Disorders - Bipolar Disorders
Lee, E. S., Vidal, C., Findling, R. L.
Objectives: The use of atypical antipsychotic medications in pediatric patients has become more prevalent in recent years.
The purpose of this review is to provide a clinically relevant update of recent selected key publications regarding the use of atypical
antipsychotics in this population. Method(s): Studies reviewed included randomized, double-blind, placebo-controlled medication trials conducted
within the past 5 years. A PubMed search was conducted for each of the 11 second-generation antipsychotic medications currently approved by the Food
and Drug Administration for use in the United States: Clozapine, risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, paliperidone,
asenapine, iloperidone, lurasidone, and cariprazine. Trials published in English with subjects 18 years of age and younger were included in this
review. Additional studies, chosen for their significance to clinical practice, were also included at the discretion of the authors. Result(s): This
review demonstrates that more empiric data are available regarding both the acute efficacy and, to a lesser extent, the longer-term efficacy and
tolerability for several of the considered antipsychotic medications. The clinical conditions for which these medications have been studied include
schizophrenia, bipolar disorder, Tourette's disorder, and autism spectrum disorder. They have also been used as an adjunctive treatment for
disruptive behavior disorders with aggression, which have not responded to treatment with stimulants. Conclusion(s): Evidence regarding the efficacy
and tolerability of antipsychotic medications for mental health disorders in children and adolescents has expanded exponentially in recent years.
However, more information is needed so that evidence-based comparisons between medications can be made. In the future, data enabling the selection of
medications based upon individual patient characteristics could potentially lead to greater efficacy and efficiency in treating what are frequently
debilitating medical conditions. Maladaptive aggression in children, often treated with antipsychotics, is one such area in which there is a dearth
of actual information available to the clinician. It is to be hoped that additional, longer-term studies of these medications will further inform
evidence-based practice in clinical settings. Copyright © 2018 Mary Ann Liebert, Inc. publishers.
Journal of Child and Adolescent
Psychopharmacology, 28(9) : 582-605
- Year: 2018
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Davico, C., Canavese, C., Vittorini, R., Gandione,
M., Vitiello, B.
Aim: Anticonvulsant medications are frequently used in clinical practice to treat psychiatric disorders in
children and adolescents, but the evidence for their efficacy is uncertain. We conducted a systematic review of published randomized controlled
trials (RCT) that assessed the psychiatric benefit of anticonvulsants in patients under 18 years of age. Method(s): The Medline, Scopus, Web of
Science, and ClinicalTrials.gov databases were systematically searched for peer-reviewed primary publications of RCTs with a minimum of 10 patients
per treatment arm through December 2017. Result(s): Out of 355 identified non-duplicative publications, 24 met the inclusion criteria. Most RCTs were
to treat bipolar disorder (n = 12) or manage recurrent aggression (n = 9). Few (n = 3) had both a multisite design and adequate statistical power.
Valproate was the most frequently studied anticonvulsant (n = 15). Out of three placebo-controlled RCTs of valproate in bipolar disorder, none showed
efficacy. In four RCTs, valproate was inferior to the antipsychotic risperidone. In several small, single-site RCTs, valproate and sulthiame were
better than placebo for the management of recurrent aggression. Conclusion(s): Currently available RCTs do not support the efficacy of
anticonvulsants as mood stabilizers in children. There is some preliminary evidence from small RCTs of the efficacy of some anticonvulsants in the
control of aggression and behavioral dyscontrol in conduct disorder, autism, and intellectual disability. © Copyright © 2018 Davico, Canavese,
Vittorini, Gandione and Vitiello.
Frontiers in Psychiatry, 9 (no
pagination) :
- Year: 2018
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Anticonvulsants/mood stabilisers (excl. lithium)
Maneeton, B., Putthisri, S., Maneeton, N., Woottiluk,
P., Suttajit, S., Charnsil,
C., Srisurapanont, M.
Background: Some studies have indicated the efficacy of quetiapine in the treatment of bipolar depression
in adult patients. However, its efficacy has been not shown in child and adolescent patients. Objective: This systematic review purposefully
determined the efficacy and acceptability of quetiapine in the treatment of children and adolescents with bipolar depression. Data sources: A
database search of EMBASE, PubMed, CINAHL, and Cochrane Controlled Trials Register was carried out in March 2016. All randomized controlled trials
(RCTs) of bipolar depression in children and adolescents were considered for inclusion in this review. Study eligibility criteria, participants, and
interventions: RCTs of quetiapine in the treatment of child and adolescent patients with bipolar depression with end point outcomes were included in
this study. Languages were not limited. Study appraisal and synthesis methods: The full-text versions of relevant clinical studies were thoroughly
examined and extracted. The primary efficacy of outcome was measured by using the pooled mean-changed scores of the rating scales for bipolar
depression. However, the response and remission rates were also measured. Results: A total of 251 randomized patients in the three RCTs of quetiapine
versus placebo in the treatment of bipolar depression for children and adolescents were eligible in this review. The pooled mean-changed score of the
quetiapine-treated group was not greater than that of the placebo-treated group. Similarly, the pooled response and remission rates were not
different between the two groups. The pooled overall discontinuation rate and the discontinuation rate due to adverse events were not different
between the two groups. Limitations: Limited studies were eligible in this review. Conclusion: According to the findings in this review, quetiapine
may not be efficacious in the treatment of bipolar depression in children and adolescents. Its acceptability, however, was comparable to a placebo.
Therefore, the use of quetiapine in children and adolescents with bipolar depression is not recommended. Further well-defined clinical studies should
be performed to confirm these outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
Neuropsychiatric Disease and Treatment, 13 : 1023
-1032
- Year: 2017
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Naglich, A., Adinoff, B., Brown, E. S.
Bipolar disorder (BD) spectrum and alcohol use disorders (AUDs) commonly occur together.
Comorbidity between the two conditions predisposes patients to elevated risks of adverse outcomes, including hospitalization and suicide, compared
with either condition alone. Despite the consistent relationship observed between BD and AUD, the underlying cause remains incompletely
characterized. Few trials conducted have been able to identify promising interventions for patients with these disease states. The antipsychotic
quetiapine has been evaluated most commonly as a therapeutic agent for patients with BD and AUD followed by naltrexone and acamprosate. Randomized
controlled trials of quetiapine have consistently reported a lack of efficacy for the treatment of patients with BD and AUD. Trials of acamprosate
have also been negative but small in size. Results of the sole randomized controlled trial of naltrexone have found large treatment effect sizes, but
no statistically significant difference between treatment groups. Other agents including the antipsychotic aripiprazole, mood stabilizing agents
including lamotrigine, lithium, and divalproex, and the antiepileptic agent topiramate have also been evaluated for the treatment of BD and AUD with
mixed findings. The lone statistically significant treatment effect was observed in a randomized, placebo-controlled trial of divalproex added on to
lithium which demonstrated a reduction in alcohol use. This review summarizes the available clinical evidence and current guideline recommendations
for the treatment of comorbid BD and AUD, and provides discussion and recommendations based on the current literature.
CNS Drugs, 31(8) : 665-
674
- Year: 2017
- Problem: Bipolar Disorders, Alcohol
Use
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Lithium
Chang, K., Del-Bello, M. P., Goldman, R., Tocco, M., Pikalov, A. A., Cucchiaro, J., Loebel, A.
Objectives: The goal
of this presentation is to evaluate the long-term effectiveness of lurasidone in children and adolescents with bipolar depression. Methods: Patients
(ages 10-17 years) with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind (DB) treatment with flexibly dosed
lurasidone (20-80 mg/day) or placebo. The primary efficacy measure was the Children's Depression Rating Scale, Revised (CDRS-R). Patients who
completed this study were eligible to enroll in a two-year, open-label extension study in which patients were continued on lurasidone (Lur-Lur) or
switched from placebo to lurasidone (Pbo-Lur). We report data from a week 28 interim analysis. Treatment response was defined as 50 percent reduction
from DB baseline in the CDRS-R total score; remission was defined as a CDRS-R total score of 28, a Young Mania Rating Scale (YMRS) total score of 8,
and a Clinical Global Severity-Bipolar (CGI-BP-S) depression score of 3. Results: A total of 347 patients were randomized to lurasidone or placebo
(mean age = 14.3 years). At the primary week 6 endpoint, treatment with lurasidone was associated with statistically significant and clinically
meaningful improvement compared with placebo in CDRS-R total score ( 21.0 vs. 15.3; P < 0.0001; effect size, 0.45). A total of 223 patients entered
the extension study, and 155 (69.5%) completed 28 weeks of treatment; 0.9 percent discontinued treatment before week 28 because of lack of efficacy.
The mean CDRS-R total score at DB baseline was 58.1. Mean improvement in CDRS-R score, from double-blind to open-label baselines, was greater for the
Lur-Lur group versus the Pbo-Lur group ( 23.4 vs. 17.4). On the CDRS-R, mean change from open-label baseline to week 28 of observed cases (OC) (last
observation carried forward, LOCF) for the Lur-Lur and Pbo-Lur groups was 7.3 ( 5.1) and 12.5 ( 10.5), respectively. On the CGI-BP-S, mean change at
week 28 for Lur-Lur and Pbo-Lur groups was as follows: 1.0 ( 0.7) and 1.2 ( 0.9), respectively. Responder rates from double-blind baseline to week 28
OC (LOCF) for Lur-Lur and Pbo-Lur were 84.0 percent (77.0%) and 86.1 percent (81.9%), and remission rates were 58.7 percent (53.1%) and 57.0 percent
(51.4%). Conclusions: In children and adolescents with bipolar depression, long-term treatment with lurasidone was associated with continued
improvement in depressive symptoms.
Journal of the American Academy of Child and Adolescent
Psychiatry, 56 (10) : S266-S267
- Year: 2017
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
Atkin, T., Nunez, N., Gobbi, G.
BACKGROUND: The management of depressive and mixed
symptoms in children and adolescents with bipolar disorder (BD) remains a matter of debate. The goal of this review is, thus, to systematically
examine the impact of atypical antipsychotics (AAPs) and mood stabilisers in the treatment of bipolar depression and/or mixed states.\rMETHODS: A
literature search was conducted for studies assessing the efficacy of pharmacological treatments for bipolar disorder type I, type II and not
otherwise specified with a recent depressive, mixed or manic episode (with depressive symptoms) following DSM-IV criteria in children and adolescents
as either acute or maintenance treatment. The databases searched were PubMed/Medline, Google Scholar and Tripdatabase, as well as ClinicalTrials.gov.
The search was limited to clinical trials, systematic reviews, meta-analyses and open-label trials published in the English language between the
years 2000 and 2015. Sixty clinical studies were found assessing the efficacy of mood stabilisers and AAPs in paediatric BD. Fifteen studies were not
included in the primary analysis because they did not assess depressive symptomology/include scores on rating scales of depressive symptoms (Online
Supplementary Material).\rRESULTS: There is sufficient evidence for a Grade A recommendation of the use of olanzapine plus fluoxetine at reducing
depressive symptoms in bipolar depression and of quetiapine at high doses for depressive symptoms occurring during mixed episodes. Importantly, even
though monotherapy with aripiprazole, risperidone, valproate and lithium was effective at controlling mania, these drugs were not effective at
reducing depressive symptoms (level A evidence for nonrecommendation).\rCONCLUSIONS: These results mostly overlap with the approved treatments for
bipolar depression in adults.
Journal of Child Psychology & Psychiatry & Allied
Disciplines, 58(8) : 865-879
- Year: 2017
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation), Lithium
Sowers, J. A., Swank, P.
The impact of an intervention on the
self-determination and career planning engagement of young adults with mental health challenges was studied. Sixty-seven young adults, 20 to 30 years
of age, with mental health diagnoses (e.g., depression, bipolar disorder) were randomly assigned to intervention and control groups. Statistically
significant greater increases were made by the intervention group versus the control group for self-determination and career planning engagement, and
self-determination at least partially mediated increases in career planning engagement. With career planning self-determination interventions, young
adults with mental health challenges might be able to achieve better career and life outcomes than is typical for this population.
Journal of Social Work in Disability & Rehabilitation, 16(2) : 161-
179
- Year: 2017
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Service Delivery & Improvement, Psychological Interventions
(any), Other Psychological Interventions, Individual placement and support (IPS), vocational
interventions
Mousavi, S. Y., Khezri, R., Karkhaneh-Yousefi, M.
A., Mohammadinejad, P., Gholamian, F., Mohammadi, M. R., Zeinoddini, A., Akhondzadeh, S.
OBJECTIVE:
Recent studies have focused on the role of inflammatory cascades as one of the possible etiologic factors of bipolar disorder. We hypothesize that
celecoxib, through its anti-inflammatory properties, may have a therapeutic role in acute bipolar mania.\rPATIENTS AND METHODS: Forty-two adolescent
inpatients with the diagnosis of acute bipolar mania participated in a parallel, randomized, double-blind controlled trial, and 40 patients underwent
an 8-week treatment with either celecoxib (100mg twice daily) or placebo as an adjunctive treatment to lithium and risperidone. Patients were
evaluated using Young Mania Rating Scale (YMRS) at baseline and weeks 2, 4, and 8. The primary outcome measure was to assess the efficacy of
celecoxib compared with placebo in improving mania symptoms.\rRESULT: General linear model repeated measures showed significant effect for
timextreatment interaction on YMRS scores [F (2.54, 96.56)=3.21, p=0.03]. Significantly greater improvement was observed in YMRS scores in the
celecoxib group compared with the placebo group from baseline YMRS score at week 8 (p=0.04). Although a 35% greater response to treatment
(considering a Clinical Global Impressions-Improvement score of <=2, very much/much improved) was observed in the celecoxib group compared with the
placebo group, the difference did not reach the statistical significance level (p=0.09). No serious adverse event was reported.\rCONCLUSIONS:
Celecoxib may be an effective adjuvant therapy in treatment of manic episodes (without psychotic features) of adolescents with bipolar mood disorder.
The mood-stabilizing role of this drug might be mediated through its action on inflammatory cascades.
Journal of Child & Adolescent Psychopharmacology, 27(6) : 494-
500
- Year: 2017
- 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), Lithium, Other biological interventions
Findling, R. L., Youngstrom, E.
A., Rowles, B. M., Deyling, E., Lingler,
J., Stansbrey, R. J., McVoy, M., Lytle, S., Calabrese, J. R., McNamara, N. K.
OBJECTIVE: To determine if acute treatment with aripiprazole (APZ) would be
superior to treatment with placebo in reducing dysfunctional symptoms of elevated mood and/or irritability in symptomatic children and adolescents at
familial high risk for bipolar disorder (BPD) whose mood episodes occur spontaneously. These are patients we have previously referred to as suffering
from \"cyclotaxia.\"\rMETHODS: This was single-site, randomized, double-blind, placebo-controlled outpatient clinical trial in which youths aged 5-17
years who met diagnostic criteria for either cyclothymic disorder (CYC) or BPD not otherwise specified (BP-NOS) were randomly assigned to receive
either APZ or placebo. Eligible participants had at least one parent with BPD, another first- or second-degree relative afflicted with a mood
disorder, and also had not responded to psychotherapy. Treatment with APZ was initiated at a dose of approximately 0.1mg/kg/day and could be
increased by approximately 0.05mg/kg/day at each study visit. Patients were seen weekly for 4 weeks and then every other week thereafter for 12
weeks. The primary outcome measure was mean change from baseline on Young Mania Rating Scale (YMRS) total score.\rRESULTS: A total of 59 patients (30
APZ, 29 placebo) aged 11.8 (SD=2.7) years were randomized and returned for at least one postbaseline assessment. The mean total daily doses of active
APZ and placebo were 7.1mg (SD=3.7) and 7.4mg (SD=4.2), respectively. At the 12-week time point, APZ was superior to placebo on the primary outcome
measure (p<0.005). Most adverse events were mild and transient in nature. There was a significant difference in weight gain from baseline between
patients who received APZ (2.3kg [SD=3.3]) and those who received placebo (0.7kg [SD=1.8]).\rCONCLUSION: This double-blind trial found that APZ was
significantly more efficacious than placebo in reducing symptoms of mania in children and adolescents with cyclotaxia.
Journal of Child & Adolescent Psychopharmacology, 27(10) : 864-
874
- Year: 2017
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: At risk (indicated or selected prevention), Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions
(any), Atypical Antipsychotics (second
generation)
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)