Mixed Methods Thematic Analysis of a Randomised Controlled Trial of Adjunctive Mitochondrial Agents for Bipolar Depression

Bipolar disorder is a common condition diagnosed by the occurrence of pathological mood elevation but most often dominated by dysphoria states. Over the past 10 years, understanding of bipolar disorder and the number of evidence-based treatments have increased dramatically. This article offers strategies for improving diagnostic confidence and simple benchmarks that facilitate integrating principles of evidence-based medicine into the management of patients with bipolar disorder. Simple systematic assessment techniques such as focusing the evaluation to assess the most extreme episode of mood elevation and longitudinal factors such as age of onset and course of illness can avoid errors of omission and raise diagnostic confidence. An iterative measurement-based treatment model that aims to bring patients and their supports into the collaborative care process for progressively better outcomes is recommended.

BackgroundBipolar disorder is a severe mental illness with high morbidity and mortality rates. Even with pharmacological treatment, frequent recurrence of episodes, long episode durations, and persistent interepisode symptoms are common and disruptive. Combining psychotherapy with pharmacotherapy improves outcomes; however, many individuals with bipolar disorder do not receive psychotherapy. Mental health technologies can increase access to self-management strategies derived from empirically supported bipolar disorder psychotherapies while also enhancing treatment by delivering real-time assessments, personalized feedback, and provider alerts. In addition, mental health technologies provide a platform for self-report, app use, and behavioral data collection to advance understanding of the longitudinal course of bipolar disorder, which can then be used to support ongoing improvement of treatment.ObjectiveA description of the theoretical and empirically supported framework, design, and protocol for a randomized controlled trial (RCT) of LiveWell, a smartphone-based self-management intervention for individuals with bipolar disorder, is provided to facilitate the ability to replicate, improve, implement, and disseminate effective interventions for bipolar disorder. The goal of the trial is to determine the effectiveness of LiveWell for reducing relapse risk and symptom burden as well as improving quality of life (QOL) while simultaneously clarifying behavioral targets involved in staying well and better characterizing the course of bipolar disorder and treatment response.MethodsThe study is a single-blind RCT (n=205; 2:3 ratio of usual care vs usual care plus LiveWell). The primary outcome is the time to relapse. Secondary outcomes are percentage time symptomatic, symptom severity, and QOL. Longitudinal changes in target behaviors proposed to mediate the primary and secondary outcomes will also be determined, and their relationships with the outcomes will be assessed. A database of clinical status, symptom severity, real-time self-report, behavioral sensor, app use, and personalized content will be created to better predict treatment response and relapse risk.ResultsRecruitment and screening began in March 2017 and ended in April 2019. Follow-up ended in April 2020. The results of this study are expected to be published in 2022.ConclusionsThis study will examine whether LiveWell reduces relapse risk and symptom burden and improves QOL for individuals with bipolar disorder by increasing access to empirically supported self-management strategies. The role of selected target behaviors (medication adherence, sleep duration, routine, and management of signs and symptoms) in these outcomes will also be examined. Simultaneously, a database will be created to initiate the development of algorithms to personalize and improve treatment for bipolar disorder. In addition, we hope that this description of the theoretical and empirically supported framework, intervention design, and study protocol for the RCT of LiveWell will facilitate the ability to replicate, improve, implement, and disseminate effective interventions for bipolar and other mental health disorders.Trial RegistrationClinicalTrials.gov NCT03088462; https://www.clinicaltrials.gov/ct2/show/NCT03088462International Registered Report Identifier (IRRID)DERR1-10.2196/30710

In this article, we review empirical research on the role of individuals' parenting and maltreatment histories as developmental antecedents for symptoms and diagnosable episodes of unipolar and bipolar spectrum disorders. Our review is focused on the following three overarching questions: (1) Do negative parenting and a history of maltreatment contribute risk to symptoms or diagnosable episodes of unipolar and bipolar disorders? (2) Are the associations of negative parenting and maltreatment histories with bipolar disorders similar to those for unipolar depression? and (3) Are the associations between negative parenting and maltreatment histories and unipolar and bipolar symptoms or disorders mediated by cognitive vulnerability to depression? We begin by discussing the methodological requirements for demonstrating a psychosocial risk factor and the methodological issues that plague the parenting and maltreatment literatures. Next, we review the extant studies on the role of parenting histories in unipolar and bipolar disorders. We consider the specificity and possible moderators of the parenting-mood disorder relationship, as well as cognitive vulnerability to depression as a mediator of this relationship. Then, we review studies on the association of maltreatment histories with unipolar and bipolar disorders and the role of cognitive vulnerability to depression as a mediator of this association. We conclude with an assessment of the state of the parenting and maltreatment literatures in unipolar and bipolar disorder with regard to our guiding questions.

Early identification and treatment of young people at high risk of recurrent mood disorders: a feasibility study

A Simple Question Answered: Adding Moderate-Dosage Lithium Does Not Help Patients With Bipolar Disorder

Flying Almost Blind

Some studies have suggested that oxcarbazepine has a role in preventing episode recurrence in bipolar affective disorder. This review attempted to investigate the existing evidence from randomised controlled trials for its use in the maintenance treatment of this illness. To review the efficacy of oxcarbazepine, relative to placebo and other agents, in the prevention of affective episodes of bipolar affective disorder. The efficacy of oxcarbazepine was considered in terms of episode recurrence, general and social functioning. Adverse effects, overall acceptability to participants and mortality were also considered. CCDANCTR-Studies and CCDANCTR-References were searched on 7/11/2007. Medline, CENTRAL, EMBASE and PsycINFO were searched in March 2007. Specialist journals and conference proceedings were handsearched. Reference lists of relevant papers and major textbooks of affective disorder were checked. Authors, experts in the field and pharmaceutical companies were contacted requesting information on published or unpublished trials. Randomised controlled trials comparing oxcarbazepine with placebo or alternative agents, where the stated intent of intervention was the maintenance treatment of bipolar affective disorder were sought. Participants with bipolar disorder, male and female, of all ages, were included. Data were extracted from the original reports individually by two review authors. The methodological quality of included studies was assessed individually by two review authors. The main outcomes were the efficacy of oxcarbazepine maintenance treatment in preventing or attenuating further episodes of bipolar affective disorder (including its efficacy in rapid cycling disorder), the acceptability of oxcarbazepine treatment to participants, the prevalence of side-effects, and mortality, if any, on oxcarbazepine treatment. Where appropriate, data concerning outcome measures and adverse effects were to be extracted from the studies and analysed using Review Manager software. Two randomised controlled trials were found that met the methodological criteria for inclusion in the review. However, they did not report data with sufficient clarity to allow their confident extraction for inclusion in the meta-analysis. Findings from the two studies were presented descriptively. There is an insufficient methodologically rigorous evidence base to provide guidance on the use of oxcarbazepine in the maintenance treatment of bipolar disorder. Given the need for more efficacious therapeutic agents, there is a need for good quality randomised controlled trials examining the therapeutic potential of this and related agents in bipolar disorder.

AGE-RELATED DIFFERENCES IN MEDICATION ADHERENCE, SYMPTOMS, FUNCTIONING, AND STIGMA LEVELS IN POORLY-ADHERENT ADULTS WITH BIPOLAR DISORDER

Eduard Vieta: unravelling bipolar disorder's mysteries

Tiagabine, an anticonvulsant, has been reported to have efficacy in prophylactic treatment of bipolar disorder in case reports and in case series. To review the efficacy and acceptability of tiagabine, relative to placebo, and other agents in the prevention and/or attenuation of episodes of bipolar affective disorder. The efficacy and acceptability of tiagabine were considered in terms of mood symptoms, mortality, general health, social functioning, adverse effects and overall acceptability to patients. The following databases were searched on 13-10-2005. The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References),The Cochrane Controlled Clinical Trials Register (CCCTR),EMBASE,MEDLINE,LILACS,PsycLIT andPsyndex. Reference lists of relevant papers and major textbooks of affective disorder were examined.Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. Specialist journals and conference proceedings were handsearched. Randomised controlled trials which compare tiagabine with placebo, alternative mood stabilisers or antipsychotics, where the stated intent of intervention was the maintenance treatment of bipolar affective disorder, were sought. Bipolar patients, male and female, of all ages were to be included. Data were to be extracted from the original reports if they met our inclusion criteria. The main outcomes to be assessed were:(1) The efficacy of tiagabine treatment in preventing or attenuating further episodes of bipolar affective disorder, including its efficacy in rapid cycling disorder.(2) The acceptability of tiagabine treatment to patients.(3) The prevalence of side effects.(4) Mortality, if any, on tiagabine treatment.Outcomes concerning relapse or recurrence were to be analysed excluding data from studies using discontinuation protocols, which were to be analysed separately. Sub-group analyses were to be performed to examine the effects of tiagabine treatment in rapid cycling bipolar disorder and previous mood stabiliser non-responders. Data were to be analysed using Review Manager version 4.2.8. No randomised controlled trials of tiagabine in the maintenance treatment of bipolar disorder were found. There is an insufficient methodologically rigorous evidence base to provide guidance on the use of tiagabine in the maintenance treatment of bipolar disorder. There is a need for randomised controlled trials examining the therapeutic potential of this agent in bipolar disorder, after the nature of reported episodes of syncope or seizure in tiagabine-treated bipolar patients has been established.

Psychotropic Medications for Patients With Bipolar Disorder in the United States: Polytherapy and Adherence

Bipolar affective disorder is an episodic mental disorder characterized by manic, hypomanic, depressive, and mixed episodes, usually recurring and can last a lifetime. Patients with bipolar disorder have annual medical costs that were four times those of patients without bipolar disorder. The aim of this study is to analyze the cost-effectiveness of combination therapy between mood stabilizers and antipsychotics in patients with the bipolar affective disorder at Grhasia Mental Hospital Yogyakarta. This study is a retrospective with cohort study design using medical records and direct medical cost data during Januari-December 2018 period. Subjects are patients who were diagnosed with bipolar affective disorder manic episode (F31.2) and received a combination of mood stabilizer and antipsychotic therapy. The results were obtained in 46 patients with the affective disorder who met the inclusion criteria. The average direct medical cost of the sodium divalproate group was IDR 6.319.933 per day and in the lithium group was IDR 5.705.953 per day. The average length of stay in the sodium divalproate group was 25,79 days and in the lithium group was 25,75 days (P = 0,991). The Average Cost Effectivity Ratio (ACER) sodium divalproat group is lower than the lithium group (IDR 221.246 per day and IDR 245.434 per day, respectively). The conclusion of this study is that the combination of sodium divalproate-antipsychotic therapy is more cost-effective than lithium-antipsychotic therapy in a patient with bipolar affective disorder manic episode

Objective To analyze effects of lithium carbonate on thyroid function in patients with bipolar affective disorder. Methods Thirty patients with bipolar disorder and depressive episode treated in Shenzhen Kangning hospital from April 2016 to November 2017 were selected as observation group. Another 30 healthy persons in the same period were selected as control group, and the thyroid function of the two groups was compared. Results The thyroxine 4(T4), free thyroxine 3(FT3) and free thyroxine 4(FT4) in observation group were significantly lower than those in control group before treatment (P 0.05). In observation group, FT4 was significantly decreased after using lithium carbonate (P<0.05). Conclusions Lithium carbonate in the treatment of bipolar affective disorder can reduce the patients’ thyroid function in a certain degree. Key words: Bipolar affective disorder; Lithium carbonate; Thyroid function

A major factor in the rapid advance of medical science over the past 50 years has been the development and refinement of the clinical research method known as the randomized controlled trial (RCT). A clinical trial is defined as a prospective scientific experiment that involves human subjects in whom treatment is initiated for the evaluation of a therapeutic intervention. In an RCT, each patient is assigned to receive a specific treatment intervention by a chance mechanism. Nothing more clearly indicates the key role of an RCT in modern clinical research than the placement of this specific research method at the top of the list of levels of evidence in evidence-based medicine.1 According to this classification, significant results of an RCT are more definitive than any other type of clinical research information. The purpose of this article is to present an overview of the design of RCTs. Some of the principles of a high-quality study, such as the use of randomization, placebos, and double-blind designs are well known. Other principles such as stratification, use of a decision-making structure, and statistical power are known by many investigators but are not universally recognized or fully understood. These features plus others that indicate the design of a high-quality RCT are discussed. A companion article on the conduct and evaluation of RCTs will appear in a future issue of this journal. One of the most easily recognized aspects of a well-designed and conducted clinical trial is the apparent clarity of the research mechanism evident in its published report. Alternatively, one of the more common problems with a published clinical trial is the apparent “design by committee” in which different members of a protocol team have different goals. Because a clinical trial is a resource-intensive undertaking, many investigators feel that the study should attempt to …

Hypomania as a Genuine Side Effect of Fluoxetine