Anticonvulsants in bipolar disorders: current research and practice and future directions

Objectives:  To determine the clinical effectiveness of drugs with anticonvulsant properties for interventions in persons with bipolar disorder and to place these findings in the context of clinicians' practices and their implications for future research to more effectively manage bipolar disorders.
Methods:  Major electronic databases were searched up to February 2009 for clinical trial data, both original studies and reviews, on drugs with anticonvulsant properties studied for bipolar disorders.
Results:  Valproate, principally as divalproex, has strong evidence for effectiveness in mania, moderately strong evidence for benefits in prophylaxis of recovered states, and recent proof-of-concept evidence for benefits in bipolar depression. Lamotrigine has strong evidence for evidence for effectiveness in maintenance treatment of bipolar disorder, principally for benefits in depressive states. Lamotrigine has been established as ineffective in mania and has lacked efficacy in acute bipolar depression in most randomized trials. Carbamazepine has strong evidence for effectiveness in mania, but lacks adequate studies in other aspects of bipolar disorder treatment. Its adverse effect profile and pharmacokinetic interference with a wide range of drugs, including many employed in bipolar disorder, warrants limitation of use to patients who have responded inadequately to other regimens.
Conclusions:  Three drugs, valproate, lamotrigine, and carbamazepine, have strong evidence-based support for use in clinical states of bipolar disorder. Other anticonvulsant drugs investigated in bipolar disorder either have evidence of lack of benefits in bipolar disorder or have been inadequately studied to determine possible effectiveness.     

Revisiting Practice-Based Research Networks as a Platform for Mental Health Services Research

Practice-based research networks (PBRNs)—collaborations of practice settings that work together to generate research knowledge—are underused in mental health services research. This article proposes an agenda for mental health services research that uses a variety of PBRN structures and that focuses on what really happens in practice, the effectiveness of practice innovations in real world care, the challenges of implementing evidence supported interventions, modification of clinician behavior, and assessment of the effect of mental health policy changes on practice. The challenges of conducting research within PBRNs are substantial, including difficulties in maintaining positive member relations, securing ongoing funding, sustaining productivity, overcoming IRB entanglements and achieving both scientific excellence in recruitment and measurement validity and utility for practitioner members. However, the awareness of these challenges allows researchers and practitioners to build networks that creatively overcome them and that infuse mental health services research with heavy doses of the realities of everyday clinical practice.     

A translational research approach to poor treatment response in patients with schizophrenia: clozapine–antipsychotic polypharmacy

Poor treatment response in patients with schizophrenia is an important clinical problem, and one possible strategy is concurrent treatment with more than one antipsychotic (polypharmacy). We analyzed the evidence base for this strategy using a translational research model focused on clozapine–antipsychotic polypharmacy (CAP). We considered 3 aspects of the existing knowledge base and translational research: the link between basic science and clinical studies of efficacy, the evidence for effectiveness in clinical research and the implications of research for the health care delivery system. Although a rationale for CAP can be developed from receptor pharmacology, there is little available preclinical research testing these concepts in animal models. Randomized clinical trials of CAP show minimal or no benefit for overall severity of symptoms. Most studies at the level of health services are limited to estimates of CAP prevalence and some suggestion of increased costs. Increasing use of antipsychotic polypharmacy in general may be a factor contributing to the under-utilization of clozapine and long delays in initiating clozapine monotherapy. Translational research models can be applied to clinical questions such as the value of CAP. Better linkage between the components of translational research may improve the appropriate use of medications such as clozapine in psychiatric practice.     

Outcomes for Implementation Research: Conceptual Distinctions,Measurement Challenges,and Research Agenda

An unresolved issue in the field of implementation research is how to conceptualize and evaluate successful implementation. This paper advances the concept of “implementation outcomes” distinct from service system and clinical treatment outcomes. This paper proposes a heuristic, working “taxonomy” of eight conceptually distinct implementation outcomes—acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability—along with their nominal definitions. We propose a two-pronged agenda for research on implementation outcomes. Conceptualizing and measuring implementation outcomes will advance understanding of implementation processes, enhance efficiency in implementation research, and pave the way for studies of the comparative effectiveness of implementation strategies.     

Early identification and intervention in cerebral palsy

Infants with possible cerebral palsy (CP) are commonly assumed to benefit from early diagnosis and early intervention, but substantial evidence for this is lacking. There is no consensus in the literature on a definition of ‘early’, but this review focuses on interventions initiated within the first 6 months after term age. We cover basic neuroscience, arguing for a beneficial effect of early intervention, and discuss why clinical research to support this convincingly is lacking. We argue that infants offered early intervention in future clinical studies must be identified carefully, and that the intervention should be focused on infants showing early signs of CP to determine an effect of treatment. Such signs may be efficiently detected by a combination of neuroimaging and the General Movements Assessment. We propose a research agenda directed at large‐scale identification of infants showing early signs of CP and testing of high‐intensity, early interventions.     

Forensic Assertive Community Treatment: A Review of the Literature

An extensive body of literature provides evidence supporting the effectiveness of assertive community treatment (ACT) with regard to non-forensic outcome measures, such as number of hospital admissions and length of stay. However, research findings on the effectiveness of ACT for forensic outcome measures, such as rearrests or detentions, is much less clear. The present review, therefore, focuses on the application of ACT in forensic populations, combining key elements of ACT with elements of forensic rehabilitation models. Specifically, a review of the literature was conducted using a systematic methodology in an attempt to combine evidence-based elements of 40 years of research on regular ACT with elements of forensic rehabilitation models. Results reveal limited yet promising evidence in support of the effectiveness of forensic ACT for forensic outcome measures. Implications for future research and clinical practice are discussed.     

Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes

The purpose of this report was to update the 2006 International League Against Epilepsy (ILAE) report and identify the level of evidence for long‐term efficacy or effectiveness for antiepileptic drugs (AEDs) as initial monotherapy for patients with newly diagnosed or untreated epilepsy. All applicable articles from July 2005 until March 2012 were identified, evaluated, and combined with the previous analysis (Glauser et al., 2006) to provide a comprehensive update. The prior analysis methodology was utilized with three modifications: (1) the detectable noninferiority boundary approach was dropped and both failed superiority studies and prespecified noninferiority studies were analyzed using a noninferiority approach, (2) the definition of an adequate comparator was clarified and now includes an absolute minimum point estimate for efficacy/effectiveness, and (3) the relationship table between clinical trial ratings, level of evidence, and conclusions no longer includes a recommendation column to reinforce that this review of efficacy/evidence for specific seizure types does not imply treatment recommendations. This evidence review contains one clarification: The commission has determined that class I superiority studies can be designed to detect up to a 20% absolute (rather than relative) difference in the point estimate of efficacy/effectiveness between study treatment and comparator using an intent‐to‐treat analysis. Since July, 2005, three class I randomized controlled trials (RCT) and 11 class III RCTs have been published. The combined analysis (1940–2012) now includes a total of 64 RCTs (7 with class I evidence, 2 with class II evidence) and 11 meta‐analyses. New efficacy/effectiveness findings include the following: levetiracetam and zonisamide have level A evidence in adults with partial onset seizures and both ethosuximide and valproic acid have level A evidence in children with childhood absence epilepsy. There are no major changes in the level of evidence for any other subgroup. Levetiracetam and zonisamide join carbamazepine and phenytoin with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures. Although ethosuximide and valproic acid now have level A efficacy/effectiveness evidence as initial monotherapy for children with absence seizures, there continues to be an alarming lack of well designed, properly conducted epilepsy RCTs for patients with generalized seizures/epilepsies and in children in general. These findings reinforce the need for multicenter, multinational efforts to design, conduct, and analyze future clinically relevant adequately designed RCTs. When selecting a patient's AED, all relevant variables and not just efficacy and effectiveness should be considered.     

Outcomes of computer‐provided treatment for aphasia

Background: Computers have become a familiar component of aphasia treatment over the past 20 years. Published research continues to indicate the influence computerised treatment may have on improving language performance of aphasic adults. As a result of the move to develop evidenced‐based clinical guidelines, there is a need to evaluate the research methodology and the level of evidence provided by computerised interventions for aphasia. Aims: The purposes of this paper are to evaluate examples of reports in the computerised treatment for aphasia outcomes research literature by applying precise definitions of the treatment outcome research terminology, placing the examples within the context of the five‐phase treatment outcomes research model, applying a level of evidence scale to rate the evidence provided by the selected examples, and speculating where we are and where we may need to go in demonstrating the influence of computer‐provided treatment on improvement in aphasia. Methods & Procedures: We applied Robey and Schultz's (1998) model for conducting clinical‐outcome research in aphasia and the level of evidence scale developed by the American Academy of Neurology (1994) to the results of computer‐provided aphasia treatment studies. Eight Phase 1 studies, three series of Phase 2 studies, and one Phase 3 study are described as examples. Outcomes & Results: While several Phase 1 and 2 studies imply that computer‐provided treatment is active in the treatment of people with aphasia, evidence to support the efficacy of computerised treatment for adults with aphasia is based on a single Phase 3 study. Additional Phase 3 studies are needed to demonstrate the efficacy of additional treatment software, and Phase 4 and Phase 5 studies are necessary to demonstrate the effectiveness and efficiency of computerised treatment for people with aphasia.     

精神动力学心理治疗的效果

精神动力学心理治疗作为临床上主要的心理治疗形式之一,其有效性一直以来受到关注,本文通过外文数据库检索相关文献并进行复习,并探讨精神动力学心理治疗的临床效力效用研究以及循证心理治疗概念,对今后疗效研究提供建议。     

ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes

PURPOSE: To assess which antiepileptic medications (AEDs) have the best evidence for long-term efficacy or effectiveness as initial monotherapy for patients with newly diagnosed or untreated epilepsy. METHODS: A 10-member subcommission of the Commission on Therapeutic Strategies of The International League Against Epilepsy (ILAE), including adult and pediatric epileptologists, clinical pharmacologists, clinical trialists, and a statistician evaluated available evidence found through a structured literature review including MEDLINE, Current Contents and the Cochrane Library for all applicable articles from 1940 until July 2005. Articles dealing with different seizure types (for different age groups) and two epilepsy syndromes were assessed for quality of evidence (four classes) based on predefined criteria. Criteria for class I classification were a double-blind randomized controlled trial (RCT) design, >or=48-week treatment duration without forced exit criteria, information on >or=24-week seizure freedom data (efficacy) or >or=48-week retention data (effectiveness), demonstration of superiority or 80% power to detect a 相似文献   

Peer-based health interventions for people with serious mental illness: A systematic literature review

Health interventions delivered by peer specialists or co-facilitated by peer specialists and health professionals can help improve the physical health of people with serious mental illness (SMI). Yet, the quality of the studies examining these health interventions and their impact on health outcomes remains unclear. To address this gap, we conducted a systematic literature review of peer-based health interventions for people with SMI. We rated the methodological quality of studies, summarized intervention strategies and health outcomes, and evaluated the inclusion of racial and ethnic minorities in these studies. We used the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines to conduct our systematic literature review. Electronic bibliographic databases and manual searches were used to locate articles that were published in English in peer-reviewed journals between 1990 and 2015, described peer-based health interventions for people with SMI, and evaluated the impact of the interventions on physical health outcomes. Two independent reviewers used a standardized instrument to rate studies' methodological quality, abstracted study characteristics, and evaluated the effects of the interventions on different health outcomes. Eighteen articles were reviewed. Findings indicated that the strength of the evidence generated from these studies is limited due to several methodological limitations. Mixed and limited intervention effects were reported for most health outcomes. The most promising interventions were self-management and peer-navigator interventions. Efforts to strengthen the evidence of peer-based interventions require a research agenda that focuses on establishing the efficacy and effectiveness of these interventions across different populations and settings.     

Comparison of combined psycho- and pharmacotherapy with monotherapy in anxiety disorders: controversial viewpoints and clinical perspectives

Anxiety disorders are among the most frequent psychiatric disorders. Experimental evidence supports both psychotherapy as well as pharmacotherapy as effective treatments. There is, however, a controversy concerning the efficacy of a combination of both approaches. While some studies suggest that combined treatment enhances efficacy, others report conflicting results. This article traces the positions in this debate. We present the results from two recent meta-analyses and discuss implications for clinical practice and further research. We suggest that a research strategy that strives to establish differential indications based on patient characteristics should be preferred over attempts to reach a global judgement of the question, which appears too simplistic given the complexity of the issue.     

Randomized controlled versus naturalistic studies: a new research agenda

The present article addresses the question of what kind of evidence is required to demonstrate that a method of psychotherapy works. Referring to recent conceptualizations of the logical structure of scientific theories, that is, the structuralistic view of theories, the author shows that randomized controlled studies (RCTs) and naturalistic studies (effectiveness studies) refer to different domains of intended applications (laboratory vs. field). This view has several important implications: (1) RCTs and naturalistic studies do not differ concerning their internal and external validity; (2) naturalistic studies do not necessarily provide lower-level evidence than RCTs; (3) evidence from RCTs cannot be transferred to psychotherapeutic practice in the field; (4) naturalistic studies are required to demonstrate that a form of therapy works in the field; (5) The proposed catalogues for levels of evidence focus on RCTs; thus, they cannot be applied to the question if a therapy works in the field; (6) It is necessary to define separate criteria for levels of evidence of naturalistic studies; and (7) a new research agenda for naturalistic studies can be derived, which is analogous to that of efficacy studies. In this article, a proposal is made to define levels of evidence of naturalistic studies. A gold standard for naturalistic studies is proposed.     

Urinary incontinence after stroke: does rehabilitation make a difference? A systematic review of the effectiveness of behavioral therapy

This study uses a comprehensive review of the literature to assess the scientific evidence for the effectiveness of behavioral therapies to treat urinary incontinence (UI) post stroke. Evidence for the different behavioral therapies was critically appraised to achieve a level of evidence based on Foley's classification of levels of evidence. Only four randomized clinical trials (RCTs), one cohort study, and recommendations from three clinical practice guidelines were found. There is limited evidence that bladder retraining with urge suppression in combination with pelvic floor exercises results in reduction of UI in male individuals with stroke. Further research is urgently needed to elucidate clinical recommendations about the efficacy of behavioral approaches.     

Efficacité et efficience des psychotropes

In current literature, the concept of efficacy refers to the knowledge about drugs obtained from randomised controlled trials, whereas effectiveness is put forward as far as results under ordinary clinical conditions are concerned. Discrepancies between results from efficacy studies and effectiveness research have been linked to differences in patients included and methods used. Advantages and pitfalls of both types of studies have been stressed too. In efficacy studies patients are selected to have but one diagnosis, whereas patients in effectiveness studies usually have multiple problems and more severe disorders. Patients in clinical practice enter a kind of treatment by active shopping; in contrast they are included in efficacy studies by the passive process of random assignment to treatment. Treatment in the field is not of fixed duration and is self correcting, in contrast to what is observed in controlled trials. Efficacy studies usually focus only on specific symptom reduction whereas treatment in clinical practice is concerned with improvement in the general functioning of patients. Beyond omitting the important symptoms and other clinical variables that identify pertinent subgroups, controlled-trials information also often omits clinical details that may be crucial for therapeutic decisions. Placebo controlled-trials have been submitted to special criticism. Results in effectiveness studies are often biased by variation in diagnostic accuracy, compliance and coverage. Recent attempts have been made to improve the transition from basic efficacy research to effectiveness studies. Phenomenology and Existential analysis may open new avenues to effectiveness research by providing new tools to understand how the patient’s subjectivity may give sense of healing to the process of change induced by psychotropic drugs.     

Cognitive hypnotherapy for pain management

Pain is a serious health care problem and there is growing evidence to support the use of hypnosis and cognitive-behavioral interventions for pain management. This article reviews clinical techniques and methods of cognitive hypnotherapy for pain management. Current research with emphasis given to randomized, controlled trials is presented and the efficacy of hypnotherapy for pain management is discussed. Evidence for cognitive hypnotherapy in the treatment in chronic pain, cancer, osteoarthritis, sickle cell disease, temporomandibular disorder, fibromyalgia, non-cardiac chest pain, and disability related chronic pains are identified. Implications for clinical practice and research are discussed in light of the accumulating evidence in support of the efficacy and effectiveness of cognitive hypnotherapy for pain management.     

General and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders: a report by the WPA section of pharmacopsychiatry

Current gold standard approaches to the treatment of depression include pharmacotherapeutic and psychotherapeutic interventions with social support. Due to current controversies concerning the efficacy of antidepressants in randomized controlled trials, the generalizability of study findings to wider clinical practice and the increasing importance of socioeconomic considerations, it seems timely to address the uncertainty of concerned patients and relatives, and their treating psychiatrists and general practitioners. We therefore discuss both the efficacy and clinical effectiveness of antidepressants in the treatment of depressive disorders. We explain and clarify useful measures for assessing clinically meaningful antidepressant treatment effects and the types of studies that are useful for addressing uncertainties. This includes considerations of methodological issues in randomized controlled studies, meta-analyses, and effectiveness studies. Furthermore, we summarize the differential efficacy and effectiveness of antidepressants with distinct pharmacodynamic properties, and differences between studies using antidepressants and/or psychotherapy. We also address the differential effectiveness of antidepressant drugs with differing modes of action and in varying subtypes of depressive disorder. After highlighting the clinical usefulness of treatment algorithms and the divergent biological, psychological, and clinical efforts to predict the effectiveness of antidepressant treatments, we conclude that the spectrum of different antidepressant treatments has broadened over the last few decades. The efficacy and clinical effectiveness of antidepressants is statistically significant, clinically relevant, and proven repeatedly. Further optimization of treatment can be helped by clearly structured treatment algorithms and the implementation of psychotherapeutic interventions. Modern individualized antidepressant treatment is in most cases a well-tolerated and efficacious approach to minimize the negative impact of otherwise potentially devastating and life-threatening outcomes in depressive disorders.

     

Intervention research in psychosis: issues related to clinical assessment

This article discusses efforts to optimize clinical assessment for intervention effectiveness trials. Generalizability is a crucial issue; investigators should choose their inclusion/exclusion criteria to increase subject inclusion and should collect data on the selection process to determine the extent of selection biases. Intervention research requires assessment instruments appropriate for a variety of treatment settings. We describe the Hillside Clinical Trials version of the Scale for the Assessment of Negative Symptoms, which has inpatient and outpatient versions to accommodate the different opportunities for social interaction in these settings. Lack of uniformity in assessment instruments complicates interpretation of results across studies and impedes communication of findings. We describe the 5-Dimensional Scale to Evaluate Psychopathology in Schizophrenia (5-STEPS), a collaborative effort to develop a standard change measure for schizophrenia treatment trials. We also discuss potential future strategies, including developing briefer yet reliable and valid diagnostic procedures, making trials more acceptable in a broad range of settings through the use of open-label treatment with blinded independent assessors, bridging efficacy and effectiveness designs by studying both a narrow efficacy and a broader effectiveness population simultaneously, and updating outcome domains to reflect current treatment strategies.     

Alzheimer's disease drug development in 2008 and beyond: problems and opportunities

Recently, a number of Alzheimer's disease (AD) multi-center clinical trials (CT) have failed to provide statistically significant evidence of drug efficacy. To test for possible design or execution flaws we analyzed in detail CTs for two failed drugs that were strongly supported by preclinical evidence and by proven CT AD efficacy for other drugs in their class. Studies of the failed commercial trials suggest that methodological flaws may contribute to the failures and that these flaws lurk within current drug development practices ready to impact other AD drug development [1]. To identify and counter risks we considered the relevance to AD drug development of the following factors: (1) effective dosing of the drug product, (2) reliable evaluations of research subjects, (3) effective implementation of quality controls over data at research sites, (4) resources for practitioners to effectively use CT results in patient care, (5) effective disease modeling, (6) effective research designs. New drugs currently under development for AD address a variety of specific mechanistic targets. Mechanistic targets provide AD drug development opportunities to escape from many of the factors that currently undermine AD clinical pharmacology, especially the problems of inaccuracy and imprecision associated with using rated outcomes. In this paper we conclude that many of the current problems encountered in AD drug development can be avoided by changing practices. Current problems with human errors in clinical trials make it difficult to differentiate drugs that fail to evidence efficacy from apparent failures due to Type II errors. This uncertainty and the lack of publication of negative data impede researchers' abilities to improve methodologies in clinical pharmacology and to develop a sound body of knowledge about drug actions. We consider the identification of molecular targets as offering further opportunities for overcoming current failures in drug development.     

Therapeutic Orthosis and Electrical Stimulation for Upper Extremity Hemiplegia After Stroke: A Review of Effectiveness Based on Evidence

Abstract

Upper extremity hemiplegia after stroke is common and disabling. Apart from conventional physical and occupational therapy, a number of additional approaches that use devices such as orthoses, prostheses, electrical stimulation, and robots have been introduced. The purpose of this review was to assess the clinical efficacy of such devices used for the affected upper extremities of acute, subacute, and chronic stroke patients. Assessments of their effectiveness and recommendations were based on the weight of published scientific evidence. The amount of evidence with respect to hand splints and shoulder slings is limited. Further study with a well-designed randomized controlled trial (RCT) is required to investigate accurately their short- and long-term efficacy. A number of studies suggested that the use of electrical stimulation for reducing shoulder subluxation or improving the function of wrist and finger extensors is effective during or shortly after the daily treatment period. The robotic approach to hemiplegic upper extremities appears to be a novel therapeutic strategy that may help improve hand and arm function. However, the longer term effectiveness after discontinuation as well as the motor recovery mechanism of electrical stimulation or robotic devices remains unclear. More research is needed to determine the evidence-based effectiveness of electrical stimulation or other devices for stroke survivors.