Disorders - Bipolar Disorders
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
-
Stage: Disorder established (diagnosed disorder)
-
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
-
Stage: Disorder established (diagnosed disorder)
-
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
-
Stage: Disorder established (diagnosed disorder)
-
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
-
Stage: Disorder established (diagnosed disorder)
-
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)
Forbes, A., Nyilas, M., Loze, J., Laughton, J., Johnson, B., Aurang, C., Iwamoto, T., Carson,
W. H., Owen, R.
Background: Early onset of
bipolar disorder is often chronic and associated with significant comorbidity, including substance abuse, violence, and suicide. Moreover, the long-
term consequences of this illness greatly impact the ability of these youths to carry out normal daily functions, with devastating effects on social
interactions, school performance, and family relationships/dynamics. Due to a lack of published long-term safety and efficacy data from large-scale,
randomized, controlled trials in this patient population, physicians are most-often guided by data from adult studies to make important decisions on
the selection of appropriate treatment as well as selection of a safe and potentially efficacious dose. This is problematic, as children and
adolescents may show a different pattern of response and seem to be more sensitive to antipsychotic-related adverse events, such as sedation,
extrapyramidal side effects, weight gain and endocrine and metabolic abnormalities [1,2]. Methods: 296 youths, ages 10-17 year-old with a DSM-IV
diagnosis of bipolar I disorder were randomized to receive either placebo or aripiprazole (10 mg or 30 mg) in a 4-week double-blind trial. Completers
continued assigned treatments for an additional 26 weeks (double-blind). A 5-member, independent, Data Safety Monitoring Board (DSMB) provided
frequent assessment of patient safety. Efficacy endpoints included mean change from the pretreatment baseline to Week 4 and to Week 30 on the Young-
Mania Rating Scale (Y-MRS); Children's Global Assessment Scale (CGAS), Clinical Global Impressions Scale-Bipolar Version (CGI-BP) severity score,
Children's Depression Rating Scale-Revised (CDRS-R) score, General Behavior Inventory Scale (GBI) score, Attention Deficit Hyperactivity Disorders
Rating Scale (ADHD-RS-IV) score, time to discontinuation due to all reasons, and response rate (defined as > 50% reduction from baseline in the YMRS
total score). Safety measures included frequency and severity of adverse events (AE), Simpson Angus Scale (SAS), Abnormal Involuntary Movement Scale
(AIMS), Barnes Akathisia Rating Scale (BARS), as well as blood chemistries and body weight. Results: Over the 30-week course of double-blind
treatment, aripiprazole (10 mg and 30 mg) was superior to placebo as early as week 1 (p < 0.002) and at all scheduled visits from week 2 through week
30 on mean change from baseline in the Y-MRS total score (p < 0.0001; all visits). Significant improvements were observed on multiple endpoints
including the CGAS, GBI, CGI-BP, ADHD-RS-IV total score, time to discontinuation, and response and remission rates. Most AEs were mild to moderate in
severity with 14% discontinuation due to adverse events over the course of 30 weeks (7% in the 4-week acute phase) in aripiprazole treated patients.
The most common AEs in the combined aripiprazole groups were somnolence, extrapyramidal disorder, and fatigue. Significant difference from placebo
was observed on the SAS (30 mg), but not on the BARS, at Week 30. Low prolactin levels were more frequent in aripiprazole treated patients than
placebo. There were no clinically significant changes in weight z-scores at end of study. Conclusions: Over 30-weeks of treatment, both doses of
aripiprazole were superior to placebo in the acute and long term treatment of pediatric bipolar patients. Aripiprazole was generally well
tolerated.
European
Neuropsychopharmacology, 18(S4) : S556-S557
- Year: 2008
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Hiremani, Raja M., Thirthalli, Jagadisha, Tharayil, Biju S., Gangadhar, Bangalore N.
Background: Method: Results: Conclusion:
Bifrontal electrode placement is as efficacious as bitemporal placement during electroconvulsive therapy (ECT) in depression but is associated with
fewer cognitive adverse effects. There are no studies comparing these techniques in acute mania. This study compared the short-term efficacy and
adverse effects of bifrontal and bitemporal ECT in the treatment of acute mania.Thirty-six DSM-IV mania inpatients referred for ECT were recruited
for study. They were randomized to receive bifrontal (BFECT; n = 17) or bitemporal (BTECT; n = 19) ECT. None of the subjects were on mood stabilizers
during the course of ECT. Severity of mania was measured on the Young Mania Rating Scale (YMRS) before beginning ECT and then on Days 3, 7, 11, 14,
and 21 of treatment. Cognitive functions were assessed eight hours after the fifth ECT session using the Mini-Mental Status Examination (MMSE),
Paired Associate Learning Test, Complex Figure Test, Verbal Fluency Test (animals and fruits categories), and Trail Making Test, Part A.The subjects
in the two groups were comparable on sociodemographic and clinical variables, including severity of mania at baseline. They were also similar in ECT
parameters, including seizure threshold and seizure duration. Mean YMRS scores showed faster decline in the BFECT than in the BTECT group. Kaplan-
Meier survival analysis showed that a greater proportion of subjects in the BFECT group responded (50% reduction in YMRS score) significantly earlier
than in the BTECT group. There were no significant differences between the groups in performance on cognitive function tests.In this pilot study,
mania patients treated with BFECT responded faster than those treated with BTECT, with comparable cognitive adverse effects. Since ECT is usually
prescribed for rapid control of symptoms, BFECT may be preferred over BTECT in the treatment of acute mania.
Bipolar Disorders, 10(6) : 701-707
- Year: 2008
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Electroconvulsive therapy (ECT)
Fountoulakis,
Konstantinos N., Vieta, Eduard
This
paper is a systematic review of the available data concerning the treatment of bipolar disorder: a systematic Medline search concerning treatment
guidelines and clinical trials. The search for treatment guidelines returned 583 articles and 913 papers for RCTs. The search was last performed on 1
March 2008. An additional search included repositories of clinical trials and previous systematic reviews in order to trace especially older trials.
The literature suggests that lithium is useful during the acute manic and the maintenance phase. Both first- and second-generation antipsychotics are
efficacious in the treatment of acute mania. Quetiapine and the olanzapine-fluoxetine combination are also effective for treating bipolar depression,
while olanzapine, quetiapine and aripiprazole are effective during the maintenance phase. Anticonvulsants, particularly valproate and carbamazepine
have antimanic properties, whereas lamotrigine may be preferably effective in the treatment of depression but not mania. Antidepressants should
always be used in combination with an antimanic agent because they were reported to induce switching to mania or hypomania, mixed episodes, and rapid
cycling when given as monotherapy. The best evidence-based psychosocial interventions for bipolar disorder are group- and family-focused
psychoeducation. Electroconvulsive therapy is an option for refractory patients. Although a variety of treatment options for bipolar disorder is
currently available, their effectiveness is far from satisfactory, especially against bipolar depression and maintenance. Combination therapy may
improve treatment outcome but it also carries the burden of more side-effects. Further research as well as the development of better guidelines and
algorithms for step-by-step rational treatment are necessary.
International Journal of Neuropsychopharmacology, 11(7) : 999-
1029
- Year: 2008
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Psychological Interventions
(any)