Mirogabalin: a novel gabapentinoid or another false dawn?

PURPOSE OF REVIEW: Mirogabalin is a novel gabapentinoid medication for the treatment of neuropathic pain. The purpose of this review is to discuss current evidence for its use. Gabapentinoids are widely prescribed for neuropathic pain. Mirogabalin offers theoretical advantages over traditional gabapentinoids due to its specificity for the α2δ-1 subunit of voltage-gated calcium channels. It is theorised that this specificity may reduce adverse drug reactions by minimising binding to the α2δ-2 subunit which is responsible for many of the gabapentinoid side effects. RECENT FINDINGS: Mirogabalin's slower dissociation from the α2δ-1 compared with α2δ-2, and its higher potency may also impart an efficacy benefit over traditional gabapentinoids. These theoretical advantages of mirogabalin remain inconclusive in clinical practice, with mixed evidence regarding mirogabalin versus traditional gabapentinoids. Some studies suggest a reduced side effect profile yet, others fail to demonstrate significant differences. Regarding efficacy, mirogabalin may be superior to placebo for several neuropathic pain syndromes, but evidence of widespread benefit over traditional gabapentinoids is currently lacking. SUMMARY: Mirogabalin offers theoretical promise, but large, independent studies are required to further assess its performance versus traditional gabapentinoids.

Conceptualizing participation in the community mental health context: Beginning with the Clubhouse model.

PURPOSE: Although participation is key to community mental health, the concept remains elusive. The study explored a conceptualization of participation in the community-based mental health agencies context from a first-person perspective, using the Clubhouse model as an example. METHODS: Qualitative data, collected from 21 Clubhouse service users through three focus groups (1 UK and 2 US) for primary analysis and secondary data from 104 individual interviews, were analysed using a grounded theory approach. RESULTS: Focus group narratives revealed three main domains of what may be named everyday participation process, Making Decisions, Doing Work, and Locating Oneself in Community, blended with each other rather than forming clear-cut stages. Sixty-six extracted primary codes, with two underlying interrelated core categories identified, named Autonomy and Egalitarian Connection, were organized by domain and by category. CONCLUSIONS: The findings suggest a 3 × 2 axial model of participation that participation signifies a behaviour, comprised of three blended activity domains, entailing actions and interactions that concern Autonomy and Egalitarian Connection, which, dynamically interacting with each other, appear to condition meaningful participation the next day. Egalitarian relationship skills development appears critical for training practitioners to help promote service users' quality everyday participation and getting-a-life-back experiences towards well-being, or meaningful life.

Threat, hostility and violence in childhood and later psychotic disorder: population-based case-control study.

BACKGROUND: A growing body of research suggests that childhood adversities are associated with later psychosis, broadly defined. However, there remain several gaps and unanswered questions. Most studies are of low-level psychotic experiences and findings cannot necessarily be extrapolated to psychotic disorders. Further, few studies have examined the effects of more fine-grained dimensions of adversity such as type, timing and severity. AIMS: Using detailed data from the Childhood Adversity and Psychosis (CAPsy) study, we sought to address these gaps and examine in detail associations between a range of childhood adversities and psychotic disorder. METHOD: CAPsy is population-based first-episode psychosis case-control study in the UK. In a sample of 374 cases and 301 controls, we collected extensive data on childhood adversities, in particular household discord, various forms of abuse and bullying, and putative confounders, including family history of psychotic disorder, using validated, semi-structured instruments. RESULTS: We found strong evidence that all forms of childhood adversity were associated with around a two- to fourfold increased odds of psychotic disorder and that exposure to multiple adversities was associated with a linear increase in odds. We further found that severe forms of adversity, i.e. involving threat, hostility and violence, were most strongly associated with increased odds of disorder. More tentatively, we found that some adversities (e.g. bullying, sexual abuse) were more strongly associated with psychotic disorder if first occurrence was in adolescence. CONCLUSIONS: Our findings extend previous research on childhood adversity and suggest a degree of specificity for severe adversities involving threat, hostility and violence.

Threatening Life Events and Difficulties and Psychotic Disorder.

OBJECTIVE: Stressful life events have been implicated in the onset of psychotic disorders, but there are few robust studies. We sought to examine the nature and magnitude of associations between adult life events and difficulties and first-episode psychoses, particularly focusing on contextual characteristics, including threat, intrusiveness, and independence. METHOD: This study forms part of the Childhood Adversity and Psychosis Study (CAPsy), an epidemiological case-control study in London, United Kingdom. Data on life events and difficulties (problems lasting 4 wk or more) during 1 year prior to onset (cases) or interview (controls) were assessed using the semi-structured Life Events and Difficulties Schedule (LEDS). Data were available on 253 individuals with a first episode of psychosis and 301 population-based controls. RESULTS: We found strong evidence that odds of exposure to threatening and intrusive events in the 1 year prior to onset were substantially higher among cases compared with controls, independent of age, gender, ethnicity, and social class (ORs > 3). This was consistent across diagnostic categories. We found further evidence that the effect of threatening events and difficulties was cumulative (1 event odds ratio [OR] 2.69 [95% confidence interval (CI) 1.51-4.79]; 2 events OR 4.87 [95% CI 2.34-10.16]; ≥3 events OR 5.27 [95% CI 1.83-15.19]; 1 difficulty OR 3.02 [95% CI 1.79-5.09]; 2 difficulties OR 9.71 [95% CI 4.20-22.40]; ≥3 difficulties OR 12.84 [95% CI 3.18-51.85]). CONCLUSIONS: Threatening and intrusive life events and difficulties are common in the year pre-onset among individuals with a first episode of psychosis. Such experiences may contribute to the development of psychotic disorders.

A comparison between self-report and interviewer-rated retrospective reports of childhood abuse among individuals with first-episode psychosis and population-based controls.

The typical reliance on self-report questionnaires in retrospective case-control studies of childhood abuse and psychotic disorders has been criticised, due to the potential for recall bias associated with, amongst other factors, cognitive impairments and detachment from reality, among individuals with psychosis. One way to establish if any substantial bias may exist is to examine whether the concordance of reports of childhood abuse established from retrospective self-report methods versus more comprehensive interviewer-rated assessments differ between individuals with psychosis and controls. Data from the Childhood Adversity and Psychosis (CAPsy) study were used to examine the accuracy, strength of agreement, and convergent validity of two distinct retrospective measures of childhood abuse: a self-report questionnaire (the Childhood Trauma Questionnaire; CTQ) and a comprehensive interview (the Childhood Experiences of Care and Abuse schedule; CECA). In a sample of 234 cases with first-episode psychosis and 293 controls, we found no strong evidence that the validity of the two measures differed between cases and controls. For reports of sexual and emotional abuse, we found fair levels of agreement between CECA and CTQ ratings in both groups (kappa coefficients 0.43-0.53), moderate to high sensitivity and specificity, and reasonably high convergent validity (tetrachoric correlations of 0.78-0.80). For physical abuse, convergent validity was slightly lower in cases compared with controls. Both measures can be used in future studies to retrospectively assess associations between childhood abuse and psychotic phenomena, but time-permitting, the CECA is preferable as it provides additional important contextual details of abuse exposure.

Comparison of Early Intervention Services vs Treatment as Usual for Early-Phase Psychosis: A Systematic Review, Meta-analysis, and Meta-regression.

Importance: The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal. Objective: To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis. Data Sources: Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017. Study Selection: Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders. Data Extraction and Synthesis: This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses. Main Outcomes and Measures: The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period. Results: Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], -0.32; 95% CI, -0.47 to -0.17; P < .001), positive symptom severity (SMD, -0.22; 95% CI, -0.32 to -0.11; P < .001), and negative symptom severity (SMD, -0.28; 95% CI, -0.42 to -0.14; P < .001). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months). Conclusions and Relevance: In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.

Sense of clubhouse community belonging and empowerment.

BACKGROUND: While the neighborhood community literature well documents a link between participation in supportive and effective community groups or activities and empowerment, there is as yet little empirical evidence of this relationship in the context of community mental health programs. AIM: The primary purpose of the study was to examine the relationship between sense of community belonging and empowerment among members of mental health clubhouses. METHODS: A secondary analysis using a hierarchical regression model was conducted on cross-sectional structured interview data collected through a self-report questionnaire from 102 clubhouse members from six clubhouses in the United States and Finland. RESULTS: The results indicated that members' sense of clubhouse community belonging positively contributes to their empowerment. CONCLUSION: Fostering sense of community belonging appears to be a valid approach to catalyze empowerment. Study limitations and future research agendas were discussed.

Identification of the delivery of cognitive behavioural therapy for psychosis (CBTp) using a cross-sectional sample from electronic health records and open-text information in a large UK-based mental health case register.

OBJECTIVE: Our primary objective was to identify cognitive behavioural therapy (CBT) delivery for people with psychosis (CBTp) using an automated method in a large electronic health record database. We also examined what proportion of service users with a diagnosis of psychosis were recorded as having received CBTp within their episode of care during defined time periods provided by early intervention or promoting recovery community services for people with psychosis, compared with published audits and whether demographic characteristics differentially predicted the receipt of CBTp. METHODS: Both free text using natural language processing (NLP) techniques and structured methods of identifying CBTp were combined and evaluated for positive predictive value (PPV) and sensitivity. Using inclusion criteria from two published audits, we identified anonymised cross-sectional samples of 2579 and 2308 service users respectively with a case note diagnosis of schizophrenia or psychosis for further analysis. RESULTS: The method achieved PPV of 95% and sensitivity of 96%. Using the National Audit of Schizophrenia 2 criteria, 34.6% service users were identified as ever having received at least one session and 26.4% at least two sessions of CBTp; these are higher percentages than previously reported by manual audit of a sample from the same trust that returned 20.0%. In the fully adjusted analysis, CBTp receipt was significantly (p<0.05) more likely in younger patients, in white and other when compared with black ethnic groups and patients with a diagnosis of other schizophrenia spectrum and schizoaffective disorder when compared with schizophrenia. CONCLUSIONS: The methods presented here provided a potential method for evaluating delivery of CBTp on a large scale, providing more scope for routine monitoring, cross-site comparisons and the promotion of equitable access.

Treatment of Veterans with depression who died by suicide: timing and quality of care at last Veterans Health Administration visit.

OBJECTIVE: To examine the recency and quality of the last Veterans Health Administration (VHA) visit for patients with depression who died by suicide. METHOD: We obtained services and pharmacy data for all 1,843 VHA patients with diagnosed depressive disorders (DSM-IV criteria) who died by suicide from April 1999 through September 2004. We ascertained the location and timing of their final VHA visit. For visits occurring within 30 days of suicide, we examined 3 quality indicators: (1) evidence that mental illness was a focus of the final visit, (2) adequacy of antidepressant dosage, and (3) recent receipt of mental health services. RESULTS: Just over half of the patients (51%) with depression diagnoses had a VHA visit within 30 days of suicide. A minority of these patients (43%) died by suicide within 30 days of a final visit with mental health services, although 64% had received such services within 91 days of their suicide. Among the 57% of patients who died by suicide within 30 days and who were seen in non-mental health settings for their final visit, only 34% had a mental health condition coded at the final visit, and only 41% were receiving adequate dosages of antidepressant (versus 55% for those last seen by mental health services) (P < .0005). CONCLUSIONS: Veterans Health Administration patients with depression who died by suicide within 30 days of their final visit received relatively high rates of mental health services, but most final visits still occurred in non-mental health settings. Increased referrals to mental health services, attention to mental health issues in non-mental health settings, and focus on antidepressant treatment adequacy by all providers might have reduced suicide risks for these patients.

Unmet need for mental health care in schizophrenia: an overview of literature and new data from a first-admission study.

We present an overview of the literature on the patterns of mental health service use and the unmet need for care in individuals with schizophrenia with a focus on studies in the United States. We also present new data on the longitudinal course of treatments from a study of first-admission patients with schizophrenia. In epidemiological surveys, approximately 40% of the respondents with schizophrenia report that they have not received any mental health treatments in the preceding 6-12 months. Clinical epidemiological studies also find that many patients virtually drop out of treatment after their index contact with services and receive little mental health care in subsequent years. Clinical studies of patients in routine treatment settings indicate that the treatment patterns of these patients often fall short of the benchmarks set by evidence-based practice guidelines, while at least half of these patients continue to experience significant symptoms. The divergence from the guidelines is more pronounced with regard to psychosocial than medication treatments and in outpatient than in inpatient settings. The expansion of managed care has led to further reduction in the use of psychosocial treatments and, in some settings, continuity of care. In conclusion, we found a substantial level of unmet need for care among individuals with schizophrenia both at community level and in treatment settings. More than half of the individuals with this often chronic and disabling condition receive either no treatment or suboptimal treatment. Recovery in this patient population cannot be fully achieved without enhancing access to services and improving the quality of available services. The recent expansion of managed care has made this goal more difficult to achieve.

Management perspectives on research contributions to practice through collaboration in the U.S. Veterans Health Administration: QUERI Series.

The Quality Enhancement Research Initiative (QUERI) is a unique quality improvement program designed to connect health services researchers to Veterans Health Administration (VHA) management and operations, as well as to provide the science and initiative for making change. Through this process, QUERI stakeholders have learned that success and impact in improving healthcare quality and outcomes largely depends on coordination and collaboration among numerous VHA programs and organizations working to develop and implement evidence-based clinical policies, practices, and quality improvement strategies. This Commentary discusses some of these collaborative efforts and perceived successes in achieving common goals from the viewpoints of two closely involved VHA Operations/Support stakeholders. The Commentary is part of a Series of articles documenting implementation science frameworks and tools developed by the U.S. Department of Veterans Affairs Quality Enhancement Research Initiative (QUERI).

Self-reported performance improvement strategies of highly successful Veterans Health Administration facilities.

The Veterans Health Administration (VHA) has achieved considerable success in improving health care through the use of clinical performance measures. This report examines the self-reported strategies used by the most successful facilities in the VHA system. For fiscal year 2002, facilities that scored the highest on any of 24 clinical performance measures were queried as to which strategies they used to achieve their level of performance. The most commonly cited strategies across all performance categories were organizational change (55.6%), clinical reminders (41.4%), audit and feedback to providers (39.6%), and staff education (32.5%). Certain strategies were more likely to be cited for 1 or more specific performance categories (eg, clinical reminders for immunization [61.1%], screening [60.6%]). These findings suggest that successful facilities are generally using evidence-based strategies to achieve high clinical performance. However, some evidence-based implementation strategies were rarely cited (eg, use of clinical champions).

Medication use patterns and two-year outcome in first-admission patients with major depressive disorder with psychotic features.

OBJECTIVE: This study examined the patterns and predictors of medication use and 24-month course/outcome in first-admission patients with major depressive disorder with psychotic features (MDD/P). METHOD: An epidemiological sample of 87 first-admission patients with research diagnoses of MDD/P received intensive clinical assessments at baseline and at 6- and 24-month follow-ups and telephone assessments at 3-month intervals. Use of medications (antidepressant [AD], antipsychotic [AP], and antimanic agents) was determined from self-reports corroborated by external sources where possible. Outcome was assessed with the Global Assessment of Functioning and consensus evaluations of illness course and time in remission. RESULTS: More patients received APs (77.0%) than ADs (57.5%) at discharge, with almost half (49.4%) receiving these in combination. At 24-month follow-up, 40.2% reported using no medications; 39.1% used ADs, and 32.2% used APs. Only early AD use predicted regular AD use during the 6- to 24-month follow-up. A minority (29%) achieved functional recovery (Global Assessment of Functioning score > or = 71) by 24 months. Although about 60% of the sample achieved a period of complete remission by 24 months, only about 40% had a sustained remission for at least 19 months. Medication use was not predictive of these outcome measures. There was little evidence that changes in medication, augmentation strategies, or electroconvulsive therapy was used to reduce symptoms during the 24-month follow-up. Fewer than half of our subjects received a MDD/P clinical diagnosis at discharge, which appeared to influence medication use patterns over the 24-month follow-up. CONCLUSIONS: These findings suggest that for most of these patients with MDD/P, outcome was suboptimal for both functional and syndromal recovery. The lack of an association between medication use and outcome suggests that medication changing and augmentation strategies, electroconvulsive therapy use, and/or strategies to improve medication adherence might be considered in the treatment of patients with MDD/P who remain low functioning and symptomatic even while receiving pharmacotherapy. Finally, our findings highlight the need for routine systematic diagnostic procedures to ensure appropriate diagnosis and treatment of MDD/P at first admission as well as the need for replication of our findings in a more contemporary sample.

Remission and relapse after the first hospital admission in psychotic depression: a 4-year naturalistic follow-up.

BACKGROUND: Few studies have examined the course of illness among severely depressed patients ascertained at first hospitalization. Using data from the Suffolk County Mental Health Project (SCMHP), we investigated the times to and predictors of the first full remission and the first relapse during a 4-year period in a first-admission cohort with major depressive disorder (MDD) with psychotic features. METHOD: The cohort included 87 county-wide, first-admission patients with a longitudinal consensus diagnosis of MDD with psychotic features who were systematically followed over a 4-year period. We examined the associations of background, clinical and treatment factors, and time-varying indices of antidepressant (AD) and antipsychotic (AP) medication use to time to remission and relapse using Cox regression. RESULTS: By the 4-year follow-up, 60 respondents (69.0%) had achieved a period of full remission (median time of 22 weeks among remitters and 54 weeks in the full sample). In the multivariable analysis, longer time to remission was associated with longer latency between initial episode and hospitalization, lower pre-hospital Global Assessment of Functioning (GAF) score, and lack of insurance, but not use of medication. Twenty-six remitters (43.3%) relapsed (median time of 50 weeks among those who relapsed and 192 weeks among all remitters). None of the risk factors or time-varying medication variables was significantly associated with time to relapse. CONCLUSION: Only two-thirds of the sample had at least one full remission by 4 years, and almost half of them subsequently relapsed. Poorer pre-hospital resources predicted remission but not relapse. Medication use over the follow-up was not associated with remission or relapse.

Mortality among first-admission patients with psychosis.

OBJECTIVE: This study compared 5- and 10-year survival and absolute and relative mortality rates among first-admission patients with 1 of 4 psychotic disorders: schizophrenia/schizoaffective disorder, bipolar disorder, major depression, and other nonorganic psychoses. METHOD: The authors conducted a prospective 10-year follow-up of subjects first admitted with a diagnosis of nonorganic psychosis to any of 12 hospitals in Suffolk County, New York, during the period 1989 to 1995. Information on their death status since study entry was ascertained from the Social Security Death Index and the National Death Index. Survival analyses were conducted using the Kaplan-Meier product-limit estimator. RESULTS: There were no significant differences in survival rates among the 4 diagnostic groups at 5-year (range, 96.3%-97.8%) or 10-year (range, 90.2%-97.8%) follow-up. Absolute mortality over the study period ranged from 2.8% of bipolars to 6.7% of those with major depression. About 60% of deaths among schizophrenic/schizoaffective subjects were due to unnatural causes, whereas for the other 3 groups, deaths were more evenly split between natural and unnatural causes. Suicides comprised most deaths from unnatural causes, most of which occurred during the 2- to 5-year follow-up period. Deaths due to natural causes tended to be related to lifestyle factors. CONCLUSIONS: First-admission patients with psychosis experience similar patterns of mortality risk over the first 10 years after index admission regardless of underlying diagnosis. Causes of death (both natural and unnatural) were potentially preventable with more intensive medical and psychiatric follow-up and intervention. Many deaths from unnatural causes occurred during or shortly after discharge from an inpatient or residential treatment setting, highlighting this period as one needing close scrutiny by treating clinicians.

Strategies for improving pneumococcal vaccination in eligible patients.

Despite the fact that invasive Streptococcus pneumoniae remains a leading cause of death, current levels of immunization in the at risk population remain low and well below the 90% goal for Healthy People 2010. A number of intervention strategies to increase immunization rates (for influenza and pneumonia) have been demonstrated to be effective in increasing these rates when used alone or in combination. A summary of this literature is presented including recent data on the effectiveness of pay-for-performance approaches for increasing preventive care. Data are also presented on intervention strategies judged to be most effective in a large health care system, the Veterans Health Administration, which has essentially reached the Healthy People 2010 goal for pneumococcal immunization.

Case-finding for depression among medical outpatients in the Veterans Health Administration.

OBJECTIVES: We sought to determine the rates and predictors of screening, screening positive, follow-up evaluation, and subsequent diagnosis of depression among medical outpatients. RESEARCH DESIGN: This was a cross-sectional study using chart-review data from the Department of Veterans Affairs (VA) 2002 External Peer Review Program merged with administrative data. SUBJECTS AND MEASURES: We studied a national sample of VA medical outpatients with no depression diagnosis or mental health visits in the past 6 months (n = 21,489) and used chart-review and administrative data to follow the chain of events from depression screening to diagnosis. RESULTS: Overall, 84.9% of eligible patients (n = 18,245) were screened for depression in the past year. Of the 8.8% who screened positive, only 54.0% received follow-up evaluation and, of these, 23.6% (n = 204) subsequently were diagnosed with a depressive disorder (representing 1.1% of the originally screened sample). Patients who were younger, unmarried, and had more medical comorbidities were less likely to be screened; however, if screened, they were more likely to screen positive. Male gender and greater medical comorbidity were associated with decreased odds of follow-up evaluation after a positive screen. At the facility level, likelihood of depression screening was inversely associated with spending on teaching and research but positively associated with spending on mental health care. CONCLUSIONS: VA's depression case-finding activities yielded relatively few positive cases, raising questions about cost-effectiveness. Targeted strategies may increase the value of case-finding among patients at greatest risk for depression and at more academically affiliated medical centers. Targeted efforts also are needed to ensure proper follow-up evaluation of suspected cases, particularly among male patients and those with increased medical comorbidity.