The rationale, design, and progress of two novel maintenance treatment studies in pediatric bipolarity

ABSTRACTIntroduction: There are no definitively established acute or maintenance treatments for juvenile bipolar disorder.Method: Two randomized, blind, maintenance clinical trials in children and adolescents with bipolar disorders are ongoing at the University Hospitals of Cleveland/Case Western Reserve University Stanley Clinical Research Center for bipolar disorder. The first is comparing the safety and effectiveness of lithium carbonate (Li+) to divalproex sodium (VPA) for up to 76 weeks in youths with stabilized bipolar illness (type 1 or 2). The second study is designed to compare the efficacy of VPA to placebo in the acute management of subsyndromal symptoms of bipolar disorder (‘cyclotaxia’) and the prevention of the full syndrome in children at risk. Both studies use the prospective life-chart method as an outcome measure.Results: Sixty-six youths have received study medication as part of the trial that is comparing Li+ to VPA as a maintenance therapy. In addition, 32 youths have received blinded treatment as part of the ‘cyclotaxia’ prevention study. Combination Li+A/PA treatment appears generally well tolerated and seems to have robust anti-manic and antidepressant effects.Discussion: Since the blind has not been broken on either of these clinical trials, conclusions about the maintenance effectiveness of either VPA or Li+ in youths with bipolar disorder type 1 or 2 cannot be made yet. Similarly, it is unclear whether VPA is superior to placebo in genetically high-risk youths with cyclotaxia. The final results of these trials should provide valuable information about the treatment of juvenile bipolar disorders.

Download Full-text

Pharmacological Treatments for Bipolar Disorder

10.1093/med:psych/9780199342211.003.0008 ◽

2015 ◽

Author(s):

Paul E. Keck ◽

Susan L. McElroy

Keyword(s):

Bipolar Disorder ◽

Bipolar Depression ◽

Bipolar Disorders ◽

Pharmacological Management ◽

Randomized Controlled ◽

Bipolar Ii ◽

Long Acting ◽

Depressive Episodes ◽

Subsyndromal Symptoms

The majority of clinical trials in patients with bipolar disorders have been conducted in groups with bipolar I illness, although a few trials have included patients with bipolar II disorder. Pharmacological management of bipolar disorder involves the treatment of acute manic, hypomanic, mixed, and depressive episodes, as well as the prevention of further episodes and subsyndromal symptoms. Lithium, divalproex, carbamazepine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine have demonstrated efficacy in the treatment of acute mania in randomized controlled (type 1) trials. Although the pharmacological treatment of acute bipolar depression remains understudied, data from randomized controlled trials indicate that lithium, olanzapine, olanzapine-fluoxetine, quetiapine, lurasidone, tricyclics, monoamine oxidase inhibitors, and fluoxetine have efficacy in this phase of the illness. Lithium, lamotrigine, olanzapine, aripiprazole, quetiapine, and risperidone (long-acting, injectable) have been shown to have efficacy in relapse prevention. Less extensive data suggest that divalproex and carbamazepine are also efficacious for prevention.

Download Full-text

Erector spinae plane block for minimally invasive mitral valve surgery: a double-blind, prospective, randomised placebo-controlled trial—a study protocol

BMJ Open ◽

10.1136/bmjopen-2020-045833 ◽

2021 ◽

Vol 11 (4) ◽

pp. e045833

Author(s):

Danny Feike Hoogma ◽

Steffen Rex ◽

Jos Tournoy ◽

Peter Verbrugghe ◽

Steffen Fieuws ◽

...

Keyword(s):

Clinical Trials ◽

Cardiac Surgery ◽

Mitral Valve ◽

Controlled Trial ◽

Mitral Valve Surgery ◽

Valve Surgery ◽

Erector Spinae ◽

University Hospitals ◽

Double Blind ◽

The University

IntroductionIn the context of enhanced recovery after cardiac surgery, surgical techniques for mitral valve surgery have witnessed substantial modifications, from approaching the heart using open approaches with traditional sternotomy to thoracoscopic access via minithoracotomy. After cardiac surgery, acute postoperative pain is frequent and caused by surgical incision and retraction. Perioperative analgesia in cardiac surgery still relies mainly on opioids. Although neuraxial techniques could be a valuable non-opioid-based analgesia regimen, they can be associated with devastating complications in situations with (iatrogenic) coagulation abnormalities. Only two randomised clinical trials describe the erector spinae plane (ESP) block to provide sufficient postoperative analgesia following cardiac surgery with median sternotomy. Regarding postoperative analgesia after cardiac surgery with a minithoracotomy approach, adequately designed trials are still lacking. We, therefore, designed a double-blind, placebo-controlled trial to prove the hypothesis that the ESP block reduces opioid consumption in patients undergoing minimally invasive mitral valve surgery (MIMVS).Methods and analysisSixty-four patients undergoing MIMVS will be included in this double-blind, prospective, placebo-controlled trial. Patients will be randomised to receive an ESP block with a catheter with either intermittent ropivacaine 0.5% (ropi group) or normal saline 0.9% (placebo group). Both groups will receive patient-controlled intravenous analgesia with morphine following extubation. Primary endpoint is the 24-hour cumulative morphine consumption after extubation. Multiple secondary endpoints will be evaluated.Ethics and disseminationThe study is approved by the ethics committee of the University Hospitals Leuven, the Clinical Trials Centre of the University Hospitals Leuven and the ‘Federaal Agentschap voor Geneesmiddelen en Gezondheidsproducten’. Dissemination of the study results will be via scientific papers.Trial registration numberEudraCT identifier: 2019-001125-27.

Download Full-text

The Efficacy of Probiotics for Treatment of Bipolar Disorder- Type 1: A Randomized, Double-Blind, Placebo-Controlled Trial

Iranian Journal of Psychiatry ◽

10.18502/ijps.v15i1.2435 ◽

2020 ◽

Author(s):

Mahin Eslami Shahrbabaki ◽

Saleheh Sabouri ◽

Abdolreza Sabahi ◽

Delaram Barfeh ◽

Parisa Divsalar ◽

...

Keyword(s):

Bipolar Disorder ◽

Placebo Group ◽

Mental Disorders ◽

Repeated Measures ◽

Rating Scale ◽

Controlled Trial ◽

Bipolar Disorders ◽

Significant Difference ◽

Disorder Type

Objective: Bipolar disorders are among the most common chronic mental disorders. Despite the recent improvement in controlling psychiatric disorders, treatment of bipolar disorders remains a challenge. The aim of this study was to determine the effect of consuming probiotics in patients with bipolar disorder-type 1 compared to the placebo group. Method: This was a permuted blocked randomized clinical trial conducted in Shahid Beheshti mental hospital in Kerman, Iran, from October 2017 to October 2018. Two psychiatrists diagnosed and hospitalized all 38 patients with type 1 bipolar disorder based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Using blind randomized blocking method size 4, patients were divided into 2 groups of placebo and probiotic. Young Mania Rating Scale (YMRS) and Hamilton's Depression Rating Scale (HDRS) were completed at the beginning, week 4, and week 8 of the study by a psychiatry resident. Independent t test, Mann-Whitney and repeated measures ANOVA tests were used. Data were analyzed using SPSS software version 20. Results: There was no significant difference between the 2 groups in age, sex, and severity of mania and depression. Consumption of probiotics reduced the scores of YMRS and HDRS over time in the probiotic group more than the placebo group, but it was not significant. Conclusion: Consumption of probiotics had non-significant effects on improvement and treatment of bipolar type 1 patients. It is suggested that future studies be conducted with different probiotic microbial strains and longer period of treatment.

Download Full-text

Pharmacological Treatments for Bipolar Disorder

A Guide to Treatments that Work ◽

10.1093/med:psych/9780195304145.003.0012 ◽

2007 ◽

pp. 323-350 ◽

Cited By ~ 1

Author(s):

Paul E. Keck ◽

Susan L. McElroy

Keyword(s):

Bipolar Disorder ◽

Bipolar Depression ◽

Antidepressant Treatment ◽

Bipolar Disorders ◽

Mood Stabilizers ◽

Pharmacological Management ◽

Randomized Controlled ◽

Bipolar Ii ◽

Depressive Episodes ◽

Subsyndromal Symptoms

The vast majority of clinical trials in patients with bipolar disorders have been conducted in groups with bipolar I illness, although a few trials have recently emerged specifically in patients with bipolar II disorder. The pharmacological management of bipolar disorder involves the treatment of acute manic, hypomanic, mixed, and depressive episodes, as well as the prevention of further episodes and subsyndromal symptoms. Lithium, divalproex, carbamazepine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole have demonstrated efficacy in the treatment of acute mania in randomized, controlled (Type 1) trials. Although the pharmacological treatment of acute bipolar depression remains understudied, data from randomized, controlled trials indicate that lithium, olanzapine, olanzapine-fluoxetine, quetiapine, lamotrigine, tricyclics, MAOIs, fluoxetine, and pramipexole have efficacy in this phase of the illness. The optimal duration of antidepressant treatment, in combination with mood stabilizers, is still unknown. Lithium, lamotrigine, olanzapine, and aripiprazole have been shown to have efficacy in relapse prevention. Less extensive data suggest that divalproex and carbamazepine are also efficacious as preventative treatments.

Download Full-text

Current research in child and adolescent bipolar disorder

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2008.10.2/cademeter ◽

2008 ◽

Vol 10 (2) ◽

pp. 215-228

Keyword(s):

Bipolar Disorder ◽

Early Intervention ◽

Children And Adolescents ◽

Current Knowledge ◽

Bipolar Disorders ◽

Research Groups ◽

Bipolar Illness ◽

The Past ◽

Subsyndromal Symptoms ◽

Longitudinal Treatment

Although recently more research has considered children with bipolar disorder than in the past, much controversy still surrounds the validity of the diagnosis. Furthermore, questions remain as to whether or not childhood expressions of bipolarity are continuous with adult manifestations of the illness. In order to advance current knowledge of bipolar disorders in children, researchers have begun to conduct phenomenological, longitudinal, treatment, and neuroimaging studies in youths who exhibit symptoms of bipolar illness, as well as offspring of parents with bipolar disorders. Regardless of the differences between research groups regarding how bipolar disorder in children is defined, it is agreed that pediatric bipolarity is a serious and pernicious illness. With early intervention during the period of time in which youths are exhibiting subsyndromal symptoms of pediatric bipolarity, it appears that the progression of the illness to the more malignant manifestation of the disorder may be avoided. This paper will review what is currently known and what still is left to learn about clinically salient topics that pertain to bipolar disorder in children and adolescents.

Download Full-text

Pregnancy and bipolar disorder: the risk of recurrence when discontinuing treatment with mood stabilisers: a systematic review

Acta Neuropsychiatrica ◽

10.1017/neu.2016.60 ◽

2016 ◽

Vol 29 (5) ◽

pp. 259-266 ◽

Cited By ~ 9

Author(s):

Erik Roj Larsen ◽

Kristina Saric

Keyword(s):

Bipolar Disorder ◽

Clinical Trials ◽

Bipolar Disorders ◽

Close Monitoring ◽

Risk Of Recurrence ◽

Electronic Search ◽

Unplanned Pregnancies ◽

A Minor ◽

Design And Methods ◽

In Pregnancy

ObjectiveBipolar disorder in pregnancy may be difficult to treat. The dilemma is whether the women should continue medication throughout pregnancy, and maybe accept a minor risk to harm their unborn child, or discontinue medication and increase the risk of recurrence, which can lead to maternal morbidity, thereby endangering themselves and their foetus.Design and methodsIn September 2016, three electronic search databases; PubMed, Scopus and PsycInfo, were used searching for clinical trials concerning this question. Eight clinical trials concerning risk of recurrence after discontinuation of medication in pregnancy were included.ResultsThere is no consensus concerning the risk of discontinuation of medication during pregnancy among bipolar women. The evidence from the trials included underscore that there seem to be a group of pregnant women who are stable despite they are not receiving mood stabilisers during pregnancy. Besides, there is a group of more severe and more unstable bipolar disorders that seem to benefit of a more close monitoring, support and prophylactic medication during pregnancy and postpartum period to prevent recurrence.ConclusionFor the more stable bipolar women we recommend a well planned and more slowly discontinuation of medication before pregnancy. For the unplanned pregnancies it is important to consider the possibility of a more slowly discontinuation. For the more severe conditions of bipolar disorder, it is important to secure a close monitoring of medication. As the risk of postpartum relapse is high, medication may be started soon after delivery.

Download Full-text