Risperidone alone or in combination for acute mania.

BACKGROUND: Risperidone, an atypical antipsychotic, is used to treat mania both alone and in combination with other medicines. OBJECTIVES: To review the efficacy and tolerability of risperidone as treatment for mania. SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies December 2004), The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL and PsycINFO were searched in December 2004. Reference lists and English language textbooks were searched; researchers in the field and Janssen-Cilag were contacted. SELECTION CRITERIA: Randomised controlled trials comparing risperidone with placebo or other drugs in acute manic or mixed episodes. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data from trial reports. Janssen-Cilag was asked to provide missing information. QUALITY ASSESSMENT: As in other trials of treatment for mania, the high proportion of imputed efficacy data resulting from rates of failure to complete treatment of between 12% and 62% may have biased the results. MAIN RESULTS: Six trials (1343 participants) of risperidone as monotherapy or as adjunctive treatment to lithium, or an anticonvulsant, were identified. Permitted doses were consistent with those recommended by the manufacturers of Haldol (haloperidol) and Risperdal (risperidone) for treatment of mania and trials involving haloperidol allowed antiparkinsonian treatment. Risperidone monotherapy was more effective than placebo in reducing manic symptoms, using the Young Mania Rating Scale (YMRS) (weighted mean difference (WMD) -5.75, 95% confidence interval (CI) -7.46 to -4.04, P<0.00001; 2 trials) and in leading to response, remission and sustained remission. Effect sizes for monotherapy and adjunctive treatment comparisons were similar. Low levels of baseline depression precluded reliable assessment of efficacy for treatment of depressive symptoms. Risperidone as monotherapy and as adjunctive treatment was more acceptable than placebo, with lower incidence of failure to complete treatment (RR 0.66, 95% CI 0.52 to 0.82, P = 0.0003; 5 trials). Overall risperidone caused more weight gain, extrapyramidal disorder, sedation and increase in prolactin level than placebo. There was no evidence of a difference in efficacy between risperidone and haloperidol either as monotherapy or as adjunctive treatment. The acceptability of risperidone and haloperidol in incidence of failure to complete treatment was comparable. Overall risperidone caused more weight gain than haloperidol but less extrapyramidal disorder and comparable sedation. AUTHORS' CONCLUSIONS: Risperidone, as monotherapy and adjunctive treatment, is effective in reducing manic symptoms. The main adverse effects are weight gain, extrapyramidal effects and sedation. Risperidone is comparable in efficacy to haloperidol. Higher quality trials are required to provide more reliable and precise estimates of its costs and benefits.

Determinants of functional outcome and healthcare costs in bipolar disorder: a high-intensity follow-up study.

BACKGROUND: Review of published studies reveals few data regarding determinants of the poor functional outcome and high healthcare costs that are characteristic of bipolar disorder. In order to identify potential mechanisms, critical to designing optimal treatment strategies, this longitudinal study investigated (a) the degree to which disease outcome is correlated with functional outcome and direct treatment costs, and (b) whether similar demographic or clinical characteristics predict disease and functional outcome and healthcare costs. METHODS: Disease and functional outcome were assessed in bimonthly structured interviews over 48 weeks in 43 outpatient veterans with bipolar disorder. Direct mental health treatment costs from the VA perspective were determined from the VA database and patient interview. Regression analysis was used to determine association among the three outcome domains, and to identify clinical or demographic variables that predicted each of the three domains. RESULTS: Functional outcome was correlated with depressive, but not manic, symptoms during follow-up. Costs were not correlated with any measure of disease or functional outcome. Several demographic, but not clinical, characteristics predicted functional outcome. In contrast, several clinical, but not demographic, characteristics predicted symptom status. No predictors were associated with direct treatment costs. LIMITATIONS: Subjects were predominantly male veterans of relatively homogeneous social class, followed prospectively for approximately one year in a clinic designed specifically to minimize barriers to care. CONCLUSIONS: Data from this and prior studies indicate that ongoing depressive symptoms are strongly associated with functional outcome, although substantial variance remains unexplained. Optimal models to explain functional outcome and healthcare costs will need to address factors besides simply disease severity and chronicity. The authors present a heuristic paradigm for understanding both the research and therapeutic aspects of these findings.

Self-reported quality of life across mood states in bipolar disorder.

In distinction to the classic conceptualization of mania and hypomania, a growing body of work indicates that these episodes are not typically characterized by euphoric mood and sense of increased well-being, but rather by significant dysphoric symptoms. However, few data exist concerning self-perceived quality of life in mania or hypomania. Such data are important both for better understanding of the illness, and are particularly important for developing appropriate cost-utility studies. Accordingly, we hypothesized that two measures of self-reported quality of life, the mental subscale of the Short Form-12 (SF-12) and the EuroQol, would show reduced quality of life in patients in manic/hypomanic or mixed episodes, compared to those who were euthymic. Eighty-six patients with bipolar disorder from four Department of Veterans Affairs (VA) medical centers were assessed in a cross-sectional design. Mood state was categorized by physician diagnosis and separately by patient self-report using the Internal State Scale (ISS). Self-reported quality of life was quantified using the SF-12 and EuroQol. Findings were identical regardless of how mood state was determined. The SF-12 mental subscale and EuroQol differed significantly across mood states. Patients with mania/hypomania were either less than (SF-12 mental subscale) or equal to (EuroQol) euthymic patients, while patients in a mixed episode resembled those in a depressive episode on both indices. In contrast, SF-12 physical subscale scores showed no intergroup differences. These quality-of-life data provide further support for the conceptualization that mania and hypomania are syndromes characterized by reduced, rather than increased, sense of well-being and quality of life. Moreover, depressive symptoms appear to be the primary determinant of quality of life in bipolar disorder, although other factors may be associated with both depression and reduced quality of life in bipolar disorder.

The collaborative practice model for bipolar disorder: design and implementation in a multi-site randomized controlled trial.

Bipolar disorder remains a high morbidity and costly illness in general clinical practice, despite the availability of efficacious medications. This 'efficacy-effectiveness gap' may be addressed by better organizing systems of care. One type of intervention is the 'collaborative practice model' which can be defined as an organization of care that a) emphasizes development in the patient of illness management skills, and b) supports provider capability and availability in order to c) engage patients in timely, joint decision-making regarding their illness. This article describes such a collaborative practice model for bipolar disorder, designed to be widely adoptable and sustainable in general clinical practice. The first part of the article describes the theoretical background from which the collaborative practice approach developed, emphasizing its origins in the lithium clinics of the 1970s, in nursing theory and practice, and more recently in the management of chronic medical diseases. The second part describes the structure of one such intervention, the Bipolar Disorders Program (BDP) developed in the Veterans Affairs health care system. The third part summarizes results from single-site studies of the intervention. The fourth part describes several key issues in its implementation in an ongoing multi-site randomized controlled trial, VA Cooperative Study Program (CSP) # 430. Data to date indicate that such collaborative practice interventions may improve important process and intermediate outcome variables for bipolar disorder. The BDP provides an example of a multi-faceted collaborative practice model that can be manualized and implemented across multiple sites in a randomized controlled trial.

An evidence-based review of psychosocial treatments for bipolar disorder.

Because somatotherapy for bipolar disorder (BD) has led to only modest improvements in outcome in general clinical practice, increasing attention has been paid to psychosocial interventions as adjuvants to standard medical-model treatment. This article complements and extends other recent reviews of this area by (1) evaluating psychotherapy studies according to the evidence rating criteria of the Agency for Health Care Policy and Research; (2) analyzing which outcome domains are impacted by which types of psychotherapy; (3) reviewing studies of care organization (contexts of care) for BD, tracing the roots of this area from descriptions of lithium clinics in the early 1970s through the recent federally funded controlled trials; and (4) identifying a core agenda common across most psychosocial interventions. The psychotherapy literature indicates that a broad array of modalities may be effective in improving clinical outcome, functional outcome, and disease management skills, with Class A studies supporting at least some couples/partners, cognitive-behavioral, family, and psychoeducational interventions. Controlled studies of context of care interventions are in their infancy, but are built on principles similar to those used in disease management programs for chronic medical illnesses. Despite the diversity of psychosocial interventions, there is substantial convergent validity for the importance of a common agenda of a collaborative approach to illness management that includes education about the illness, and identification of patient-specific symptom patterns, and development of action plans for response to relapse. A research agenda focusing on interventions that are sustainable in general clinical practice is of the highest priority.

Principles of effectiveness trials and their implementation in VA Cooperative Study #430: 'Reducing the efficacy-effectiveness gap in bipolar disorder'.

Despite the availability of efficacious treatments for bipolar disorder, their effectiveness in general clinical practice is greatly attenuated, resulting in what has been called an 'efficacy-effectiveness gap'. In designing VA Cooperative Studies Program (CSP) Study #430 to address this gap, nine principles for conducting an effectiveness (in contrast to an efficacy) study were identified. These principles are presented and discussed, with specific aspects of CSP #430 serving as illustrations of how they can be implemented in an actual study. CSP #430 hypothesizes that an integrated, clinic-based treatment delivery system that emphasizes (1) algorithm-driven somatotherapy, (2) standardized patient education, and (3) easy access to a single primary mental health care provider to maximize continuity-of-care, will address the efficacy-effectiveness gap and improve disease, functional, and economic outcome. It is an 11-site, randomized controlled clinical trial of this multi-modal, clinic-based intervention versus usual VA care running from 1997 to 2003. The trial has enrolled 191 subjects in each arm, using minimal exclusion criteria to maximize the external validity of the study. Subjects are followed for 3 years. The intervention is highly specified in a series of operations manuals for each of the three components. Several continuous quality improvement (CQI) interventions, process measures, and statistical techniques deal with drift of care in both the intervention and usual care arms to ensure the internal validity of the study. CSP #430 is designed to have impact well beyond the VA, since it evaluates a basic health care operational principle: that augmenting ambulatory access for major mental illness will improve outcome and reduce overall treatment costs. If results are positive, this study will provide a reason to reconsider the prevailing trend toward limitation of ambulatory services that is characteristic of many managed care systems today.

Establishing a function-based mental health service line in a VA medical center.

From 1994 through 1996, a general Veterans Affairs (VA) medical center reorganized its mental health services from a traditional discipline-based structure to a unitary service line organized around patient care functions. A comparison of data from 1993 and 1997 indicated increased efficiency, substantial transfer of patients from inpatient to outpatient care, and growth in academic programs not explainable solely by temporal, regional, or national trends or by trends within the VA medical center. Although the results should be interpreted conservatively because of the observational nature of the study, the reorganization appeared to facilitate the positive changes that occurred over the study period.

Comparison of the internal state scale to clinician-administered scales in asthma patients receiving corticosteroid therapy.

Mood symptoms are reported frequently in asthma patients, particularly during corticosteroid therapy. This investigation compared the Internal State Scale (ISS), a self-report measure of symptoms of mania and depression, to the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS) in a group of asthma patients (n=60 at baseline) before, during, and after a 1-2 week burst of prednisone. The depression and well being subscales of the ISS correlated well with HDRS scores. The perceived conflict subscale correlated with the BPRS scores. However, none of the ISS subscales correlated consistently and specifically with the YMRS in this population. Possible explanations for differences observed in bipolar versus asthma patients given the ISS are discussed. These data suggest the ISS may be a useful tool for depression symptoms and overall psychopathology in asthma patients and in patients receiving corticosteroid therapy. However, its ability may be attenuated outside of the population for which it was designed.

The Internal State Scale: replication of its discriminating abilities in a multisite, public sector sample.

OBJECTIVE: The Internal State Scale (ISS) is a self-report instrument that has been validated for discriminating mood states in patients with bipolar disorder. This study a) extends investigation to a multisite public sector sample and b) tests a revised scoring algorithm that formally identifies patients in mixed states. METHODS: Eighty-six patients with bipolar disorder from four Veterans Affairs medical centers were assessed in a cross-sectional design. Physician-conducted semi-structured interviews used DSM-IV criteria to identify subjects as meeting criteria for euthymia, mania or hypomania, depression, or mixed state (mania or hypomania plus depression). A revised ISS scoring algorithm independently assigned mood state. Mean subscale scores were analyzed across groups. Receiver-operating characteristic (ROC) curve analysis was conducted to determine optimal algorithm structure. RESULTS: Analysis of mean scores for the ISS subscales replicated original results for Activation, Well-Being, and Perceived Conflict, but indicated differences from the original results for the Depression Index. The ROC curve analysis identified optimal cut-off scores for the revised algorithm. The overall kappa score indicated moderate agreement between ISS and physician ratings of mood state, including mixed states. LIMITATIONS: The study used a sample consisting primarily of male veterans. Mood state was assigned by experts using expert clinician diagnosis, not structured interviews. CONCLUSION: The performance of the ISS in this multisite, public sector sample was similar to the performance in the initial research clinic sample. This finding confirms the validity of the ISS as a discriminator of mood states in bipolar disorder. The development of a revised scoring algorithm makes feasible formal identification of mixed episodes with the ISS.

Sinogenic subdural empyema and Streptococcus anginosus.

Subdural empyema (SDE) is most commonly caused by sinusitis and, without early diagnosis and neurosurgical intervention, is associated with high mortality. In a patient with sinusitis who presents with mental status changes, the diagnosis of SDE should be suspected on clinical grounds, even in the absence of significant computed tomographic findings. Computed tomography with contrast is a useful aid in the diagnosis of SDE, but findings may be subtle, and contrasted magnetic resonance imaging is superior. The association of Streptococcus anginosus sinusitis and related intracranial sequelae is important owing to the potentially catastrophic complications and should be recognized by otolaryngologists. In view of the rapidly progressing nature of sinogenic SDE, physicians should strongly consider early institution of aggressive therapy consisting of craniotomy with concurrent sinus drainage in patients in whom sinogenic SDE is suspected on clinical grounds, particularly in the presence of S. anginosus-positive sinus cultures.

Psychosocial interventions for bipolar disorder.

The limitations of pharmacotherapy and the emergence of data supporting a role for psychosocial factors in the course of bipolar disorder have led to increased interest in the use of psychosocial interventions to improve outcomes. Although this area of study has suffered from a lack of systematic data, preliminary evidence suggests that the combined use of psychosocial interventions and medication is superior to pharmacologic treatment alone. Further research is necessary to identify and the psychosocial risk factors associated with bipolar disorder to design effective interventions to diminish their effects and improve outcome. The introduction of formal, manual-based psychotherapeutic interventions that include specific educational components has been particularly promising.

Clinical practice guidelines for bipolar disorder from the Department of Veterans Affairs.

BACKGROUND: For the last several years, the Department of Veterans Affairs (VA) has been involved in the development of practice guidelines for major medical, surgical, and mental disorders. This article describes the development and content of the VA-Clinical Practice Guidelines for Bipolar Disorder, which are available in their entirety on the Journal Web site (http://www. psychiatrist.com). METHOD: A multidisciplinary work group composed of content experts in the field of bipolar disorder and practitioners in general clinical practice was convened by the VA's Office of Performance and Quality and the Mental Health Strategic Health Group. The work group was instructed in algorithm development and methods of evidence evaluation. Draft guidelines were developed over the course of 6 months of meetings and conference calls, and that draft was then sent to nationally prominent content experts for final critique. RESULTS: The Bipolar Guidelines are part of the family of the VA Clinical Guidelines for Management of Persons with Psychosis and consist of explicit algorithms supplemented by annotations that explain the specific decision points and their basis in the scientific literature. The guidelines are organized into 5 modules: a Core Module for diagnosis and assignment to mood state plus 4 treatment modules (Manic/Hypomanic/Mixed Episode, Bipolar Depressive Episode, Rapid Cycling, and Bipolar Disorder With Psychotic Features). The modules specify particular diagnostic and treatment tasks at each step, including both somatotherapeutic and psychotherapeutic interventions. CONCLUSION: The VA Bipolar Guidelines are designed for easy clinical reference in decision making with individual patients, as well as for use as a scholarly reference tool. They also have utility in training activities and quality improvement programs.

Manual-based group psychotherapy for bipolar disorder: a feasibility study.

BACKGROUND: The Life Goals Program is a structured, manual-based group psychotherapy program for bipolar disorder that seeks to improve patient participation in medical model treatment (phase 1) and assist patients in meeting functional status goals (phase 2). The goals of this initial study were (a) to determine whether the procedures could be exported from the authors to other therapists and (b) to quantify tolerability and impact of procedures on patients. METHOD: Four therapists across 2 sites and 29 patients from the Veterans Affairs (VA) Medical Center were studied in an open feasibility study. Therapists were trained, and subsequent compliance with manual procedures was quantified. Several process indices measuring tolerability and impact on patients were analyzed. RESULTS: Therapists covered 90% to 96% of phase 1 psychoeducational content, indicating excellent fidelity to manual procedures. Sixty-nine percent of patients completed phase 1, and participation scores were in the good to excellent range for 56%. Completion of phase 1 was associated with significant increase in knowledge about bipolar disorder. Fourteen (70%) of 20 patients enrolled in phase 2 reached their self-identified, behaviorally based goal (48% of the total sample who began phase 1 of the program). Mean +/- SD time to goal completion was 8.7 +/- 5.3 months (median [95% confidence interval] = 7 [5.1-12.3 months]; range, 2-17 months). CONCLUSION: The manual-based intervention can be exported with fidelity to other therapists and sites (for phase 1). Data indicate reasonable tolerability and good achievement of process (for phases 1 and 2) for those who accept this group modality. Comparison with other manual-based psychotherapies indicates remarkable consistency regarding content for psychotherapy for bipolar disorder; major differences among the psychotherapies include mode of delivery and relative emphasis of specific components.

Adaptation of a simple patient satisfaction instrument to mental health: psychometric properties.

The authors describe the psychometric properties of a simple patient satisfaction self-report instrument originally developed for use in primary care patients, adapted for use in mental health clinic patients of varied educational and socioeconomic backgrounds. The instrument demonstrated a single major principal component, high internal consistency reliability, high test-retest reliability, and sensitivity to change with experimental manipulations in clinical programming. The results also indicate that patient satisfaction is unidimensional in mental health patients as it is for primary care patients.

Predictors of service utilization in veterans with bipolar disorder: a prospective study.

This study prospectively followed 103 bipolar patients enrolled in a VA treatment program for 1 year. Mental health service utilization was recorded and aggregated using the VA Cost Distribution Report. We hypothesized that previously reported predictors of disease severity would also predict service utilization, and that several other predictors of service utilization might also be identified. Analyses indicated that only the presence of a major affective episode at clinic intake and a recalled history of childhood physical abuse predicted mental health service utilization. Contrary to expectations, previously reported predictors of disease severity were not significant predictors. Implications for the study of economic outcome are discussed. In particular, we propose that economic outcome is a complex function of both patient and system factors, rather than simply being passively driven by disease severity.

[Genetic diagnosis of the hypotonic newborn]. / Diagnóstico genético del recién nacido hipotónico.

Assessment of hypotonic newborn babies implies not only neurological studies, but; also new methods of molecular genetics, to reach a diagnosis of the aetiology. The Prader-Willi, Werdnig-Hoffmann and Myotonic Dystrophy syndromes are three conditions with neurological symptoms which have recently been defined at a molecular level.

Impact of an easy-access VA clinic-based program for patients with bipolar disorder.

OBJECTIVE: The study examined the impact of easy access to ambulatory services for patients with bipolar disorder in a clinic-based program at a Veterans Affairs medical center. Core program components included medication administration based on treatment algorithms, standardized psychoeducation, and easy access to a single primary nurse provider to enhance continuity of care. The program had no community outreach or extensive rehabilitation components. METHODS: The study used a mirror-image design to compare patients' data from the year before program entry when patients received standard clinical care with data for the first year in the program. Process and outcome data from the first 103 patients to complete one year are reported. RESULTS: The findings indicated increased patient satisfaction and increased intensity of medication treatment without increased side effects at one year. Although scheduled ambulatory clinic visits increased as expected, use of the emergency room and the psychiatric triage team decreased significantly. Patients who were high utilizers of care before program entry experienced significant reductions in psychiatric hospital days and total mental health expenditures. CONCLUSIONS: Easy access to ambulatory care, even if limited to clinic-based services, may have beneficial effects on important process and outcome measures for bipolar disorder. These effects may be attributable to on-demand access to services, continuity of care with a single primary provider, or improved medication delivery to reduce the "efficacy-effectiveness gap" for patients with bipolar disorder. Results indicate that augmenting, rather than limiting, access to ambulatory care for patients with major mental illnesses such as bipolar disorder may reduce overall mental health expenditures.

Evaluation of a hemostasis model for teaching basic surgical skills.

The need for alternative methods of teaching veterinary medicine and surgery has increased in recent years because of increasing costs and changing public opinion. For these reasons a hemostasis model was developed that mimics the arteries and veins of the peripheral vascular system, and can be used to teach the basic skills involved in blood vessel ligation and division. This study evaluated the effectiveness of the fluid hemostasis model compared with using live animals for teaching these skills. Forty sophomore veterinary students participated in the study. Two groups of 20 students each received identical instruction in the basic techniques required for vessel ligation and division. The students then completed various exercises using inanimate models to objectively evaluate their psychomotor skills. Both groups then practiced the techniques for equal time periods; one group used the hemostasis model and the other performed a splenectomy on live dogs. After the practice session, the students were videotaped (for later evaluation), as they performed vessel ligations and divisions. The students then repeated the exercises using the inanimate models for evaluation of skills improvement. Questionnaire responses before and after the project were obtained to determine the students' views on the need for inanimate models for teaching purposes. Results of this study indicate that the hemostasis model was as effective as live animals for teaching the basic skills involved in blood vessel ligation. The students' opinions regarding the use of properly designed inanimate models for teaching these skills were dramatically changed.

Evidence of chaotic mood variation in bipolar disorder.

BACKGROUND: Using long-term daily mood records obtained from patients with bipolar disorder and normal subjects, we sought to determine the temporal pattern of mood in bipolar disorder. METHODS: Time series of 1.0 to 2.5 years from seven rapid-cycling patients with bipolar disorder and 28 normal controls were obtained. These were evaluated with several techniques to identify whether the temporal pattern of mood originates from a periodic, a random, or a deterministic source. RESULTS: True cyclicity was not apparent in the power spectra of either the normal subjects or the patients with bipolar disorder. Instead, spectra with a broadband "l/f" shape were observed in both groups, and these spectra were significantly flatter in normal subjects (P = .02). Correlation dimension estimates are a measure of nonlinear deterministic structure, and convergent estimates could be obtained for six of the seven patients with bipolar disorder and none of the normal subjects (P < .001). Additional findings are consistent with these results. CONCLUSIONS: These studies indicate that mood in patients with bipolar disorder is not truly cyclic for extended periods. Nonetheless, self-rated mood in bipolar disorder is significantly more organized than self-rated mood in normal subjects and can be characterized as a low-dimensional chaotic process. This characterization of the dynamics of bipolar disorder provides a unitary theoretical framework that can accommodate neurobiologic and psychosocial data and can reconcile existing models for the pathogenesis of the disorder. Furthermore, consideration of the dynamical structure of bipolar disorder may lead to new methods for predicting and controlling pathologic mood.