An overview of pharmacotherapy for bipolar I disorder

Introduction: Bipolar I disorder (BD I) is complex with a chronic course that significantly impacts a sufferer’s quality of life. As of right now, there are many available treatments that aim to rapidly treat manic or depressive episodes and stabilize mood. The purpose of this report is to provide an up-to-date comprehensive review of the available evidence-based trials of pharmacotherapy for the treatment of BD I.

Areas covered: This paper reviews randomized active comparator-controlled or placebo-controlled trials evaluating the use of current pharmacotherapy in adults with BD I from phase III to clinical practice. Monotherapy and combination therapy for acute and long-term treatment were reviewed for this purpose.

Expert opinion: There are many treatments available for BD mania; however, the depressive and stabilization phases of the illness remain a clinical challenge. Unfortunately, randomized controlled trials do not represent ‘real world’ patients, as their strict inclusion and exclusion criteria do not allow for different features sometimes present in patients to be considered. Research efforts must also focus on treating cognitive deficits, which adds to lower functional outcome. The authors believe that there is dire need for new, more targeted treatments in BD I, with a critical view of the side effects.     

Pharmacotherapeutic strategies for managing comorbid depression and diabetes

ABSTRACT

Introduction: The increasing prevalence of comorbid depression and diabetes exerts a heavy burden on global health. Co-occurrence of depression and diabetes is common, affecting 14% to 35.8% of patients with diabetes, leading to a higher mortality and morbidity rate, more micro- and macro-vascular diseases and more cognitive decline.

Areas covered: In this paper, the authors address various areas from epidemiology, the association between depression and diabetes, treatment strategies and future directions based on the currently available literature to provide novel insight into the pharmacotherapeutic management of comorbid depression and diabetes.

Expert opinion: Pharmacotherapy can help patients with comorbid depression and diabetes by relieving depressive symptoms and improving glycemic control. When combined with psychological therapy, as a collaborative care effort, pharmacological therapy based on selective serotonin reuptake inhibitors (SSRIs) is recommended for comorbid depression with diabetes. Furthermore, studies with larger sample sizes that can help to define different subtypes of diabetes and severity of depression are needed so that clinicians can draw up a precise and applicable management guidelines for the personalized therapy of these diseases.     

Bipolar depression: the clinical characteristics and unmet needs of a complex disorder

Objective: We reviewed important clinical aspects of bipolar depression, a progressive psychiatric condition that is commonly treated in primary care. Bipolar depression is associated with considerable burden of illness, high suicide risk, and greater morbidity and mortality than bipolar mania.

Methods: We identified articles relevant to our narrative review using a multistep search of the literature and applying terms that were relevant to bipolar depression or bipolar disorder.

Results: Bipolar depression accounts for the majority of time spent unwell for patients with bipolar disorder; high rates of morbidity and mortality arise from full symptomatic episodes and interepisode subsyndromal symptoms. Bipolar depression is an important contributor to long-term dysfunction for patients with bipolar disorder due to psychosocial impairment, loss of work productivity and high rates of substance abuse. Missed and delayed diagnosis is prevalent due to overlapping symptoms with unipolar depression and other diagnoses. Medical comorbidities (i.e. cardiovascular disease, hypertension, obesity, metabolic syndrome) and psychiatric comorbidities (i.e. anxiety disorder, personality disorder, eating disorder, attention-deficit/hyperactivity disorder) are common. Currently, only three treatments are FDA-approved for bipolar depression; monotherapy antidepressants are not a recommended treatment option.

Conclusions: Bipolar disorder is common among primary care patients presenting with depression; it is often treated exclusively in primary care. Clinicians should be alert for symptoms of bipolar disorder in undiagnosed patients, know what symptoms probabilistically suggest bipolar versus unipolar depression, have expertise in providing ongoing treatment to diagnosed patients, and be knowledgeable about managing common medication-related side effects and comorbidities. Prompt and accurate diagnosis is critical.     

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.     

Pharmacological treatment of schizophrenia with comorbid substance use disorder

Introduction: While antipsychotics remain the cornerstone of treatment for schizophrenic patients with comorbid substance use disorder (SUD), such treatment is nonetheless complicated by frequent medical comorbidity and poor adherence to medication. Areas covered: Randomised controlled trials (RCTs) on the efficacy of antipsychotics for the treatment of schizophrenic patients with comorbid SUD are reviewed and analysed on the basis of a systematic literature search (PubMed) ranging from 1985 to 2015. On the same basis, findings from RCTs on the efficacy of psychotropic and other medications used for primary SUD are summarised, and the main issues liable to influence treatment choice are discussed, including pharmacodynamic as well as pharmacokinetic interactions, adherence, medical comorbidity and the impact on brain structure. Expert opinion: As far as the treatment of schizophrenic patients with SUD is concerned, direct and indirect evidence tends to stand in favour of the use of second-generation antipsychotics (SGAs), and particularly those with lower metabolic, cardiovascular and extrapyramidal side effects, as well as those with a depot formulation. A few of the usual medications for the treatment of primary SUD, such as naltrexone and disulfiram for alcohol use and bupropion for tobacco cessation, can also be safely and efficiently administered to schizophrenic patients with SUD.     

Double-blind placebo-controlled trial of fluoxetine in adolescents with comorbid major depression and an alcohol use disorder

Objective

This study compared the acute phase (12-week) efficacy of fluoxetine versus placebo for the treatment of the depressive symptoms and the drinking of adolescents with comorbid major depression (MDD) and an alcohol use disorder (AUD). We hypothesized that fluoxetine would demonstrate efficacy versus placebo for the treatment of both the depressive symptoms and the drinking of comorbid MDD/AUD adolescents.

Methods

We conducted the first double-blind placebo-controlled study of fluoxetine in adolescents with comorbid MDD/AUD. All participants in both treatment groups also received intensive manual-based Cognitive Behavioral Therapy (CBT) and Motivation Enhancement Therapy (MET).

Results

Fluoxetine was well tolerated in this treatment population. No significant group-by-time interactions were noted for any depression-related or drinking-related outcome variable. Subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in both depressive symptoms and level of alcohol consumption. End-of-study levels of depression and drinking were low in both treatment groups.

Conclusions

The lack of a significant between-group difference in depressive symptoms and in drinking may reflect limited medication efficacy, or may result from limited sample size or from efficacy of the CBT/MET psychotherapy. Large multi-site studies are warranted to further clarify the efficacy of SSRI medications in this adolescent MDD/AUD population.     

Pharmacotherapy of postpartum depression

Background: The prevalence and recurrence rates of postpartum depression (PPD) are 13 and 25%, respectively. Despite its detrimental impact on the health of the mother–infant dyad, there is a paucity of data in the literature regarding the efficacy of pharmacological treatment of PPD. Objectives: i) To review the literature on the use of antidepressants and hormonal supplements for the prevention and the treatment of PPD; ii) to give the authors' opinion on the current status of the pharmacological treatment of PPD; and iii) to discuss developments that are likely to be important in the future. Methods: An electronic search was performed by using PubMed, Medline, and PsychINFO. Inclusion criteria were: i) empirical articles in peer-reviewed English-language journals; ii) well-validated measures of depression; and iii) a uniform scoring system for depression among the sample. Results/conclusion: The electronic search yielded a total of 19 articles (12 on treatment and 7 on prevention of PPD) with the following study designs: eight randomized clinical trials (six using placebo control and two using active control groups), and 11 open-label studies. The selection of the specific antidepressant for a woman with PPD should derive from a personalized risk–benefit analysis.     

Therapeutic potential of melanin-concentrating hormone-1 receptor antagonists for the treatment of obesity

The compelling genetic and pharmacological evidence implicating melanin-concentrating hormone-1 receptor (MCH-1R) signalling in the regulation of food intake and energy expenditure has generated a great deal of interest by pharmaceutical companies for the discovery of MCH-1R antagonists, evidenced by the increased number of patents describing MCH-1R antagonists for the treatment of obesity and metabolic syndrome. The structural diversity of small molecular weight drug-like MCH-1R antagonists produced and preclinical studies showing hypophagia and weight loss with small molecular weight and peptidal antagonists in rodents is encouraging and suggests that the identification of clinical candidates will be forthcoming.     

Pathobiological targets of depression

Introduction: Depression is one of the most prevalent and life-threatening forms of mental illness associated with significant disability and mortality. About 21% of the world's population is affected by depression.

Areas covered: The various pathological factors involved in depression are: monoamine hypothesis, neurotransmitter receptor hypothesis, neurotrophic factor hypothesis, hypothalamic–pituitary–adrenal (HPA) dysregulation, oxidative stress, cytokine hypothesis and NO pathway. Recent drug therapies used to treat depression include: selective serotonin re-uptake inhibitors, norepinephrine and dopamine re-uptake inhibitors and several herbal drugs. The present review focuses on recently unraveled pathogenetic hypotheses and therapeutics of mental depression. Moreover, various evaluation models for antidepressants are discussed.

Expert opinion: Stress can be considered as a major contributor to the development of depressive disorder due to the dysregulation of HPA axis. Cytokine effects on behavior are believed to be related in part to their effects on neurotransmitter and neuropeptide function, synaptic plasticity and neuroendocrine function. Although there are multiple pathways that are involved in the pathogenesis of depression, the current antidepressants mainly target monoaminergic pathway. However, the therapeutic potential of other pathways is still under investigation. Drugs targeting NO, cytokines and the kynurenine acid pathway might be the drugs of choice in near future.     

Current pharmacotherapy for obesity: extrapolation of clinical trials data to practice

Introduction: When used prudently and in combination with lifestyle modification, pharmacotherapy has an important role in the management of obesity.

Areas covered: This review covers targets for antiobesity drugs, challenges and limitations, failed translation of basic science to clinical practice, methodological and regulatory issues in clinical trials of pharmacotherapy, efficacy and risks of drugs currently approved for obesity, and clinical practice issues when using antiobesity drugs with emphasis on recently approved drugs.

Expert opinion: Drugs currently approved for long-term therapy of obesity offer modest benefits for most patients, substantial benefits for some and no benefits for others. Numerous methodological problems including exclusion of the type of patients who are most often seen in clinical practices, inadequate enrollment of men and minorities, exclusion of patients taking antidepressants, high dropout rates, lack of follow-up after treatment discontinuation, and less than ideal imputation methods in data analysis limit the interpretation of clinical trials data and generalizability. Single-drug therapies offer small to moderate weight-loss benefits, but are generally better tolerated. Efficacy is enhanced with combination drug therapies, but so are the hazards. Clinicians should base their decisions on the expected and observed benefit-to-risk balance.     

儿童青少年抑郁症的药物治疗

儿童青少年抑郁症是儿童青少年期常见的一种精神疾病,其病程长,复发率高,可严重影响患者的身心健康.儿童青少年抑郁症的治疗主要有心理治疗和药物治疗,轻度抑郁患者可选择心理治疗,但严重抑郁患者需首选药物治疗.本综述结合儿童青少年抗抑郁治疗现状,分析治疗过程中需要注意的问题,提出治疗建议.     

癫痫与抑郁症共病:从临床走向基础

癫痫与抑郁症共病很常见,两者之间存在双向联系,对患者的生活质量造成很大影响。本文从影响因素、发病机制、临床特点和治疗等方面对癫痫与抑郁症共病进行综述。     

脑卒中急性期患者焦虑抑郁共病的临床研究

目的对脑卒中急性期患者进行焦虑抑郁共病的发生率、临床特征、相关因素研究。方法入组患者于发病第二周由两名专训人员对82例进行焦虑、抑郁量表评分与脑卒中患者临床神经功能缺损程度、社会支持量表及应付方式问卷的测评。结果神经功能缺损程度评分分值越高,患脑卒中焦虑抑郁共病（PSCAD）的危险性就越大;社会支持和支持利用度的分值越高,PSCAD发生的危险性就越小。应付方式中积极应付方式分值越高,患PSCAD的危险眭就越小,消极应付方式分值越高,患PSCAD的危险性就越大。结论神经功能缺损严重程度为PSCAD的危险因素,社会支持为PSCAD的保护因素。     

Acute phase and five-year follow-up study of fluoxetine in adolescents with major depression and a comorbid substance use disorder: a review

This paper reviews the results of an acute phase trial and a five-year follow-up study of fluoxetine in adolescents with major depression and a substance use disorder (SUD). This study included a 12-week open label acute phase study of 13 comorbid adolescents, followed by comprehensive assessments conducted 1, 3, and 5 years after entry into an acute phase fluoxetine trial. The results of the acute phase study and of the 1, 3, and 5-year follow-up assessments have already been published in four papers. The current paper was designed to cover the results of the study across the entire 5-year time spectrum of the study, and to summarize the clinical results across that entire time period. The data from this pilot study suggest that the long-term (5-year) clinical course for the Alcohol Dependence, Cannabis Dependence, and academic functioning of comorbid adolescents following acute phase treatment with SSRIs is generally good. However, the long-term clinical course for the Major Depression of that comorbid adolescent population is surprisingly poor.     

The pharmacological management of patients with comorbid psoriasis and obesity

Introduction: Psoriasis is a chronic inflammatory skin disease that is increasingly being recognized as a complex disorder affecting multiple systems. Systemic inflammation is considered the pathogenic link between psoriasis and its comorbid conditions that include arthritis, metabolic disorders, depression, and cardiovascular diseases. The presence of comorbid conditions modifies both its clinical management and the therapeutic approach in psoriatic patients.

Areas covered: This review describes the clinical, epidemiological, and pathogenic link between psoriasis and obesity. Furthermore, data related to the effects of synthetic antipsoriatic drugs on obesity are collated.

Expert opinion: Obesity is one of the most common comorbid conditions that is relevant both for a patient’s overall health and the clinical outcomes of antipsoriatic therapies. Indeed, some treatments of psoriasis might be impaired by adiposity. Moreover, obesity’s association with dyslipidemia, hypertension, and increased liver enzymes could further be worsened by acitretin, cyclosporine and methotrexate, respectively. Therefore, the identification of therapeutic targets whose blockade could have positive effects on both psoriasis and mechanisms regulating body weight homeostasis may be of great relevance to the treatment of patients with psoriasis.     

Current and emerging pharmacotherapies for treating tobacco dependence

Tobacco dependence remains the leading cause of death and disease in the US and a major cause of mortality around the world, yet 1 out of 5 American adults smoke and 1.3 billion adults smoke worldwide. Nicotine replacement therapies (NRTs), bupropion and varenicline, are approved by the US FDA as first-line treatments for nicotine dependence. Clonidine and nortriptyline are recommended as second-line treatments by the Agency for Healthcare Research and Quality. Although recent data suggest that varenicline is superior to bupropion for treating nicotine dependence, a majority of smokers fail to maintain long-term abstinence from smoking using FDA-approved pharmacotherapies. Thus, continued investigation of novel medications for nicotine dependence remains a critical priority. Guided by research on multiple neurobiological mechanisms of nicotine dependence, several novel medications that mimic and/or attenuate nicotine’s rewarding effects, or reduce nicotine withdrawal, are under investigation. Although existing data are limited or conflicting, there is some evidence for the efficacy of selegiline, fluoxetine, naltrexone and mecamylamine in certain subgroups of smokers. New research directions, such as fast-acting NRTs, the tailored use of NRTs for subtypes of smokers, and pharmacogenetics, hold promise for new treatment approaches and, ultimately, for reducing rates of tobacco use in the US and worldwide.     

Post-traumatic stress disorder: an evaluation of existing pharmacotherapies and new strategies

Post-traumatic stress disorder (PTSD) is often a chronic and disabling anxiety disorder that develops after exposure to a traumatic event. Researchers have demonstrated efficacy for both pharmacologic and psychosocial interventions in the treatment of PTSD. First-line pharmacotherapeutic options are the selective serotonin re-uptake inhibitors and serotonin noradrenaline re-uptake inhibitors. Older antidepressant agents, such as the tricyclic antidepressants and the monoamine oxidase inhibitor, phenelzine, have also proven efficacy in PTSD among more established agents. However, concerns for side effects have limited frequent use of these. Existing pharmacologic agents produce meaningful results and bear the advantage of treating depression and other co-morbid disorders, yet still fall short of being ideal due to limited response and remission rates and tolerability issues. The need for improving pharmacotherapy of PTSD remains compelling and directions for further research are discussed.     

Pharmacotherapeutic options for co-morbid depression and alcohol dependence

Introduction: Depression and alcohol dependence are frequently co-morbid and among the most prevalent mental disorders. They are a serious global health problem with social, interpersonal, and legal interpolations. Among pharmacological alternatives, anti-craving compounds as well as antidepressants, antipsychotics, anticonvulsants, benzodiazepines, and beta-blockers have shown efficacy for depression as well as alcohol consumption. The pharmacological treatment of both complex interwoven mental diseases is still challenging given the inconsistent results of open and double-blind randomized placebo-controlled studies with approved and open label medications.

Areas covered: The authors provide a systematic review of the literature with PubMed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to obtain an overview of the pharmacotherapeutic options for co-morbid depression and alcohol dependence.

Expert opinion: The effect of treating only depressive or alcohol-related symptoms appears limited. Therapies directly targeting the addiction are warranted among such dually diagnosed patients. Despite limited data, the reviewed pharmacotherapeutic treatments demonstrated efficacy in most but not in all relevant parameters of alcohol dependence and depression.     

Lithium augmentation of topiramate for bipolar disorder with comorbid binge eating disorder and obesity

OBJECTIVE: To evaluate the effectiveness of lithium augmentation of topiramate on mood symptoms, binge eating behavior, and body weight in obese bipolar patients with binge eating disorder (BED) seeking weight management. METHOD: We conducted a naturalistic study of 12 consecutive outpatients with bipolar disorders, BED, and obesity who received lithium augmentation for mood instability during the course of topiramate-based pharmacotherapy for obesity and BED. Lithium was added to topiramate (mean dose 514 mg i.d.) and titrated to a mean dose of 1009 mg i.d. (mean plasma concentration 0.7 mmol/L). Treatment response was assessed by comparing changes in clinical severity scales for mood and eating disorders, weekly binge eating frequency, and weight for the 2 months before and the first 2 months during lithium treatment. RESULTS: A statistically significant improvement in global severity of mood symptoms was observed after as compared to before lithium augmentation. Statistically insignificant reductions in weight and in binge frequency and severity were also observed after lithium addition. CONCLUSION: Optimal weight loss treatment in obese patients with comorbid bipolar and BEDs may require stabilization of mood. The combination of lithium and topiramate may have a role in the management of this difficult-to-treat population.