Antonio Benabarre

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.

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.

Impact of a psychoeducational family intervention on caregivers of stabilized bipolar patients.

Background: Environmental stress has an important role in the course of bipolar disorder. Some findings have shown that family beliefs about the illness could predict family burden, and this burden could influence the outcome of bipolar disorder. To the best of our knowledge, there is scant information about the effects of family intervention on the caregiver’s burden in bipolar disorder. The aim of this study was to assess the effects of psychoeducational family intervention on bipolar patients’ caregivers, including the assessment of the caregiver’s burden. Methods: 45 medicated euthymic bipolar outpatients were randomized into an experimental and a control group. Relatives of patients from the experimental group received 12 psychoeducational, 90-min sessions about bipolar disorder and coping skills. The caregivers’ knowledge of bipolar disorder, the relationship subscales of the Family Environment Scale, and the family burden subscales from an adapted version of the Social Behavior Assessment Schedule were assessed for both caregiver groups before and after the intervention. Results: Psychoeducated caregivers significantly improved their knowledge of bipolar disorder and reduced both the subjective burden and the caregiver’s belief about the link between the objective burden and the patient. No significant differences were found in the objective burden nor in the family relationship subscales. Conclusions: These preliminary results suggest that psychoeducational intervention on caregivers of bipolar patients may improve the caregiver’s knowledge of the illness, reduce their distress or subjective burden and alter their beliefs about the link between the disruptions in their life and the patient’s illness.

Do Cognitive Complaints in Euthymic Bipolar Patients Reflect Objective Cognitive Impairment

Background: In clinical practice, bipolar patients complain of cognitive deficits such as attentional or memory disturbances. The main aim of this study was to determine whether subjective cognitive complaints were associated with objective neuropsychological impairments. Method: Sixty euthymic bipolar patients were assessed through a neuropsychological battery. A structured clinical interview was used to determine subjective cognitive complaints in patients. Thirty healthy controls were also included in the study in order to compare the neuropsychological performance among groups. Results: Bipolar patients with a higher number of episodes, especially the number of mixed episodes, longer duration of the illness and the onset of the illness at an earlier age showed more subjective complaints. Furthermore, bipolar patients with subjective complaints showed lower scores in several cognitive measures related to attention, memory and executive function compared with the control group. Nevertheless, patients without complaints also performed less well than controls in some neuropsychological measures. Conclusion: Bipolar patients who were aware of cognitive deficits were more chronic, had presented more previous episodes, especially mixed type, and their illness had started at an earlier age compared with patients who did not complain about cognitive problems. Moreover, patients with good cognitive insight also had a poorer social and occupational functioning as well as a poorer neuropsychological performance. However, the bipolar group without complaints also obtained lower scores in several tests compared with healthy controls. Cognitive status of bipolar patients should be routinely assessed, regardless of the patients awareness about their cognitive deficits.

Bipolar disorder, schizoaffective disorder and schizophrenia: epidemiologic, clinical and prognostic differences.

The validity and nosologic status of schizoaffective disorder is still a controversial issue. This study was conducted to analyze the demographic, clinical and prognostic variables that determine the validity of the diagnosis of schizoaffective disorder bipolar type. We analyzed and compared 138 outpatients: 67 with type I bipolar disorder, 34 with schizoaffective disorder bipolar type and 37 with schizophrenia. They were all diagnosed following research diagnostic criteria and assessed according to the Schedule for Affective Disorders and Schizophrenia. Schizoaffective unipolar patients were excluded. The results reaffirmed that, from the standpoints of demographics, clinical features and prognosis, schizoaffective disorders bipolar type can be classified as a phenotypic form at an intermediate point between bipolar I disorder and schizophrenia. These results emphasize the importance of longitudinal follow-up in the diagnosis and assessment of psychotic syndromes. Although cross-sectional symptoms were closer to the schizophrenia spectrum, the course of the illness resembled more that of bipolar patients, resulting in an intermediate outcome.

Neuropsychological Performance in Depressed and Euthymic Bipolar Patients

Introduction: Recent studies have suggested that the presence of persistent cognitive dysfunctions in bipolar patients is not restricted to acute episodes, but they persist even during remission states. Nevertheless, there are several methodological pitfalls in most studies, such as unclear remission criteria, diagnostic heterogeneity or small sample sizes. Patients and Methods: Several domains of cognitive function were examined in 30 depressed bipolar patients [DSM-IV criteria for major depression, Hamilton Depression Scale (HDRS) ≧17] and 30 euthymic bipolar patients (at least 6 months of remission, HDRS ≤8 and Young Mania Rating Scale, YMRS ≤6). Psychosocial functioning was assessed through General Assessment of Functioning. Results: The two groups showed a similar pattern of neuropsychological performance. However, the depressed group was significantly impaired on the Controlled Oral Word Association Test, FAS (COWAT), a measure of verbal fluency, compared with the euthymic group. On the other hand, functional outcome in euthymic patients was related to verbal fluency, even after controlling for residual depressive symptoms. Conclusions: Neuropsychological performance was similar in both groups, except for verbal fluency, which was lower in the depressed group. Poor verbal fluency was related to a poor social outcome in euthymic patients. Further research including longitudinal designs aimed at evaluating changes in cognition in these patients is warranted.

Effects on weight and outcome of long-term olanzapine-topiramate combination treatment in bipolar disorder

Abstract: Olanzapine is an effective drug for the long-term treatment of bipolar disorder but is associated with burdensome weight gain. Topiramate is a novel anticonvulsant that may induce weight loss in some patients. This is the first study to address the long-term efficacy and impact on weight of the combination of olanzapine and topiramate in bipolar patients. Twenty-six Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar spectrum patients received olanzapine plus topiramate cotherapy for treatment of their manic (n = 14), hypomanic (n = 6), depressive (n = 2), and mixed (n = 1) symptoms for 1 year. Three rapid cycling patients were also enrolled despite being euthymic. Efficacy was assessed with the Young Mania Rating Scale, the Hamilton Depression Rating Scale, and the Modified Clinical Global Impressions for Bipolar Disorder. Weight, body mass index, and side effects were collected at every visit. Thirteen (50%) patients completed the 1-year follow-up. By intent-to-treat, patients significantly improved from baseline in Young Mania Rating Scale scores (P < 0.0001), Hamilton Depression Rating Scale (P < 0.05), and Modified Clinical Global Impressions for Bipolar Disorder subscales (mania P < 0.0001, depression P < 0.05, overall P < 0.0001). Most patients gained weight during the first month of combined treatment (mean weight gain 0.7 ± 0.6 kg), but at the 12-month endpoint, the mean weight change was −0.5 ± 1.1 kg. The combination of olanzapine and topiramate was efficacious for the long-term treatment of bipolar patients and appeared to carry some benefits for controlling weight gain. Given the limitations of the open, uncontrolled design, further trials are warranted with this combination.

Role of risperidone in bipolar II: an open 6-month study

BACKGROUND Since treatment approaches thought to be useful for mania are presumably suitable for hypomania as well, little systematic research has been done on the treatment of hypomanic episodes and their long-term outcome. As systematic trials have shown that the atypical antipsychotic risperidone may be effective and safe in the treatment of acute mania, we decided to conduct an open-label study of its effectiveness and tolerability in hypomania associated with bipolar II. METHODS Forty-four DSM-IV bipolar II patients with Young Mania Rating Scale (YMRS) scores above 7 were included and followed-up for 6 months. Efficacy was measured by means of the YMRS and the Clinical Global Impression for Bipolar Disorder (CGI-BD). Treatment-emergent depression was measured by the Hamilton Depression Rating Scale (HDRS-17), and the Udvalg for Kliniske Undersøgelser (UKU) subscale was used for neurological/extrapyramidal side-effects. RESULTS Thirty-four patients completed the trial. The mean dose of risperidone at endpoint was 2.8 mg/day. Last observation-carried-forward analysis showed significant reduction of YMRS scores from the first week of treatment, which continued until the endpoint (P<0.0001). At 6-month follow-up, 60% of patients were assymptomatic according to the CGI. The 32% who received risperidone in monotherapy seemed to respond equally well. Risperidone, as used in this study, appeared to be most protective against hypomanic than depressive recurrences. Nine patients (12%) had a depressive relapse during 6-month follow-up, one patient (2%) had an hypomanic relapse and another (2%) had both. No patients developed tardive dyskinesia during the duration of the study. Although most patients received risperidone in combination with standard mood-stabilizers, only three patients discontinued risperidone because of other side-effects. LIMITATIONS In the absence of a placebo arm, it is uncertain to what extent the foregoing results could be ascribed to spontaneous remission of bipolar II disorder. CONCLUSIONS Risperidone, either in combination with mood-stabilizers or alone was well-tolerated in bipolar II patients, who presented in a hypomanic state, and appeared efficacious. Further controlled research on the role of atypical antipsychotics in the treatment of less-than-manic forms of bipolar illness is warranted.

Cardiovascular risk in patients with bipolar disorder.

BACKGROUND To date, little is known about cardiovascular risk (CVR) in terms of coronary heart disease (CHD) and cardiovascular mortality risk (CMR) in patients with bipolar disorder. This study provides data on the overall risk of any fatal or non-fatal coronary heart disease (CHD) and on the cardiovascular mortality risk (CMR) within 10 years in these patients. METHODS Naturalistic, cross-sectional, multicenter study conducted in Spain. Patients were evaluated for cardiovascular risk using the Framinghan function (CHD) and the Systematic COronary Risk Evaluation (SCORE) function (CMR). RESULTS The mean age was 46.6 years and 49% were male. Forty-six percent were in remission. Ten-year CHD risk was 7.6% (males 10.2% versus females 4.7%, p<0.001) and 10-year CMR was 1.8% (males 2.2% versus females 1.3%, p 0.161). Fifty-one percent smoked and 34% was obese. Metabolic syndrome was present in 22.4% of the sample (35.6% according to AHA and NHLBI criteria). Cardiovascular risk significantly increases with age, body mass index and presence of metabolic syndrome. LIMITATIONS The cross-sectional design of the study. CONCLUSIONS Cardiovascular risk is high in patients with bipolar disorder. It is associated with age, body mass index and metabolic syndrome. Psychiatrists should be aware of this issue and carefully monitor these patients for cardiovascular risk factors, including cigarette smoking, as part of the standard of care when treating them.

Enhanced corticotropin response to corticotropin-releasing hormone as a predictor of mania in euthymic bipolar patients.

BACKGROUND Dysregulation of corticotropin (ACTH) and cortisol response after corticotropin-releasing hormone (CRH) stimulation has been reported in bipolar patients. Most findings involve the pathophysiology of the depressive phase of the illness and its prediction. However, the possible predictive value of the CRH challenge test with respect to manic episodes remains unknown. METHODS The ACTH and free cortisol response to the injection of 100 microg of synthetic human CRH and plasma cortisol-binding globulin levels were measured in 42 lithium-treated patients suffering from Research Diagnostic Criteria bipolar I disorder in remission, and 21 age- and sex-matched normal controls. A 1-year follow-up was conducted to assess any possible relationship between outcome and the hormonal response. RESULTS Bipolar patients showed higher baseline and peak ACTH concentrations than control subjects. A higher area under ACTH concentration curve after CRH stimulation predicted manic/hypomanic relapse within 6 months by multiple regression analysis. CONCLUSION Bipolar patients in remission show mild abnormalities in ACTH levels before and after CRH stimulation. CRH challenge may be a potentially good predictor of manic or hypomanic relapse in remitted bipolar patients.