The long-term efficacy of psychological interventions for bipolar disorders has not been tested. ... more The long-term efficacy of psychological interventions for bipolar disorders has not been tested. This study assessed the efficacy of group psychoeducation to prevent recurrences and to reduce time spent ill for people with bipolar disorders. 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. 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). 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.
Recent studies have suggested that the presence of persistent cognitive dysfunctions in bipolar p... more 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. Several domains of cognitive function were examined in 30 depressed bipolar patients [DSM-IV criteria for major depression, Hamilton Depression Scale (HDRS) > or =17] and 30 euthymic bipolar patients (at least 6 months of remission, HDRS < or =8 and Young Mania Rating Scale, YMRS < or =6). Psychosocial functioning was assessed through General Assessment of Functioning. 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. 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.
Clinical Practice & Epidemiology in Mental Health, 2007
Background: Numerous studies have documented high rates of functional impairment among bipolar di... more Background: Numerous 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.
Objective: To determine the effect on the serum lithium levels of a psychoeducational program in... more Objective: To determine the effect on the serum lithium levels of a psychoeducational program in patients with bipolar disorder.Method: This is a subanalysis of data obtained from a larger study on the efficacy of group psychoeducation in the prophylaxis of recurrences in bipolar disorders. Data on plasma lithium levels were obtained at five time points: baseline, 6, 12, 18 and 24 months. Serum lithium levels of patients who had received psychoeduction (psychoeducated) (N = 49) and non-psychoeducated patients (N = 44) were compared.Results: Mean serum lithium levels were significantly higher and more stable for the psychoeducation group.Conclusions: As changes in serum lithium level may be a powerful predictor of recurrence for bipolar patients, the addition of group psychoeducation to standard pharmacological treatment may be beneficial to optimize serum lithium levels and, thereby improve outcome.
In clinical practice, bipolar patients complain of cognitive deficits such as attentional or memo... more 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. 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. 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. 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.
The validity and reliability of the diagnosis of bipolar II disorder has been questioned by means... more The validity and reliability of the diagnosis of bipolar II disorder has been questioned by means of comorbidity with nonaffective disorders, including substance abuse, personality disorders, and anxiety disorders. This study examined the comorbid diagnosis of a sample of bipolar II patients, comparing patients with comorbidity and those with ''pure'' bipolar II disorder.
The goal of this study was to assess the efficacy and safety of risperidone in bipolar and schizo... more The goal of this study was to assess the efficacy and safety of risperidone in bipolar and schizoaffective disorders. 541 patients entered this open, multicenter, 6-month study. Patients were entered provided that they fulfilled DSM-IV criteria for bipolar disorder or schizoaffective disorder, bipolar type, during a manic, hypomanic, mixed, or depressive episode. Risperidone was added to any previous mood-stabilizing medication that the patients were taking. Efficacy was assessed with the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Depression (HAM-D), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impressions scale (CGI). Extrapyramidal symptoms (EPS) were assessed using the UKU Side Effect Rating Scale. 430 patients completed the study. Addition of risperidone produced highly significant improvements (p < .0001) on the YMRS and HAM-D at both 6 weeks and 6 months and on the CGI and the scales of the PANSS at both 4 weeks and 6 months. There was a significant reduction in UKU total and subscale scores at 6 months. The mean dose of risperidone was 3.9 mg/day. There was no single case of new-emergent tardive dyskinesia, and there was a very low incidence of exacerbation of mania within the first 6 weeks (2%). Adverse events were few and mostly mild. the most frequent being EPS and weight gain. This large study provides additional evidence that risperidone is effective and well tolerated when combined with mood stabilizers in the treatment of bipolar disorder and schizoaffective disorder, bipolar type. Previous concerns about exacerbation of manic symptoms were not confirmed.
Background: Since treatment approaches thought to be useful for mania are presumably suitable for... more 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.
Australian and New Zealand Journal of Psychiatry, 2005
To determine and correlate alterations in neuropsychological function and cerebral blood flow in ... more To determine and correlate alterations in neuropsychological function and cerebral blood flow in bipolar patients. Assessments included the Positive and Negative Symptom Scale, Global Assessment Functioning, Wechsler Adult Intelligence Scale (WAIS), Wisconsin Card Sorting Test (WCST), Stroop test, Trail Making Test (TMT), California Verbal Learning Test (CVLT), Wechsler Memory Scale (WMS) and phonetic verbal fluency/controlled oral word association tests. Single photon emission computed tomography (SPECT) was carried out with the administration of 99mTc-HMPAO. Forty-three outpatients out of 85 fulfilling RDC diagnostic criteria for bipolar disorder and six healthy subjects were included in the study. SPECT and neuropsychological assessments were performed in 30 patients in manic (n = 7), hypomanic (n = 8), depressed (n = 12) or euthymic (n = 3) states. All assessments were carried out before starting treatment. Several corrected correlations between neuropsychological function and cerebral blood flow (CBF) were identified: executive function (WCST) and striatal, frontal, temporal, cerebellum, parietal and cingulate CBF; memory (WMS, WAIS-Digits) and striatal, frontal, temporal and parietal CBF; attentional tasks (Stroop) and striatal, temporo-medial and parietal CBF; verbal learning (CVLT) and frontal, posterior temporal, cingulate and occipital CBF; psychomotor disturbances (TMT) and anterior temporal CBF; poorer intelligence performance scores (WAIS-Vocabulary) and cerebellum and parietal CBF. This study confirms the presence of functional disturbances in fronto-subcortical structures, the cerebellum and limbic system in bipolar patients.
Background: It has been reported that patients with bipolar disorder (BD) remain about 10 years s... more Background: It has been reported that patients with bipolar disorder (BD) remain about 10 years symptomatic before the correct diagnosis is made. This fact is particularly important for patients with predominantly depressed polarity who tend to be diagnosed as suffering from unipolar major depressive disorder and treated with antidepressants. The present study was carried out to assess clinical differences between predominantly manic and depressed BD patients with a special focus on the time that patients remained undiagnosed. Methods: Clinical and socio-demographic characteristics were obtained from a sample of 149 euthymic bipolar outpatients. Patients were divided into depressive or manic predominance of polarity. Clinical features, number of years undiagnosed (NYU) and occupational functioning were assessed in the two groups. Results: Forty-five patients were classified as a "Depressive Polarity" whilst forty-seven were considered as "Manic Polarity". Depressive Polarity was associated with a longer delay to be diagnosed (F = 14.43, df = 89, p = 0.001). The predominantly depressive patients tended to present a depressive onset of illness, earlier age of onset, longer duration of illness and higher number of suicide attempts than manic polarity patients. Conclusion: There was a marked clinical difference between predominantly manic and depressive bipolar patients. Predominantly depressive polarity is associated with a longer delay in receiving a correct diagnosis and effective treatment which has an important impact on the management of the illness.
Objective: The aim of this paper was to review the association of most commonly used psychopharm... more Objective: The aim of this paper was to review the association of most commonly used psychopharmacological drugs with weight gain in bipolar disorder.Method: Information was retrieved from a PubMed/Medline literature search reviewing weight gain in pharmacological studies in bipolar disorder.Results: Obesity and overweight in bipolar disorder are partly related to prescribed drugs with a strong effect of clozapine and olanzapine. Lesser but still relevant weight gain is caused by quetiapine, risperidone, lithium, valproate, gabapentin and by some antidepressants. Ziprasidone, aripiprazole, carbamazepine and lamotrigine do not seem to cause significant overweight.Conclusion: Careful monitoring of weight changes in patients before and after drug prescription should be implemented in the clinical routine and drugs which potentially cause weight gain should be avoided in overweight patients with bipolar disorder. Furthermore, eating habits and daily activities should be targeted as they may also have a significant impact on overall health and weight-related issues.
Background: Identifying and modifying burdensome aspects might reduce the level of burden and the... more Background: Identifying and modifying burdensome aspects might reduce the level of burden and their negative effects both on caregivers and patients' outcome. Most studies evaluate acutely ill patients, whereas the most relevant problems may be related to subthreshold symptoms and long-term outcome. The aims of the present study were to assess caregiver's subjective burden, to analyse which were the most burdensome aspects for caregivers and to study which variables could explain the caregiver's subjective burden. Methods: Caregivers of 86 euthymic bipolar patients completed the subjective burden subscale from an adapted version of the Social Behaviour Assessment Schedule. Results: Caregivers showed a moderate level of subjective burden. The highest levels of distress were reported regarding the patient's behaviour; the most distressing behaviours were hyperactivity, irritability, sadness and withdrawal. Regarding the patient's role performance, the most worrying aspects were those associated with the patient's work or study and social relationships. Regarding adverse effects on others, caregivers were especially distressed by the way the illness had affected their emotional health and their life in general. Poorer social and occupational functioning, an episode in the last 2 years, history of rapid cycling and the caregiver being responsible for medication intake explained a quarter of the variance of the caregiver's subjective burden.
Objectives: A number of studies have now shown that subjects with bipolar disorder (BD) have sig... more Objectives: A number of studies have now shown that subjects with bipolar disorder (BD) have significant psychosocial impairment during interepisode intervals. This study was carried out to assess the level of functioning as well as to identify potential predictors of functioning in a well-defined, euthymic bipolar sample.Methods: The study included 71 euthymic bipolar patients and 61 healthy controls. The Functioning Assessment Short Test (FAST) was used to assess multiple areas of functioning such as autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time. Multivariate analysis was used to determine the global and specific clinical predictors of outcome.Results: Sixty percent (n = 42) of the patients had overall functional impairment (defined as a FAST total score > 11) compared to 13.1% (n = 8) of the control group (p = 0.001). Bipolar patients showed a worse functioning in all the areas of the FAST. Only four variables—older age, depressive symptoms, number of previous mixed episodes, and number of previous hospitalizations—were associated with poor functioning, on a linear regression model, which accounted for 44% of the variance (F = 12.54, df = 58, p < 0.001).Conclusions: A substantial proportion of bipolar patients experience unfavorable functioning, suggesting that there is a significant degree of morbidity and dysfunction associated with BD, even during remission periods. Previous mixed episodes, current subclinical depressive symptoms, previous hospitalizations, and older age were identified as significant potential clinical predictors of functional impairment.
Environmental stress has an important role in the course of bipolar disorder. Some findings have ... more 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&amp;amp;#39;s burden in bipolar disorder. The aim of this study was to assess the effects of psychoeducational family intervention on bipolar patients&amp;amp;#39; caregivers, including the assessment of the caregiver&amp;amp;#39;s burden. 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&amp;amp;#39; 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. Psycho-educated caregivers significantly improved their knowledge of bipolar disorder and reduced both the subjective burden and the caregiver&amp;amp;#39;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. These preliminary results suggest that psychoeducational intervention on caregivers of bipolar patients may improve the caregiver&amp;amp;#39;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&amp;amp;#39;s illness.
Studies on individual psychotherapy indicate that some interventions may reduce the number of rec... more Studies on individual psychotherapy indicate that some interventions may reduce the number of recurrences in bipolar patients. However, there has been a lack of structured, well-designed, blinded, controlled studies demonstrating the efficacy of group psychoeducation to prevent recurrences in patients with bipolar I and II disorder. One hundred twenty bipolar I and II outpatients in remission (Young Mania Rating Scale score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6, Hamilton Depression Rating Scale-17 score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;8) for at least 6 months prior to inclusion in the study, who were receiving standard pharmacologic treatment, were included in a controlled trial. Subjects were matched for age and sex and randomized to receive, in addition to standard psychiatric care, 21 sessions of group psychoeducation or 21 sessions of nonstructured group meetings. Subjects were assessed monthly during the 21-week treatment period and throughout the 2-year follow-up. Group psychoeducation significantly reduced the number of relapsed patients and the number of recurrences per patient, and increased the time to depressive, manic, hypomanic, and mixed recurrences. The number and length of hospitalizations per patient were also lower in patients who received psychoeducation. Group psychoeducation is an efficacious intervention to prevent recurrence in pharmacologically treated patients with bipolar I and II disorder.
The long-term efficacy of psychological interventions for bipolar disorders has not been tested. ... more The long-term efficacy of psychological interventions for bipolar disorders has not been tested. This study assessed the efficacy of group psychoeducation to prevent recurrences and to reduce time spent ill for people with bipolar disorders. 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. At the 5-year follow-up, time to any recurrence was longer for the psychoeducation group (log rank=9.953, P&amp;amp;lt;0.002). The psychoeducation group had fewer recurrences (3.86 v. 8.37, F=23.6, P&amp;amp;lt;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). 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.
Recent studies have suggested that the presence of persistent cognitive dysfunctions in bipolar p... more 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. Several domains of cognitive function were examined in 30 depressed bipolar patients [DSM-IV criteria for major depression, Hamilton Depression Scale (HDRS) &amp;amp;gt; or =17] and 30 euthymic bipolar patients (at least 6 months of remission, HDRS &amp;amp;lt; or =8 and Young Mania Rating Scale, YMRS &amp;amp;lt; or =6). Psychosocial functioning was assessed through General Assessment of Functioning. 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. 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.
Clinical Practice & Epidemiology in Mental Health, 2007
Background: Numerous studies have documented high rates of functional impairment among bipolar di... more Background: Numerous 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.
Objective: To determine the effect on the serum lithium levels of a psychoeducational program in... more Objective: To determine the effect on the serum lithium levels of a psychoeducational program in patients with bipolar disorder.Method: This is a subanalysis of data obtained from a larger study on the efficacy of group psychoeducation in the prophylaxis of recurrences in bipolar disorders. Data on plasma lithium levels were obtained at five time points: baseline, 6, 12, 18 and 24 months. Serum lithium levels of patients who had received psychoeduction (psychoeducated) (N = 49) and non-psychoeducated patients (N = 44) were compared.Results: Mean serum lithium levels were significantly higher and more stable for the psychoeducation group.Conclusions: As changes in serum lithium level may be a powerful predictor of recurrence for bipolar patients, the addition of group psychoeducation to standard pharmacological treatment may be beneficial to optimize serum lithium levels and, thereby improve outcome.
In clinical practice, bipolar patients complain of cognitive deficits such as attentional or memo... more 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. 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. 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. 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.
The validity and reliability of the diagnosis of bipolar II disorder has been questioned by means... more The validity and reliability of the diagnosis of bipolar II disorder has been questioned by means of comorbidity with nonaffective disorders, including substance abuse, personality disorders, and anxiety disorders. This study examined the comorbid diagnosis of a sample of bipolar II patients, comparing patients with comorbidity and those with ''pure'' bipolar II disorder.
The goal of this study was to assess the efficacy and safety of risperidone in bipolar and schizo... more The goal of this study was to assess the efficacy and safety of risperidone in bipolar and schizoaffective disorders. 541 patients entered this open, multicenter, 6-month study. Patients were entered provided that they fulfilled DSM-IV criteria for bipolar disorder or schizoaffective disorder, bipolar type, during a manic, hypomanic, mixed, or depressive episode. Risperidone was added to any previous mood-stabilizing medication that the patients were taking. Efficacy was assessed with the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Depression (HAM-D), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impressions scale (CGI). Extrapyramidal symptoms (EPS) were assessed using the UKU Side Effect Rating Scale. 430 patients completed the study. Addition of risperidone produced highly significant improvements (p &amp;amp;amp;amp;lt; .0001) on the YMRS and HAM-D at both 6 weeks and 6 months and on the CGI and the scales of the PANSS at both 4 weeks and 6 months. There was a significant reduction in UKU total and subscale scores at 6 months. The mean dose of risperidone was 3.9 mg/day. There was no single case of new-emergent tardive dyskinesia, and there was a very low incidence of exacerbation of mania within the first 6 weeks (2%). Adverse events were few and mostly mild. the most frequent being EPS and weight gain. This large study provides additional evidence that risperidone is effective and well tolerated when combined with mood stabilizers in the treatment of bipolar disorder and schizoaffective disorder, bipolar type. Previous concerns about exacerbation of manic symptoms were not confirmed.
Background: Since treatment approaches thought to be useful for mania are presumably suitable for... more 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.
Australian and New Zealand Journal of Psychiatry, 2005
To determine and correlate alterations in neuropsychological function and cerebral blood flow in ... more To determine and correlate alterations in neuropsychological function and cerebral blood flow in bipolar patients. Assessments included the Positive and Negative Symptom Scale, Global Assessment Functioning, Wechsler Adult Intelligence Scale (WAIS), Wisconsin Card Sorting Test (WCST), Stroop test, Trail Making Test (TMT), California Verbal Learning Test (CVLT), Wechsler Memory Scale (WMS) and phonetic verbal fluency/controlled oral word association tests. Single photon emission computed tomography (SPECT) was carried out with the administration of 99mTc-HMPAO. Forty-three outpatients out of 85 fulfilling RDC diagnostic criteria for bipolar disorder and six healthy subjects were included in the study. SPECT and neuropsychological assessments were performed in 30 patients in manic (n = 7), hypomanic (n = 8), depressed (n = 12) or euthymic (n = 3) states. All assessments were carried out before starting treatment. Several corrected correlations between neuropsychological function and cerebral blood flow (CBF) were identified: executive function (WCST) and striatal, frontal, temporal, cerebellum, parietal and cingulate CBF; memory (WMS, WAIS-Digits) and striatal, frontal, temporal and parietal CBF; attentional tasks (Stroop) and striatal, temporo-medial and parietal CBF; verbal learning (CVLT) and frontal, posterior temporal, cingulate and occipital CBF; psychomotor disturbances (TMT) and anterior temporal CBF; poorer intelligence performance scores (WAIS-Vocabulary) and cerebellum and parietal CBF. This study confirms the presence of functional disturbances in fronto-subcortical structures, the cerebellum and limbic system in bipolar patients.
Background: It has been reported that patients with bipolar disorder (BD) remain about 10 years s... more Background: It has been reported that patients with bipolar disorder (BD) remain about 10 years symptomatic before the correct diagnosis is made. This fact is particularly important for patients with predominantly depressed polarity who tend to be diagnosed as suffering from unipolar major depressive disorder and treated with antidepressants. The present study was carried out to assess clinical differences between predominantly manic and depressed BD patients with a special focus on the time that patients remained undiagnosed. Methods: Clinical and socio-demographic characteristics were obtained from a sample of 149 euthymic bipolar outpatients. Patients were divided into depressive or manic predominance of polarity. Clinical features, number of years undiagnosed (NYU) and occupational functioning were assessed in the two groups. Results: Forty-five patients were classified as a "Depressive Polarity" whilst forty-seven were considered as "Manic Polarity". Depressive Polarity was associated with a longer delay to be diagnosed (F = 14.43, df = 89, p = 0.001). The predominantly depressive patients tended to present a depressive onset of illness, earlier age of onset, longer duration of illness and higher number of suicide attempts than manic polarity patients. Conclusion: There was a marked clinical difference between predominantly manic and depressive bipolar patients. Predominantly depressive polarity is associated with a longer delay in receiving a correct diagnosis and effective treatment which has an important impact on the management of the illness.
Objective: The aim of this paper was to review the association of most commonly used psychopharm... more Objective: The aim of this paper was to review the association of most commonly used psychopharmacological drugs with weight gain in bipolar disorder.Method: Information was retrieved from a PubMed/Medline literature search reviewing weight gain in pharmacological studies in bipolar disorder.Results: Obesity and overweight in bipolar disorder are partly related to prescribed drugs with a strong effect of clozapine and olanzapine. Lesser but still relevant weight gain is caused by quetiapine, risperidone, lithium, valproate, gabapentin and by some antidepressants. Ziprasidone, aripiprazole, carbamazepine and lamotrigine do not seem to cause significant overweight.Conclusion: Careful monitoring of weight changes in patients before and after drug prescription should be implemented in the clinical routine and drugs which potentially cause weight gain should be avoided in overweight patients with bipolar disorder. Furthermore, eating habits and daily activities should be targeted as they may also have a significant impact on overall health and weight-related issues.
Background: Identifying and modifying burdensome aspects might reduce the level of burden and the... more Background: Identifying and modifying burdensome aspects might reduce the level of burden and their negative effects both on caregivers and patients' outcome. Most studies evaluate acutely ill patients, whereas the most relevant problems may be related to subthreshold symptoms and long-term outcome. The aims of the present study were to assess caregiver's subjective burden, to analyse which were the most burdensome aspects for caregivers and to study which variables could explain the caregiver's subjective burden. Methods: Caregivers of 86 euthymic bipolar patients completed the subjective burden subscale from an adapted version of the Social Behaviour Assessment Schedule. Results: Caregivers showed a moderate level of subjective burden. The highest levels of distress were reported regarding the patient's behaviour; the most distressing behaviours were hyperactivity, irritability, sadness and withdrawal. Regarding the patient's role performance, the most worrying aspects were those associated with the patient's work or study and social relationships. Regarding adverse effects on others, caregivers were especially distressed by the way the illness had affected their emotional health and their life in general. Poorer social and occupational functioning, an episode in the last 2 years, history of rapid cycling and the caregiver being responsible for medication intake explained a quarter of the variance of the caregiver's subjective burden.
Objectives: A number of studies have now shown that subjects with bipolar disorder (BD) have sig... more Objectives: A number of studies have now shown that subjects with bipolar disorder (BD) have significant psychosocial impairment during interepisode intervals. This study was carried out to assess the level of functioning as well as to identify potential predictors of functioning in a well-defined, euthymic bipolar sample.Methods: The study included 71 euthymic bipolar patients and 61 healthy controls. The Functioning Assessment Short Test (FAST) was used to assess multiple areas of functioning such as autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time. Multivariate analysis was used to determine the global and specific clinical predictors of outcome.Results: Sixty percent (n = 42) of the patients had overall functional impairment (defined as a FAST total score > 11) compared to 13.1% (n = 8) of the control group (p = 0.001). Bipolar patients showed a worse functioning in all the areas of the FAST. Only four variables—older age, depressive symptoms, number of previous mixed episodes, and number of previous hospitalizations—were associated with poor functioning, on a linear regression model, which accounted for 44% of the variance (F = 12.54, df = 58, p < 0.001).Conclusions: A substantial proportion of bipolar patients experience unfavorable functioning, suggesting that there is a significant degree of morbidity and dysfunction associated with BD, even during remission periods. Previous mixed episodes, current subclinical depressive symptoms, previous hospitalizations, and older age were identified as significant potential clinical predictors of functional impairment.
Environmental stress has an important role in the course of bipolar disorder. Some findings have ... more 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&amp;amp;#39;s burden in bipolar disorder. The aim of this study was to assess the effects of psychoeducational family intervention on bipolar patients&amp;amp;#39; caregivers, including the assessment of the caregiver&amp;amp;#39;s burden. 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&amp;amp;#39; 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. Psycho-educated caregivers significantly improved their knowledge of bipolar disorder and reduced both the subjective burden and the caregiver&amp;amp;#39;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. These preliminary results suggest that psychoeducational intervention on caregivers of bipolar patients may improve the caregiver&amp;amp;#39;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&amp;amp;#39;s illness.
Studies on individual psychotherapy indicate that some interventions may reduce the number of rec... more Studies on individual psychotherapy indicate that some interventions may reduce the number of recurrences in bipolar patients. However, there has been a lack of structured, well-designed, blinded, controlled studies demonstrating the efficacy of group psychoeducation to prevent recurrences in patients with bipolar I and II disorder. One hundred twenty bipolar I and II outpatients in remission (Young Mania Rating Scale score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;6, Hamilton Depression Rating Scale-17 score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;8) for at least 6 months prior to inclusion in the study, who were receiving standard pharmacologic treatment, were included in a controlled trial. Subjects were matched for age and sex and randomized to receive, in addition to standard psychiatric care, 21 sessions of group psychoeducation or 21 sessions of nonstructured group meetings. Subjects were assessed monthly during the 21-week treatment period and throughout the 2-year follow-up. Group psychoeducation significantly reduced the number of relapsed patients and the number of recurrences per patient, and increased the time to depressive, manic, hypomanic, and mixed recurrences. The number and length of hospitalizations per patient were also lower in patients who received psychoeducation. Group psychoeducation is an efficacious intervention to prevent recurrence in pharmacologically treated patients with bipolar I and II disorder.
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Papers by Maria Reinares