Disorders - Bipolar Disorders
Singh, M., Goldman, R., Tocco, M., Pikalov, A., Deng, L., Cucchiaro, J., Loebel, A.
Background and Aims: To evaluate change in specific depressive symptoms in children and adolescents presenting with bipolar depression who received short-term treatment with lurasidone. Method: Data in this secondary analysis were derived from a study of patients 10-17 years (N=343) with a DSM-5 diagnosis of bipolar I depression who were randomized to 6 weeks of double-blind treatment with lurasidone 20-80 mg/d or placebo. The primary endpoint was change from Baseline to Week 6 on the Children's Depression Rating Scale, Revised (CDRS-R) total score. Change from Baseline to Week 6 for each individual CDRS-R item was assessed with an ANCOVA using an LOCF approach. Cohen's deffect sizes were also calculated at Week 6. Results: At the primary Week 6 endpoint, treatment with lurasidone was associated with significant improvement vs. placebo in the CDRS-R total score (-21.0 vs. -15.3; P<0.0001; effect size [d]=0.45). A total of 13 CDRS-R items (76%) were significantly improved on lurasidone: impaired school work (P=0.023; d=0.25), difficulty having fun (P=0.004; d=0.31), social withdrawal (P<0.0001; d=0.43), sleep disturbance (P=0.0001; d=0.43), appetite disturbance (P<0.05; d=0.22), irritability (P=0.026; d=0.24), excessive guilt (P=0.0032; d=0.32), low self-esteem (P=0.012; d=0.27), depressed feelings (P=0.0068; d=0.29), excessive weeping (P=0.014; d=0.27), depressed facial affect (P=0.0009; d=0.36), listless speech (P<0.0001; d=0.43), and hypoactivity (P=0.012; d=0.27). The remaining CDRS-R items were not significant. Conclusion: In this placebo-controlled study of children and adolescents with bipolar depression, 6 weeks of treatment with lurasidone was effective in treating a wide range of depressive symptoms assessed by the CDRS-R.
Bipolar Disorders, 20 (Supplement 1) : 66
- Year: 2018
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Tocco, M., Pikalov, A., Siu, C., Loebel, A.
Background and Aims: To evaluate the efficacy and safety of lurasidone in the treatment of children and adolescents with bipolar depression presenting with mixed (subsyndromal hypomanic) features. Method: Patients 10-17 years of age with a DSM-IV-TR diagnosis of bipolar I depression, were randomized to 6 weeks of double-blind treatment with flexible dose lurasidone 20-80 mg/d or placebo. The presence of mixed features was defined as a YMRS score >=5 at study baseline. Efficacy analyses included change from baseline to week 6 in Children Depression Rating Scale, Revised (CDRS-R) score, and Clinical Global Impressions-Bipolar Severity of Depression Score (CGI-BP-S). Results: Treatment with lurasidone (vs placebo) was associated with significantly greater reduction in CDRS-R score at week 6 in pediatric bipolar depressed patients with mixed features (-21.5 vs -15.9; P<0.01; effect size, 0.45), and without mixed features (-20.4 vs -14.8; P<0.01; effect size, 0.45). Similar significant improvement was observed for reduction in CGI-BP-S score at week 6 in the mixed features group (-1.6 vs -1.1; P<0.001; effect size 0.57), and in the group without mixed features (-1.3 vs -1.0; P=0.05; effect size 0.30). Rates of protocol-defined treatment-emergent hypomania or mania were comparable for lurasidone and placebo in patients with and without mixed features. Conclusion: In this post-hoc analysis of a placebo controlled trial, lurasidone was found to be efficacious in the treatment of child and adolescent patients with bipolar depression presenting with and without mixed (subsyndromal hypomanic) features.
Bipolar Disorders, 20 (Supplement 1) : 66-67
- Year: 2018
- Problem: Bipolar Disorders
- Type: Randomised controlled trials
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Amerio, A., Ossola, P., Scagnelli, F., Odone, A., Allinovi, M., Cavalli, A., Iacopelli, J., Tonna, M., Marchesi, C., Ghaemi, S. N.
Introduction: Many clinicians are reluctant to use traditional mood-stabilizing agents, especially lithium, in children and adolescents. This review examined the evidence for lithium's safety and efficacy in this population. Methods: A systematic review was conducted on the use of lithium in children and adolescents with bipolar disorder (BD). Relevant papers published through June 30th 2018 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. Results: 30 articles met inclusion criteria, including 12 randomized controlled trials (RCTs). Findings from RCTs demonstrate efficacy for acute mania in up to 50% of patients, and evidence of long-term maintenance efficacy. Lithium was generally safe, at least in the short term, with most common side effects being gastrointestinal, polyuria, or headache. Only a minority of patients experienced hypothyroidism. No cases of acute kidney injury or chronic kidney disease were reported. Conclusions: Though the available literature is mostly short-term, there is evidence that lithium monotherapy is reasonably safe and effective in children and adolescents, specifically for acute mania and for prevention of mood episodes. Copyright © 2018 Elsevier Masson SAS
European Psychiatry, 54 : 85-97
- Year: 2018
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Lithium
Channing, J., Mitchell, M., Cortese, S.
Objective: To perform a systematic review of studies of lurasidone in children and/or adolescents and to present a case report aimed to add further insights into its use in clinical practice with youth. Methods: We searched the following databases for empirical studies, of any design, focusing on the pharmacokinetics, efficacy, or safety of lurasidone in children and/or adolescents: Pubmed (Medline), OVID (PsycInfo, EMBASE+EMBASE classic, OVID Medline), Web of Knowledge, and ClinicalTrials.gov (last search January 23, 2018). Results: From a pool of 301 potentially relevant references, we retained 12 pertinent studies (reported in 28 references), including 1 pharmacokinetics study, 1 double blind randomized controlled trial (RCT) for bipolar depression (BD) with 1 related interim analysis study of its extension phase and 1 related external posterior predictive check study, 1 double blind RCT for schizophrenia with 3 related interim analyses of its extension phase, 1 RCT and 1 case report for autism spectrum disorder, and 2 open-label studies focusing on a variety of disorders. Overall, these studies show that lurasidone is significantly more efficacious than placebo, with moderate effect sizes, and is well tolerated for BD and schizophrenia in youth. Published studies in youth have in general used doses up to 80 mg/day. Our case report suggests that high doses of lurasidone (148 mg/day) were well tolerated and might have contributed to substantial functional improvement in a 14-year old girl with psychosis and a previous history of anorexia nervosa, who had not responded to previous antipsychotics (olanzapine, risperidone, aripiprazole). Conclusions: There is increasing evidence that lurasidone may be moderately effective and well tolerated for the treatment of BD and psychosis in youth and may have procognitive effects. Our case report suggests that future RCTs should assess the efficacy and tolerability of high doses (>80 mg/day) of lurasidone in youth. © Copyright 2018, Mary Ann Liebert, Inc., publishers 2018.
Journal of Child and Adolescent Psychopharmacology, 28(7) : 428-436
- Year: 2018
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, Atypical Antipsychotics (second generation)
Duffy, A., Heffer, N., Goodday, S. M., Weir, A., Patten, S., Malhi, G. S., Cipriani, A.
Objectives: To assess the efficacy and tolerability of lithium for the treatment of acute mania in children and adolescent diagnosed with bipolar disorder. Methods: A systematic literature search up to August 2017 was conducted for clinical trials that included lithium in males and females up to 18 years of age with a diagnosis of bipolar disorder and experiencing a manic or mixed episode according to standardized diagnostic criteria. The protocol was registered in PROSPERO (CRD42017055675). Results: Four independent studies described in seven manuscripts met the inclusion criteria. Overall, 176 patients were treated with lithium either as a monotherapy or adjunct to risperidone. Efficacy results suggest that lithium may be superior to placebo (standardized mean difference [SMD] -0.42, 95% confidence interval [CI] -0.88 to 0.04), comparable to sodium divalproex (SMD -0.07, 95% CI: -0.31 to 0.18), but significantly less effective than risperidone for treating protracted manic/mixed episodes and comorbid attention-deficit hyperactivity disorder (ADHD) in prepubertal children (SMD 0.85, 95% CI: 0.54 to 1.15). Lithium was not associated with serious adverse events, and was generally well tolerated with common side effects similar to those reported in adults. Conclusions: Limited data suggests that lithium may be an effective and tolerable treatment for some forms of paediatric mania. However, lithium is clearly inferior in efficacy to risperidone in prepubertal patients diagnosed with protracted manic/mixed episodes and comorbid ADHD. There is a lack of data concerning the efficacy and tolerability of lithium as an acute treatment for classical mania in adolescents and important clinical issues remain unaddressed. Copyright © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Bipolar Disorders., 20 : 583 - 593
- Year: 2018
- Problem: Bipolar Disorders
- Type: Systematic reviews
-
Stage: Disorder established (diagnosed disorder)
-
Treatment and intervention: Biological Interventions (any)
, 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.
METHODS: 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).
RESULTS: 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).
CONCLUSIONS: 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.
PATIENTS 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.
RESULT: 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.
CONCLUSIONS: 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."
METHODS: 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.
RESULTS: 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]).
CONCLUSION: 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)