Disorders - Bipolar Disorders
Berk, M., Daglas, R., Dandash, O., Yucel, M., Henry, L., Hallam, K., Macneil, C., Hasty, M., Pantelis, C., Murphy, B. P., Kader, L., Damodaran, S., Wong, M. T. H., Conus, P., Ratheesh, A., McGorry, P. D., Cotton, S. M.
Background Lithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other. Aims To investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania. Method Maintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry - ACTRN12607000639426.) Results In total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment6visit interactions were observed for measures of overall psychopathology, psychotic symptoms and functioning. Planned and post hoc comparisons further demonstrated the superiority of lithium treatment over quetiapine. Conclusions In people with first-episode mania treated with a combination of lithium and quetiapine, continuation treatment with lithium rather than quetiapine is superior in terms of mean levels of symptoms during a 1-year evolution. Copyright © The Royal College of Psychiatrists 2017.
British Journal of Psychiatry, 210(6) : 413-421
- Year: 2017
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
, Relapse prevention
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Lithium
DelBello, M. P., Goldman, R., Phillips, D., Deng, L., Cucchiaro, J., Loebel, A.
Objective: To evaluate the efficacy and safety of lurasidone in children and adolescents with bipolar depression. Method: Patients 10 to 17 years old with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with flexible doses of lurasidone 20 to 80 mg/day. The primary endpoint was change from baseline to week 6 in the Children's Depression Rating Scale-Revised (CDRS-R) total score, evaluated by a mixed-model repeated-measures analysis. Results: A total of 347 patients were randomized and received at least 1 dose of lurasidone (n = 175; mean age 14.2 years; mean dose 33.6 mg/day) or placebo (n = 172; mean age 14.3 years). At week 6, treatment with lurasidone was associated with statistically significant improvement compared with placebo in CDRS-R total score (-21.0 versus -15.3; p < .0001; effect size 0.45). Lurasidone also was associated with statistically significant improvement in the Clinical Global Impression-Bipolar Severity depression score (key secondary measure) and in measures of anxiety, quality of life, and global functioning. Study completion rates were 92.0% in the lurasidone group and 89.7% in the placebo group; discontinuation rates due to adverse events were the same for the 2 groups (1.7%). The 2 most common adverse events on lurasidone were nausea and somnolence. Treatment with lurasidone was associated with few effects on weight and metabolic parameters. Conclusion: In this placebo-controlled study, monotherapy with lurasidone, in the dose range of 20 to 80 mg/day, significantly decreased depressive symptoms in children and adolescents with bipolar depression. Lurasidone was well tolerated, with minimal effects on weight and metabolic parameters. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
Journal of the American Academy of Child & Adolescent Psychiatry, 56(12) : 1015-1025
- Year: 2017
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Goldstein, B. I., Birmaher, B., Carlson, G. A., DelBello, M. P., Findling, R. L., Fristad, M., Kowatch, R. A., Miklowitz, D. J., Nery, F. G., Perez-Algorta, G., VanMeter, A., Zeni, C. P., Correll, C. U., Kim, H. W., Wozniak, J., Chang, K. D., Hillegers, M., Youngstrom, E. A.
Objectives: Over the past two decades, there has been tremendous growth in research regarding bipolar disorder (BD) among children and adolescents (ie, pediatric BD [PBD]). The primary purpose of this article is to distill the extant literature, dispel myths or exaggerated assertions in the field, and disseminate clinically relevant findings. Methods: An international group of experts completed a selective review of the literature, emphasizing areas of consensus, identifying limitations and gaps in the literature, and highlighting future directions to mitigate these gaps. Results: Substantial, and increasingly international, research has accumulated regarding the phenomenology, differential diagnosis, course, treatment, and neurobiology of PBD. Prior division around the role of irritability and of screening tools in diagnosis has largely abated. Gold-standard pharmacologic trials inform treatment of manic/mixed episodes, whereas fewer data address bipolar depression and maintenance/continuation treatment. Adjunctive psychosocial treatment provides a forum for psychoeducation and targets primarily depressive symptoms. Numerous neurocognitive and neuroimaging studies, and increasing peripheral biomarker studies, largely converge with prior findings from adults with BD. Conclusions: As data have accumulated and controversy has dissipated, the field has moved past existential questions about PBD toward defining and pursuing pressing clinical and scientific priorities that remain. The overall body of evidence supports the position that perceptions about marked international (US vs elsewhere) and developmental (pediatric vs adult) differences have been overstated, although additional research on these topics is warranted. Traction toward improved outcomes will be supported by continued emphasis on pathophysiology and novel therapeutics. Copyright © 2017 The Authors Bipolar Disorders Published by John Wiley & Sons Ltd
Bipolar Disorders, 19(7) : 524-543
- Year: 2017
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
, At risk (indicated or selected prevention)
-
Treatment and intervention: Biological Interventions (any)
, Complementary & Alternative Interventions (CAM)
, Psychological Interventions (any)
Wiener, C. David., Molina, M. L., Moreira, F. P., dos-Passos, M. B., Jansen, K., da-Silva, R. A., de-Mattos, S., Luciano, D., Oses, J. P.
The aim of this study was to evaluate the impact of psychoeducation in serum levels of BDNF, NGF and GDNF in young adults presenting bipolar disorder (BD). This is a randomized clinical trial including 39 young adults (18-29 years) diagnosed with BD through the Structured Clinical Interview for DSM-IV (SCID-CV). Participants were randomized in two treatment groups: usual treatment (medication) and combined intervention (medication plus psychoeducation). Depressive symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) and severity of manic and hypomanic symptoms was evaluated through the Young Mania Rating Scale (YMRS). The serum levels of trophic factors were measured with an ELISA kit. In both intervention groups, there was an improvement in depressive symptoms significantly between baseline and post-intervention. In the combined intervention, GDNF serum levels increased significantly from baseline to post-intervention. However, there were no differences in BDNF and NGF serum levels. In the usual treatment group, no changes were observed in serum levels of GDNF, BDNF, and NGF the post-intervention in individuals. Our data suggests that only combined intervention was effective in improving depressive symptoms and increasing GDNF levels in a sample of young adults with bipolar disorder. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
Psychiatry Research, 257 : 367-371
- Year: 2017
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions (any)
, Psychoeducation
Reinares, M., Bonnin, C. M., Hidalgo-Mazzei, D., Sanchez-Moreno, J., Colom, F., Vieta, E.
The reciprocal relationship between bipolar disorder (BD) and the family system highlights the importance of adjunctive family intervention. However, its implementation in clinical practice is not widespread. To update the knowledge in this field and identify areas of uncertainty this manuscript present a comprehensive overview of the bidirectional relationship between BD and family variables, and a systematic review of the evidence-based studies published up to March 2015 on the efficacy of adjunctive family intervention in BD. Findings show that not only specific family's attitudes/interactions affect the course of BD but that equally the illness itself has a strong impact on family functioning, caregivers' burden and health. Regarding family intervention, there are methodological differences between studies and variability in the sample characteristics and the intervention used. Most evidence-based studies support the efficacy of adjunctive family treatment in the illness outcomes, both in youth and adult population, as well as benefits for caregivers. The results emphasize the need to involve caregivers in the therapeutic management of BD through tailored interventions based on patients' characteristics and family needs.
Clinical Psychology Review, 43 : 47-57
- Year: 2016
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
, At risk (indicated or selected prevention)
-
Treatment and intervention: Psychological Interventions (any)
, Other Psychological Interventions
Strakowski, S. M., Fleck, D. E., Welge, J., Eliassen, J. C., Norris, M., Durling, M., Komoroski, R. A., Chu, W. J., Weber, W., Dudley, J. A., Blom, T. J., Stover, A., Klein, C., Strawn, J. R., DelBello, M. P., Lee, J. H., Adler, C. M.
OBJECTIVES: We tested the hypothesis that, with treatment, functional magnetic resonance imaging (fMRI) regional brain activation in first-episode mania would normalize - i.e., that differences from healthy subjects would diminish over time, and would be associated with clinical remission status, potentially identifying neuroanatomic treatment response markers.
METHODS: Forty-two participants with bipolar I disorder were recruited during their first manic episode, pseudo-randomized to open-label lithium or quetiapine, and followed for 8 weeks. fMRI scans were obtained at baseline and then after 1 and 8 weeks of treatment, while participants performed a continuous performance task with emotional distracters. Healthy participants received fMRI scans at these same intervals. Specific region-of-interest (ROI) activations within prefrontal emotional networks were assessed as potential measures of treatment response.
RESULTS: ROI data were reduced using exploratory factor analysis, which identified five factors that were organizationally consistent with functional anatomic models of human emotion modulation. Half of the participants with bipolar disorder achieved remission by Week 8 and were contrasted with the other half that did not. Analyses demonstrated that, in the bipolar disorder group in general, treatment led to decreases in activation across brain regions toward healthy subject values. However, differences in activation changes were observed between subjects with bipolar disorder who did or did not achieve remission in subcortical and amygdala factors.
CONCLUSIONS: These findings provide evidence for potential neuroanatomic treatment response markers in first-episode bipolar disorder.
Bipolar Disorders, 18(6) : 490-501
- Year: 2016
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Lithium
MacPherson, H. A., West, A. E., Weinstein, S.
Objectives: Mediation analyses are important for discerning mechanisms of change and essential therapeutic components in CBT. Few studies have identified mediators of CBT for youth-internalizing disorders; only one trial evaluated treatment mechanisms for youth with mixed mood diagnoses. The current study evaluated mediators in the randomized trial of child- and family-focused CBT (CFF-CBT), with adjunctive to pharmacotherapy versus enhanced treatment as usual (TAU) for pediatric BD. Methods: Sixty-nine children (ages 7-13 years; mean age= 9.19 years; SD= 1.61; 58 percent male; 52 percent Caucasian) with pediatric BD were randomly assigned to CFF-CBT or TAU. Both treatments consisted of 12 short-term and six maintenance sessions. CFF-CBT included an intensive focus on parent and family-level interventions, including psychoeducation, parenting skills, selfcare, and family problem-solving skills. Primary outcomes (child mania, depression, global functioning) and candidate mediators (family functioning and environment, parenting skills and coping, child coping) were assessed at baseline and at 4, 8, 12 (post-treatment), and 39 weeks (follow-up). Results: Children receiving CFF-CBT exhibited significant improvement in mania and depression by posttreatment and global functioning over a 6-month follow-up. Candidate child, family, and parent mediators were evaluated via a series of mixed-effects regression models following the test of joint significance approach. Mediators were assessed at each wave via parent/child self-report. Parenting skills/coping, family flexibility, and family-coping skills significantly improved across treatment in CFF-CBT versus TAU (P < 0.05, d= 0.50-0.59). Moreover, parenting skills/coping mediated improvements in child mania (d= 0.62) and global functioning (d= 0.55), family flexibility mediated enhanced global functioning (d= 0.48), and family coping mediated reduced depression (d= 0.81). Child coping was not a significant mediator. Conclusions: CFF-CBT may affect children's mood and functioning by improving parenting skills and coping, family flexibility, and family-positive reframing. Limitations include concurrent change of mediators and outcomes and attrition. Clinical implications include a focus on parent and family functioning as key treatment mechanisms of child symptom response to CFF-CBT.
Journal of the American Academy of Child and Adolescent Psychiatry, 55 (10 Supplement 1) : S14
- Year: 2016
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions (any)
, Cognitive & behavioural therapies (CBT)
Fallah, E., Arman, S., Najafi, M., Shayegh, B.
Objective Many studies have supported the role of protein kinase C (PKC) inhibitors in the physiopathology and treatment of bipolar disorder in adults. Tamoxifen is one of the drugs with the effect of PKC inhibition. This study aimed to determine the effect of tamoxifen on the rate of improvement mania symptoms in the sample of children and adolescents with acute mania. Materials & Methods In this randomized, placebo-controlled clinical trial study, registered in www.irct.ir with the code of IRCT201410126418N3, overall 44 patients with bipolar disorder with acute manic episode were randomly assigned into treatment and control groups. The serum levels of lithium and tamoxifen among the participants in the treatment groups were 0.8 -1.1 mg and 20-40 mg per day respectively. Serum level of lithium among participants in the control group was similar. The main comparisons were made based on the Young Mania Rating Scale (YMRS) and Children Depression Inventory (CDI) scores of the participants at baseline and at the end of each study week. The pharmacological side effects of serum level of lithium were examined weekly. Analysis of Covariance(ANCOVA) test was used for the statistical analysis. Results There was no difference in the baseline score of YMRS and CDI in the treatment and control groups while a statistical significant difference (P < 0.05) in these scores was found between and within the groups. Conclusion The addition of tamoxifen to lithium causes a significant difference in reducing the symptoms of mania and depression in the treatment group compared to the control group. Copyright © 2016 Iranian Child Neurology Society. All Rights Reserved.
Iranian Journal of Child Neurology, 10(2) : 16-25
- Year: 2016
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Lithium, Other biological interventions
Daglas, R., Cotton, S. M., Allott, K., Yucel, M., Macneil, C. A., Hasty, M. K., Murphy, B., Pantelis, C., Hallam, K. T., Henry, L. P., Conus, P., Ratheesh, A., Kader, L., Wong, M. T., McGorry, P. D., Berk, M.
BACKGROUND: Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania.
METHODS: The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points.
RESULTS: There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition.
CONCLUSION: Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.
European Psychiatry: the Journal of the Association of European Psychiatrists, 31 : 20-8
- Year: 2016
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Lithium
Detke, H. C., DelBello, M. P., Landry, J,, Hoffmann, V. P., Heinloth, A., Dittmann, R. W.
Objectives: To evaluate the 52-week safety/tolerability of oral olanzapine for adolescents with schizophrenia or bipolar mania and compare effectiveness of a standard versus intense behavioral weight intervention in mitigating risk of weight gain. Methods: Patients 13-17 years old with schizophrenia (Brief Psychiatric Rating Scale for Children [BPRS-C] total score > 30; item score >= 3 for hallucinations, delusions, or peculiar fantasies) or bipolar I disorder (manic or mixed episode; Young Mania Rating Scale [YMRS] total score >= 15) received open-label olanzapine (2.5-20 mg/day) and were randomized to standard (n = 102; a single weight counseling session) or intense (n = 101; weight counseling at each study visit) weight intervention. The primary outcome measure was mean change in body mass index (BMI) from baseline to 52 weeks using mixed-model repeated measures. Symptomatology was also assessed. Results: No statistically significant differences between groups were observed in mean baseline-to-52-week change in BMI (standard: +3.6 kg/m2; intense: +2.8 kg/m2; p = 0.150) or weight (standard: +12.1 kg; intense: +9.6 kg; p = 0.148). Percentage of patients at endpoint who had gained >= 15% of their baseline weight was 40% for the standard group and 31% for the intense group (p = 0.187). Safety/tolerability results were generally consistent with those of previous olanzapine studies in adolescents, with the most notable exception being the finding of a mean decrease in prolactin. On symptomatology measures, patients with schizophrenia had a mean baseline-to-52-week change in BPRS-C of -32.5 (standard deviation [SD] = 10.8), and patients with bipolar disorder had a mean change inYMRSof -16.7 (SD = 8.9), with clinically and statistically significant improvement starting at 3-4 days for each. Conclusions: Long-term weight gain was high in both groups, with no statistically significant differences between the standard or intense behavioral weight interventions in BMI or weight. Safety, tolerability, and effectiveness findings were generally consistent with the known profile of olanzapine in adolescents. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
Journal of Child and Adolescent Psychopharmacology, 26(10) : 922-934
- Year: 2016
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Other Psychological Interventions
Cardoso, T. de A., Campos-Mondin, T., Reyes, A. N., Zeni, C. P., Souza, L. D. de M., da-Silva, R. A., Jansen, K.
The objective was to evaluate the effect of psychoeducation on biological rhythm and in the reduction of depressive, anxious, and manic symptoms at 12 months' follow-up. This was a randomized clinical trial with young adults aged 18 to 29 years, diagnosed with bipolar disorder. Biological rhythm was assessed with the Biological Rhythm Interview Assessment in Neuropsychiatry (BRIAN). Participants were randomized for combined intervention (psychoeducation plus medication) or treatment-as-usual (medication alone). The sample consisted of 61 patients (29 TAU; 32 combined intervention). Although it failed to separate by a marginal difference, the combined intervention seems to be more effective than TAU in relation to improvement of depressive symptoms at post-intervention (p = 0.074) and regulation of sleep/social domain at 6 months' follow-up (p = 0.057). Improvement of depressive symptoms as well as regulation of sleep and social activities are known to prevent episode onset and thus improve long-term outcomes.;
The Journal Of Nervous And Mental Disease, 203(10) : 792-797
- Year: 2015
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Psychological Interventions (any)
, Psychoeducation
Conus, P., Berk, M., Cotton, S. M., Kader, L., Macneil, C., Hasty, M. K., Hallam, K., Lambert, M., Murphy, B. P., McGorry, P. D.
Background: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments.; Methods: Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures.; Results: Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons.; Conclusions: Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.; Copyright © 2015 Elsevier Masson SAS. All rights reserved.
European Psychiatry, 30(8) : 975-982
- Year: 2015
- Problem: Bipolar Disorders, Psychosis Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
, First episode (psychosis only)
-
Treatment and intervention: Biological Interventions (any)
, Typical Antipsychotics (first generation)
, Atypical Antipsychotics (second generation)
, Lithium