Pharmacotherapy for bipolar depression: an economic assessment

Bipolar disorder (BPD) is a common, severe and recurrent mood disorder associated with high rates of comorbidities, suicide, dysfunction and a high socioeconomic burden. Although the management of BPD has traditionally focused on the acute treatment of mania, the chronic nature of BPD necessitates long-term maintenance treatment. Bipolar depression is the predominant abnormal affective pole and causes greater disability and economic burden than mania. Maintenance pharmacotherapy can reduce rates of future episodes, and subsequently, the associated risks, functional disability and economic burden of bipolar illness.     

Risperidone long-acting injection as monotherapy and adjunctive therapy in the maintenance treatment of bipolar I disorder

Importance of the field: It is very rare for patients with bipolar disorder to have a single episode of mania or depression over a lifetime and the vast majority of these individuals need long-term prophylactic/maintenance treatment. However, treatment nonadherence is a major issue for close to half of subjects with bipolar disorder who are prescribed medications. Risperidone long-acting injection (LAI) has proven efficacious for the maintenance phase of bipolar disorder and may mitigate the problem of nonadherence in the substantial group of patients for whom this is a significant concern.

Areas covered in this review: This paper comprises a review and commentary regarding the use of risperidone LAI in bipolar disorder.

What the reader will gain: The reader will gain an understanding regarding the risks and benefits of risperidone LAI in bipolar disorder. We review the available evidence and discuss the strengths and weaknesses of published studies, providing an opinion about the clinical usefulness of risperidone LAI as well as suggestions for future research.

Take home message: The use of risperidone LAI, through improved adherence, has the potential to ameliorate the course of bipolar disorder.     

Akathisia and Newer Second-Generation Antipsychotic Drugs: A Review of Current Evidence

Akathisia continues to present a significant challenge in clinical practice. As a class, so-called atypical, or second-generation, antipsychotics (SGAs) are the mainstay of treatment for schizophrenia and are commonly used to treat mood disorders. These medications have traditionally been distinguished from first-generation antipsychotics by their lowered risk of extrapyramidal side effects (EPS) such as dystonia, dyskinesia, akathisia, and pseudoparkinsonism. However, the occurrence of EPS, particularly akathisia, has been demonstrated to some degree in all commercially available SGAs. This review examines the incidence of akathisia in nine newer SGAs in patients with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We performed a search of PubMed, ClinicalTrials.gov, Cochrane Central Register, and Google Scholar, as well as manufacturer websites and product labeling for published and unpublished clinical trials, meta-analyses, and systematic reviews. Studies evaluating adult patients with schizophrenia, bipolar disorder, or MDD were eligible for inclusion. Data on treatment-emergent akathisia rates were gathered from each study, and potential dose-response relationships were explored. A total of 177 studies were included in this review, comprising 58,069 patients across 414 treatment arms. Compared with placebo with a composite 3.7% incidence of akathisia, individual SGAs produced akathisia at total composite rates ranging from 2.9–13.0% across the included studies. High doses of an SGA were generally associated with an increased risk of akathisia. Clinicians should consider the risk of akathisia when choosing a treatment option and monitor for akathisia in patients beginning therapy with an SGA or following a dose increase of the SGA.     

Brexpiprazole for the Treatment of Schizophrenia and Major Depressive Disorder: A Comprehensive Review of Pharmacological Considerations in Clinical Practice

Mood and psychotic disorders are a group of illnesses that affect behavior and cognition. Schizophrenia is characterized by positive symptoms, such as delusions and hallucinations, as well as negative symptoms. Major depressive disorder (MDD) is a mood disorder that affects the patient’s emotions, energy, and motivation. Brexpiprazole works as a partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A. Schizophrenia and MDD have a wide range of risk factors, both biological and environmental. Third generation antipsychotics, which include brexpiprazole, are the latest group of drugs to reach the market, demonstrating efficacy and tolerability. Patients with acute schizophrenia have responded well to brexpiprazole. In this regard, in patients who have MDD plus anxiety symptoms, brexpiprazole can be effective as an adjunctive therapy and can reduce anxiety symptoms. In summary, brexpiprazole has proved to be an effective alternative to typical or first and second-generation atypical antipsychotics.     

A Review on Attachment and Adolescent Substance Abuse: Empirical Evidence and Implications for Prevention and Treatment

Background: This paper reviews research on the relation of attachment and substance use disorders (SUD) in adolescence. Based on a theoretical introduction, we review evidence for a possible general link between SUD and insecure attachment, for links between specific forms of SUD and specific patterns of attachment, and for studies on family patterns of attachment in adolescence. Methods: Using medical and psychological databases, we identified 10 studies on adolescent SUD and another 13 studies on adult SUD. Results: Empirical evidence strongly supports the assumption of insecure attachment in SUD samples. With regard to specific patterns of attachment, results mainly point towards fearful and dismissing-avoidance, whereas single studies report preoccupied and unresolved patterns. Results indicate different patterns of attachment in different groups of substance abusers, that is, fearful-avoidant attachment in heroin addicts and more heterogeneous results in abusers of other substances. Explorative data suggest different types of insecure family attachment patterns, which might imply different functions of substance abuse and lead to different treatment recommendations. Methodological problems such as poor assessment of SUD and the use of different measures of attachment limit comparability. Conclusions: Although a lot of research is still needed to address the unknowns in the relation between attachment and SUD, there is strong evidence for a general link between SUD and insecure attachment. Data on connections between different patterns of attachment and different pathways towards SUD are less conclusive but mainly point to disorganized and externalizing pathways. Evidence suggests that fostering attachment security might improve the outcome of state-of-the-art approaches in both early interventional treatment and prevention. Implications for individual and family approaches are outlined.     

The safety and tolerability of atypical antipsychotics in bipolar disorder

Atypical antipsychotics (aAPs), have become a first-line treatment option, both in schizophrenia and bipolar disorders. Almost all aAPs now have proven efficacy in acute mania, some also in bipolar depression and in maintenance treatment. This provides reliable data on their safety and tolerability in this particular group of patients. This review focuses on the safety and tolerability of aAPs in the treatment of bipolar disorders. Both tolerability, for example, extrapyramidal symptoms, and safety issues, for example, occurrence of weight gain and hyperglycaemia, will be highlighted for olanzapine, quetiapine, risperidone, ziprasidone and aripiprazole.     

Combination of aripiprazole with mood stabilizers for the treatment of bipolar disorder: from acute mania to long-term maintenance

Introduction: Bipolar disorder is characterized by a complex set of symptoms, including recurrent manic, depressive or mixed episodes. Acute and long-term treatment of patients with bipolar disorder is mandatory to prevent symptom relapse and episode recurrences. Outcomes with monotherapy are often unsatisfactory in clinical practice, hence combinations of mood stabilizers and antipsychotics are widely utilized in patients showing no or partial response to, as well as intolerance to, monotherapies. This may offer a therapeutic advantage, however, the possibility of an increased incidence of side effects should be considered.

Areas covered: This paper reviews the current treatment guidelines for the treatment of bipolar disorder and examines the rationale behind the use of aripiprazole in combination with mood stabilizers for acute and long-term treatment of bipolar disorder.

Expert opinion: The combination of aripiprazole and mood stabilizers seems to offer an effective and relatively well-tolerated option for the treatment of acute mania and for the maintenance treatment of patients with bipolar I disorder. The combination presents a lower risk of metabolic side effects compared with other combination therapies, but increases the risk of extrapyramidal side effects with long-term treatment. The aripiprazole–valproate combination seems to be particularly promising in the treatment of patients with comorbidities such as anxiety and drug abuse, obsessive-compulsive disorder and bipolar disorder, as well as in mixed depressive disorder. Controlled trials are necessary in order to confirm these observations and to provide a useful insight for improving the use of drug combinations in bipolar patients.     

拉莫三嗪治疗双相情感障碍的研究进展

拉莫三嗪作为心境稳定剂治疗双相情感障碍已经应用于临床。在2013年最新的CANMAT指南中新增了拉莫三嗪单药或联合其他药物的治疗方案,提示目前应用拉莫三嗪治疗双相情感障碍已受到广泛关注。本文综述了近几年拉莫三嗪在治疗双相情感障碍各亚型中的临床研究、安全性及应用前景,为双相障碍的治疗提供新观点及新思路。     

Challenges and Outcomes of Parallel Care for Patients With Co-Occurring Psychiatric Disorder in Methadone Maintenance Treatment

Objective: Most opioid users seeking treatment in community-based substance abuse treatment programs have at least one co-occurring psychiatric disorder, and the presence of psychiatric comorbidity in this population is associated with increased psychological distress, poorer quality of life, and reduced response to substance abuse treatment. This observational study describes clinical outcomes of referring patients receiving methadone maintenance with at least one co-occurring psychiatric disorder to a community psychiatry program located on the same hospital campus. Methods: Participants (n = 156) were offered priority referrals to a community psychiatry program that included regularly scheduled psychiatrist appointments, individual and group therapy, and enhanced access to psychiatric medications for 1 year. Psychiatric distress was measured with the Symptom Checklist (SCL-90-R), which participants completed monthly. Results: While about 80% of the sample (n = 124) initiated psychiatric care, the average length of treatment was only 128.2 days (SD = 122.8), participants attended only 33% of all scheduled appointments (M = 14.9 sessions, SD = 14.1), and 84% (n = 104) did not complete a full year of care. Of those who did not complete a full year, over half (55%, n = 68) left psychiatric care while still receiving substance abuse treatment. Exploratory negative binomial regression showed that baseline cocaine and alcohol use disorder (p =.002 and.022, respectively) and current employment (p =.034) were associated with worse psychiatric treatment retention. Modest reductions in psychiatric distress over time were observed (SCL-90-R Global Severity Index change score = 2.5; paired t = 3.54, df = 121, p =.001). Conclusions: Referral of patients with co-occurring psychiatric disorders receiving methadone maintenance to a community psychiatry program is often ineffective, even after reducing common barriers to care. Service delivery models designed to improve attendance and retention, such as integrated care models, should be evaluated. This study is part of a larger clinical trial, registered at www.clinicaltrials.gov under #NCT00787735.     

Aripiprazole for the treatment of bipolar disorder: a review of current evidence

Introduction: Several medications are available for the treatment of different phases of bipolar disorder, yet many of the drugs that are currently approved carry a substantial burden of side effects or do not lead all treated patients to remission.

Areas covered: This paper comprises a review and commentary regarding the use of oral and intramuscular aripiprazole in the acute and maintenance phases of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration of aripiprazole with other medications are provided. This paper presents practical strategies to translate the data from clinical research into clinical practice.

Expert opinion: Aripiprazole has proven to be an effective medication for the acute treatment of manic and mixed episodes, as well as for the prophylactic–maintenance phase of bipolar disorder in patients recovering from a manic/mixed episode. Choosing the appropriate dosing and tapering strategy, addressing the side effects, controlling withdrawal symptoms from previous medications and using adjunctive medications when necessary are key to successful treatment with aripiprazole.     

The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review

Levomilnacipran, the more active enantiomer of the serotonin and norepinephrine reuptake inhibitor (SNRI) milnacipran, was recently approved in the US for the treatment of major depressive disorder (MDD). The drug was developed as an extended release (ER) capsule formulation to allow for once-daily administration, thereby improving patient adherence. This agent differs from other available SNRIs in having a greater potency for inhibition of norepinephrine relative to serotonin reuptake. The efficacy of levomilnacipran ER has been evaluated in seven randomised, double-blind clinical trials (one Phase II and four Phase III trials, and two long-term efficacy studies). These studies documented that levomilnacipran is generally more effective than placebo for the treatment of MDD in the short-term, whereas no firm evidence exists on long-term efficacy for relapse prevention. Preliminary evidence suggests that levomilnacipran ER may be effective in improving not only depressive symptoms but also symptoms related to functioning (social life, work, and family life). Short-and longer-term studies found that the rate of withdrawal from levomilnacipran therapy due to adverse events was rather low. Moreover the drug appeared to be generally well tolerated. The most common adverse effects included nausea, hyperhidrosis, constipation, tachycardia, palpitations, erectile dysfunction and ejaculation disorder. As hypertension or orthostatic hypotension may occur in a few patients, the cardiovascular safety of levomilnacipran needs to be more extensively investigated especially on long-term treatment. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of levomilnacipran ER in the treatment of MDD in relation to currently available antidepressants including other SNRIs.     

Efficacy and safety of fluoxetine monotherapy in bipolar depression: a systematic review

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries with up to 30% of the population affected. Since NAFLD is associated with an increased risk of cardiovascular (CV) disease, these patients should be stratified for CV risk factors, including atherogenic dyslipidemia, and managed accordingly. Lifestyle modifications represent an effective treatment for NAFLD, since most patients are overweight or obese. Also, promising, but not conclusive, results are available for current pharmacologic treatment. Drugs potentially effective against NAFLD include insulin sensitisers as well as fibrates and omega-3 polyunsaturated fatty acids, while there is reluctance to use statins in patients with suspected or established chronic liver disease. Several other therapeutic options are potentially available, and more data are expected from new peroxisome proliferator-activated receptor agonists and incretin-based therapies.     

社会牙周治疗需要指数与血脂的相关性研究

目的 了解社会牙周治疗需要指数与血脂水平的关系.方法 1 879名来大庆油田总医院进行健康体检者被纳入本项研究.所有实验对象均取静脉血检测胆固醇、甘油三酯、高密度脂蛋白胆固醇,低密度脂蛋白胆固醇.牙周状况采用牙周治疗需要指数评价.校正了性别、吸烟情况、血糖、年龄、体重指数、舒张压等影响因素后,对牙周治疗需要指数与血脂水平进行相关性分析.结果 牙周治疗需要指数与血清总胆固醇、低密度脂蛋白存在正相关,且具有统计学意义.牙周治疗需要指数与血清高密度脂蛋白、甘油三脂不存在统计学意义的相关关系.结论 牙周病的严重程度与血清总胆固醇、低密度脂蛋白的水平有关,牙周病对血脂水平的影响可能是其促成动脉粥样硬化的病变基础.     

Changes in Neuropsychological Status during the Initial Phase of Abstinence in Alcohol Use Disorder: Neurocognitive Impairment and Implications for Clinical Care

Background: Neuropsychological deficits are common in individuals with alcohol use disorder (AUD) and impact daily functioning and AUD treatment outcomes. Longitudinal studies demonstrate that extended abstinence improves neuropsychological functioning. The effects of short-term abstinence are less clear. Objectives: This study examined changes in neuropsychological functioning after acute detoxification over a 10-day period at the beginning of residential AUD treatment. Notably, this study evaluated cognitive functioning according to diagnostic classifications for neurocognitive disorder according to DSM-5. Methods: Using a within-subjects design, neuropsychological functioning of participants (N = 28) undergoing a 14-day residential AUD treatment program was assessed at two time points over 10 days (i.e., treatment entry, prior to treatment discharge). Tests of immediate memory, visuospatial abilities, attention, language abilities, delayed memory, and executive functioning were administered. Results: After completing acute detoxification, almost all participants (93%) were clinically impaired in at least one of the five cognitive domains at residential treatment entry, with one third of the sample impaired on ≥3 domains. Ten days later, 71% remained clinically impaired in at least one of five cognitive domains, with 29% of the sample impaired on ≥3 domains. Significant improvement over the 10-day period was observed for immediate memory, visuospatial abilities, and overall cognitive functioning. Clinical significance of these changes is also reported. Conclusions/Importance: The results from this study help to characterize cognitive functioning in terms of neurocognitive impairment. A brief period of abstinence begins to ameliorate neuropsychological deficits, but many individuals remain cognitively impaired throughout treatment. Implications for treatment are discussed.     

Repeated Addiction Treatment use in Sweden: A National Register Database Study

Sweden has a free, universal addiction treatment system, yet few studies exist examining utilization of treatment in this country. This study identified predisposing, enabling, and need factors associated with history of number of voluntary addiction treatment episodes for a national sample of 12,009 individuals assessed for an alcohol and/or drug use disorder in Sweden. On average, people reported 4.3 prior treatment episodes. Linear regression methods identified that predisposing factors such as older age and being male were associated with more voluntary addiction treatment episodes compared to younger and female clients; a higher Addiction Severity Index (ASI) employment score (an enabling factor) was associated with more voluntary addiction treatment episodes; and need factors including a history of inpatient mental health treatment, a higher ASI psychiatric score, a higher ASI alcohol score, higher levels of illicit drug use, more compulsory addiction treatment episodes, a lower ASI legal score, and a history of criminal justice involvement were all associated with more voluntary addiction treatment episodes compared to their counterparts.. There were no differences in the number of treatment episodes by education or immigrant status. Implications: (1) Need is a key factor associated with more treatment use. (2) Further studies are needed to identify gender differences in access/use of treatment. (3) Given multiple treatment histories, Swedish addiction treatment policy should reflect a chronic care model rather than an acute care model.     

Monocyte and Lymphocyte Activation in Bipolar Disorder: A New Piece in the Puzzle of Immune Dysfunction in Mood Disorders

Background:

This study tested the hypothesis that the low-grade inflammation presented in patients with bipolar disorder (BD) is associated with expansion of activated T cells, and this activated state may be due to a lack of peripheral regulatory cells.

Methods:

Specifically, we investigated the distribution of monocytes and lymphocyte subsets, and investigated Th1/Th2/Th17 cytokines in plasma by flow cytometry. Twenty-one BD type I patients and 21 age- and sex-matched controls were recruited for this study.

Results:

BD patients had increased proportions of monocytes (CD14+). Regarding lymphocyte populations, BD patients presented reduced proportions of T cells (CD3+) and cytotoxic T cells (CD3+CD8+). BD patients also exhibited a higher percentage of activated T CD4+CD25+ cells, and a lower percentage of IL-10 expressing Treg cells.

Conclusions:

Our data shed some light into the underlying mechanisms involved with the chronic low-grade inflammatory profile described in BD patients.     

Refractive Index Measurement of Pharmaceutical Solids: A Review of Measurement Methods and Pharmaceutical Applications

Refractive index is an important optical parameter that can be used to characterize the physicochemical properties of pharmaceutical solids. The complexity of most drugs and solid oral dosage systems introduces challenges for refractive index measurement methods. These challenges are highlighted, and different types of measurement methods are discussed in this review article. These measurements provide pharmaceutical scientists the opportunity to improve the drug-development process and enhance product quality. Pharmaceutical applications range from identification and quantification of drug crystallinity and polymorphism to mechanical strength assessment of tablets. This review article surveys the literature and evaluates the current and potential future characterization of pharmaceutical solids using refractive index measurements.     

人均限定疗程和药物利用指数比较研究

目的:提出人均限定疗程的概念,并以围术期抗菌药物应用为例,探讨药物利用监测指标的合理选择。方法:收集我院2009年12月-2010年4月147例Ⅰ类切口围术期患者抗菌药物的应用情况,计算所用药品的药物利用指数(DUI)和人均限定疗程,比较2个指标对抗菌药物应用情况的评价结果。结果:我院Ⅰ类切口抗菌药物的DUI和人均限定疗程对不规范用药的阳性检出率分别为61.3%和83.9%(P=0.016);以2d为界的分组统计结果为:疗程≤2d组2项指标对不规范用药检出率比较差异无统计学意义(P>0.05),疗程>2d组2项指标对不规范用药检出率差异有统计学意义(P=0.016),人均限定疗程检出率较高。结论:人均限定疗程是一个比DUI更敏感、易得的药物利用监测指标。