J.M. Goikolea

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.

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.

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.

POLARITY INDEX OF PHARMACOLOGICAL AGENTS USED FOR MAINTENANCE TREATMENT OF BIPOLAR DISORDER

Over one half of bipolar patients have been reported to be more prone to either depressive or manic relapses. This study aimed to define profiles of drugs used for maintenance treatment of bipolar disorder (BD) by the means of Polarity Index. Polarity Index is a new metric indicating the relative antimanic versus antidepressive preventive efficacy of drugs. Polarity Index was retrieved by calculating Number Needed to Treat (NNT) for prevention of depression and NNT for prevention of mania ratio, as emerging from the results of randomized placebo-controlled trials. Included trials were randomized and double blind, with a minimal duration of 24 weeks, assessing effectiveness of a mood stabilizer or antipsychotic drug alone or in combination with a mood stabilizing agent versus a placebo comparator in BD maintenance treatment. Polarity Index value above 1.0 indicates a relative greater antimanic prophylactic efficacy, number below 1.0 a relative greater antidepressive efficacy. The polarity index for the drugs used in maintenance therapy for bipolar disorder was 12.09 for risperidone, 4.38 for aripiprazole, 3.91 for ziprasidone, 2.98 for olanzapine, 1.39 for lithium, 1.14 for quetiapine, and 0.40 for lamotrigine. Polarity index of valproate and oxcarbazepine may not be reliable due to the failure of their maintenance trials. The polarity index provides a measure of how much antidepressant versus antimanic a drug is in bipolar disorder prophylaxis, and may guide the choice of maintenance therapy in bipolar patients.

Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis

Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression.

New treatment guidelines for acute bipolar mania: A critical review

A number of treatment guidelines for bipolar disorder have been published and updated in the last few years. They are aimed at providing a synthesis of the best available scientific knowledge, and their application to every-day work should be helpful to clinicians. The aim of this report is to critically review recent guidelines focusing on the treatment of manic/hypomanic and mixed episodes. Guidelines are quite heterogeneous in methodology and conclusions, but they all agree that the treatment of manic/hypomanic and mixed episodes should generally be initiated with a medication such as lithium (Li), valproate (VPA) or atypical antipsychotics (AAP), including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone as monotherapy. All guidelines agree on stopping ongoing antidepressant medication during mania. Combination therapy including Li or VPA with an AAP is suggested usually as second-line choice, sometimes as first-choice treatment for severe mania. Carbamazepine is mostly suggested as second line and not recommended in combination. Other antiepileptic drugs are not recommended for the treatment of mania, although lamotrigine may be maintained if it was prescribed previously for the prevention of depressive episodes. Main sources of discrepancies among guidelines include benefit-risk ratio issues (how much priority is given to efficacy over safety and tolerability), starting with combination versus monotherapy, and how to deal with treatments which are more experience-based than evidence-based (i.e.: electroconvulsive therapy).

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.

Psychoeducation for bipolar II disorder: An exploratory, 5-year outcome subanalysis

BACKGROUND Bipolar II represents a significant subgroup of bipolar patients. However, there is limited evidence regarding the efficacy of pharmacological and/or psychosocial therapies. METHOD Post-hoc analyses were undertaken using data on 20 (out of 120) patients who fulfilled DSM-IV criteria for BP II who had participated in a single-blind randomized controlled treatment trial (RCT) exploring the acute and long-term efficacy of group psychoeducation plus standard pharmacological treatment as compared with unstructured support groups plus standard pharmacological treatment. Eight BP II subjects had been randomized to a psychoeducation group and 12 to an unstructured support group. RESULTS Psychoeducated, as compared to control group bipolar II patients, had significantly better 5-year outcomes, with lower mean number of BP episodes (p<.02), hypomanic episodes (p<.03) and depressive episodes (p<.03), fewer days spent in mood episodes (p=.004) and higher mean levels of functioning (p<.05). CONCLUSIONS Although these findings should be treated with caution, it appears that psychoeducation plus medication can benefit bipolar II subjects. Dedicated treatment trials will need to clarify whether these therapies require modifications in duration and/or content to meet the needs of bipolar II patients.

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.