treated with adjunctive asenapine or other adjunctive antipsychotics and the costs of the treatment. METHODS A combined prospective and retrospective data collection and analysis was conducted from January 2011 to December 2013 following a clinical interview and assessment of manic and depressive symptoms (YMRS, HDRS-17), clinical state (CGI-BP-M), psychosocial functioning (FAST), sexual dysfunction (PRSexDQ) and health resource costs associated with treatment with adjunctive asenapine versus other adjunctive antipsychotics. RESULTS Hundred and fifty-two patients from different university hospitals were included. Fifty-three patients received adjunctive asenapine and 99 received other adjunctive antipsychotics concomitantly to mood stabilizers. Considering inpatients, those treated with adjunctive asenapine presented a significantly less severe manic episode (P=0.001), less psychotic symptoms (P=0.030) and more comorbid personality disorder (P=0.002). Regarding outpatients, those treated with adjunctive asenapine showed significantly less severe manic episode (P=0.046), more previous mixed episodes (P=0.013) and more sexual dysfunction at baseline (P=0.036). No significant differences were found in mean total costs per day. CONCLUSION Clinicians tended to use adjunctive asenapine in patients with less severe manic symptoms but more complex clinical profile, including more mixed episodes in the past, concomitant personality disorder, and sexual problems. Treatment with adjunctive asenapine was not associated with higher costs when compared to other options.

Predictors of functional outcome after a manic episode

BACKGROUND The identification of functional outcome predictors after acute episodes of bipolar disorders (BD) may allow designing appropriate treatment aiming at restoring psychosocial functioning. Our objective was to identify the best functional outcome predictors at a 6-month follow-up after an index manic episode. METHODS We conducted a naturalistic trial (MANACOR) focusing on the global burden of BD, with special emphasis on manic episode-associated costs. We observed patients with BD seen in services of four hospitals in Catalonia (Spain).The total sample included 169 patients with chronic DSM-IV-TR BD I suffering from an acute manic episode who were followed-up for 6 months. In this subanalysis we report the results of a stepwise multiple regression conducted by entering in the model those clinical and sociodemographic variables that were identified through preliminary bivariate Pearson correlations and using total scores on the Functioning Assessment Short Test (FAST) at the 6-month follow-up as the dependent variable. RESULTS Number of previous depressive episodes (Beta=3.25; t=3.23; p=0.002), presence of psychotic symptoms during the manic index episode (Beta=7.007; t=2.2; p=0.031) and the Body Mass Index (BMI) at baseline (Beta=0.62; t=2.09; p=0.041) were best predictors of functional outcome after a manic episode. LIMITATIONS The main limitations of this study include the retrospective assessment of the episodes, which can be a source of bias, and the 6-month follow-up might have been too short for assessing the course of a chronic illness. CONCLUSIONS Psychotic symptoms at index episode, number of past depressive episodes, and BMI predict worse outcome after 6 months follow-up after a manic episode, and may constitute the target of specific treatment strategies.

The Impact of Obesity on Cognitive Functioning in Euthymic Bipolar Patients: A Cross-Sectional and Longitudinal Study

OBJECTIVE To determine the influence of body mass index (BMI) on cognition in euthymic bipolar patients and healthy matched controls in a post hoc study of 2 cross-sectional and longitudinal exploratory studies. METHOD A total sample of 121 individuals was examined, which included 52 euthymic bipolar disorder I or II patients (DSM-IV-TR criteria) and 69 healthy controls matched by age and gender, categorized in 2 subgroups in terms of body mass index (BMI-factor): normal weight (BMI: 18.5-24.9 kg/m²) versus overweight-obesity (overweight, BMI: 25.0-29.9 kg/m²; and obese, BMI ≥ 30 kg/m²). Demographic, clinical, cognitive, and psychosocial functioning data were collected from 2003 until 2011. Cognitive domains studied were executive function, attention, processing speed, verbal memory, and visual memory. Fifty-four subjects (28 bipolar and 26 healthy controls) were reevaluated after 6 years of follow-up. RESULTS Obesity and bipolar disorder showed a significant effect on cognition in cross-sectional and long-term MANOVA analyses (F₇,₁₁₁ = 2.54, P = .018 and F₁₉,₂₃ = 2.25, P = .033, respectively). In the cross-sectional linear regression model, global cognitive functioning was predicted by the interaction of BMI-factor by group (β = -0.44, SE = 0.14, P = .002), current age (β = -0.44, P < .0001), and premorbid IQ (β = 0.28, P = .0002), which explained 56% of variance (F₅,₁₁₅ = 29.6, P < .0001). Change in cognitive functioning over time was predicted by the interaction of BMI-factor by group (β = -0.8, SE = 0.33, P = .022) and cognition at baseline (β = -0.46, SE = 0.15, P = .004), which explained 27.65% of variance (F₆,₄₀ = 2.548, P = .0349). Generalized estimating equations analysis showed that interaction of group by BMI (Wald χ²₁ = 5.37, P = .02), age (Wald χ²₁ = 22.08, P < .0001), and premorbid IQ (Wald χ²₁ = 25.65, P < .0001) were the significant predictors. CONCLUSIONS Obesity was significantly associated with cognitive impairment in euthymic bipolar patients, and it also appeared to affect cognition in the long term.