Pharmacotherapy of postpartum psychosis

The term postpartum psychosis (PP) is not a discrete nosological entity but rather, refers to a group of heterogeneous disorders that share the common features of the presence of psychosis and onset of symptoms during the postpartum period. Although there remains a debate regarding its diagnostic status, PP is generally considered as belonging to the bipolar spectrum. The prognosis for the individual episodes is considered generally favourable but it is a potentially serious illness due to the increased risk of suicide and infanticide. Furthermore, puerperal and non-puerperal recurrences are quite common. There is paucity of controlled trials in the acute and prophylactic treatment of PP and the data are limited largely to the use of lithium and oestrogen. Strategies for the clinical management of PP should include early identification of women at risk; close monitoring of mood state during pregnancy, prompt recognition of impending psychosis and aggressive pharmacotherapy. In general, treatment for PP is essentially the same as for similar non-puerperal episodes.     

心境稳定剂在精神疾病治疗中的应用

目前临床上常用的心境稳定剂包括锂盐、抗惊厥药物和非典型抗精神病药物。此外,现还新上市了一些具有潜在心境稳定作用的药物或辅助用药。本文概要介绍主要心境稳定剂及其在精神疾病治疗中的应用。     

The combination of olanzapine and fluoxetine in mood disorders

Depression can occur either with or without alternation with periods of mania. Depression that alternates with mania (bipolar depression) is a particularly difficult problem in clinical practice. The evidence base of the treatment for this condition is not strong and the choices at best are limited. Furthermore, although there are a number of effective antidepressants for the non-cycling variety (‘unipolar’ major depression), > 50% of patients experience incomplete response to any given drug. Given the proportion of the population involved, these represent fairly sizeable markets. Studies over the last several years indicate that the combination of the novel antipsychotic olanzapine and the serotonin-selective re-uptake inhibitor (SSRI), fluoxetine, may be effective for both conditions. One trial in 28 patients showed that this combination was an effective treatment, compared to the individual components with unipolar depressed patients who had not responded to two antidepressants of different chemical classes. Two subsequent large-scale attempts at replication have resulted in failed trials. Patients randomly assigned to antidepressant monotherapies showed a good response, indicating that the populations being studied were not actually treatment-resistant; therefore, more research is needed. Alternatively, a recent study showed that monotherapy with olanzapine produced a greater effect than placebo in bipolar depression and the combination of olanzapine and fluoxetine yielded an even more robust response. However, important questions remain, e.g., the issue of comparative effectiveness, that is to say, whether the same result could occur with combinations of other novel antipsychotics and SSRIs. In addition, there remain significant concerns regarding the safety and tolerability of olanzapine in these populations. Essential questions about the potential for substantial weight gain, Type II diabetes and for the development of tardive dyskinesia (a syndrome of permanent, disfiguring abnormal involuntary movements) remain. These problems will have to be vigorously addressed in order to achieve a substantial market penetration for these conditions.     

GABA and glutamate systems as therapeutic targets in depression and mood disorders

Advances made in diverse areas of neuroscience suggest that neurotransmitter systems, additional to the monoaminergic, contribute to the pathophysiology of mood disorders. This ever accruing body of preclinical and clinical research is providing increased recognition of the contribution made by amino acid neurotransmitters to the neurobiology of mood disorders. This review examines evidence supporting the role of GABA and glutamate in these processes and explores the potential to target these systems in the development of novel compounds; the viability of these agents for treatment-related co-morbidities will also be considered.     

Epidemiology of Comorbid Tobacco Use and Schizophrenia: Thinking About Risks and Protective Factors

ABSTRACT

A meta-analytic review demonstrated that, when compared with the general population, schizophrenia is consistently and strongly associated with current tobacco smoking with a world average odds ratio (OR) of 5.3 (95% confidence interval, CI 4.9–5.7). The world average OR of current smoking appears to combine four possible components: increased smoking initiation in severe mental illnesses (SMIs), increased smoking initiation that is specific to schizophrenia (beyond the SMI effect), decreased smoking cessation in SMIs, and decreased smoking cessation that is specific to schizophrenia (beyond the SMI effect). In a Kentucky study, only the first three of these four respective ORs were significant: OR = 2.8 (CI 2.0–3.8), OR = 1.9 (CI 1.2–2.8), OR = 4.7 (CI 2.9–7.6) and OR = 1.2 (CI 0.68–2.1). Increased smoking initiation in SMI may be multifactorial. Increased smoking initiation that is specific to schizophrenia probably has a genetic component. Decreased smoking cessation in SMIs may be explained by their high nicotine dependence and the lack of availability and limited success of current smoking cessation treatments. The economic and health costs of smoking in the general population are well understood, but they have received little attention in schizophrenia. More knowledge is needed to develop preventive strategies for the risks and protective factors involved in smoking in persons with schizophrenia. In summary, the main objective of this article is to assess the relative importance of these four components of the association between smoking and schizophrenia, the variables affecting them, and what they tell us about risks and protective factors.     

Pharmacotherapy of Comorbid Mood,Anxiety, and Substance Use Disorders

Mood and anxiety disorders commonly co-occur with substance use disorders. Exploration of the neurobiology of substance use disorders and mood and anxiety disorders have found that the neural circuitry in mood, anxiety, and substance use disorders is clearly overlapping. These discoveries have encouraged the exploration of a number of pharmacotherapeutic agents in the treatment of co-occurring mood, anxiety, and substance use disorders. In this article, recent data on the pharmacotherapeutic treatment of mood and anxiety disorders in individuals with substance use disorders are reviewed. Some of the barriers to the use of pharmacotherapy in individuals with substance use disorders are discussed.     

Role of melatonin in mood disorders and the antidepressant effects of agomelatine

Introduction: Disturbances of circadian rhythms and sleep play an important role in various types of mood disorders like major depressive disorder (MDD), bipolar depressive disorder (BPD) and seasonal affective disorder (SAD). Malfunctioning of the SCN–pineal–melatonin link has been suggested as the main cause for these disorders. As a rhythm-regulating factor and as a hormone involved in the regulation of sleep, melatonin is essential for the control of mood and behavior.

Areas covered: Melatonin's involvement in various mood disorders is reviewed based on studies undertaken in patients with MDD, BPD and SAD. The chemistry and metabolism of the newly introduced antidepressant, agomelatine, a MT1/MT2 melatonin receptor agonist and 5-HT2c antagonist in brain areas involved in mood regulation are also discussed. Its clinical role in mood regulation, agomelatine's efficacy, safety and tolerability are also reviewed.

Expert opinion: Agomelatine, a melatonergic antidepressant with a rapid onset of action, has been shown effective in various types of mood disorders (e.g., MDD, BPD, SAD). Some studies find it superior to other common antidepressants (SSRIs, SNRIs) that are in clinical use today. Agomelatine's efficacy, good tolerability and safety profile suggest that it may become a preferred antidepressant in the near future.     

Pharmacotherapy of Down syndrome

ABSTRACT

Introduction: Comorbid psychiatric disorders are common in Down syndrome (DS). Evidence for pharmacotherapy of psychiatric co-morbidity in DS is limited.

Areas covered: This article reviews the literature on the pharmacotherapy of psychiatric conditions co-occurring with DS, including major depressive disorder (MDD), bipolar disorder, anxiety disorders, obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), psychosis, and catatonia. A section on the phenomenon of regression is included.

Expert opinion: For MDD, we typically begin with selective serotonin reuptake inhibitors (SSRIs). For bipolar disorder, we often use carbamazepine. For psychotic symptoms, we begin with risperidone or aripiprazole. We use buspirone to treat anxiety. For obsessional slowness/OCD, we begin with an SSRI. For stereotypical repetitive behavior, we tend to use buspirone. For ADHD, we begin with guanfacine. For irritability of comorbid ASD, we use risperidone or aripiprazole. For dementia in DS, we refer to a neurologist for medical work-up and medication management. We treat catatonia-like ‘regression’ with lorazepam. If ineffective, we use memantine or clozapine. Electroconvulsive therapy is considered if pharmacotherapy is ineffective. We treat ‘regression’ with symptoms of MDD ± psychosis, with an antidepressant and an antipsychotic if needed. Randomized controlled trials of medications for comorbid psychiatric disorders in DS are warranted.     

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.     

Oxidative stress markers in affective disorders

Affective disorders are a medical condition with a complex biological pattern of etiology, involving genetic and epigenetic factors, along with different environmental stressors. Increasing numbers of studies indicate that induction of oxidative and nitrosative stress (O&NS) pathways, which is accompanied by immune-inflammatory response, might play an important role in the pathogenic mechanisms underlying many major psychiatric disorders, including depression and bipolar disorder.Reactive oxygen and nitrogen species have been shown to impair the brain function by modulating activity of principal neurotransmitter (e.g., glutamatergic) systems involved in the neurobiology of depression. Both preclinical and clinical studies revealed that depression is associated with altered levels of oxidative stress markers and typically reduced concentrations of several endogenous antioxidant compounds, such as glutathione, vitamin E, zinc and coenzyme Q10, or enzymes, including glutathione peroxidase, and with an impairment of the total antioxidant status. These oxidative stress parameters can be normalized by successful antidepressant therapy. On the other hand, some antioxidants (zinc, N-acetylcysteine, omega-3 free fatty acids) may exhibit antidepressant properties or enhance standard antidepressant therapy. These observations introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present paper reviews selected animal and human studies providing evidence that oxidative stress is implicated in the pathophysiology and treatment of depression and bipolar disorder.     

丙戊酸盐治疗双相情感障碍的研究进展

作为心境稳定剂,丙戊酸盐治疗各型双相情感障碍均有一定的疗效。近年来对各型双相情感障碍患者进行的临床研究证实：丙戊酸盐能改善躁狂症状;联合镇静药物治疗可有效改善抑郁症状;联合抗抑郁药物预防抑郁发作的疗效优于锂盐。丙戊酸盐与其他心境稳定剂联合治疗快速循环型双相情感障碍患者时可能更有益,也更适用于非快速循环型双相情感障碍患者的长程治疗。     

Anticonvulsants in the treatment of mood disorders: assessing current and future roles

Anticonvulsants are frequently used in the treatment of affective illnesses, especially for patients refractory to or intolerant of other treatments. The differential therapeutic roles of anticonvulsants, however, remain largely undetermined. The author reviews the available efficacy data for carbamazepine, oxcarbazepine, valproate, lamotrigine, gabapentin and topiramate. Valproate is efficacious in the monotherapy of acute manic presentations but confirmatory evidence of the efficacy of valproate in long-term maintenance has been elusive. Valproate and possibly carbamazepine, may provide a therapeutic advantage over lithium in non-classic bipolar conditions such as mixed mood states and rapid cycling conditions. Lamotrigine is unique among the anticonvulsants in its monotherapy efficacy for bipolar I depression. Emerging data also suggest a role for lamotrigine in the adjunctive treatment of depressive mixed states and rapid cycling conditions in the absence of prominent manic symptoms. Controlled trials have found gabapentin ineffective for acute mania and refractory bipolar conditions. The role of gabapentin in the treatment of other aspects of affective illness remains uncertain. Definitive statements regarding the differential psychotropic use of topiramate and oxcarbazepine are not possible, though active investigation is underway to better characterise the utility of topiramate. The author suggests that current diagnostic models utilised in controlled trials may limit identification of differential therapeutic benefits. Caution is advised in generalising from the ability or inability of an agent to demonstrate antimanic activity. Future studies of newer anticonvulsants should include dimensional perspectives and soft bipolar presentations, as the greatest contribution of the newer anticonvulsants may be in treatment of mood conditions other than acute mania.     

Safety of olanzapine use in adolescents

Introduction: Olanzapine was the second first-line atypical antipsychotic medication approved by the Food and Drug Administration (FDA) for the treatment of adult schizophrenia and later approved for adolescent schizophrenia and bipolar disorder. Initial studies performed on adults demonstrated efficacy compared to placebo and a first-generation antipsychotic medication. Initial assessments in adolescents with schizophrenia demonstrated significant symptom reduction without movement disorder, but with weight gain. Later studies reported efficacy for bipolar disorder in teenagers, but with weight gain. The assessment of olanzapine safety in teenagers has shown substantial weight gain and metabolic measures. Because of equivalent efficacy to other atypical antipsychotic medications and the metabolic side-effects, olanzapine is often recommended as a second-use medication.

Areas covered: Studies of olanzapine use in adolescents with schizophrenia or bipolar disorder demonstrate significant reduction in symptoms while causing no movement disorder side-effects. There has been reduction in use of olanzapine with adolescents as newer atypical antipsychotics have emerged associated with less weight gain.

Expert opinion: Studies of olanzapine have demonstrated effectiveness in adolescents with a psychotic illness. Metabolic side-effects are a strong concern of the field and have led to the recommendation of using the medication in a secondary fashion.     

Recent developments in the treatment of bipolar disorders

Recently, many new therapeutic options have become available for the treatment of bipolar disorder. Most of these options are agents originally developed to treat other conditions, such as anticonvulsants and antipsychotics. Some older agents have also been rediscovered or reformulated. New drug combinations and treatment strategies have enabled a more comprehensive treatment of the spectrum of bipolar symptoms, as well as bipolar disorder complicated by a range of comorbidities, to be targeted. A growing range of novel therapeutic options for the treatment of bipolar disorder is under investigation. This paper summarises some of the data regarding these potential therapeutic options.     

A randomized controlled double blind study of zuclopenthixol acetate compared to haloperidol in acute psychosis

This study is a double blind randomized controlled trial comparing zuclopenthixol acetate to haloperidol administered parenterally initially and followed by oral medication for 28 days in the treatment of acute psychosis. The sample included 44 patients with schizophrenia, schizophreniform disorder and substance-induced psychotic disorder who required acute neuroleptic treatment. The patients were assessed using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Improvement Scale (CGI) and the Simpson Angus Scale (SAS). While patients in both groups improved on all outcome measures, there was no significant differences between the two agents in terms of either efficacy or tolerability. © 1998 John Wiley & Sons, Ltd.     

香港抑郁症治疗概况(英文)

在香港抑郁症是较为普遍,病人可以适当地被曾受训处理抑郁症的家庭医生所医治,而严重者则需要接受精神专科治疗。但是共病性疾病及躁狂抑郁症仍然被忽略。虽然现今有很多种类的抗抑郁药,但因价格昂贵而未能普遍使用,在公营医疗服务中,情况更甚。