The impact of early detection (ED) campaigns on care presentations: Beyond DUP reduction.

We examined the effects of an early detection (ED) campaign (Mindmap), that successfully shortened the duration of untreated psychosis (DUP), on patient presentation profiles at two receiving coordinated specialty care (CSC) services. Data were collected between 2015 and 2019 during a test of ED delivered at one CSC (STEP, n = 147) compared to usual detection at another CSC (PREP, n = 63). Regression models were used to test the effects of ED and DUP on presentation. Before the launch of ED, there were no differences in presentation between STEP and PREP. However, the ED changed the profile of presentations to STEP such that patients were admitted with better negative and total symptoms scores, but worse GAF current and GAF social and with a greater decline in function over the prior year (GAF-Δ). Site-by-time interaction effects were not significant. During the campaign years, STEP vs. PREP recruited patients with better negative and total symptoms, GAF role, and pre-morbid adjustment scores but with worse positive symptoms, GAF current, and GAF-Δ. Nonetheless, mediation analysis revealed that DUP reduction accounted for very little (<8 %) of these differences in presentation. Early detection campaigns while successfully reducing access delays, can have salutary effects on presentation independent of DUP reduction.

The effect of duration of untreated psychosis (DUP) on the risk for hospitalization after admission to a first episode service.

Engagement with a first episode-psychosis service (FES) reduces the risk of psychiatric hospitalization. However, the role of the duration of untreated psychosis (DUP) in impacting this outcome is disputed. This study aimed to examine whether DUP was an effect modifier of the post-FES reduction of risk of hospitalization, and to explore associations between patients' characteristics and hospitalization post-FES. Individuals aged 16-35 with recent onset (< 3 years) of non-affective psychosis, admitted to the Program for Specialized Treatment Early in Psychosis (STEP), a FES serving the Greater New Haven area, Connecticut, between 2014 and 2019 were included (N = 189). Medical records were queried from 2013 through 2020 for number and duration of psychiatric hospitalizations. Poisson regression models were used to estimate incidence rate ratios for hospitalization rates across all explanatory variables. Negative binomial regression was used to compare the length of stay (LOS) before vs after STEP enrollment. STEP admission was associated with a significant 90 % reduction in the frequency and duration of hospitalizations. This effect was moderated by DUP: with 30-day prolongations in components of DUP (supply, demand, and total) there was less reduction in hospitalizations and LOS after FES enrollment (p < .0001). Only DUP supply (time from first antipsychotic use to STEP admission) differentiated those who were hospitalized during the first year after STEP enrollment from those who were not (median: 35 vs. 15 weeks, p = .003). To fully harness the positive impact of FES on hospitalization, a detailed effort should be pursued to reduce all DUP components.

Re-examining the utility and validity of benign ethnic neutropenia: A narrative literature review.

OBJECTIVE: To conduct a narrative literature review of published evidence documenting racial differences in white blood cells (WBCs) resulting in the legitimization of benign ethnic neutropenia (BEN) as a diagnosis. METHOD: A search of English-language U.S.-based articles was undertaken using the following electronic databases: Medline (1860 to 1990); PsycINFO (1860 to 1990); and EMBASE (1860 to 1990), which resulted in a total of eight studies. A narrative literature review of the eight studies was conducted to assess how race was utilized in the study methods. RESULTS: Of the eight studies, several themes emerged within the scientific literature that demonstrate imprecise, problematic use of race in research practice. 1) Researchers embedded flawed notions of biological differences between racial groups (mostly focused on Black people compared to white people) within the research hypotheses, methods, and conclusions, 2) studies were unclear on how racial group membership was defined and identified within the study samples, 3) studies did not adequately account for structural or historical determinants of health that may drive racial differences in immune status (i.e., neutropenia). CONCLUSIONS: Given the limitations in this U.S.-based scientific literature, BEN is a diagnosis of limited construct validity that reinforces false notions of biological race, warrants renaming to remove "ethnic" language (to include "familial" or "hereditary"), and suggests a need for global expansion of the existing absolute neutrophil count reference ranges in the clozapine monitoring guidelines.

Reducing the Duration of Untreated Psychosis (DUP) in a US Community: A Quasi-Experimental Trial.

Objective: Duration of Untreated Psychosis (DUP) remains unacceptably long and limits effectiveness of care. To determine whether an early detection campaign ("Mindmap") can reduce DUP in a US community setting. Methods: In this nonrandomized controlled trial, Mindmap targeted the catchment of one specialty first-episode service or FES (STEP, Greater New Haven) from 2015 to 2019, while usual detection efforts continued at a control FES (PREP, Greater Boston). Mindmap targeted diverse sources of delay through mass & social media messaging, professional outreach & detailing, and rapid enrollment of referrals. Both FES recruited 16-35 years old with psychosis onset ≤3 years. Outcome measures included DUP-Total (onset of psychosis to FES enrollment), DUP-Demand (onset of psychosis to first antipsychotic medication), and DUP-Supply (first antipsychotic medication to FES enrollment). Results: 171 subjects were recruited at STEP and 75 at PREP. Mindmap was associated with an increase in the number of referrals and in efficiency of engagement at STEP. Pre-campaign DUP (2014-2015) was equivalent, while Mindmap was associated with DUP reductions at STEP but not PREP. DUP-Total fell significantly in both the first and the second quartile (11.5 and 58.5 days reduction per campaign year, respectively). DUP-Demand and DUP-Supply fell in the third quartiles only (46.3 and 70.3 days reduction per campaign year, respectively). No reductions were detectable across all quartiles at PREP, but between site comparisons were not significant. Conclusions: This is the first controlled demonstration of community DUP reduction in the US, and can inform future early detection efforts across diverse settings.

First help-seeking attempt before and after psychosis onset: measures of delay and aversive pathways to care.

PURPOSE: Delay in receiving effective treatment for psychosis adversely impacts outcomes. We investigated the timing of the first help-seeking attempt in individuals with recent onset non-affective psychosis by comparing those who sought help during the prodrome to those who sought help after psychosis onset across sociodemographic and clinical characteristics, overall functioning, and occurrence of aversive events during their pathways to care. METHODS: Patients were admitted from February 1st, 2014 to January 31st, 2019 to the Program for Specialized Treatment Early in Psychosis (STEP) in New Haven, CT. Psychosis-onset date was ascertained using the Structured Interview for Psychosis-risk Syndromes. Key dates before and after psychosis onset, along with initiators and aversive events, were collected via semi-structured interview. RESULTS: Within 168 individuals, 82% had their first help-seeking episode after psychosis onset and did not differ in terms of sociodemographic characteristics from prodrome help seekers. When the first help-seeking episode started before (i.e., during prodrome) vs after psychosis onset it was mostly initiated by patients vs family members (Cramer's V = 0.23, p = 0.031) and led to a faster prescription of an antipsychotic once full-blown psychosis emerged (time to antipsychotic since psychosis onset = 21 vs 56 days, p = 0.03). No difference in aversive events before STEP enrollment was detected across groups. CONCLUSION: Help seeking during the prodrome is associated with faster initiation of antipsychotic treatment and is more likely to be self-initiated, compared to help seeking after psychosis onset. Early detection efforts that target prodromal samples may improve the length and experience of pathways to care.

Neural cell-derived plasma exosome protein abnormalities implicate mitochondrial impairment in first episodes of psychosis.

Neuroprotective and other functional proteins of mitochondria were quantified in extracts of plasma neural-derived exosomes from ten first-episode psychosis (FP) patients and ten matched psychiatrically normal controls (ctls). Astrocyte-derived extracellular vesicles (ADEVs) and neuron-derived extracellular vesicles (NDEVs) were immunoabsorbed separately from physically precipitated plasma total EVs. Extracted mitochondrial ATP synthase was specifically immunofixed to plastic wells for quantification of catalytic activity based on conversion of NADH to NAD+ . Other extracted mitochondrial functional proteins were quantified by ELISAs. All protein levels were normalized with EV content of the CD81 exosome marker. FP patient ADEV level but not NDEV level of mitochondrial ATP synthase activity was significantly lower than that of ctls. FP patient ADEV and NDEV levels of the functionally critical mitochondrial proteins mitofusin 2 and cyclophilin D, but not of transcription factor A of mitochondria, and of the mitochondrial short open-reading frame neuroprotective and metabolic regulatory peptides humanin and MOTS-c were significantly lower than those of ctls. In contrast, FP patient NDEV, but not ADEV, level of the mitochondrial-tethering protein syntaphilin, but not of myosin VI, was significantly higher than that of ctls. The distinctively different neural levels of some mitochondrial proteins in FP patients than ctls now should be correlated with diverse clinical characteristics. Drugs that increase depressed levels of proteins and mimetics of deficient short open-reading frame peptides may be of therapeutic value in early phases of schizophrenia.

Systematic review of racial disparities in clozapine prescribing.

OBJECTIVE: To conduct a systematic review of published evidence on clozapine prescribing disparities across racial and ethnic categories, estimate the size of these disparities, and assess possible causes to inform future monitoring and intervention. METHODS: Electronic databases (MEDLINE, Embase, PsycINFO, Web of Science) were searched for directly relevant studies. Three independent reviewers selected studies: (1) of US samples; (2) directly addressed ethnic and/or racial disparities in prescribing of antipsychotic medications; (3) identified specific ethnic and/or racial groups (e.g. White, Blacks, Hispanics, non-Hispanic etc.); (4) reported clozapine prescription rates and (5) reported relevant covariates (i.e. gender, age, co-morbidities etc.). FINDINGS: 16 studies met our eligibility criteria. All studies reported clozapine underutilization in ethnic and racial minority patients when compared to their white counterparts. These findings remained consistent despite different time periods, designs, data set types, and after controlling for relevant covariates such as: length of hospital stay, institutional setting, and disease severity. CONCLUSION: The reasons for underutilization of clozapine in minority patients remain unclear. Various contributors can be categorized as: clinician-related factors (e.g. prescriber lack of experience), patient-related factors (e.g. distrust or suspicion of clinician), and institution-related factors (e.g. state operated facilities). Direct examination of these factors can help inform efforts to reduce clozapine prescription disparities.

Decreased mitochondrial electron transport proteins and increased complement mediators in plasma neural-derived exosomes of early psychosis.

Potentially neurotoxic systems involved in traumatic and degenerative diseases of the brain were assessed in acute psychosis. Astrocyte-derived exosomes (ADEs) and neuron-derived exosomes (NDEs) were immunoprecipitated from plasma of ten untreated first-episode psychotics (FPs) and ten matched normal controls (Cs). Neural mitochondrial electron transport and complement proteins were extracted, quantified by ELISAs and normalized with levels of CD81 exosome marker. Levels of subunits 1 and 6 of NADH-ubiquinone oxidoreductase (complex I) and subunit 10 of cytochrome b-c1 oxidase (complex III), but not of subunit 1 of cytochrome C oxidase (complex IV) or superoxide dismutase 1 (SOD1) were significantly lower in ADEs and NDEs of FPs than Cs. This dysregulated pattern of electron transport proteins is associated with increased generation of reactive oxygen species. ADE glial fibrillary acidic protein levels were significantly higher in FPs than Cs, indicating a higher percentage of inflammatory astrocytes in FPs. ADE levels of C3b opsonin were significantly higher and those of C5b-9 attack complex was marginally higher in FPs than Cs. A significantly lower ADE level of the C3 convertase inhibitor CD55 may explain the higher levels of C3 convertase-generated C3b. ADE levels of the neuroprotective protein leukemia inhibitory factor (LIF) were significantly lower in FPs than Cs, whereas levels of IL-6 were no different. Plasma neural exosome levels of electron transport and complement proteins may be useful in predicting FP and guiding therapy. SOD mimetics, C3 convertase inhibitors and LIF receptor agonists also may have therapeutic benefits in FP.

Antipsychotic Exposure in Pregnancy and the Risk of Gestational Diabetes: A Systematic Review and Meta-analysis.

BACKGROUND: We have limited knowledge about the effects of antipsychotic exposure on the development of gestational diabetes mellitus (GDM). Aim of this study is to perform a systematic review and meta-analysis to assess GDM risk associated with antipsychotic exposure in pregnancy. METHODS: Systematic literature search was performed using PubMed, Science Direct, Scopus, and Web of Science databases up to August 22, 2018. No restrictions to language or date were applied. Randomized, controlled trials, case-control, or cohort studies reporting GDM risk in antipsychotic-exposed, healthy controls or antipsychotic-ceased patients were included in the meta-analysis. The primary outcomes were study defined GDM, including number of events, odds ratios, and/or risk ratios (RR) with confidence intervals (CI). RESULTS: Ten studies were included in the meta-analysis. The total number of subjects was 6213 for the antipsychotic-exposed group, 6836 for antipsychotic-ceased control group, and 1 677 087 for the healthy control group. Compared with the healthy controls, the unadjusted cumulative RR for GDM associated with antipsychotic use was 1.63 (95% CI = 1.20-2.22). Adjusted risk for GDM was significantly higher in antipsychotic exposure group than in healthy controls (RR = 1.30, 95% CI = 1.023-1.660). The adjusted RR for GDM was similar between the antipsychotic-exposed group and the antipsychotic-ceased group (RR = 0.78, 95% CI = 0.281-2.164). No significant association was found between study quality, smoking, alcohol use, gestational age, and cumulative GDM risk. DISCUSSION: Our results indicate an increased risk of GDM with antipsychotic exposure in pregnant women, who may benefit from close pregnancy monitoring, early testing for GDM, targeting modifiable risk factors, and lifestyle modifications.

The synergistic benefits of physical and cognitive exercise in schizophrenia: Promoting motivation to enhance community effectiveness.

Emerging research highlights the potential cognitive benefits of physical exercise (PE) programs for schizophrenia (SCZ). The few recent efficacy studies that examined augmenting cognitive training (CT) with PE suggest superior effects of the combination. The next step is to consider strategies to enhance adherence in real-world settings if this type of combined treatment is going to be effective. We present the first community effectiveness data for PE and CT that included a motivationally-enhancing, self-determined approach to exercise, in lieu of participant payment. Eighty-five outpatients with schizophrenia attending an intensive outpatient program were randomized to 18 h of either (A) self-determined PE regimen with choice from a menu of different activities; (B) tablet-based neurofeedback CT focused on processing speed (PS) and working memory (WM), or (C) a time-matched combination of PE and CT. Assessments were conducted at baseline, post, and follow-up (2 mo). All groups improved in WM from baseline to post, with greatest gains in the PE only group. At follow-up, cognitive gains originally observed in the PE-only group disappeared, while the PE + CT group evidenced improvements in WM and psychotic symptoms. Notably, attrition for PE was only 7%. Our data shows that combining PE and CT leads to lasting effects that are superior to those of either intervention alone. The low PE drop-out rate suggests a self-determined approach to the exercise regimen was tolerable, and may be an important component of future community implementation efforts.

Parsing the impact of early detection on duration of untreated psychosis (DUP): Applying quantile regression to data from the Scandinavian TIPS study.

BACKGROUND: Prolonged duration of untreated psychosis (DUP) is associated with poor outcomes. The TIPS study halved DUP with an early detection (ED) campaign; however, conventional statistical analyses, focused on mean estimates, failed to reveal the effects of ED across the full DUP distribution, restricting inferences about ED's effectiveness. Utilizing a novel quantile regression based analysis, we examined the differential impact of ED across DUP. Secondary analysis explored possible predictors of DUP, and moderators of the effect of the campaign. METHODS: The TIPS ED campaign was conducted in two health care sectors in Norway, with two equivalent health care sectors serving as controls. Quantile regression analysis was performed to analyze ED campaign's effect. RESULTS: 281 patients with first episode psychosis were recruited, including 141 from the ED area. ED had no effect on the first quartile (Q1) of DUP, whereas a significant reduction in Q2 (11weeks), and Q3 (41weeks) of DUP was observed. The effect of ED was significantly stronger on reducing Q3 than Q1 or Q2, suggesting that the campaign was more effective in longer DUP samples. Male gender and single status predicted longer DUP in Q3: by 38 and 27weeks, respectively. Single status, but not gender, emerged as a significant moderator of ED campaign effect. CONCLUSIONS: Quantile regression provided in depth information about the non-uniformity, and moderators, of TIPS's ED effort across the full distribution of DUP, demonstrating the value of this analytic approach to re-examine prior, and plan analyses for future, early detection efforts.

Glucose metabolism dysregulation at the onset of mental illness is not limited to first episode psychosis: A systematic review and meta-analysis.

AIM: To compare the differences of glucose metabolism outcomes between treatment-naïve, patients with first episode psychosis (FEP) and mood disorders. METHODS: We conducted a systematic review and meta-analysis of glucose intolerance in treatment-naïve, first episode patients with severe mental illnesses (SMIs). RESULTS: We identified 31 eligible studies. Compared to healthy controls, FEP group have higher insulin and insulin resistance levels, and both groups have higher glucose tolerance test results. No significant differences were found in glucose metabolism outcomes between FEP and mood disorder groups. CONCLUSIONS: Our results highlight impaired glucose metabolism at the onset of SMIs, suggesting both patients with psychosis and mood disorders are high-risk groups for diabetes development.

An Economic Evaluation of Coordinated Specialty Care (CSC) Services for First-Episode Psychosis in the U.S. Public Sector.

BACKGROUND: Schizophrenia spectrum disorders exert a large and disproportionate economic impact. Early intervention services may be able to alleviate the burden of schizophrenia spectrum disorders on diagnosed individuals, caregivers, and society at large. Economic analyses of observational studies have supported investments in specialized team-based care for early psychosis; however, questions remain regarding the economic viability of first-episode services in the fragmented U.S. healthcare system. The clinic for Specialized Treatment Early in Psychosis (STEP) was established in 2006, to explicitly model a nationally-relevant U.S. public-sector early intervention service. The purpose of this study was to conduct an economic evaluation of STEP, a Coordinated Specialty Care service (CSC) based in a U.S. State-funded community mental health center, relative to usual treatment (UT). METHODS: Eligible patients were within 5 years of psychosis onset and had no more than 12 weeks of lifetime antipsychotic exposure. Participants were randomized to STEP or UT. The annual per-patient cost of the STEP intervention per se was estimated assuming a steady-state caseload of 30 patients. A cost-offset analysis was conducted to estimate the net value of STEP from a third-party payer perspective. Participant healthcare service utilization was evaluated at 6 months and over the entire 12 months post randomization. Generalized linear model multivariable regressions were used to estimate the effect of STEP on healthcare costs over time, and generate predicted mean costs, which were combined with the per-patient cost of STEP. RESULTS: The annual per-patient cost of STEP was $1,984. STEP participants were significantly less likely to have any inpatient or ED visits; among individuals who did use such services in a given period, the associated costs were significantly lower for STEP participants at month 12. We did not observe a similar effect with regard to other healthcare services. The predicted average total costs were lower for STEP than UT, indicating a net benefit for STEP of $1,029 at month 6 and $2,991 at month 12; however, the differences were not statistically significant. CONCLUSIONS: Our findings are promising with regard to the value of STEP to third-party payers.

Prevalence of obesity and diabetes in patients with schizophrenia.

AIM: To compare the prevalence of diabetes in patients with schizophrenia treated at a community mental health center with controls in the same metropolitan area and to examine the effect of antipsychotic exposure on diabetes prevalence in schizophrenia patients. METHODS: The study was a comprehensive chart review of psychiatric notes of patients with schizophrenia and schizoaffective disorder treated at a psychosis program in a community mental health center. Data collected included psychiatric diagnoses, diabetes mellitus diagnosis, medications, allergies, primary care status, height, weight, body mass index (BMI), substance use and mental status exam. Local population data was downloaded from the Centers for Disease Control Behavioral Risk Factor Surveillance System. Statistical methods used were χ2 test, Student's t test, general linear model procedure and binary logistic regression analysis. RESULTS: The study sample included 326 patients with schizophrenia and 1899 subjects in the population control group. Demographic data showed control group was on average 7.6 years older (P = 0.000), more Caucasians (78.7% vs 38.3%, P = 0.000), and lower percentage of males (40.7% vs 58.3%, P = 0.000). Patients with schizophrenia had a higher average BMI than the subjects in the population control (32.11, SD = 7.72 vs 27.62, SD = 5.93, P = 0.000). Patients with schizophrenia had a significantly higher percentage of obesity (58.5% vs 27%, P = 0.000) than the population group. The patients with schizophrenia also had a much higher rate of diabetes compared to population control (23.9% vs 12.2%, P = 0.000). After controlling for age sex, and race, having schizophrenia was still associated with increased risk for both obesity (OR = 3.25, P = 0.000) and diabetes (OR = 2.42, P = 0.000). The increased risk for diabetes remained even after controlling for obesity (OR = 1.82, P = 0.001). There was no difference in the distribution of antipsychotic dosage, second generation antipsychotic use or multiple antipsychotic use within different BMI categories or with diabetes status in the schizophrenia group. CONCLUSION: This study demonstrates the high prevalence of obesity and diabetes in schizophrenia patients and indicates that antipsychotics may not be the only contributor to this risk.

How accurate are self-reported height and weight in the seriously mentally ill?

AIMS: (1) Determine the accuracy of self-reported height, weight, and body mass index (BMI) calculated from those values in a population suffering from both serious mental illness (SMI) and overweight/obesity; (2) identify any associations that may predict error in self-reported measurements. Data were collected from screening appointments for two clinical trials for adult patients with SMI and overweight/obesity (BMI > 28) who gained weight while on antipsychotic medications. Both studies were conducted at the same urban community mental health center. Differences in self-reported and measured height, weight, and BMI were calculated. Analysis included age, sex, race, psychiatric diagnosis, and level of education. BMI calculated from self-reported height and weight were significantly lower (-0.47kg/m2) than measured values. Height was significantly overestimated (1.04cm), while weight was underestimated (0.055kg). Men underestimated BMI more than women (0.55 vs. 0.41kg/m2). Increasing age correlated with lower accuracy of self-reported height and BMI. No differences due to psychiatric diagnosis, race, or education were found. BMI calculated from self-reported height and weight from patients with SMI and overweight/obesity is as accurate as the self-reported measurements collected from the general population and, while measurement is best, self-reports can be used as a tool for screening for obesity.

Examining the reliability and validity of the Clinical Assessment Interview for Negative Symptoms within the Management of Schizophrenia in Clinical Practice (MOSAIC) multisite national study.

The current study sought to expand on prior reports of the validity and reliability of the CAINS (CAINS) by examining its performance across diverse non-academic clinical settings as employed by raters not affiliated with the scale's developers and across a longer test-retest follow-up period. The properties of the CAINS were examined within the Management of Schizophrenia in Clinical Practice (MOSAIC) schizophrenia registry. A total of 501 participants with a schizophrenia spectrum diagnosis who were receiving usual care were recruited across 15 national Patient Assessment Centers and evaluated with the CAINS, other negative symptom measures, and assessments of functioning, quality of life and cognition. Temporal stability of negative symptoms was assessed across a 3-month follow-up. Results replicated the two-factor structure of the CAINS reflecting Motivation and Pleasure and expression symptoms. The CAINS scales exhibited high internal consistency and temporal stability. Convergent validity was supported by significant correlations between the CAINS subscales with other negative symptom measures. Additionally, the CAINS was significantly correlated with functioning and quality of life. Discriminant validity was demonstrated by small to moderate associations between the CAINS and positive symptoms, depression, and cognition (and these associations were comparable to those found with other negative symptom scales). Findings suggest that the CAINS is a reliable and valid tool for measuring negative symptoms in schizophrenia across diverse clinical samples and settings.

Understanding Social Situations (USS): A proof-of-concept social-cognitive intervention targeting theory of mind and attributional bias in individuals with psychosis.

OBJECTIVES: In this proof-of-concept trial, we examined the feasibility and preliminary efficacy of Understanding Social Situations (USS), a new social-cognitive intervention that targets higher level social-cognitive skills using methods common to neurocognitive remediation, including drill and practice and hierarchically structured training, which may compensate for the negative effects of cognitive impairment on learning. METHOD: Thirty-eight individuals with schizophrenia spectrum disorders completed the same baseline assessment of cognitive and social-cognitive functioning twice over a 1-month period to minimize later practice effects, then received 7-10 sessions of USS training, and then completed the same assessment again at posttreatment. RESULTS: USS training was well tolerated and received high treatment satisfaction ratings. Large improvements on the USS Skills Test, which contained items similar to but not identical to training stimuli, suggest that we were effective in teaching specific training content. Content gains generalized to improvements on some of the social-cognitive tasks, including select measures of attributional bias and theory of mind. Importantly, baseline neurocognition did not impact the amount of learning during USS (as indexed by the USS Skills Test) or the amount of improvement on social-cognitive measures. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: USS shows promise as a treatment for higher level social-cognitive skills. Given the lack of relationship between baseline cognition and treatment effects, it may be particularly appropriate for individuals with lower range cognitive function. (PsycINFO Database Record

Naltrexone HCI/bupropion HCI for chronic weight management in obese adults: patient selection and perspectives.

Naltrexone, an opiate antagonist, and bupropion, a noradrenergic/dopaminergic antidepressant, have many effects on the reward systems of the brain. These medications impact eating behavior, presumably via their impact on food reward. However, only bupropion induces weight loss in obese individuals, while naltrexone does not have any appreciable effect. The combination of 32 mg of naltrexone and 360 mg of bupropion in a sustained-release combination pill form has been recently approved for obesity treatment. Studies have shown that the combination of these two medications is more effective in inducing weight loss, when combined with lifestyle intervention and calorie reduction, than each individual medicine alone. The naltrexone-bupropion combination, when combined with lifestyle intervention and modest calorie reduction, seems to be quite effective for 6-month and 1-year outcomes for clinically significant weight loss (over 5% of total body weight). These medications are not devoid of serious side effects, however, and careful patient selection can reduce dramatic complications and increase positive outcomes. This paper reviews existing weight loss clinical trials with bupropion and the bupropion-naltrexone combination. Additionally, the rationale for the suggested patient selection and clinical strategies for special patient populations are discussed.