Disorders - Bipolar Disorders
Nandagopal, J. J., DelBello, M. P., Kowatch, R.
Bipolar disorder (BPD) is being diagnosed with increasing frequency in the pediatric population as the phenomenology of this disorder is becoming more clearly delineated. Early diagnosis and treatment of pediatric BPD is important to minimize psychosocial disability and improve prognosis. Traditional mood stabilizers and atypical antipsychotic agents are frequently used to treat BPD in youth, and there are emerging data to support their use in this population. This article provides a review of the literature on appropriate pharmacologic treatment strategies for BPD in children and adolescents. The complex treatment issues of comorbid BPD and attention deficit/hyperactivity disorder also are addressed. (copyright) 2009 Elsevier Inc. All rights reserved.
Child & Adolescent Psychiatric Clinics of North America, 18(2) : 455-469
- Year: 2009
- Problem: Bipolar Disorders
- Type: Systematic reviews
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
Miklowitz, David J., Scott, Jan
Objectives: Methods: Results: Conclusions: Randomized trials of adjunctive psychotherapy for bipolar disorder are reviewed, in tandem with discussion of cost-effectiveness, mediating mechanisms, and moderators of effects.Systematic searches of the MEDLINE and PSYCHLIT databases yielded 19 randomized controlled trials of individual family and group therapies. Outcome variables included time to recovery, relapse or recurrence, symptom severity, medication adherence, and psychosocial functioning.Meta-analyses consistently show that disorder-specific psychotherapies [cognitive-behavioral therapy (CBT), interpersonal, family, and group] augment mood stabilizers in reducing rates of relapse (OR = 0.57; 95% CI: 0.39-0.82) over 1-2 years. Specific mediating mechanisms include, but are not limited to, increasing medication adherence, teaching self-monitoring and early intervention with emergent episodes, and enhancing interpersonal functioning and family communication. All therapies have strengths and weaknesses. One group psychoeducation trial, demonstrated effect sizes for recurrence that are at least equivalent to individual therapies, but findings await replication. Family interventions have been successfully administered in both single and multi-family formats, but no studies report the comparative cost-effectiveness of these formats. The best-studied psychotherapy modality, CBT, can have beneficial effects on depression, but findings are inconsistent across studies and vary with sample characteristics and comparison treatments.Adjunctive psychotherapies can be cost-effective when weighed against observed reductions in recurrence, hospitalization and functional impairments. Future trials need to (i) clarify which populations are most likely to benefit from which strategies; (ii) identify putative mechanisms of action; (iii) systematically evaluate costs, benefits, and generalizability; and (iv) record adverse effects. The application of psychosocial interventions to young-onset populations deserves further study.
Bipolar Disorders, 11 Suppl 2 : 110-122
- Year: 2009
- Problem: Bipolar Disorders
- Type: Systematic reviews
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Psychological Interventions (any)
Miklowitz, D. J., Axelson, D. A., George, E. L., Taylor, D. O., Schneck, C. D., Sullivan, A. E., Dickinson, L. M., Birmaher, B.
Objective: Family interventions have been found to be effective in pediatric bipolar disorder (BD). This study examined the moderating effects of parental expressed emotion (EE) on the 2-year symptomatic outcomes of adolescent BD patients assigned to family-focused therapy for adolescents (FFT-A) or a brief psychoeducational treatment (enhanced care [EC]). Method: A referred sample of 58 adolescents (mean age 14.5 (plus or minus)1.6 years, range 13-17 years) with BD I, II, or not otherwise specified was randomly allocated after a mood episode to FFT-A or EC, both with protocol pharmacotherapy. Levels of EE (criticism, hostility, or emotional overinvolvement) in parents were assessed through structured interviews. Adolescents and parents in FFT-A underwent 21 sessions in 9 months of psychoeducation, communication training, and problem-solving skills training, whereas adolescents and parents in EC underwent 3 psychoeducation sessions. Independent "blind" evaluators assessed adolescents' depressive and manic symptoms every 3 to 6 months for 2 years. Results: Parents rated high in EE described their families as lower in cohesion and adaptability than parents rated low in EE. Adolescents in high-EE families showed greater reductions in depressive and manic symptoms in FFT-A than in EC. Differential effects of FFT-A were not found among adolescents in low-EE families. The results could not be attributed to differences in medication regimens. Conclusions: Parental EE moderates the impact of family intervention on the symptomatic trajectory of adolescent BD. Assessing EE before family interventions may help determine which patients are most likely to benefit from treatment. J. Am. Acad. ChildAdolesc. (copyright) 2009 by the American Academy of Child and Adolescent Psychiatry.
Journal of the American Academy of Child & Adolescent Psychiatry, 48(6) : 643-651
- Year: 2009
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Psychological Interventions (any)
, Psychoeducation, Other Psychological Interventions
Stewart, Michelle, DelBello, Melissa P., Versavel, Mark, Keller, David
Objective: Methods: Results: Conclusion: The aim of this study was to examine global functioning, health-related quality of life (HRQOL), and clinical outcome in children and adolescents with bipolar I disorder, schizophrenia, or schizoaffective disorder following ziprasidone treatment.Sixty-three subjects (aged 10-17 years) received open-label ziprasidone, titrated from 10 to 40 mg twice a day (b.i.d.) (low-dose group) or from 20 to 80 mg b.i.d. (high-dose group); fixed doses were used until week 3, followed by flexible doses for 6 months. The Children's Global Assessment Scale (CGAS) characterized functional impairment at baseline and following treatment. The Child Health Questionnaire (CHQ) assessed HRQOL at baseline.Baseline CHQ showed greater impairment in psychosocial functioning than in physical health. Baseline mean CGAS scores were substantially below normal (i.e., <70), indicating functional impairment. Improvement in CGAS scores occurred as early as the first week of treatment. The low correlations between both CHQ and CGAS and the efficacy measures at baseline indicate that these scales measure different constructs. Nevertheless, there was good correlation between improvements in the CGAS and changes in Brief Psychiatric Rating Scale-Anchored (BPRS-A) and Young Mania Rating Scale (YMRS) during ziprasidone treatment.CHQ and CGAS scales may be useful together with standard efficacy measures for children and adolescents with these disorders.
Journal of Child & Adolescent Psychopharmacology, 19(6) : 635-640
- Year: 2009
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
, Tricyclic antidepressants
Wozniak, J., Mick, E., Waxmonsky, J., Kotarski, M., Hantsoo, L., Biederman, J.,
Background: The aim of this study was to test the efficacy and safety of olanzapine+topiramate versus olanzapine monotherapy in the treatment of bipolar disorder (BPD) and treatment-attendant weight gain in children and adolescents. Method: Subjects (N=40) were outpatients of both sexes, 6-17 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BPD (manic, hypomanic, or mixed) and Young Mania Rating Scale (YMRS) total score of >15 treated over 8-week periods in two partially concurrent open-label trials with olanzapine (n=17) or olanzapine+topiramate (n=23). Results: Subjects in both groups experienced a statistically significant reduction in YMRS scores after 8-week, open-label treatment with olanzapine (baseline YMRS=26.7(plus or minus)9.5; end-point YMRS=18.2(plus or minus)12.5, p=0.04) and olanzapine+topiramate (baseline YMRS=31.3(plus or minus)7.9; end-point YMRS=20.4(plus or minus)11.4, p=0.04). There was no difference in response between the two groups based on YMRS or Clinical Global Impressions-Improvement (CGI-I) scores. Adverse events were few and mild and similar between the two groups, with the exception of weight gain. The weight gain in the olanzapine group was 5.3(plus or minus)2.1kg and the weight gain in the olanzapine+topiramate group was statistically significantly lower, 2.6(plus or minus)3.6kg. Conclusions: Augmentation of olanzapine with topiramate resulted in a reduced weight gain over the course of an 8-week, open-label trial when compared with olanzapine treatment alone, but did not lead to greater reduction in symptoms of mania. (copyright) 2009, Mary Ann Liebert, Inc.
Journal of Child & Adolescent Psychopharmacology, 19(5) : 539-545
- Year: 2009
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Anticonvulsants/mood stabilisers (excl. lithium)
Tramontina, S., Zeni, C. P., Ketzer, C. R., Pheula, G. F., Narvaez, J., Rohde, L. A.
Objective: To assess response to treatment with aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/ hyperactivity disorder (ADHD). Method: Children and adolescents were extensively assessed according to DSM-IV criteria for bipolar disorder comorbid with ADHD (n = 710). Those with this comorbidity who were acutely manic or in mixed states were randomly assigned in a 6-week double-blind, placebo-controlled trial to aripiprazole (n = 18) or placebo (n = 25). Primary outcome measures were assessed weekly and included the Young Mania Rating Scale; the Swanson, Nolan, and Pelham Scale-Version IV; and weight. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness scale, the Child Mania Rating Scale-Parental Version (CMRS-P), the Children's Depression Rating Scale-Revised, the Kutcher Adolescent Depression Scale, and adverse events. The trial was conducted at the Hospital de Clinicas de Porto Alegre, Rio Grande do Sul, Brazil, from January 2005 to November 2007. Results: The group receiving aripiprazole showed a significantly greater reduction in YMRS scores (P = .02, effect size [ES] = 0.80), CMRS-P scores (P = .02; ES = 0.54), and CGI-S scores (P = .04; ES = 0.28) from baseline to endpoint than the placebo group. In addition, higher rates of response (P = .02) and remission (P = .01) were found for the aripiprazole group. No significant between-group differences were found in weight, ADHD symptoms, and depressive symptoms. Adverse events significantly more frequent in the aripiprazole group were somnolence and sialorrhea. Conclusions: Aripiprazole was effective in reducing manic symptoms and improving global functioning without promoting severe adverse events or weight gain. No significant treatment effect in ADHD symptoms was observed. Studies are needed to assess psychopharmacologic interventions for improving ADHD symptoms in juvenile bipolar disorder comorbid with ADHD. Trial Registration: clinicaltrials.gov Identifier: NCT00116259. (copyright) Copyright 2009 Physicians Postgraduate Press, Inc.
Journal of Clinical Psychiatry, 70(5) : 756-764
- Year: 2009
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Wagner, K. D., Redden, L., Kowatch, R. A., Wilens, T. E., Segal, S., Chang, K., Wozniak, P., Vigna, N. V., Abi-Saab, W., Saltarelli, M.,
OBJECTIVE:: To compare the efficacy and safety of divalproex extended-release (ER) to placebo in a 28-day double-blind study of bipolar disorder in children and adolescents and evaluate the safety of divalproex ER in a 6-month open-label extension study. METHOD:: In the double-blind study, 150 patients (manic or mixed episode, aged 10-17 years) with baseline Young Mania Rating Scale (YMRS) score of 20 or higher were randomized to once-daily placebo or divalproex ER, which was titrated to clinical response or serum valproate concentration of 80 to 125 (mu)g/mL. Sixty-six patients enrolled in the extension study. RESULTS:: In the double-blind study, a treatment effect was not observed with divalproex ER based on change in mean YMRS score (divalproex ER -8.8 [n = 74]; placebo -7.9 [n = 70]) or secondary measures. Divalproex was similar to placebo based on incidence of adverse events. Four subjects treated with divalproex ER and three treated with placebo discontinued because of adverse events. Mean ammonia levels increased in the divalproex ER group, but only one patient was symptomatic. In the long-term study, YMRS scores decreased modestly (2.2 points from baseline). The most common adverse events were headache and vomiting. CONCLUSIONS:: The results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder, mixed or manic state. Further controlled trials are required to confirm or refute the findings from this study. Copyright (copyright) 2009 American Academy of Child and Adolescent Psychiatry.
Journal of the American Academy of Child & Adolescent Psychiatry, 48(5) : 519-532
- Year: 2009
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
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Stage: Disorder established (diagnosed disorder)
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Treatment and intervention: Biological Interventions (any)
, Anticonvulsants/mood stabilisers (excl. lithium)
Zeni, Cristian Patrick, Tramontina, Silza, Ketzer, Carla Ruffoni, Pheula, Gabriel Ferreira, Rohde, Luis Augusto
In clinical samples, juvenile bipolar disorder (JBPD) is frequently accompanied by co-morbid attention-deficit/hyperactivity disorder (ADHD). Clinical trials assessing combined psychopharmacological interventions in this population are scarce, and methylphenidate (MPH) may worsen manic symptoms. We conducted a randomized crossover trial with MPH and placebo (2 weeks each) combined with aripiprazole in children and adolescents (n = 16; 8-17 years old) with JBPD and ADHD who had a significant response in manic symptoms with aripiprazole but still presented clinically significant symptoms of ADHD. ADHD, manic, and depressive symptoms were assessed by means of standard scales. Fourteen out of the 16 subjects completed the trial. No significant differences between the effects of methylphenidate and placebo were detected in ADHD (F(1, 43.22) = 0.00; p = 0.97) or manic (F(1, 40.19) = 0.93; p = 0.34) symptoms. Significant improvement in depressive symptoms was observed in the MPH group (F(1,19.03) = 7.75; p = 0.01) according to a secondary self-reported outcome measure. One patient using aripiprazole and MPH discontinued the trial due to the onset of a severe mixed episode. No other significant adverse events were observed. Although MPH did not worsen manic symptoms, it was not more effective than placebo in improving ADHD symptoms in children and adolescents with JBPD co-morbid with ADHD stabilized with aripiprazole. Further investigations are warranted. This study is registered at www.clinicaltrials.gov under the identifier NCT00305370.
Journal of Child & Adolescent Psychopharmacology, 19(5) : 553-561
- Year: 2009
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
, Other biological interventions
Strawn, J. R., DelBello, M. P.
Background: The second-generation antipsychotic olanzapine has been shown to be efficacious as a treatment for adults with bipolar disorder and is approved by the United States Food and Drug Administration for the treatment of acute manic or mixed episodes as well as for maintenance treatment in bipolar adults. Objective: This review examines the use of olanzapine for the treatment of children and adolescents with bipolar disorder and presents a discussion of the mechanism of action, pharmacokinetic and pharmacodynamic properties of olanzapine in children and adolescents. in addition, efficacy and safety data are reviewed and the risks and benefits of using olanzapine in bipolar youth are summarized. Methods: Articles published in English were identified using a search of the National Library of Medicine from 1990 to 2007 with manual review of references of each article as well as review of the US Clinical Trials database. Articles describing the use of olanzapine in children or adolescents were included. Conclusions: Olanzapine appears to have a rapid onset of action for mixed and manic episodes, but is associated with metabolic side effects including hyperprolactinemia, diabetes and weight gain. Therefore, olanzapine may best be used in the acute treatment of children and adolescents experiencing a manic or mixed episode as its side-effect profile may limit its use as a maintenance agent in this population. (copyright) 2008 Informa UK Ltd.
Expert Opinion on Pharmacotherapy, 9(3) : 467-474
- Year: 2008
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Miklowitz, D. J., Axelson, D. A., Birmaher, B., George, E. L., Taylor, D. O., Schneck, C. D., Beresford, C. A., Dickinson, L. M., Craighead, W. E., Brent, D. A.
Context: Family interventions have been found to hasten episode recovery and delay recurrences among adults with bipolar disorder. Objective: To examine the benefits of family-focused treatment for adolescents (FFT-A) and pharmacotherapy in the 2-year course of adolescent bipolar disorder. Design: Two-site outpatient randomized controlled trial with 2-year follow-up. Patients: A referred sample of 58 adolescents (mean [SD] age, 14.5 [1.6] years) with bipolar I (n=38), II (n=6), or not otherwise specified disorder (n= 14) with a mood episode in the prior 3 months. Interventions: Patients were randomly assigned to FFT-A and protocol pharmacotherapy (n = 30) or enhanced care (EC) and protocol pharmacotherapy (n= 28). The FFT-A consisted of 21 sessions in 9 months of psychoeducation, communication training, and problem-solving skills training. The EC consisted of 3 family sessions focused on relapse prevention. Main Outcome Measures: Independent "blind" evaluators assessed patients every 3 to 6 months for 2 years. Outcomes included time to recovery from the index episode, time to recurrence, weeks in episode or remission, and mood symptom severity scores. Results: Analyses were by intent to treat. Rates of 2-year study completion did not differ across the FFT-A (60.0%) and EC conditions (64.3%). Although there were no group differences in rates of recovery from the index episode, patients in FFT-A recovered from their baseline depressive symptoms faster than patients in EC (hazard ratio, 1.85; 95% confidence interval, 1.04-3.29; P=.04). The groups did not differ in time to recurrence of depression or mania, but patients in FFT-A spent fewer weeks in depressive episodes and had a more favorable trajectory of depression symptoms for 2 years. Conclusions: Family-focused therapy is effective in combination with pharmacotherapy in stabilizing bipolar depressive symptoms among adolescents. To establish full recovery, FFT-A may need to be supplemented with systematic care interventions effective for mania symptoms. (copyright)2008 American Medical Association. All rights reserved.
Archives of General Psychiatry, 65(9) : 1053-1061
- Year: 2008
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Psychological Interventions (any)
, Psychoeducation, Other Psychological Interventions
Barekatain, Majid, Jahangard, Leila, Haghighi, Mohammad, Ranjkesh, Farzad
Objectives: Methods: Results: Conclusions: To compare the efficacy and safety of moderate-dose bifrontal (BF) with low-dose bitemporal (BT) electroconvulsive therapy (ECT) in the treatment of patients with severe mania.In a parallel, double-blind, randomized clinical trial, 28 patients with severe mania admitted to a university hospital were assigned randomly to moderate-dose BF (n = 14) and low-dose BT (n= 14) ECT. The primary outcome measures included the Mini-Mental State Examination (MMSE) and the Young Mania Rating Scale (YMRS).All patients received at least 6 sessions of ECT. The 2 groups did not show any difference in their baseline MMSE or YMRS scores (P > 0.05). There was a significant difference between the MMSE scores of the BF compared with the BT group after both the sixth ECT (P < 0.05) and final ECT treatments (P < 0.05). Young Mania Rating Scale scores did not differ between the 2 groups after either the sixth or the last ECT sessions (P > 0.05).Moderate-dose BF ECT was as effective as BT ECT but was associated with fewer cognitive side effects in the treatment of patients with severe mania.
Journal of ECT, 24(3) : 199-202
- Year: 2008
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Electroconvulsive therapy (ECT)
Bishop, J. R., Pavuluri, M. N.
Risperidone is a commonly used medication for the treatment of bipolar disorder and schizophrenia in children and adolescents. It has been studied as a monotherapy treatment in early onset schizophrenia and as both monotherapy and combination therapy for pediatric bipolar disorder. Studies to date indicate that risperidone is an effective treatment for positive and negative symptoms of schizophrenia and mania symptoms of bipolar disorder. In young patient populations, side effects such as weight gain, extrapyramidal side effects, and prolactin elevation require consideration when evaluating the risk benefit ratio for individual patients. Here we review published studies of risperidone for the treatment of bipolar disorder and schizophrenia in children and adolescents to provide practitioners with an overview of published data on the efficacy and safety of risperidone in these patient populations. (copyright) 2008 Dove Medical Press Limited. All rights reserved.
Neuropsychiatric Disease & Treatment, 4(1 A) : 55-68
- Year: 2008
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)