Aim The first-episode psychosis (FEP) represents a critical period to prevent cardiovascular and metabolic morbidity decades later. Antipsychotic (AP)-induced weight gain is one modifiable factor in this period. The purpose of this study is to conduct a meta-analysis of AP-induced weight and body mass index (BMI) change in FEP. Methods A comprehensive literature search identified 28 articles that reported data on AP-specific weight or BMI change in FEP. We conducted a meta-analysis of short- and long-term mean weight and BMI differences between placebo and AP medications. We also performed subgroup and meta-regression analysis to examine weight, BMI outcomes and their relationship with location (Asian vs. Western), sponsorship and baseline weight and BMIs. Results Compared to placebo, AP-caused mean weight gain was 3.22 kg and 1.4 points BMI in the short-term, and 5.30 kg and 1.86 points BMI in the long term. Clinically significant weight gain risk increased about twofold with AP use. Weight gain was associated with duration of AP use. AP medications were associated with more weight gain in Western samples as opposed to Asian samples. Most AP medications were associated with significant body weight gain and BMI increase in FEP patients, except for ziprasidone. Olanzapine and clozapine caused the highest weight gain compared to placebo. Conclusion Except for ziprasidone, most AP medications were associated with body weight gain and BMI increase in FEP patients. Early and continuing effects of various AP medications on weight gain and BMI increase should be taken into consideration by clinicians.

Objective This study seeks to determine the effectiveness of a comprehensive first-episode service (the clinic for Specialized Treatment Early in Psychosis, STEP) based in an urban U.S. community mental health center, compared to treatment as usual. Methods This pragmatic randomized controlled trial enrolled 120 ‘first-episode psychosis’ patients within 5 years of illness onset and 12 weeks of antipsychotic exposure. Referrals were mostly from area inpatient psychiatric units and enrollees were randomly allocated to STEP or referral to routine care (TU). Main outcomes included hospital utilization (primary), ability to work, attend age-appropriate schooling or actively seek these opportunities (‘vocational engagement’), and general functioning. Analysis was by modified intent to treat (excluding only 3 who withdrew consent) for hospitalization and completers for other outcomes. Results After one year, STEP effected reductions on all measures of inpatient utilization vs. usual treatment: not psychiatrically hospitalized (77% vs. 56%, RR 1.38, 95% confidence interval (CI) 1.08–1.58); mean hospitalizations (0.33±0.70 vs. 0.68±0.92, p=0.02) and mean bed days (5.34±13.53 vs. 11.51±15.04, p=0.05). For every 5 patients allocated in STEP vs. usual treatment, one additional patient avoided psychiatric hospitalization over the first year (NNT = 5, CI 2.7–26.5). STEP also delivered better vocational engagement (91.7% vs. 66.7%, RR 1.40, 95% CI 1.18–1.48) and salutary trends in measures of global functioning. Conclusions This trial demonstrates the feasibility and effectiveness of a U.S. public sector model of early intervention for psychotic illnesses. Such services can also support translational research and are a relevant model for other serious mental illnesses. Trial registration www.ClinicalTrials.gov: NCT00309452.

BackgroundEarly intervention services for psychotic disorders optimally interlock strategies to deliver: (i) Early Detection (ED) to shorten the time between onset of psychotic symptoms and effective treatment (i.e. Duration of Untreated Psychosis, DUP); and (ii) comprehensive intervention during the subsequent 2 to 5 years. In the latter category, are teams (‘First-episode Services’ or FES) that integrate several empirically supported treatments and adapt their delivery to younger patients and caregivers. There is an urgent need to hasten access to established FES in the U.S. Despite improved outcomes for those in treatment, these FES routinely engage patients a year or more after psychosis onset. The Scandinavian TIPS study was able to effectively reduce DUP in a defined geographic catchment. The guiding questions for this study are: can a U.S. adaptation of the TIPS approach to ED substantially reduce DUP and improve outcomes beyond existing FES?Methods/DesignThe primary aim is to determine whether ED can reduce DUP in the US, as compared to usual detection. ED will be implemented by one FES (STEP) based in southern Connecticut, and usual detection efforts will continue at a comparable FES (PREPR) serving the greater Boston metropolitan area. The secondary aim is to determine whether DUP reduction can improve presentation, engagement and early outcomes in FES care. A quasi-experimental design will compare the impact of ED on DUP at STEP compared to PREPR over 3 successive campaign years. The campaign will deploy 3 components that seek to transform pathways to care in 8 towns surrounding STEP. Social marketing approaches will inform a public education campaign to enable rapid and effective help-seeking behavior. Professional outreach and detailing to a wide variety of care providers, including those in the healthcare, educational and judicial sectors, will facilitate rapid redirection of appropriate patients to STEP. Finally, performance improvement measures within STEP will hasten engagement upon referral.DiscussionSTEP-ED will test an ED campaign adapted to heterogeneous U.S. pathways to care while also improving our understanding of these pathways and their impact on early outcomes.Trial registrationClinicalTrials.gov: NCT02069925. Registered 20 February 2014.

Objectives Obesity is associated with significant morbidity and mortality rates. Even modest weight loss may be associated with health benefits. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant. Studies have suggested anti-obesity properties of ALA; however, results are inconsistent. The purpose of this study is to conduct a meta-analysis of the effect of ALA on weight and body mass index (BMI). Methods A comprehensive, systematic literature search identified 10 articles on randomized, double-blind, placebo-controlled studies involving ALA. We conducted a meta-analysis of mean weight and BMI change differences between ALA and placebo treatment groups. Results ALA treatment coincided with a statistically significant 1.27 kg (CI=0.25 to 2.29) greater mean weight loss compared to the placebo group. A significant overall mean BMI difference of -0.43 kg/m2 (CI=-0.82 to -0.03) was found between the ALA and placebo groups. Meta-regression analysis showed no significance in ALA dose on BMI and weight changes. Study duration significantly affected BMI change, but not weight change. Conclusions ALA treatment showed small, yet significant short-term weight loss compared to placebo. Further research is needed to examine the effect of different doses and the long-term benefits of ALA on weight management.