脑梗死后抑郁及其对神经功能康复的影响探析

目的研究和探讨脑卒中后抑郁（post-stroke depression,PSD）及其对神经功能康复的影响。方法选取本院2011年1月至2012年12月收治的80例急性脑梗死患者,对所有患者诊断后的2、4、6个月观察后抑郁及其对神经功能康复情况,分别使用汉密尔顿抑郁量表评分（HAMD）,神经功能缺损评分（SSS）和日常生活能力评分（Activity of Daily1iving Seale,ADL）。同时进行抑郁自评表（self-Rat-ing Depression Scale,SDS）和焦虑自评量表（Self-Rating Anxiety scale,SAS）。将所得的资料进行回顾性分析研究。结果神经功能的缺损会影响脑卒中后抑郁的发生率,且日常生活能力的不足也会进一步加重抑郁。结论脑梗死后抑郁会影响神经功能康复的时间和速度,临床上建议进行抗抑郁治疗,既可以缓解脑梗死后抑郁,也能提高患者的日常生活能力,逐步恢复患者神经功能。     

Raising the expectations of long-term treatment strategies in anxiety disorders

This article describes the long-term course of anxiety disorders based on the findings of the Harvard/Brown Anxiety Research Program (HARP) study--a prospective, naturalistic, longitudinal study of patients with anxiety disorders. Data from the HARP study emphasize both the chronicity of anxiety disorders and their frequent psychiatric comorbidity with other anxiety disorders and depression. Social phobia and generalized anxiety disorder are more chronic than panic disorder, although the latter has higher rates of relapse following recovery. Anxiety disorders have a major impact on the everyday lives of sufferers. The detrimental effects on social, psychological, and physical functioning are comparable with other chronic medical and psychiatric conditions, including diabetes, heart disease, and depression. Comorbidity with depression significantly increases the probability of suicide and is associated with poorer outcome. Findings from the HARP study have significant implications for treatment, which currently tends to focus on short-term outcomes. Future studies should emphasize the role of preventive pharmacotherapy to improve the long-term course of anxiety and to reduce its associated suffering, suicide, and occupational and social impairment.     

Post-stroke Movement Disorders: Clinical Manifestations and Pharmacological Management

Involuntary abnormal movements have been reported after ischaemic and haemorrhagic stroke. Post stroke movement disorders can appear as acute or delayed sequel. At the moment, for many of these disorders the knowledge of pharmacological treatment is still inadequate. Dopaminergic and GABAergic systems may be mainly involved in post-stroke movement disorders. This article provides a review on drugs commonly used in post-stroke movement disorders, given that some post-stroke movement disorders have shown a partial benefit with pharmacological approach.     

卒中后抑郁病理机制及药物治疗进展

卒中后抑郁（post stroke depression，PSD）是卒中后神经精神并发症中最常见的一种，在中国大陆卒中患者中的发病率>40%，对卒中患者的肢体功能恢复、脑功能改善、生活质量等均有不利的影响，同时增加了卒中的致残率和致死率。但迄今为止针对PSD的发病机制尚无明确定论，其过程可能涉及到了炎症免疫系统、单胺类神经递质系统、氧化应激和神经营养因子等诸多因素。临床发现药物干预对PSD的治疗、预防均有较好的效果，并且可能有助于卒中患者肢体功能和认知水平的恢复，但研究证据仍不足以支持常规使用药物对PSD进行预防。由此，PSD进一步的发病机制研究及相关的生物标志物筛查将为制定合理的药物治疗方案提供依据。本文对PSD的发病机制、药物治疗现状以及PSD潜在生物标志物等的研究进展进行综述。     

Burden of bipolar depression: impact of disorder and medications on quality of life

Bipolar disorder is a complex, chronic psychiatric condition characterized by recurring episodes of depressive illness and mania or hypomania. Although the manic or hypomanic episodes define the disorder, recent research has shown that depressive symptoms predominate over manic symptoms in the majority of patients, and that bipolar depression accounts for much of the significant morbidity and mortality associated with bipolar disorder. Given these findings, there has been a recent upsurge of interest in furthering our understanding of the burden of depression in bipolar disorder. At the same time, increasing scientific attention is now being paid to expanding the measurement of outcome in bipolar disorder to encompass broader indicators of response, one of which is the assessment of quality of life (QOL). In this review, we provide a summary of the current knowledge about QOL in the depressive phase of bipolar disorder, and the effects of pharmacological treatment interventions for bipolar disorder upon QOL. It appears that QOL is poorer in bipolar disorder than in other mood disorders and anxiety disorders, but that schizophrenia might compromise QOL more severely than bipolar disorder. Existing data also suggest that, for patients with bipolar disorder, QOL is negatively associated with depression, both as a cross-sectional mood state and perhaps also as a feature of the patient's course. Despite its clinical and public health importance, bipolar depression has only recently started to receive the attention it warrants in clinical trials, and many important questions about its optimal pharmacological management remain to be answered. There is also a paucity of information about the impact of pharmacological interventions on QOL in bipolar depression. To our knowledge, only two clinical trials to date have specifically examined the impact of medications on QOL in patients with bipolar depression. A small number of other studies have examined the effects of depressive symptoms on QOL in patients who are experiencing manic or mixed episodes. Nonetheless, QOL appears to be a meaningful and important indicator of outcome and recovery in this patient population, and one that warrants further scientific interest and energy.     

Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders

There is extensive comorbidity between depression and anxiety disorders. Dimensional psychiatric and psychometric approaches have suggested that dysregulation of a limited number of behavioural dimensions that cut across diagnostic categories can account for both the shared and unique symptoms of depression and anxiety disorders. Such an approach recognizes that anxiety, the emotional response to stress, is a key element of depression as well as the defining feature of anxiety disorders, and many antidepressants appear to be effective in the treatment of anxiety disorders as well as depression. Therefore, the pharmacological actions of these drugs must account for their efficacy in both. Brain noradrenergic and serotonergic systems, and perhaps to a more limited extent the dopaminergic system, regulate or modulate many of the same behavioural dimensions (e.g. negative or positive affect) that are affected in depression and anxiety disorders, and that are ameliorated by drug treatment. Whereas much recent research has focused on the regulatory effects of antidepressants on synaptic function and cellular proteins, less emphasis has been placed on monoaminergic regulation at a more global systemic level, or how such systemic alterations in monoaminergic function might alleviate the behavioural, cognitive, emotional and physiological manifestations of depression and anxiety disorders. In this review, we discuss how chronic antidepressant treatment might regulate the tonic activity and/or phasic reactivity of brain monoaminergic systems to account for their ability to effectively modify the behavioural dimensions underlying improvement in both depression and anxiety disorders.     

Axis I and Axis II disorders in alcoholics and drug addicts: fact or artifact?

OBJECTIVE: It has been argued that Axis I and Axis II disorders diagnosed in substance users refer to substance-induced conditions rather than to independent psychiatric conditions; this argument will be referred to as the substance-related artifact hypothesis. Furthermore, Axis II symptoms co-occurring with Axis I disorders have been attributed to the contamination of personality assessment by mood and/or anxiety state effects (the trait-state artifact hypothesis). The present study is the first to prospectively examine the validity of these two hypothesized "artifacts" in substance users. METHOD: In 276 individuals (57.6% female) applying for substance use treatment, current substance use disorders, mood/anxiety disorders and Axis II disorders were diagnosed using semistructured interviews both at baseline and at 1-year follow-up. The substance-related artifact hypothesis is tested by examining the covariation between recovery from substance use disorders on the one hand and recovery from and/or improvement of mood/anxiety and Axis II disorders on the other hand. The trait-state artifact hypothesis is tested by examining the covariation between recovery from mood/anxiety disorders on the one hand and recovery from and/or improvement of Axis II disorders on the other hand. RESULTS: Recovery from substance use disorders covaried with recovery from and improvement of mood/anxiety disorders, but not with recovery from or improvement of Axis II pathology. Furthermore, recovery from mood/anxiety disorders covaried with recovery from and improvement of personality disorders, in particular Cluster C disorders. CONCLUSIONS: Results from this study suggest that mood/anxiety disorders, but not personality disorders, diagnosed among people with substance use disorder may partly reflect substance-related artifacts. Furthermore, this study provides evidence for the contention that semistructured interview assessment of Axis II, at least without inquiry on an item-by-item basis, is susceptible to contamination by mood/anxiety state effects.     

Serotonergic drugs in the treatment of depressive and anxiety disorders

Serotonergic dysfunction has been implicated in the aetiology of several psychiatric conditions, including depressive and anxiety disorders. Much of the evidence for the role of serotonin (5-HT) in these disorders comes from treatment studies with serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs), 5-HT(1A) agonists and 5-HT antagonists. This review considers the place of these drugs in the treatment of panic disorder, obsessive-compulsive disorder (OCD), social phobia, and generalized anxiety disorder (GAD). Among these agents, the SSRIs stand out with proven efficacy in the treatment of a spectrum of disorders, such as depression, panic disorder, OCD and social phobia. They may also be a suitable treatment for GAD. 5-HT(1A) agonists have been used extensively for the treatment of depression and GAD but evidence of their efficacy in other anxiety disorders is equivocal. 5-HT antagonists are the least well studied of these agents: while they may have activity in depression, their efficacy has not been fully investigated in anxiety disorders. However, preliminary reports suggest that they may be useful as adjuvants to SSRIs in treatment-refractory OCD. The high incidence of comorbidity amongst psychiatric disorders means that pharmacotherapy that is effective against a range of disorders, such as the SSRIs, is of considerable use to clinicians. Future research into the biological mechanisms underlying such disorders is likely to further enhance pharmacotherapy. Copyright 2000 John Wiley & Sons, Ltd.     

Pharmacotherapy of alcoholism in patients with co-morbid psychiatric disorders

There has been an exponential increase in recent years of literature pertaining to the treatment of individuals with alcohol use disorders and co-morbid psychiatric disorders. Patients with mood and anxiety disorders in particular have a very high prevalence of alcoholism. Alcoholism confers significant morbid risks to patients with psychiatric disorders, and vice versa, including markedly increased risk of suicide. Only recently have studies examined the impact of various psychiatric medications on alcohol use among patients with these disorders. Evidence supporting the benefits of antidepressants for co-morbid alcoholism and depression continues to mount. Although these studies have demonstrated benefits in terms of quantitative decreases in the volume and frequency of consumption, the benefits in terms of remission from alcoholism have yet to be shown conclusively. The first randomised, controlled trial involving subjects with co-morbid alcoholism and bipolar disorder was recently conducted, yielding promising results for valproate in this population. The literature regarding co-morbid alcoholism and anxiety disorders has also seen recent progress, particularly in the study of post-traumatic stress disorder (PTSD). A placebo-controlled study of sertraline suggests some benefit in terms of alcohol use among individuals with early-onset PTSD and less severe alcohol dependence. Atypical antipsychotics such as olanzapine and quetipaine have been examined in several open studies of subjects with alcoholism co-morbid with a variety of psychiatric conditions including bipolar disorder, PTSD and schizophrenia. This paper selectively reviews the evidence that is currently available for the pharmacological management of alcoholism among persons with co-morbid psychiatric illness. Effectiveness, safety and tolerability are considered, and directions for future study are discussed.     

Unraveling the diagnostic clues of depression and GAD: the primary care challenge

Anxiety and depression are commonly encountered in primary care, with a prevalence ranging from 5% to 10%. These disorders are associated with significant and persistent impairment in functioning, risk of suicide, and substantial economic cost. Comorbidity of depression and anxiety is frequent and intensifies the burden of illness. However, patients with anxiety and depression often present to primary care physicians (PCPs) with ill-defined somatic symptoms, and both disorders are under-recognized and under-treated. PCPs should be aware that the typical presentation of anxiety and depression may not be with classical psychological symptoms, but rather with vague somatic symptoms that are often hard to treat and result in frequent repeat visits. Once anxiety and depression are accurately recognized, most patients can successfully be managed in primary care. A wide range of effective drugs is available, allowing selection of an optimal treatment for each patient. Antidepressants are effective as monotherapy in comorbid patients, and newer agents such as selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors have been shown to be effective in the treatment of anxiety and depression. Adherence to medication can be improved if drug treatment is integrated into a package of patient education and support. PCPs have a vital role to play in identifying anxiety and depression amongst their patients, and building a therapeutic partnership to achieve successful treatment.     

Clinical significance of selective serotonin reuptake inhibitor (SSRI) in the treatment of depression

SSRIs have had a great impact on the diagnosis and treatment of depression, as well as the search for its pathophysiology. Since SSRIs have relatively few adverse effects, it is also effective for treating in a mild forms of depression, which were formerly thought to be treated adequately with only psychotherapy or anti-anxietics. Recent studies on the natural history of depression have revealed the chronicity of this disease. SSRI is now the first-line drug for the continuation and maintenance therapy of depression. Since SSRI primary acts on the serotonergic system, wide use of this drug has questioned the postulated dichotomy of the biological hypothesis of depression, the so-called serotonin depression or norepinephrine depression. A new insight into the monoamine hypothesis of depression has been yielded by SSRI. SSRIs are also effective in the treatment of anxiety disorders such as obsessive-compulsive disorder, panic disorder and social phobia. Thus, SSRIs have also brought new insight into the role of serotonin in the pathophysiology of anxiety.     

Substance abuse and psychiatric disorders in HIV-positive patients: epidemiology and impact on antiretroviral therapy

There is a high prevalence of substance abuse and psychiatric disorders among HIV-infected individuals. Importantly, drug and alcohol-use disorders are frequently co-morbid with depression, anxiety and severe mental illness. Not only do these disorders increase the risk of contracting HIV, they have also been associated with decreased highly active antiretroviral therapy (HAART) utilisation, adherence and virological suppression. The literature evaluating the relationship between substance abuse and HIV outcomes has primarily focused on injection drug users, although there has been increasing interest in alcohol, cocaine and marijuana. Similarly, the mental health literature has focused largely on depression, with a lesser focus on severe mental illness or anxiety. To date, there is little literature evaluating the association between co-occurring HIV, substance abuse and mental illness on HAART uptake, adherence and virological suppression. Adherence interventions in these populations have demonstrated mixed efficacy. Both directly observed therapy and pharmacist-assisted interventions appear promising, as do integrated behavioural interventions. However, the current intervention literature has several limitations: few of these studies are randomised, controlled trials; the sample sizes have generally been small; and co-occurring substance abuse and mental illness has not specifically been targeted in these studies. Future studies examining individual substances of abuse, psychiatric disorders and co-occurring substance abuse and psychiatric disorders on HIV outcomes will inform targeted adherence interventions.     

Intergenerational transmission of chronic physical disease via chronic mental disorders: the potential role of addictive behaviors

There has been growing evidence of a link between chronic respiratory diseases, asthma in particular, and mental disorders among youth. The mechanism for this link remains unknown. Several studies have empirically addressed the question of this pathway, and accumulating results may shed new light on the nature of this association. The goal of the current paper is to provide an integrative summary of the literature to date and to present a new interdisciplinary hypothesis for one possible mechanism explaining the link between asthma and anxiety/depression among youth. This hypothesis posits that comorbid anxiety/depression and nicotine dependence among adults, may be one pathway leading to the comorbidity of asthma and anxiety/depression among youth. We propose this mechanism operates via exposure to environmental tobacco smoke and/or prenatal tobacco use, which confers an increased risk for asthma, and parental anxiety/depression which confers increased risk of anxiety/depression among offspring via familial transmission. We predict that further testing of this hypothesis will help to reveal the largely neglected problem of nicotine dependence especially among women - and the far-reaching impact of this addiction on the health of children.     

Designing new treatments for depression and anxiety

Depression and anxiety are disabling disorders that affect many individuals. Drugs that interfere with the reuptake and/or metabolism of biogenic amines have been used to treat depression for more than four decades. An important development in the treatment of depression has been the emergence of triple reuptake inhibitors (SNDRIs), which inhibit the reuptake of serotonin, norepinephrine and dopamine. Preclinical and clinical research indicates that drugs inhibiting the reuptake of all of these neurotransmitters can produce a more rapid onset of action and greater efficacy than traditional antidepressants. Allosteric modulation of GABAA receptors can produce anxiolytic, sedative/hypnotic and anesthetic effects, presumably from enhancing the inhibitory neurotransmission of GABAA through a facilitation of receptor function. Benzodiazepines have been used with great success as anxiolytics, but the use of these drugs is limited because of their addictive potential and sedative side effects. This feature review discusses the design and synthesis of antidepressants based on the monoamine hypothesis of depression, and presents the current status of research on GABAA receptor modulators as a potential treatment for anxiety disorders.     

Review of sertraline and its clinical applications in psychiatric disorders

Sertraline (Zoloft, Pfizer) has been shown in numerous controlled studies to have similar efficacy to other selective serotonin (5-HT) re-uptake inhibitors (SSRIs) in the treatment of depression and anxiety disorders. Further research is indicating that the efficacy of sertraline extends even beyond the treatment of depression and anxiety to include utility in eating disorders, premenstrual dysphoric disorder (PMDD) and possibly substance abuse treatment. Along with other SSRIs, sertraline offers several advantages over older antidepressants, including improved patient tolerability, low risk of lethality in overdose and no dependence potential. In head-to-head comparisons, sertraline appears to be at least as well-tolerated as other SSRIs and may even have a more favourable side effect profile. Low potential for pharmacokinetic drug interactions is another advantage of sertraline. Unlike fluoxetine, fluvoxamine and paroxetine, sertraline is not a potent inhibitor of any of the cytochrome P450 isoenzyme systems. As a result of its proven efficacy, good tolerability and lack of pharmacokinetic interactions, sertraline should be considered first-line in the treatment of anxiety and depressive disorders.     

Epistasis between 5-HTTLPR and ADRA2B polymorphisms influences attentional bias for emotional information in healthy volunteers

Individual differences in emotional processing are likely to contribute to vulnerability and resilience to emotional disorders such as depression and anxiety. Genetic variation is known to contribute to these differences but they remain incompletely understood. The serotonin transporter (5-HTTLPR) and α2B-adrenergic autoreceptor (ADRA2B) insertion/deletion polymorphisms impact on two separate but interacting monaminergic signalling mechanisms that have been implicated in both emotional processing and emotional disorders. Recent studies suggest that the 5-HTTLPR s allele is associated with a negative attentional bias and an increased risk of emotional disorders. However, such complex behavioural traits are likely to exhibit polygenicity, including epistasis. This study examined the contribution of the 5-HTTLPR and ADRA2B insertion/deletion polymorphisms to attentional biases for aversive information in 94 healthy male volunteers and found evidence of a significant epistatic effect (p<0.001). Specifically, in the presence of the 5-HTTLPR s allele, the attentional bias for aversive information was attenuated by possession of the ADRA2B deletion variant whereas in the absence of the s allele, the bias was enhanced. These data identify a cognitive mechanism linking genotype-dependent serotonergic and noradrenergic signalling that is likely to have implications for the development of cognitive markers for depression/anxiety as well as therapeutic drug effects and personalized approaches to treatment.     

Managing the patient with co-morbid depression and an anxiety disorder

Depression and anxiety disorders frequently co-occur. This type of co-morbidity is associated with higher severity, suicidality, chronicity and treatment resistance. However, available treatment guidelines mainly focus on treatment for singular disorders. The current paper describes diagnostic and treatment issues relevant for adequately addressing patients with depression and an anxiety disorder, using information from both guidelines and a search of recent literature. Apart from differential diagnosis, the diagnostic evaluation should include a thorough assessment of the symptoms of both disorders, preferably by using a structured clinical interview, and an assessment of depression severity in terms of suicidality, psychotic symptoms and impairment. Treatment should first address the primary disorder in terms of severity and risk. As a rule, severe depression should be treated before the anxiety disorder, using antidepressant medication or combined treatment (plus psychotherapy). In less severe pathology, the primary focus may be determined by examining the temporal pattern and the subjective burden of each disorder as experienced by the patient. Treatment is often sequential. Treatment of the primary disorder may or may not relieve the co-morbid disorder as well. If the primary disorder is an anxiety disorder, co-morbid depression generally implies earlier use of an antidepressant. Co-morbid mild depression may also react favourably to psychotherapeutic treatment of the anxiety disorder. Recent literature on concurrent treatment of both depression and anxiety shows that modern antidepressants such as sertraline, paroxetine, fluoxetine, venlafaxine, nefazodone and bupropion have demonstrated efficacy in relieving both depressive and anxiety symptoms compared with placebo. Head-to-head comparisons, although relatively scarce, tend to show superiority over tricyclic antidepressants. Venlafaxine was found to be more effective than fluoxetine in some studies. However, these results should be interpreted with caution because studies vary considerably in terms of patient selection, assessment of anxiety and primary outcome measures. Only one randomized controlled trial compared atypical antipsychotics with placebo. Psychotherapy was generally shown to have a beneficial effect on the co-morbid conditions, and available evidence appears to favour combined treatment. The results should be interpreted with caution because the number of studies on this issue was relatively small, with considerable clinical and methodological heterogeneity.     

Development of CRF1 receptor antagonists as antidepressants and anxiolytics: progress to date

Depression and anxiety disorders are highly prevalent forms of mental illness that are considered to be stress-related disorders because some form of stressful life event often triggers their symptoms. Corticotropin-releasing factor (CRF) is a 41-amino-acid neuropeptide involved in mediating neuroendocrine, autonomic and behavioural responses to stress, and clinical studies provide evidence for the role of CRF in the development of depression and anxiety disorders. Two CRF receptor subtypes have been identified to date - the CRF(1) receptor and the CRF(2) receptor. Preclinical models provide evidence of a role for CRF(1) receptors in the activation of the stress response. Data from these experiments suggest that antagonism of CRF(1) receptor activity may provide an effective pharmacological treatment for stress-related psychiatric disorders.This review highlights progress to date with the development of CRF(1) receptor antagonists as potential pharmacotherapies for depression and anxiety disorders. Although additional research is needed to fully investigate the efficacy and safety profiles of CRF(1) receptor antagonists as candidate medications for these disorders, the results of preclinical experiments and clinical trials are encouraging. Further development of these compounds is warranted.     

Potential treatment paradigms for anxiety disorders

The current classification system of anxiety disorders allows us to match treatment with the particular form of disorder presented. The first part of this paper presents the main features of each anxiety disorder with the approved pharmacological treatment. Despite progress in this field, treatment has to be improved to resolve resistant symptoms and to eliminate adverse side effects of the drugs currently used. The efficacy of antidepressants in chronic anxiety disorders as compared to classic 'anxiolytics' has been shown. For treatment of acute phase of anxiety, new drugs have been proposed as an alternative to benzodiazepines (BZD), but to date, no individual agent has demonstrated a better effectiveness. Interesting results may be provided by drugs acting on CCK receptors or with 5HT blockers. Preliminary results are listed and prospects in the field are proposed. The discussion focuses on an improved definition of anxiety and on the overlap of anxiety symptoms with those of depression.     

Potential treatment paradigms for anxiety disorders

The current classification system of anxiety disorders allows us to match treatment with the particular form of disorder presented. The first part of this paper presents the main features of each anxiety disorder with the approved pharmacological treatment. Despite progress in this field, treatment has to be improved to resolve resistant symptoms and to eliminate adverse side effects of the drugs currently used. The efficacy of antidepressants in chronic anxiety disorders as compared to classic ‘anxiolytics’ has been shown. For treatment of acute phase of anxiety, new drugs have been proposed as an alternative to benzodiazepines (BZD), but to date, no individual agent has demonstrated a better effectiveness. Interesting results may be provided by drugs acting on CCK receptors or with 5HT blockers. Preliminary results are listed and prospects in the field are proposed. The discussion focuses on an improved definition of anxiety and on the overlap of anxiety symptoms with those of depression.