EMDR therapy vs. supportive therapy as adjunctive treatment in trauma-exposed bipolar patients: A randomised controlled trial.

INTRODUCTION: Patients with bipolar disorder (BD) are frequently exposed to traumatic events which worsen disease course, but this study is the first multicentre randomised controlled trial to test the efficacy of a trauma-focused adjunctive psychotherapy in reducing BD affective relapse rates. MATERIALS AND METHODS: This multicentre randomised controlled trial included 77 patients with BD and current trauma-related symptoms. Participants were randomised to either 20 sessions of trauma-focused Eye Movement Desensitization and Reprocessing (EMDR) therapy for BD, or 20 sessions of supportive therapy (ST). The primary outcome was relapse rates over 24-months, and secondary outcomes were improvements in affective and trauma symptoms, general functioning, and cognitive impairment, assessed at baseline, post-treatment, and at 12- and 24-month follow-up. The trial was registered prior to starting enrolment in clinical trials (NCT02634372) and carried out in accordance with CONSORT guidelines. RESULTS: There was no significant difference between treatment conditions in terms of relapse rates either with or without hospitalisation. EMDR was significantly superior to ST at the 12-month follow up in terms of reducing depressive symptoms (p=0.0006, d=0.969), manic symptoms (p=0.027, d=0.513), and improving functioning (p=0.038, d=0.486). There was no significant difference in dropout between treatment arms. CONCLUSIONS: Although the primary efficacy criterion was not met in the current study, trauma-focused EMDR was superior to ST in reducing of affective symptoms and improvement of functioning, with benefits maintained at six months following the end of treatment. Both EMDR and ST reduced trauma symptoms as compared to baseline, possibly due to a shared benefit of psychotherapy. Importantly, focusing on traumatic events did not increase relapses or dropouts, suggesting psychological trauma can safely be addressed in a BD population using this protocol.

High incidence of PTSD diagnosis and trauma-related symptoms in a trauma exposed bipolar I and II sample.

Background: Post-traumatic stress disorder (PTSD) is an established comorbidity in Bipolar Disorder (BD), but little is known about the characteristics of psychological trauma beyond a PTSD diagnosis and differences in trauma symptoms between BD-I and BD-II. Objective: (1) To present characteristics of a trauma-exposed BD sample; (2) to investigate prevalence and trauma symptom profile across BD-I and BD-II; (3) to assess the impact of a lifetime PTSD diagnosis vs. a history of trauma on BD course; and (4) to research the impacts of sexual and physical abuse. Methods: This multi-center study comprised 79 adult participants with BD with a history of psychological trauma and reports baseline data from a trial registered in Clinical Trials (https://clinicaltrials.gov; ref: NCT02634372). Clinical variables were gathered through clinical interview, validated scales and a review of case notes. Results: The majority (80.8%) of our sample had experienced a relevant stressful life event prior to onset of BD, over half of our sample 51.9% had a lifetime diagnosis of PTSD according to the Clinician Administered PTSD scale. The mean Impact of Event Scale-Revised scores indicated high levels of trauma-related distress across the sample, including clinical symptoms in the PTSD group and subsyndromal symptoms in the non-PTSD group. Levels of dissociation were not higher than normative values for BD. A PTSD diagnosis (vs. a history of trauma) was associated with psychotic symptoms [2(1) = 5.404, p = 0.02] but not with other indicators of BD clinical severity. There was no significant difference between BD-I and BD-II in terms of lifetime PTSD diagnosis or trauma symptom profile. Sexual abuse significantly predicted rapid cycling [2(1) = 4.15, p = 0.042], while physical abuse was not significantly associated with any clinical indicator of severity. Conclusion: Trauma load in BD is marked with a lack of difference in trauma profile between BD-I and BD-II. Although PTSD and sexual abuse may have a negative impact on BD course, in many indicators of BD severity there is no significant difference between PTSD and subsyndromal trauma symptoms. Our results support further research to clarify the role of subsyndromic PTSD symptoms, and highlight the importance of screening for trauma in BD patients.

Functional Impairment in Older Adults With Bipolar Disorder.

Data describing bipolar disorder in older adults people are scarce, particularly with regard to functional status. This observational, comparative study assessed psychosocial functioning in 33 euthymic older adults with bipolar disorder compared with 30 healthy controls. In addition, we evaluated the association between clinical variables and poor functioning in the patient group. The mean age of the group was 68.70 years. Patients with bipolar disorder experienced poorer psychosocial functioning (19.15 ± 11.36) than healthy controls (5.17 ± 3.72; p = 0.0001), as assessed using the Functioning Assessment Short Test. Significant differences between the groups were found for specific domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, and interpersonal relationships (p = 0.0001, respectively). The largest variation was observed in overall functioning (Cohen's d = 0.63). The number of previous hospitalizations was strongly associated with poor overall functioning (F = 7.217, p = 0.002). Older patients with bipolar disorder had a greater functional impairment than the healthy control group. Implementation of novel rehabilitation models is critical to help patients manage their illness.

Eye movement desensitization and reprocessing therapy versus supportive therapy in affective relapse prevention in bipolar patients with a history of trauma: study protocol for a randomized controlled trial.

BACKGROUND: Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD. METHODS/DESIGN: This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-Salovey-Caruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale. DISCUSSION: The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma symptoms. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov, identifier: NCT02634372 . Registered on 3 December 2015.

Family functioning in bipolar disorder: Characteristics, congruity between patients and relatives, and clinical correlates.

Functional improvement has become one of the aims of the treatment of bipolar disorder. However, scant attention has been given to family functioning, even though it has a role in the illness outcome and is affected by the disorder. The aims of this study were to compare family functioning reported by euthymic patients with bipolar disorder and healthy controls; explore the level of congruence in the perception of family environment between patients with bipolar disorder and their relatives; and analyse the relationship between clinical variables and family functioning. The sample comprised 82 adult euthymic subjects with bipolar disorder, 82 family caregivers of these patients and 47 healthy controls. Participants completed the Family Environment Scale. Results showed moderate correlations and a mean pattern almost identical between relatives' and patients' reported scores in family functioning subscales. There were significant differences between patients and controls, favourable for the latter, in the subscales cohesion (p<0.005), expressiveness (p=0.002), conflict (p=0.038), intellectual-cultural orientation (p=0.001), active-recreational orientation (p<0.005), and a non-significant trend in organization (p=0.064). Significant associations were found between family environment and clinical variables of severity. These findings contribute to increasing the understanding of family functioning in bipolar disorder and highlight the importance of family work.

Biological rhythm disturbance in remitted bipolar patients.

BACKGROUND: Biological rhythm disturbance is common in bipolar patients and seems to affect the course and prognosis of the illness negatively. The main aim of the current study was to assess biological rhythms in remitted bipolar patients. We also assessed whether there was an association between clinical variables or functioning and biological rhythms in remitted bipolar participants. METHODS: The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) was used to assess biological rhythm disturbance. It is an 18-item interviewer-administered instrument which allows us to investigate the main areas related to circadian rhythm disturbance (sleep/social, activities, and eating pattern) in bipolar disorder. RESULTS AND DISCUSSION: Bipolar patients (n = 107) experienced greater biological rhythm alterations than the control group (n = 100) (BRIAN total scores 35.36 ± 7.11 vs. 32.48 ± 6.10, t = 6.912, p = 0.002, Cohen's d = 0.43, r = 0.21). In particular, patients were more impaired than the control group with regard to sleep/social (14.67 ± 4.14 vs. 13.49 ± 2.91, t = 10.61, p = 0.018, Cohen's d = 0.33, r = 0.16) and activity (8.49 ± 2.51 vs. 7.07 ± 2.13, t = 3.90, p = 0.001, Cohen's d = 0.61, r = 0.29) domains. Furthermore, a significant correlation was found between biological rhythms with residual depressive symptoms (r = 0.459, p < 0.001) and functioning (r = 0.432, p < 0.001). These findings suggest a potential link between biological rhythms and the pathophysiology of bipolar disorder. It highlights the importance of novel instruments (e.g., BRIAN) which allow us to assess biological rhythm disturbance in psychiatry. Finally, specific psychosocial interventions focused on lifestyle regularity may be considered as a supplemental treatment of bipolar illness episodes.

Six-month functional outcome of a bipolar disorder cohort in the context of a specialized-care program.

OBJECTIVES: A marked disparity between functional recovery and symptomatic improvement has been demonstrated in bipolar disorder. However, most of the previous studies have been conducted in the United States, and there is little prospective research from Europe on this topic. The main objective of the present six-month follow-up study was to assess functioning in a sample of Spanish bipolar disorder patients following an acute episode or subsyndromal state. Additionally, we also evaluated the sensitivity to change of the Functioning Assessment Short Test (FAST). METHODS: A total of 97 bipolar disorder patients with syndromal (n = 59) or subsyndromal (n = 38) symptoms were evaluated using the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale. The FAST was the primary measure to assess multiple areas of psychosocial functioning. Functioning was evaluated at four different time periods: baseline, 21 days, three months, and six months. RESULTS: A significant improvement in global functioning was found in the whole sample over the six-month period, as indicated by a reduction of FAST total score (mean ± standard deviation) from 39.97 ± 15.10 to 30.65 ± 16.93 (F = 36.104, p = 0.0001). This was also evident in all areas of functioning studied. However, only 26.4% of remitted patients (n = 42) achieved functional recovery, while 79.6% of the total sample (N = 97) experienced clinical remission of acute symptoms. CONCLUSIONS: Although many patients presented syndromal recovery, only a minority of them achieved favorable functioning in multiple areas, even after specialized mental health care. Furthermore, the FAST scale was sensitive to detect minimal changes in functioning in both short (21 days) and long (6 months) periods, which may be relevant to the use of this scale in clinical trials.

Functional impairment and disability across mood states in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) represents a chronic and recurrent illness that can lead to severe disruptions in family, social, and occupational functioning. The severity of mood symptomatology has been associated with functional impairment in this population. However, the majority of studies have assessed global functioning without considering specific domains. The main objective of the current study was to assess specific life domains of functioning as well as the overall functioning in patients with BD across different mood states ([hypo] mania, depression, or euthymia) compared with healthy controls by the means of a standardized scale validated for BD. METHODS: The sample included 131 subjects with BD (68 in remission, 31 hypo [manic], and 32 depressed) and 61 healthy controls. The Functioning Assessment Short Test was used to assess overall and multiple areas of functional impairment (autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time). RESULTS: The results showed significant intergroup differences; depressed patients had the lowest functioning (48.03 ± 12.38) followed by (hypo) manic patients (39.81 ± 13.99). The euthymic group showed least impairment in functioning compared with the depression and (hypo) mania groups (11.76 ± 12.73) but still displayed significant impairment when compared with the healthy control group (5.93 ± 4.43). CONCLUSIONS: This study indicates that depressive symptoms are associated with greater negative impact on psychosocial functioning than (hypo) manic symptoms. Further deficits in functioning seem to persist during remission. The results highlight the importance of aggressively treating depression and mania and the need to develop psychosocial interventions targeting to improve functional outcomes.

Clinical predictors of functional outcome of bipolar patients in remission.

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.

Ziprasidone in the treatment of affective disorders: a review.

Ziprasidone was the fifth atypical antipsychotic approved by Food and Drug Administration (FDA) for use in bipolar mania and mixed episodes. This atypical antipsychotic has a unique profile, as it acts primarily through serotonergic and dopaminergic receptor antagonism, but also exerts effects as an inhibitor of norepinephrine reuptake. Moreover, one of the advantages of ziprasidone is its safety profile as it is not associated with clinically significant metabolic side effects and little or no effect on prolactin level or anticholinergic side effects. Most of the studies evaluating ziprasidone's efficacy and safety are short-term double-blind, placebo-controlled studies in acute mania and mixed episodes. In two of them, ziprasidone was associated to significant improvement in the primary measures assessed. However, an add-on study, lithium plus ziprasidone showed similar results than lithium monotherapy, although there was a significant advantage for the combination within the first week. In a more recent trial, ziprasidone was compared with placebo and haloperidol as monotherapies, again beating placebo. In that trial, ziprasidone appeared to be safer and better tolerated, although less likely efficacious than haloperidol. Particularly, subjects treated with ziprasidone were less likely to switch to depression. Despite the well-studied efficacy of ziprasidone in the first weeks of treatment, there are no controlled trials that evaluate the role and efficacy of ziprasidone in long-term treatment of bipolar disorder (BD). Overall, in the open-label extension studies, there was a global improvement at all visits compared with baseline scores. Furthermore, ziprasidone appears to offer some antidepressant effect in patients with major depressive episode and resistant to treatment, as demonstrated in add-on open-label studies with ziprasidone plus selective serotonin reuptake inhibitor (SSRI).

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.

A double-blind, randomized, placebo-controlled prophylaxis trial of oxcarbazepine as adjunctive treatment to lithium in the long-term treatment of bipolar I and II disorder.

We evaluated the prophylactic efficacy and the long-term tolerability of oxcarbazepine administration in the treatment of bipolar I and II disorder as an adjunctive therapy to lithium. We conducted a 52-wk, double-blind, randomized, placebo-controlled, parallel-group, multicentre, clinical trial. Bipolar I and II DSM-IV outpatients, having had two or more episodes in the last year, but currently being in remission, were randomly assigned on a 1:1 ratio to oxcarbazepine (n=26) or placebo (n=29) as adjuncts to ongoing treatment with lithium. The primary efficacy variable was the length of the remission period assessed by means of the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS). Other assessments were the Clinical Global Impression (CGI-BP-M), functional activity (GAF), anxiety (HAMA) and impulsiveness (BIS-11). The average time until first recurrence of any type was 19.2+/-13.9 wk and 18.6+/-17.0 wk for oxcarbazepine and placebo respectively (p=0.315). Ten (38.46%) patients had a recurrence of any kind in the oxcarbazepine group vs. 17 (58.62%) in the placebo group (p=0.1354). There was a trend for depressive episodes being less likely in the oxcarbazepine group compared to the placebo group (11.54% and 31.03% respectively, p=0.085), and for better functionality with the GAF (p=0.074). Impulsivity was significantly better prevented by oxcarbazepine (p=0.0443). Overall, oxcarbazepine was well tolerated. This pilot, randomized clinical trial, suggests that oxcarbazepine might have some prophylactic efficacy with regards to impulsivity and perhaps mood episodes in patients taking lithium, although further, adequately powered controlled trials are needed to confirm these findings.

Olanzapine monotherapy and olanzapine combination therapy in the treatment of mania: 12-week results from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) observational study.

BACKGROUND: To evaluate the 12-week outcomes (effectiveness, tolerability, and patterns of medication use) of olanzapine (either in antimanic monotherapy or in combination with other antipsychotics, anticonvulsants, and/or lithium) in patients with bipolar mania or mixed mania. METHOD: EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 24-month prospective observational study of in- and outpatients with acute mania/mixed mania conducted in 14 European countries. Primary outcome measures included Clinical Global Impressions-Bipolar Disorder scale (overall, mania, and depression); 5-item Hamilton Depression Rating Scale; and Young Mania Rating Scale. Tolerability measures included a questionnaire to assess patients' symptomatic complaints. RESULTS: Overall, 2004 patients received olanzapine (olanzapine monotherapy, n=673; olanzapine combination, n=1331). Concomitant therapy with antidepressants and/or anxiolytics was possible in both groups. The countries significantly differed in the use of olanzapine monotherapy versus olanzapine combination (p<.0001). Baseline-to-endpoint changes on the CGI-BP subscales, YMRS, and HAMD-5 were significant within both treatment groups (p<.0001). Olanzapine monotherapy was generally better tolerated than olanzapine combination, particularly with regard to sedation (12% vs 17%; p<.001), tremor (2% vs 5%; p<.001), and akathisia (3% vs 6%; p<.001). DISCUSSION: The acute-phase EMBLEM results suggest that in naturalistic settings, olanzapine (both as monotherapy and combination) may be effective in treating patients with bipolar mania. The use of olanzapine monotherapy or combination varies significantly across countries, but combination is generally the rule, rather than the exception.

Validity and reliability of the Functioning Assessment Short Test (FAST) in bipolar disorder.

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. METHODS: 101 patients with DSM-IV TR bipolar disorder and 61 healthy controls were assessed in the Bipolar Disorder Program, Hospital Clinic of Barcelona. The psychometric properties of FAST (feasibility, internal consistency, concurrent validity, discriminant validity (euthymic vs acute patients), factorial analyses, and test-retest reliability) were analysed. RESULTS: The internal consistency obtained was very high with a Cronbach's alpha of 0.909. A highly significant negative correlation with GAF was obtained (r = -0.903; p < 0.001) pointing to a reasonable degree of concurrent validity. Test-retest reliability analysis showed a strong correlation between the two measures carried out one week apart (ICC = 0.98; p < 0.001). The total FAST scores were lower in euthymic (18.55 +/- 13.19; F = 35.43; p < 0.001) patients, as compared with manic (40.44 +/- 9.15) and depressive patients (43.21 +/- 13.34). CONCLUSION: The FAST showed strong psychometrics properties and was able to detect differences between euthymic and acute BD patients. In addition, it is a short (6 minutes) simple interview-administered instrument, which is easy to apply and requires only a short period of time for its application.

[Bipolar disorder in Spain: functional status and resource use on the basis of the Spanish sample of the observational, Pan European EMBLEM study]. / El trastorno bipolar en España: Estado funcional y consumo de recursos según la muestra española del estudio observacional paneuropeo EMBLEM.

RATIONALE: There are very few data as to the social and occupational adaptation of patients with bipolar disorder in Spain and even less is known about the resource use they generate. OBJECTIVE: To determine the functional status and healthcare resource use of the Spanish sample of the pan European EMBLEM (European Mania in Bipolar Longotudinal Evaluation of Medication) study of bipolar patients in manic or mixed phase. METHOD: The EMBLEM study recruited 3536 patients, 312 of whom (8.82%) were enrolled in Spain. Patients had to be adults with a diagnosis of bipolar disorder who were initiating at the discretion of their treating psychiatrist oral treatment for an acute manic phase. They were evaluated using the Spanish versions of rating scales for the severity of mania (Young Mania Rating Scale), bipolar disorder (CGI BD) for mania, depression and hallucinations delusions, and depression (HAMD 5 item version of the Hamilton Scale); the Life Chart Method (LCM) and 2 items of the SLICE of LIFE were used to evaluate functioning. Information was collected on healthcare resource utilization during the preceding year. RESULTS: Sixty three percent of the patients presented with moderate to very severe work related difficulties in the year preceding his her manic episode. Forty percent of the patients failed to comply either totally or partly with their prescribed treatment. Subjects required an average of 1.5 hospitalizations during the year prior to enrollment, with a mean stay of approximately 10 days, and between 7 and 8 outpatient visits per year.

Cognitive impairment in bipolar II disorder.

BACKGROUND: Persistent impairments in neurocognitive function have been described in bipolar disorder. AIMS: To compare the cognitive performance of patients with bipolar II disorder with that of patients with bipolar I disorder and a healthy control group. METHOD: The study included 71 euthymic patients with bipolar disorder (38 bipolar I, 33 bipolar II), who were compared on clinical and neuropsychological variables (e.g. executive function, attention, verbal and visual memory) and contrasted with 35 healthy controls on cognitive performance. RESULTS: Compared with controls, both bipolar groups showed significant deficits in most cognitive tasks including working memory (DigitSpan Backwards, P=0.002) and attention (DigitSpan Forwards, P=0.005; Trail Making Test, P=0.001). Those with type II disorders had an intermediate level of performance between the bipolar I group and the control group in verbal memory (P<0.005) and executive functions (Stroop interference task, P=0.020). CONCLUSIONS: Cognitive impairment exists in both subtypes of bipolar disorder, although more so in the bipolar I group. The best predictors of poor psychosocial functioning in bipolar II disorder were subclinical depressive symptoms, early onset of illness and poor performance on a measure related to executive function.

A double-blind, randomized, placebo-controlled, prophylaxis study of adjunctive gabapentin for bipolar disorder.

OBJECTIVE: To conduct the first randomized, controlled trial assessing the prophylactic efficacy of gabapentin in bipolar disorder. METHOD: We conducted a 1-year, double-blind, randomized, comparative, placebo-controlled, parallel-group, multicenter study. As this was a pure prophylactic trial, only euthymic bipolar I and II patients (DSM-IV) were randomly assigned in a 1:1 ratio to gabapentin (N = 13) or placebo (N = 12) added to the current treatment (lithium, valproate, carbamazepine, or any combination but not antipsychotics or antidepressants). Subjects participated in the study for 12 months. The primary efficacy parameter was the Clinical Global Impressions scale for Bipolar Illness, Modified (CGI-BP-M), which was assessed at all visits. Other assessments were the Young Mania Rating Scale (YMRS), Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Pittsburgh Sleep Quality Index (PSQI), and the systematic collection of reported adverse events. Data were collected from May 1999 to February 2004. RESULTS: The change from baseline to month 12 in mean CGI-BP-M scores between groups was statistically significant (p = .0046). Mean score change from baseline to endpoint in the gabapentin group was -2.1, and the mean score change in the placebo group was -0.6. No emerging manic or depressive symptoms were seen in either group as measured with the YMRS, HAM-D, HAM-A, and PSQI. In the PSQI-6 subscale (use of sleeping medication), the mean score change at month 12 in the gabapentin group was 0.9, and the mean score change in the placebo group was 0.05 (p = .0267). Overall, gabapentin was well tolerated. CONCLUSION: This small, randomized clinical trial comparing the prophylactic efficacy of adjunctive gabapentin to placebo suggests that, despite lack of acute efficacy, treatment with gabapentin might provide some benefit on the long-term outcome of bipolar disorder.

Cognitive functioning in bipolar patients receiving lamotrigine: preliminary results.

Despite the increasing use of lamotrigine (LTG) in bipolar disorder, little is known about its impact on cognition in bipolar patients. Therefore, we have evaluated 33 bipolar I and II patients on cognitive measures (verbal memory, attention, executive functions) while receiving either LTG (n = 15) or another anticonvulsant (carbamazepine or valproate; n = 18). Patients receiving LTG were generally diagnosed as having bipolar II disorder, had experienced more depressive episodes but a lesser number of hospitalizations, and had better performance than the patients receiving carbamazepine or valproate on the verbal fluency task. A moderate effect size also suggests that both groups may differ on the immediate verbal memory test (California Verbal Learning Test). These preliminary results suggest a safer neurocognitive profile of LTG on bipolar patients, as compared with other anticonvulsants.

An open-label study of amisulpride in the treatment of mania.

BACKGROUND: Amisulpride is a selective D(2)-D(3) antagonist that has been reported to be effective in the treatment of schizophrenia and major depressive disorder. However, no prospective study to date has assessed the effectiveness and tolerability of this compound in mania. METHOD: Twenty DSM-IV-defined acutely ill manic bipolar patients with a Young Mania Rating Scale (YMRS) score of 20 or more entered this open, prospective, 6-week study. Assessments included the YMRS, the Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impressions Scale for Bipolar Disorder, Modified (CGI-BP-M), and the systematic report of adverse events. Amisulpride was added to other medications, but other antipsychotics were not allowed. RESULTS: Fourteen patients (70%) completed the study. Using last-observation-carried-forward (LOCF) analyses, amisulpride produced significant improvements on the YMRS (p = .0001), the HAM-D (p < .0141), and the overall (p = .0003), mania (p = .0001), and depression (p = .0268) subscales of the CGI-BP-M. The most common side effect was sedation (N = 5, 25%), but there were also some extrapyramidal symptoms, galactorrhea, insomnia, and agitation. The mean amisulpride dose was 680 mg/day (LOCF) and 786 mg/day in completers. CONCLUSIONS: This first prospective study on amisulpride in the treatment of mania suggests that, despite the limitations of the open, observational design and small sample size, amisulpride may be effective and reasonably safe in the treatment of bipolar mania. D(2) and D(3) antagonism may be involved in the mechanisms of the therapeutic response to antipsychotics in mania.

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

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.