Implementation of an Interprofessional Nutrition Workshop to Integrate Nutrition Education into a Preclinical Medical School Curriculum.

Objective: The patient-physician encounter provides an ideal opportunity to assess a patient's dietary history and its impact on total health. However, nutrition assessments and counseling in physician-patient encounters is often lacking. Insufficient nutrition education during medical school may lead to insecurity in assessing and counseling patients.Methods: Physicians and registered dietitians (RD) co-developed and co-facilitated a nutrition workshop for first-year medical students. Goals included increasing recognition of nutrition's impact on health and promoting student confidence and skills when attaining a nutrition history, assessing risk factors, and advising.Results: Seventy percent of students attested to having "sufficient" knowledge to counsel a patient on nutrition after the session compared to 38% before (Z= -4.46, p < 0.001). Sixty eight percent felt comfortable completing a nutritional assessment after the session compared to 35% before (Z= -4.30, p < 0.001). Sixty-three percent felt confident in advising patients about nutrition after the session compared to 32% before (Z= -4.20, p < 0.001). Students also significantly outperformed a control cohort on a nutrition-related component of an Objective Standardized Clinical Examination.Conclusions: Clinical nutrition education can be successfully integrated into the medical school curriculum as early as the first year. Interprofessional collaboration with RDs provided evidence-based content and authentic clinical experience in both the development of the workshop and in facilitating student discussion.

Attenuated psychotic and basic symptom characteristics in adolescents with ultra-high risk criteria for psychosis, other non-psychotic psychiatric disorders and early-onset psychosis.

While attenuated psychotic symptoms (APS) and basic symptoms (BS) are the main current predictors of psychosis in adults, studies in adolescents are scarce. Thus, we (1) described the prevalence and severity of positive, negative, disorganization, general, and basic symptoms in adolescent patients at ultra-high risk for psychosis (UHR), with other non-psychotic psychiatric disorders (PC) and with early-onset psychosis (EOP); and (2) investigated BS criteria in relation to UHR criteria. Sixty-nine 12-18-year-old adolescents (15.3 ± 1.7 years, female = 58.0 %, UHR = 22, PC = 27, EOP = 20) were assessed with the structured interview for prodromal syndromes (SIPS) and the schizophrenia proneness instrument-child and youth version (SPI-CY). Despite similar current and past 12-month global functioning, both UHR and EOP had significantly higher SIPS total and subscale scores compared to PC, with moderate-large effect sizes. Expectedly, UHR had significantly lower SIPS positive symptom scores than EOP, but similar SIPS negative, disorganized, and general symptom scores. Compared to PC, both EOP and UHR had more severe basic thought and perception disturbances, and significantly more often met cognitive disturbances criteria (EOP = 50.0 %, UHR = 40.9 %, PC = 14.8 %). Compared to UHR, both EOP and PC significantly less often met cognitive-perceptive BS criteria (EOP = 35.0 %, UHR = 68.2 %, PC = 25.9 %). BS were significantly more prevalent in both EOP and UHR than PC, and UHR were similar to EOP in symptom domains. Given the uncertain outcome of adolescents at clinical high-risk of psychosis, future research is needed to determine whether the combined assessment of early subjective disturbances with observable APS can improve the accuracy of psychosis prediction.

Virtual teaching kitchen classes and cardiovascular disease prevention counselling among medical trainees.

Background: Hands-on culinary medicine education for medical trainees has emerged as a promising tool for cardiovascular health promotion. Purpose: To determine whether virtual culinary medicine programming associates with Mediterranean diet (MedDiet) adherence and lifestyle medicine competencies among medical trainees across the USA. Method: A total of 1433 medical trainees across 19 sites over a 12-month period were included. The Cooking for Health Optimisation with Patients-Medical Trainees survey composed of 61 questions regarding demographics, nutritional attitudes, dietary habits including MedDiet score and lifestyle medicine counselling competencies. Multivariable logistic regression assessed the association of virtual culinary medicine education with MedDiet intake and nutritional attitudes. Results: There were 519 medical trainees who participated in virtual culinary medicine education and 914 medical trainees who participated in their standard nutrition curricula. More than one-half of participants were women (n=759) and the mean age was 27 years old. Compared with students enrolled in traditional nutrition curricula, participants in virtual culinary medicine education were 37% more likely to adhere to MedDiet guidelines for fruit intake (OR 1.37, 95% CI 1.03 to 1.83, p=0.03). Virtual culinary medicine education was associated with higher proficiency in lifestyle medicine counselling categories, notably recommendations involving fibre (OR 4.03; 95% CI 3.05 to 5.34), type 2 diabetes prevention (OR 4.69; 95% CI 3.51 to 6.27) and omega fatty acids (OR 5.21; 95% CI 3.87 to 7.02). Virtual culinary medicine education had a similar, although higher magnitude association with MedDiet counselling competency (OR 5.73, 95% CI 4.26 to 7.70) when compared with historical data previously reported using hands-on, in-person culinary medicine courseware (OR 4.97, 95% CI 3.89 to 6.36). Conclusions: Compared with traditional nutritional educational curricula, virtual culinary medicine education is associated with higher MedDiet adherence and lifestyle medicine counselling competencies among medical trainees. Both virtual and hands-on culinary medicine education may be useful for cardiovascular health promotion.

Impact of an Expansion of a Clinical Nutrition Curriculum on Pre-Clerkship Medical Students' Perception of Their Knowledge and Skills Related to Performing a Nutritional Assessment.

Learning how to provide nutritional counseling to patients should start early in undergraduate medical education to improve the knowledge, comfort, and confidence of physicians. Two nutrition workshops were developed for first-year medical students. The first workshop, co-led by physicians and registered dieticians, focused on obtaining nutrition assessments. The second workshop focused on the appropriate dietary counseling of patients with chronic kidney disease and cardiovascular risk. We surveyed students before workshop 1, after workshop 1, and after workshop 2 to assess their perceptions of the value of physician nutrition knowledge and counseling skills as well as their own comfort in the area of nutritional knowledge, assessment, and counseling. We found a significant improvement in their self-assessed level of knowledge regarding counseling patients, in their comfort in completing a nutritional assessment, and in their confidence in advising a patient about nutrition by the end of the first workshop. By the time of the second workshop five months later, students continued to report a high level of knowledge, comfort, and confidence. The implementation of clinical nutrition workshops with a focus on assessment, management, and counseling was found to be effective in increasing student's self-assessed level of knowledge as well as their confidence and comfort in advising patients on nutrition. Our findings further support the previous assertion that clinical nutrition education can be successfully integrated into the pre-clerkship medical school curriculum.

Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo-controlled trials.

OBJECTIVE: To compare antipsychotic and mood stabilizer (MS) efficacy and tolerability in youth and adults with bipolar mania. METHODS: Medline/PubMed search for studies including: (i) youth (< 18 years) or adults (> or = 18 years); (ii) bipolar I disorder; (iii) double-blind, randomized, placebo-controlled trial (DB-RPCT); (iv) < or = 12 weeks of treatment; and (v) calculable effect sizes (ES) and/or numbers needed to treat/harm (NNT/NNH) +/- 95% confidence intervals (CI). Non-overlapping 95% CIs determined significant group differences. RESULTS: We identified nine DB-RPCTs in youth (n = 1,609), 5 evaluating second-generation antipsychotics (SGAs) (n = 1,140) and 4 evaluating MSs (n = 469). We also identified 23 DB-RPCTs in adults (n = 6,501), 14 including SGAs (n = 3,297), 5 using haloperidol as an active comparator (n = 580), and 11 including MSs (n = 2,581). Young Mania Rating Scale scores improved significantly more with SGAs than MSs in youth (ES = 0.65, CI: 0.53-0.78 versus 0.24, CI: 0.06-0.41) and adults (ES = 0.48, CI: 0.41-0.55 versus 0.24, CI: 0.17-0.31). After excluding topiramate studies, SGAs had larger ES than MSs only in youth (ES = 0.65, CI: 0.53-0.78 versus 0.20, CI: 0.02-0.39), but not adults (ES = 0.48, CI: 0.41-0.55 versus 0.46, CI: 0.37-0.55). However, in adults SGAs had significantly larger ES regarding Clinical Global Impressions scores than MSs, even without topiramate (ES = 0.75, CI: 0.68-0.82 versus 0.24, CI: 0.07-0.41). Rates of response, remission, and discontinuation due to any reason compared to placebo were similar between medication and age groups, except for more favorable NNTs for remission with SGAs than MSs in adults after excluding topiramate. SGAs caused more weight gain than MSs in youth (ES = 0.53, CI: 0.41-0.66 versus 0.10, CI: -0.12-0.33), but not in adults (ES = 0.13, CI: 0.05-0.22 versus 0.00, CI: -0.08-0.08). However, results were heterogeneous and not significant in either age group after excluding topiramate. Nevertheless, SGA-related weight gain was significantly greater in youth than adults. In youth, SGA-related somnolence was greater than with MSs (NNH = 4.7, CI: 3.9-6.0 versus 9.5, CI: 6.3-23.5), and more likely than in adults (NNH = 7.1, CI: 6.1-8.8). Conversely, youth experienced less akathisia with SGAs than adults (NNH = 20.4, CI: 14.1-36.5 versus 10.2, CI: 8.1-13.7), likely due to lower doses/slower titration. CONCLUSIONS: In treating mania, potentially greater short-term efficacy compared to placebo with SGAs versus MS needs to be balanced against increased adverse events, especially in youth.

Metformin add-on vs. antipsychotic switch vs. continued antipsychotic treatment plus healthy lifestyle education in overweight or obese youth with severe mental illness: results from the IMPACT trial.

Antipsychotics are used for many psychiatric conditions in youth. Although developmentally inappropriate weight gain and metabolic abnormalities, which are risk factors for premature cardiovascular mortality, are especially frequent in youth, optimal strategies to reduce pediatric antipsychotic-induced overweight/obesity are unclear. The Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) was a randomized, parallel group, 24-week clinical trial which enrolled overweight/obese, psychiatrically stable youth, aged 8-19 years, with a DSM-IV diagnosis of severe mental illness (schizophrenia spectrum disorder, bipolar spectrum disorder or psychotic depression), at four US universities. All of them had developed substantial weight gain following treatment with a second-generation antipsychotic. The centralized, computer-based randomization system assigned participants to unmasked treatment groups: metformin (MET); antipsychotic switch (aripiprazole or, if already exposed to that drug, perphenazine or molindone; SWITCH); or continued baseline antipsychotic (CONTROL). All participants received healthy lifestyle education. The primary outcome was body mass index (BMI) z-score change from baseline, analyzed using estimated least squares means. Altogether, 127 participants were randomized: 49 to MET, 31 to SWITCH, and 47 to CONTROL. BMI z-score decreased significantly with MET (week 24: -0.09±0.03, p=0.002) and SWITCH (week 24: -0.11±0.04, p=0.003), while it increased non-significantly with CONTROL (week 24: +0.04±0.03). On 3-way comparison, BMI z-score changes differed significantly (p=0.001). MET and SWITCH were each superior to CONTROL (p=0.002), with effect sizes of 0.68 and 0.81 respectively, while MET and SWITCH did not differ. More gastrointestinal problems occurred in MET than in SWITCH or CONTROL. The data safety monitoring board closed the perphenazine-SWITCH arm because 35.2% of subjects discontinued treatment due to psychiatric worsening. These data suggest that pediatric antipsychotic-related overweight/obesity can be reduced by adding metformin or switching to a lower risk antipsychotic. Healthy lifestyle education is not sufficient to prevent ongoing BMI z-score increase.

Neuropsychological Test Performance to Enhance Identification of Subjects at Clinical High Risk for Psychosis and to Be Most Promising for Predictive Algorithms for Conversion to Psychosis: A Meta-Analysis.

OBJECTIVE: To compare neuropsychological performance in people at clinical high risk for psychosis (CHR), healthy controls (HCs), or subjects with first-episode psychosis (FEP). DATA SOURCES: Systematic PubMed/MEDLINE search through January 2014, without language restrictions, using search terms prodrome OR clinical high-risk OR ultra-high risk AND cognition OR individual test names. STUDY SELECTION: Studies reporting neuropsychological data in CHR versus a HC or FEP groups or comparing CHR subjects who converted to psychosis (CHR-P) with CHR subjects who did not convert to psychosis (CHR-NP). DATA EXTRACTION: Two authors independently extracted and compared neurocognitive test data. RESULTS: A meta-analysis was performed on 60 neuropsychological tests from 9 domains in 32 studies with 21 nonoverlapping samples (CHR = 1,684 patients, HC = 986, FEP = 405). Compared to HCs, people with CHR performed significantly worse in 7 of 9 domains (Hedges g effect size [95% confidence limit] = -0.17 [-0.30, -0.04] [attention/vigilance] to -0.42 [-0.64, -0.20] [verbal learning, speed of processing] and -0.43 [-0.68, -0.18] [social cognition]), except reasoning/problem solving and working memory (which separated in longitudinal studies). California Verbal Learning Test (-0.65 [-0.84, -0.46]) and Digit Symbol Test (-0.63 [-0.86, -0.40]) separated groups the most. Compared to FEP subjects, people with CHR performed significantly better in 5 of 6 domains (from 0.29 [0.03, 0.56] [speed of processing] to 0.39 [0.17, 0.62] [attention/vigilance, verbal learning] and -0.40 [0.18, 0.64] [working memory]), except reasoning/problem solving. CHR-P and CHR-NP performed significantly worse than HC (except visual learning, working memory in CHR-NP). Compared to CHR-NP, CHR-P performed significantly worse in 6 of 8 domains (from -0.24 [-0.44, -0.03] [attention/vigilance] to -0.49 [-0.76, -0.22] [verbal learning] and -0.54 [-0.80, -0.27] [visual learning]), without differences in reasoning/problem solving and working memory. Three individual tests (Rey-Osterrieth Complex Figure Test, Verbal Fluency Test/Controlled Oral Word Association Test, and California Verbal Learning Test) discriminated the best between CHR-P and CHR-NP (-0.49 [-0.82, -0.16], -0.45 [-0.86, -0.03], and -0.40 [-0.80, -0.00], respectively). CONCLUSIONS: CHR has mild to moderate globally distributed neuropsychological performance deficits that lie between FEP and HCs. Neuropsychological performance deficits are greater in CHR-P than in CHR-NP, but they overlap, reducing their current utility for risk stratification.

Correlates of Subjective Caregiver Strain in Caregivers of Youth Evaluated in a Pediatric Psychiatric Emergency Room.

BACKGROUND: Although caregiver burden is relevant to the outcome for psychiatrically ill youth, most studies have focused on caregiver burden in the community or research settings. Therefore, we aimed at evaluating the subjective caregiver strain (SCS) at the time of presentation of youth to a pediatric psychiatric emergency room (PPER), assessing potential correlates to provide leads for improvements in formal support systems. METHODS: In this retrospective cohort study, the internalized, externalized, and total SCS were assessed in caregivers of youth <18 years of age consecutively evaluated at a PPER during a 1 year period using the Caregiver Strain Questionnaire. Sociodemographic and a broad range of clinical data were collected during the PPER visit using a 12-page semistructured institutional evaluation form. The Appropriateness of Pediatric Psychiatric Emergency Room Contact scale, incorporating acuity, severity and harm potential, was used to rate appropriateness of the visit. RESULTS: In caregivers of 444 youth, the internalized SCS was significantly higher than the externalized SCS (p < 0.001). Multivariable analyses indicated that higher total and externalized SCS were associated with disruptive behavior or substance abuse/dependent disorder diagnosis, presenting complaint of aggression, and discharge plan to the police. Higher total and internalized SCS were associated with lower child functioning, whereas total and internalized SCS were lower in adopted children. In addition, higher externalized SCS was associated with investigator-rated inappropriateness of the emergency visit, presenting complaint of defiance, and a lack of prior psychiatric ER visits. CONCLUSIONS: High levels of CS in PPER highlight the necessity to adhere to existing guidelines regarding the inclusion of caregivers' perceptions into comprehensive psychiatric assessments. The particularly high strain in caregivers of children with externalizing disorders and in families with low-functioning youth may need to prompt PPER staff to provide efficient information on appropriate treatment options for these children and on support facilities for the parents.

Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics.

OBJECTIVE: Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS. METHOD: Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS. RESULTS: In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline, psychostimulant use was associated with dyskinesia, and number of psychotropic comedications was associated with subjective EPS. CONCLUSION: In youth, SGA-related EPS rates did not generally exceed those reported in adults, with particularly low rates with quetiapine and olanzapine.

Outcome of Youth with Early-Phase Schizophrenia-Spectrum Disorders and Psychosis Not Otherwise Specified Treated with Second-Generation Antipsychotics: 12 Week Results from a Prospective, Naturalistic Cohort Study.

OBJECTIVES: The purpose of this study was to assess differences in the outcomes of youth with schizophrenia-spectrum disorders (SCZ-S) and psychotic disorder not otherwise specified (PsyNOS) during early antipsychotic treatment. METHODS: The study was a prospective, naturalistic, inception cohort study of youth ≤19 years old with SCZ-S (schizophrenia, schizoaffective disorder, schizophreniform disorder) or PsyNOS (PsyNOS, brief psychotic disorder) and ≤24 months of lifetime antipsychotic treatment receiving clinician's choice antipsychotic treatment. Baseline demographic, illness and treatment variables, and effectiveness outcomes were compared at 12 weeks last-observation-carried-forward across SCZ-S and PsyNOS patients, adjusting for significantly different baseline variables. RESULTS: Altogether, 130 youth with SCZ-S (n=42) or PsyNOS (n=88), mostly antipsychotic naïve (76.9%), were prescribed risperidone (47.7%), olanzapine (19.2%), aripiprazole (14.6%), quetiapine (11.5%), or ziprasidone (6.9%). Compared with those with PsyNOS, SCZ-S youth were older (16.4±2.1 vs. 14.8±3.2, p=0.0040), and less likely to be Caucasian (19.1% vs. 42.5%, p=0.009). At baseline, SCZ-S patients had significantly higher Clinical Global Impressions-Severity (CGI-S) scores (6.0±0.9 vs. 5.5±0.8, p=0.0018) and lower Children's Global Assessment Scale (CGAS) scores (29.6±9.2 vs. 36.1±8.9, p=0.0002) and were more likely to be in the severely ill CGAS group (i.e., CGAS≤40). SCZ-S and PsyNOS patients did not differ regarding all-cause discontinuation (40.5 vs. 40.3%. p=0.49), discontinuation because of adverse effects (12.2% vs. 12.4%, p=0.97), or nonadherence (29.3% vs. 30.9%, p=0.88), but somewhat more SCZ-S patients discontinued treatment for inefficacy (19.5% vs. 7.4%, p=0.063). CGI-S and CGAS scores improved significantly in both diagnostic groups (p=0.0001, each). Adjusting for baseline differences, PsyNOS patients experienced significantly better CGI-I improvement (CGI-I) scores (p=0.012) and more frequently reached higher categorical CGAS group status (p=0.021) than SCZ-S patients. CONCLUSIONS: Both youth with SCZ-S and those with PsyNOS experienced significant improvements with clinician's choice antipsychotic treatment. However, treatment discontinuation was common within 12 weeks, with greater inefficacy-related discontinuation in the SCZ-S group, whereas CGI-I and CGAS score-based improvements were greater in the PsyNOS group.

Frequency and correlates of DSM-5 attenuated psychosis syndrome in a sample of adolescent inpatients with nonpsychotic psychiatric disorders.

OBJECTIVES: DSM-5 conceptualized attenuated psychosis syndrome (APS) as self-contained rather than as a risk syndrome, including it under "Conditions for Further Study," but also as a codable/billable condition in the main section. Since many major mental disorders emerge during adolescence, we assessed the frequency and characteristics of APS in adolescent psychiatric inpatients. METHODS: Consecutively recruited adolescents hospitalized for nonpsychotic disorders (September 2009-May 2013) were divided into APS youth versus non-APS youth, based on the Structured Interview of Prodromal Syndromes (SIPS) and according to DSM-5 criteria, and compared across multiple characteristics. RESULTS: Of 89 adolescents (mean ± SD age = 15.1 ± 1.6 years), 21 (23.6%) had APS. Compared to non-APS, APS was associated with more comorbid disorders (2.7 ± 1.0 vs 2.2 ± 1.3), major depressive disorder (61.9% vs 27.9%), oppositional defiant disorder/conduct disorder (52.4% vs 25.0%), and personality disorder traits (57.1% vs 7.4%, the only diagnostic category surviving Bonferroni correction). APS youth were more severely ill, having higher SIPS total positive, negative, and general symptoms; Brief Psychiatric Rating Scale total and positive scores; depression and global illness ratings; and lower Global Assessment of Functioning (GAF). Conversely, Young Mania Rating Scale scores, suicidal behavior, prescribed psychotropic medications, and mental disorder awareness were similar between APS and non-APS groups. In multivariable analysis, lowest GAF score in the past year (odds ratio [OR] = 51.15; 95% confidence interval [CI], 2.46-2,439.0) and social isolation (OR = 27.52; 95% CI, 3.36-313.87) were independently associated with APS (r(2) = 0.302, P < .0001). Although psychotic disorders were excluded, 65.2% (APS = 57.1%, non-APS = 67.7%, P = .38) received antipsychotics. CONCLUSION: One in 4 nonpsychotic adolescent inpatients met DSM-5 criteria for APS. APS youth were more impaired, showing a complex entanglement with a broad range of psychiatric symptoms and disorders, including depression, impulse-control, and, especially, emerging personality disorders. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01383915.

Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods.

BACKGROUND: Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain. METHODS: The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research. RESULTS: The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8-19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth. CONCLUSION: Antipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to maintain psychiatric stability. The IMPACT study provides a model for pediatric research on adverse event management using state-of-the art methods. The results of this study will provide needed data on risks and benefits of two pharmacologic interventions that are already being used in pediatric clinical settings but that have not yet been compared directly in randomized trials. TRIAL REGISTRATION: Clinical Trials.gov NCT00806234.

Are antipsychotics effective for the treatment of anorexia nervosa? Results from a systematic review and meta-analysis.

OBJECTIVE: To assess the utility of antipsychotics for weight gain and improvement of illness-related psychopathology in patients with anorexia nervosa. DATA SOURCES: PubMed, the Cochrane Library databases, and PsycINFO citations from the inception of the databases until March 27, 2012, were searched without language restrictions using the following keywords: randomized, random, randomly, and anorexia nervosa. In addition, we hand-searched for additional studies eligible for inclusion in this meta-analysis and contacted authors for unpublished data. STUDY SELECTION: Included in this study were randomized placebo- or usual care-controlled trials of antipsychotics in patients with anorexia nervosa. DATA EXTRACTION: Two independent evaluators extracted data. The primary outcome of interest was body weight, expressed as the standardized mean difference (SMD) between the 2 groups in baseline to endpoint change of body mass index (BMI), endpoint BMI, or daily weight change. SMD, risk ratio (RR), and number needed to harm (NNH) ± 95% confidence interval (CI) were calculated. RESULTS: Across 8 studies (mean duration = 9.6 weeks; range, 7-12 weeks), 221 patients (mean age = 22.5 years, 219 [99.1%] females) with anorexia nervosa were randomly assigned to olanzapine (n = 54), quetiapine (n = 15), risperidone (n = 18), pimozide (n = 8), sulpiride (n = 9), placebo (n = 99), or usual care (n = 18). Both individually (P = .11 to P = .47) and pooled together (SMD = 0.27, 95% CI, -0.01 to 0.56; P = .06, I2 = 0%; 7 studies, n = 195), weight/BMI effects were not significantly different between antipsychotics and placebo/usual care. Moreover, pooled antipsychotics and placebo/usual care did not differ regarding scores on questionnaires related to anorexia nervosa (P = .32, 5 studies, n = 114), body shape (P = .91, 4 studies, n = 100), depressive symptoms (P = .08, 4 studies, n = 103), and anxiety (P = .53, 4 studies, n = 121). Individually, quetiapine (1 study, n = 33) outperformed usual care regarding eating disorder attitudes (P = .01) and anxiety (P = .02). While rates of dropout due to any reason (P = .83, I2 = 0%) and due to adverse events (P = .54, I2 = 5%) were similar in both groups, drowsiness/sedation occurred significantly more often with antipsychotics than placebo/usual care (RR = 3.69, 95% CI, 1.37-9.95; I2 = 67%, P = .01; NNH = 2, P = .001; 5 studies, n = 129), but most other adverse effects were only sparsely reported. CONCLUSIONS: Although limited by small samples, this meta-analysis failed to demonstrate antipsychotic efficacy for body weight and related outcomes in females with anorexia nervosa.

Mesolimbic effects of the antidepressant fluoxetine in Holtzman rats, a genetic strain with increased vulnerability to stress.

This is the first metabolic mapping study of the effects of fluoxetine after learned helplessness training. Antidepressants are the most commonly prescribed medications, but the regions underlying treatment effects in affectively disordered brains are poorly understood. We hypothesized the antidepressant action of fluoxetine would produce adaptations in mesolimbic regions after 2 weeks of treatment. We used Holtzman rats, a genetic strain showing susceptibility to novelty-evoked hyperactivity and stress-evoked helplessness, to map regional brain metabolic effects caused by fluoxetine treatment. Animals underwent learned helplessness, and subsequently immobility time was scored in the forced swim test (FST). On the next day, animals began receiving 2 weeks of fluoxetine (5mg/kg/day) or vehicle and were retested in the FST at the end of drug treatment. Antidepressant behavioral effects of fluoxetine were analyzed using a ratio of immobility during pre- and post-treatment FST sessions. Brains were analyzed for regional metabolic activity using quantitative cytochrome oxidase histochemistry as in our previous study using congenitally helpless rats. Fluoxetine exerted a protective effect against FST-induced immobility behavior in Holtzman rats. Fluoxetine also caused a significant reduction in the mean regional metabolism of the nucleus accumbens shell and the ventral hippocampus as compared to vehicle-treated subjects. Additional networks affected by fluoxetine treatment included the prefrontal-cingulate cortex and brainstem nuclei linked to depression (e.g., habenula, dorsal raphe and interpeduncular nucleus). We concluded that corticolimbic regions such as the prefrontal-cingulate cortex, nucleus accumbens, ventral hippocampus and key brainstem nuclei represent important contributors to the neural network mediating fluoxetine antidepressant action.

Novelty-evoked activity in open field predicts susceptibility to helpless behavior.

Learned helplessness in animals has been used to model disorders such as depression and post-traumatic stress disorder (PTSD), but there is a lack of knowledge concerning which individual behavioral characteristics at baseline can predict helpless behavior after exposure to inescapable stress. The first aim of this study was to determine behavioral predictors of helplessness using the novel and familiar open-field tests, sucrose consumption, and passive harm-avoidance tasks before learned helplessness training and testing. Individual differences in physiologic responses to restraint stress were also assessed. A cluster analysis of escape latencies from helplessness testing supported the division of the sample population of Holtzman rats into approximately 50% helpless and 50% non-helpless. Linear regression analyses further revealed that increased reactivity to the novel environment, but not general activity or habituation, predicted susceptibility to learned helplessness. During restraint stress there were no mean differences in heart rate, heart rate variability, and plasma corticosterone between helpless and non-helpless rats; however, a lower heart rate during stress was associated with higher activity levels during exploration. Our most important finding was that by using an innocuous screening tool such as the novel and familiar open-field tests, it was possible to identify subjects that were susceptible to learned helplessness.

In vivo low-level light therapy increases cytochrome oxidase in skeletal muscle.

Low-level light therapy (LLLT) increases survival of cultured cells, improves behavioral recovery from neurodegeneration and speeds wound healing. These beneficial effects are thought to be mediated by upregulation of mitochondrial proteins, especially the respiratory enzyme cytochrome oxidase. However, the effects of in vivo LLLT on cytochrome oxidase in intact skeletal muscle have not been previously investigated. We used a sensitive method for enzyme histochemistry of cytochrome oxidase to examine the rat temporalis muscle 24 h after in vivo LLLT. The findings showed for the first time that in vivo LLLT induced a dose- and fiber type-dependent increase in cytochrome oxidase in muscle fibers. LLLT was particularly effective at enhancing the aerobic capacity of intermediate and red fibers. The findings suggest that LLLT may enhance the oxidative energy metabolic capacity of different types of muscle fibers, and that LLLT may be used to enhance the aerobic potential of skeletal muscle.

Lack of effect of stimulant combination with second-generation antipsychotics on weight gain, metabolic changes, prolactin levels, and sedation in youth with clinically relevant aggression or oppositionality.

BACKGROUND: Second-generation antipsychotics (SGAs) are associated with weight gain, metabolic abnormalities, sedation/sleep disturbance, and prolactin abnormalities, especially in youths. Although stimulants have opposing dopamine receptor and adverse effects, it is unclear whether stimulant co-treatment counteracts the therapeutic or side effects of antipsychotics. METHODS: This was a naturalistic cohort study including 153 antipsychotic trials in youths aged 4-19 (mean, 11.3 +/- 3.0) years, started on an SGA for clinically significant aggression or oppositionality associated with oppositional defiant disorder, conduct disorder, disruptive behavior disorder not otherwise specified (NOS), impulse control disorder NOS, intermittent explosive disorder, Tourette's disorder, autistic disorder, and pervasive developmental disorder NOS. Patients underwent fasting assessments of body composition, lipids, glucose, insulin, prolactin, sedation, and general efficacy at baseline, weeks 4, 8, and 12, comparing patients co-prescribed stimulants (n = 71) with those not co-prescribed stimulants (n = 82). RESULTS: Patients received risperidone (33.3%), aripiprazole (29.4%), quetiapine (18.4%), olanzapine (11.8%), ziprasidone (5.9%), or clozapine (0.7%). With and without adjustment for differences in baseline variables (sex, prior stimulant use, primary Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition [DSM-IV] disorders, co-morbid attention-deficit/hyperactivity disorder [ADHD], present in 46.3% of youths not receiving stimulants, and some body composition parameters), patients on versus off stimulants did not differ on any of the assessed outcomes (all p values > or = 0.1). CONCLUSIONS: In contrast to guidelines, stimulant use did not precede or accompany antipsychotic use during the current episode of aggression/oppositionality in almost half of those youths who had aggressive/oppositional behavior and a DSM-IV diagnosis of ADHD. At the clinically prescribed doses, stimulant co-treatment of SGAs did not seem to significantly reduce antipsychotic effects on body composition, metabolic parameters, prolactin, sedation, and broad efficacy.