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Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
There have been no previous factor analytic studies of the Hamilton Depression Rating Scale (HDRS) in samples with bipolar I depression, and no investigations of the utility of any derived factors in determining treatment response in this condition. This study aimed to identify and compare factors of a 31-item version of the HDRS (HDRS-31) in large samples of patients with bipolar depression and Major Depressive Disorder (MDD), then examine the responsiveness of such factors to lamotrigine compared with placebo in the bipolar depressed sample.
This multivariate analytical study was performed on 2 large depressed samples (one bipolar and the other MDD) that had been recruited for separate, contemporaneous, double-blind placebo-controlled trials of lamotrigine. The 2 studies had similar designs and assessment tools, the major measures being the Montgomery–Asberg Depression Rating Scale (MADRS) and HDRS-31. To identify the constructs underlying the scale, exploratory factor analyses were conducted using HDRS-31 baseline scores. Treatment responsiveness in the bipolar depressed sample—as indicated by improvement in the total MADRS and HDRS-31, as well as HDRS factors—were examined using both a mixed-effects analysis and individual time-point t-tests.
Seven factors of the HDRS-31 were identified: I—“depressive cognitions,” II—“psychomotor retardation,” III—“insomnia,” IV—“hypersomnia,” V—“appetite and weight change,” VI—“anxiety,” and VII—“anergia.” A significant therapeutic effect of lamotrigine in bipolar depression was found for the “depressive cognitions” factor (from week 3) and “psychomotor retardation” (from week 4).
This study has identified 7 factors of the HDRS in a large sample of patients with bipolar depression. The results suggest that that the clinical benefits of lamotrigine in acute bipolar depression are primarily upon depressive cognitions and psychomotor slowing.
There is uncertainty about the efficacy of lamotrigine in bipolar depressive episodes.
To synthesise the evidence for the efficacy of lamotrigine in bipolar depressive episodes.
Systematic review and meta-analysis of individual patient data from randomised controlled trials comparing lamotrigine with placebo.
Individual data from 1072 participants from five randomised controlled trials were obtained. More individuals treated with lamotrigine than placebo responded to treatment on both the Hamilton Rating Scale for Depression (HRSD) (relative risk (RR)=1.27, 95% CI 1.09–1.47, P=0.002) and Montgomery– åsberg Depression Rating Scale (MADRS) (RR=1.22, 95% CI 1.06–1.41, P=0.005). There was an interaction (P=0.04) by baseline severity of depression: lamotrigine was superior to placebo in people with HRSD score >24 (RR=1.47, 95% CI 1.16–1.87, P=0.001) but not in people with HRSD score 24 (RR=1.07, 95% CI 0.90–1.27, P=0.445).
There is consistent evidence that lamotrigine has a beneficial effect on depressive symptoms in the depressed phase of bipolar disorder. The overall pool effect was modest, although the advantage over placebo was larger in more severely depressed participants.
The aim of this study is to determine if personality traits contribute to the likelihood of substance abuse in Bipolar Disorder (BD).
Subjects/materials and methods
Fifty-nine patients meeting DSM-IV criteria for BD: 20 without any history of Substance Related Disorder (SRD), 21 with a lifetime history of SRD but without current SRD, and 18 with current SRD. Patients filled out the TCI, the differences were analyzed by ANOVA and the likelihood was obtained by Multinomial Logistic Regression.
Only Novelty Seeking (NS) is statistically different between the groups. Patients with BD with current SRD have higher rates in NS than those with past SRD, and those without a history of SRD. NS was confirmed as a predicting variable, both to current SRD (OR [CI 95%] = 1.039/1.351; p = 0.011) and past SRD (OR [CI 95%] = 1.004/1.277; p = 0.042) on patients with BD.
The results shown would appear to confirm the relationship of NS with the SRD, so long as there is no clear evidence that indicates the association of NS with BD.
There appears a greater predisposition to develop SRD in those patients with a higher degree of NS. The use of the Cloninger's TCI could be used in BD to determine the risk of developing an SRD. Early detection might help improve prognosis.
Sub-syndromal symptoms in bipolar disorder impair functioning and
diminish quality of life.
To examine factors associated with time spent with sub-syndromal symptoms
and to characterise how these symptoms influence outcomes.
In a double-blind randomised maintenance trial, patients received either
olanzapine or lithium monotherapy for 1 year. Stepwise logistic
regression models were used to identify factors that were significant
predictors of percentage time spent with sub-syndromal symptoms. The
presence of sub-syndromal symptoms during the first 8 weeks was examined
as a predictor of subsequent relapse.
Presence of sub-syndromal depressive symptoms during the first 8 weeks
significantly increased the likelihood of depressive relapse (relative
risk 4.67, P<0.001). Patients with psychotic features
and those with a greater number of previous depressive episodes were more
likely to experience sub-syndromal depressive symptoms (RR=2.51,
P<0.001 and RR=2.35, P=0.03
These findings help to identify patients at increased risk of affective
relapse and suggest that appropriate therapeutic interventions should be
considered even when syndromal-level symptoms are absent.
The goal of this paper is to review assessment research of bipolar
disorder in children and adolescents. The review addresses numerous
themes: the benefits and costs of involving clinical judgment in the
diagnostic process, particularly with regard to diagnosis and mood
severity ratings; the validity of parent, teacher, and youth self-report
of manic symptoms; how much cross-situational consistency is typically
shown in mood and behavior; the extent to which a parent's mental
health status influences their report of child behavior; how different
measures compare in terms of detecting bipolar disorder, the challenges in
comparing the performance of measures across research groups, and the
leading candidates for research or clinical use; evidence-based strategies
for interpreting measures as diagnostic aids; how test performance changes
when a test is used in a new setting and what implications this has for
research samples as well as clinical practice; the role of family history
of mood disorder within an assessment framework; and the implications of
assessment research for the understanding of phenomenology of bipolar
disorder from a developmental framework.We
thank the families who participated in this program of research. This work
was supported in part by NIMH R01 MH066647, as well as a Center Grant from
the Stanley Medical Research Institute.
This study examined healthcare utilization in the past year by subjects who screened positive for bipolar versus unipolar depression.
A self-administered survey was completed in 2002 by a United States population-based sample. Respondents were categorized into one of three subgroups: bipolar depressed screen positive (BP DEP+, n=394); unipolar depressed screen positive (UP DEP+, n=794); and control subjects (n=1,612).
For depressive symptoms in the past year, BP DEP+ respondents were significantly more likely than UP DEP+ respondents to report a healthcare visit to a number of diverse care providers. In analyses controlled for demographics and depression severity, the differences in psychiatric hospitalization, psychologist/counselor outpatient visit, substance abuse/social services visit, and number of emergency room visits remained significant between BP DEP+ and UP DEP+ respondents.
Subjects with self-reported bipolar depression sought care more often from a number of diverse healthcare resources than subjects with self-reported unipolar depression. These findings underscore the morbidity associated with bipolar depression.
Omar Elhaj, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, USA,
Joseph R. Calabrese, Case Western Reserve School of Medicine and University Hospitals of Cleveland, Cleveland, OH, USA
The frequent recurrence of treatment-refractory depression is emerging as the greatest unmet need in the clinical management of patients with rapid-cycling bipolar disorder, and particularly those comorbid presentations with alcohol and drug abuse. The age-corrected risk of major affective disorder was 23.5% in 179 relatives of rapid cyclers and 31% in 189 relatives of matched non-rapid cyclers, suggesting that rapid cycling is not genetic and does not aggregate within families. Findings from neuroimaging studies continue to enrich our understanding of the pathophysiology of mood disorders generally and rapid-cycling bipolar disorder particularly. Researchers found that the clinical presentation of bipolar disorder I (BP-I) was similar in children and adolescents. Despite being the oldest among the pharmacological armamentarium in the treatment of bipolar disorder, lithium continues to draw attention to its utility as an effective agent in the treatment of different aspects and phases of this disorder.
Few controlled studies examine the treatment of depressive features in mania.
To evaluate the efficacy of olanzapine, in combination with lithium or valproate, for treating depressive symptoms associated with mania.
Secondary analysis of a 6-week, double-blind, randomised study of olanzapine (5–20 mg/day) or placebo combined with ongoing valproate or lithium open treatment for 344 patients in mixed or manic episodes. This analysis focused on a dysphoric subgroup with baseline Hamilton Rating Scale for Depression (HRSD) total scores of 20 or over contrasted with non-dysphoric patients.
In the dysphoric subgroup (n=85) mean HRSD total score improvement was significantly greater in olanzapine co-therapy patients than in those receiving placebo plus lithium or valproate (P<0.001). Substantial contributors to this superiority included the HRSD Maier sub-scale (P=0.013) and the suicide item (P=0.001). Total Young Mania Rating Scale improvement was also superior with olanzapine co-therapy.
In patients with acute dysphoric mania, addition of olanzapine to ongoing lithium or valproate monotherapy significantly improved depressive symptom, mania and suicidality ratings.
Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder.
To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone.
Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6–1.2 mmol/l) or valproate (50–125 μg/ml) received lithium or valproate plus either olanzapine 5–20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months.
The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy42 days; P=0.023).
Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy.
During the development of a new treatment for bipolar disorder, maintenance studies are used to evaluate the ability of the putative mood stabiliser to prevent relapse and recurrence of further episodes. Comparisons with the early bipolar disorder maintenance studies indicate that the methodologies of recent trials have evolved substantially.
To review the methods used in the first- and second-generation maintenance studies, highlighting the differences of the various designs.
Methods that have evolved the most include patient enrolment, randomisation schemes and the use of outcome measures and statistical analyses. In addition, regulatory and commercial issues have also influenced study design.
There is little consensus on the methodology of bipolar disorder maintenance studies. As the integration of newer therapies into routine clinical practice is dependent on the evidence from controlled studies, it is essential that future maintenance trials in bipolar disorder achieve adequate methodological rigour without sacrificing overall feasibility.
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