BACKGROUND: Weight regain often occurs after weight loss in overweight individuals. We aimed to compare the effectiveness of 2 support programs and 2 diets of different macronutrient compositions intended to facilitate long-term weight maintenance. METHODS: Using a 2 x 2 factorial design, we randomly assigned 200 women who had lost 5% or more of their initial body weight to an intensive support program (implemented by nutrition and activity specialists) or to an inexpensive nurse-led program (involving "weigh-ins" and encouragement) that included advice about high-carbohydrate diets or relatively high-monounsaturated-fat diets. RESULTS: In total, 174 (87%) participants were followed-up for 2 years. The average weight loss (about 2 kg) did not differ between those in the support programs (0.1 kg, 95% confidence interval [CI] -1.8 to 1.9, p = 0.95) or diets (0.7 kg, 95% CI -1.1 to 2.4, p = 0.46). Total and low-density lipoprotein (LDL) cholesterol levels were significantly higher among those on the high-monounsaturated-fat diet (total cholesterol: 0.17 mmol/L, 95% CI 0.01 to 0.33; p = 0.040; LDL cholesterol: 0.16 mmol/L, 95% CI 0.01 to 0.31; p = 0.039) than among those on the high-carbohydrate diet. Those on the high-monounsaturated-fat diet also had significantly higher intakes of total fat (5% total energy, 95% CI 3% to 6%, p < 0.001) and saturated fat (2% total energy, 95% CI 1% to 2%, p < 0.001). All of the other clinical and laboratory measures were similar among those in the support programs and diets. INTERPRETATION: A relatively inexpensive program involving nurse support is as effective as a more resource-intensive program for weight maintenance over a 2-year period. Diets of different macronutrient composition produced comparable beneficial effects in terms of weight loss maintenance. ClinicalTrials.gov trial register no.

Seizure control and biochemical profile on the ketogenic diet in young children with refractory epilepsy-Indian experience.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

AIM: This study evaluated the efficacy and tolerability of the ketogenic diet (KD) in young Indian children with refractory epilepsy. The changes in biochemical and lipid profile with KD were also assessed. METHODS: Children aged 6 months to 5 years who had daily seizures (or at least 7 seizures/week) despite the appropriate use of at least three antiepileptic drugs were enrolled. KD was introduced using a non-fasting gradual initiation protocol. Seizure frequency, biochemical profile (liver and kidney function tests, fasting lipid profile, and spot urinary calcium-creatinine ratio) and adverse effects were recorded. Patients continuing KD were followed up for a minimum period of 12 months. RESULTS: Twenty-seven children were enrolled. Non-fasting gradual KD initiation was well tolerated. Eighty-eight percent remained on KD at 3 months, 55% remained on KD at 6 months, and 37% remained on it at 1 year. Intention-to-treat analysis revealed that 48% (13 of 27) had >50% reduction in seizures, and four children (15 %) were seizure free at 6 months. At 1 year, 37% had >50% reduction in seizures and five children (18.5%) were seizure free. Adverse effects included constipation (74%), weight loss (14.8%), edema due to hypo-albuminemia (7.4%) and renal stones (3.7%). Biochemical profile did not reveal significant changes over time, except for reduced serum albumin and increased spot urinary calcium-creatinine ratio. CONCLUSION: KD is an effective and well-tolerated treatment option in young Indian children with refractory epilepsy. However, careful ongoing medical supervision is needed. 

Effect of CLA isomers and their mixture on aging C57Bl/6J mice.

Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA.

BACKGROUND: Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted for weight loss management over the counter. Recently, FDA approved the CLA as Generally Recognized as Safe category so that it can be used in various food and beverages. The combined effect of CLA isomers have been studied extensively in animals and humans, however, the role of individual isomers remains unraveled. AIM: The present investigation addresses the effects of CLA isomers on body composition and body weight as well as safety using female C57Bl/6J aging mice. METHODS: Two main CLA isomers and their mixture were fed to 12-months-old female C57Bl/6J mice. Ten percent corn oil (CO) based fat diet supplemented with 0.5% purified cis 9 trans 11 (c9,t11) CLA or trans 10 cis 12 (t10,c12) CLA or their mixture (CLA mix, 50:50) for 6 months. The lean mass, fat mass, glucose, non-esterified fatty acids, and insulin were examined at the end of study. RESULTS: As a result of 6 months dietary intervention, both t10,c12 CLA and CLA mix groups showed increased lean mass and reduced fat mass compared to that of c9,t11 CLA and CO group. However, insulin resistance and liver hypertrophy were observed in t10,c12 CLA and CLA mix groups based on the results of homeostasis model assessment, revised quantitative insulin-sensitivity check index (R-QUICKI), intravenous glucose tolerance test, and liver histology. Liver histology revealed that increased liver weight was due to hypertrophy. CONCLUSION: In conclusion, the major CLA isomers have a distinct effect on fat mass, glucose, and insulin metabolism. The t10,c12 isomer was found to reduce the fat mass and to increase the lean mass but significantly contributed to increase insulin resistance and liver hypertrophy, whereas c9,t11 isomer prevented the insulin resistance. Between the two major CLA isomers, the t10,c12 was attributed to reduce fat mass whereas, c9,t11 improves the insulin sensitivity.

Obesity and restless legs syndrome in men and women.

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. xiang.gao@channing.harvard.edu

BACKGROUND: Obesity and restless legs syndrome (RLS) are both associated with hypofunction of dopamine in the CNS. We therefore examined whether individuals who are obese have an increased risk of RLS in two ongoing US cohorts, the Nurses' Health Study II and the Health Professional Follow-up Study. METHODS: We included 65,554 women and 23,119 men free of diabetes, arthritis, and pregnancy in the current analyses. Information on RLS was assessed using a set of standardized questions. Participants were considered to have RLS if they met four RLS diagnostic criteria recommended by the International RLS Study Group and had restless legs > or =5 times/month. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic regression models adjusting for age, smoking, use of antidepressant, phobic anxiety score, and other covariates. Log ORs from the two cohorts were pooled by a fixed-effects model. RESULTS: There were 6.4% of women and 4.1% of men who were considered to have RLS. Multivariate adjusted ORs for RLS were 1.42 (95% CI: 1.3, 1.6; p trend <0.0001) for participants with body mass index (BMI) >30 vs <23 kg/m(2) and 1.60 (95% CI: 1.5, 1.8; p trend <0.0001) for highest vs lowest waist circumference quintiles. Greater BMI in early adulthood (age 18-21 years) and weight gain were also associated with a higher prevalence of RLS (p trend <0.01 for both). CONCLUSIONS: Both overall and abdominal adiposity are associated with increased likelihoods of having restless legs syndrome (RLS). Further prospective studies are warranted to clarify causative association between obesity and risk of developing RLS.

2009 Apr 7;72(14):1255-61.

Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus. 

Bremen Institute for Prevention Research and Social Medicine, Bremen, Germany. frank.andersohn@charite.de

OBJECTIVE: Use of antidepressants has been reported to cause considerable weight gain. The aim of this study was to assess the risk of diabetes mellitus associated with antidepressant treatment and to examine whether the risk is influenced by treatment duration or daily dose. METHOD: This was a nested case-control study in a cohort of 165,958 patients with depression who received at least one new prescription for an antidepressant between January 1, 1990, and June 30, 2005. Data were from from the U.K. General Practice Research Database. Patients were at least 30 years of age and without diabetes at cohort entry. RESULTS: A total of 2,243 cases of incident diabetes mellitus and 8,963 matched comparison subjects were identified. Compared with no use of antidepressants during the past 2 years, recent long-term use (>24 months) of antidepressants in moderate to high daily doses was associated with an increased risk of diabetes (incidence rate ratio=1.84, 95% CI=1.35-2.52). The magnitude of the risk was similar for long-term use of moderate to high daily doses of tricyclic antidepressants (incidence rate ratio=1.77, 95% CI=1.21-2.59) and selective serotonin reuptake inhibitors (incidence rate ratio=2.06, 95% CI=1.20-3.52). Treatment for shorter periods or with lower daily doses was not associated with an increased risk. CONCLUSIONS: Long-term use of antidepressants in at least moderate daily doses was associated with an increased risk of diabetes. This association was observed for both tricyclic antidepressants and selective serotonin reuptake inhibitors.

2009 May;166(5):591-8. Epub 2009 Apr 1.

A proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to prevent weight gain on smoking cessation.

Primary Care Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. a.c.parsons@bham.ac.uk

BACKGROUND: St John's wort is an effective antidepressant that can reduce tobacco withdrawal symptoms, but it is not known whether it assists cessation. Chromium assists weight loss and might limit post cessation weight gain. METHODS: In a factorial design, we randomised smokers stopping smoking to 900 mg St John's wort (SJW) active or placebo and also randomised them to 400 microm chromium or placebo daily. Treatment started 2 weeks prior to quit day and continued for 14 weeks. Participants and researchers were blind to treatment allocation. All participants received weekly behavioural support. The primary endpoints were biochemically confirmed prolonged abstinence and mean weight gain in abstinent smokers 4 weeks after quitting. RESULTS: 6/71 (8.5%) participants on active SJW and 9/72 (12.5%) on placebo achieved prolonged abstinence at 4 weeks, an odds ratio (OR) (95% confidence interval) of 0.65 (0.22-1.92). At 6 months, 3 (4.2%) SJW active and 6 (8.3%) SJW placebo participants were still abstinent, an OR of 0.49 (0.12-2.02). Among these participants, the mean difference in weight gain between active chromium and placebo was -0.8 1kg (-3.79 to 2.18) at 4 weeks and -3.88 kg (-12.13 to 4.38) at 6 months. CONCLUSIONS: Taking together the absolute quit rates, the small difference between active and placebo, and lack of effects on withdrawal shows that SJW is ineffective for smoking cessation. Insufficient people stopped smoking to properly test the efficacy of chromium in preventing weight gain, but the point estimate indicates a potentially worthwhile benefit.

2009 Jun 1;102(1-3):116-22. Epub 2009 Mar 27.

Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes.

Women's Behavioral HealthCARE and the Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, 3811 O'Hara St., Pittsburgh, PA 15213, USA. wisnerkl@upmc.edu

OBJECTIVE: Selective serotonin reuptake inhibitor (SSRI) use during pregnancy incurs a low absolute risk for major malformations; however, other adverse outcomes have been reported. Major depression also affects reproductive outcomes. This study examined whether 1) minor physical anomalies, 2) maternal weight gain and infant birth weight, 3) preterm birth, and 4) neonatal adaptation are affected by SSRI or depression exposure. METHOD: This prospective observational investigation included maternal assessments at 20, 30, and 36 weeks of gestation. Neonatal outcomes were obtained by blinded review of delivery records and infant examinations. Pregnant women (N=238) were categorized into three mutually exclusive exposure groups: 1) no SSRI, no depression (N=131); 2) SSRI exposure (N=71), either continuous (N=48) or partial (N=23); and 3) major depressive disorder (N=36), either continuous (N=14) or partial (N=22). The mean depressive symptom level of the group with continuous depression and no SSRI exposure was significantly greater than for all other groups, demonstrating the expected treatment effect of SSRIs. Main outcomes were minor physical anomalies, maternal weight gain, infant birth weight, pregnancy duration, and neonatal characteristics. RESULTS: Infants exposed to either SSRIs or depression continuously across gestation were more likely to be born preterm than infants with partial or no exposure. Neither SSRI nor depression exposure increased risk for minor physical anomalies or reduced maternal weight gain. Mean infant birth weights were equivalent. Other neonatal outcomes were similar, except 5-minute Apgar scores. CONCLUSIONS: For depressed pregnant women, both continuous SSRI exposure and continuous untreated depression were associated with preterm birth rates exceeding 20%.

2009 May;166(5):557-66. Epub 2009 Mar 16

An integrated analysis of olanzapine/fluoxetine combination in clinical trials of treatment-resistant depression.

Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9119, USA. madhukar.trivedi@utsouthwestern.edu

OBJECTIVE: To evaluate the efficacy of olanzapine/fluoxetine combination (OFC) versus olanzapine or fluoxetine monotherapy across all clinical trials of treatment-resistant depression sponsored by Eli Lilly and Company. METHOD: Efficacy and safety data from 1146 patients with a history of nonresponse during the current depressive episode who subsequently exhibited nonresponse during a 6- to 8-week antidepressant open-label lead-in phase and were randomly assigned to OFC (N = 462), fluoxetine (N = 342), or olanzapine (N = 342) for double-blind treatment were analyzed. All patients had a diagnosis of major depressive disorder as defined by DSM-III or DSM-IV criteria. The dates in which the trials were conducted ranged from May 1997 to July 2005. RESULTS: After 8 weeks, OFC patients demonstrated significantly greater Montgomery-Asberg Depression Rating Scale improvement (mean change = -13.0) than fluoxetine (-8.6, p < .001) or olanzapine (-8.2, p < .001) patients, via a mixed-effects model repeated-measures analysis. Remission rates were 25.5% for OFC, 17.3% (p = .006) for fluoxetine, and 14.0% (p < .001) for olanzapine. Adverse events in >or= 10% of OFC patients were weight gain, increased appetite, dry mouth, somnolence, fatigue, headache, and peripheral edema. Random glucose mean change (mg/dL) was +7.92 for the OFC group, +1.62 for the fluoxetine group (p = .020), and +9.91 for the olanzapine group (p = .485). Random cholesterol mean change (mg/dL) was +12.4 for OFC, +2.3 for fluoxetine (p < .001), and +3.1 for olanzapine (p < .001); incidence of treatment-emergent increase from normal to high cholesterol (baseline < 200 mg/dL and >or= 240 subsequently) was significantly higher for the OFC group (10.2%) than for the fluoxetine group (3.1%, p = .017) but not the olanzapine group (8.0%, p = .569). Mean weight change (kg) was +4.42 for OFC, -0.15 for fluoxetine (p < .001), and +4.63 for olanzapine (p = .381), with 40.4% of OFC patients gaining >or= 7% body weight (vs. olanzapine: 42.9%, p = .515; fluoxetine: 2.3%, p < .001). CONCLUSION: Results of this analysis showed that OFC-treated patients experienced significantly improved depressive symptoms compared with olanzapine- or fluoxetine-treated patients following failure of 2 or more antidepressants within the current depressive episode. Safety results for OFC were generally consistent with those for its component monotherapies. The total cholesterol increase associated with OFC was more pronounced than with olanzapine alone.

2009 Mar;70(3):387-96. Epub 2009 Mar 10

Antidepressant phenelzine alters differentiation of cultured human and mouse preadipocytes.

Institut National de la Santé et de la Recherche Médicale U693, University Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, France.

Change in body weight is a frequent side effect of antidepressants and is considered to be mediated by central effects on food intake and energy expenditure. The antidepressant phenelzine (Nardil) potently inhibits both monoamine oxidase and semicarbazide-sensitive amine oxidase activities, two enzymes that are highly expressed in adipose tissue, raising the possibility that it could directly alter adipocyte biology. Treatment with this compound is rather associated with weight gain. The aim of this work was to examine the effects of phenelzine on differentiation and metabolism of cultured human and mouse preadipocytes and to characterize the mechanisms involved in these effects. In all preadipocyte models, phenelzine induced a time- and dose-dependent reduction in differentiation and triglyceride accumulation. Modulation of lipolysis or glucose transport was not involved in phenelzine action. This effect was supported by the reduced expression in the key adipogenic transcription factors peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer binding protein-alpha, which was observed only at the highest drug concentrations (30-100 microM). The PPAR-gamma agonists thiazolidinediones did not reverse phenelzine effects. By contrast, the reduction in both cell triglycerides and sterol regulatory element-binding protein-1c (SREBP-1c) was detectable at lower phenelzine concentrations (1-10 microM). Phenelzine effect on triglyceride content was prevented by providing free fatty acids to the cells and was partially reversed by overexpression of a dominant-positive form of SREBP-1c, showing the privileged targeting of the lipogenic pathway. When considered together, these findings demonstrate that an antidepressant directly and potently inhibits adipocyte lipid storage and differentiation, which could contribute to psychotropic drug side effects on energy homeostasis.

2009 May;75(5):1052-61. Epub 2009 Feb 6

Adjunctive aripiprazole in major depressive disorder: analysis of efficacy and safety in patients with anxious and atypical features.

UT Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9119, USA. Madhukar.Trivedi@UTSouthwestern.edu

OBJECTIVE: To evaluate the efficacy of adjunctive aripiprazole to standard antidepressant therapy (ADT) for patients with DSM-IV major depressive disorder with anxious/atypical features at baseline. METHOD: Data from 2 identical 14-week studies (an 8-week prospective ADT treatment phase and a 6-week randomized, double-blind phase) of aripiprazole augmentation were pooled to evaluate efficacy and safety in the 2 subgroups. The primary efficacy endpoint was mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from end of ADT treatment to end of randomized treatment (last observation carried forward). Anxious depression was defined by a Hamilton Rating Scale for Depression anxiety/somatization factor score > or = 7, and atypical depression was defined by previously described criteria on the Inventory of Depressive Symptomatology-Self-Report. Both anxious and atypical subtypes were defined based on symptoms at entry into prospective ADT (week 0). Patients were enrolled between June 2004 and April 2006 in one study and from September 2004 to December 2006 in the other (total randomized population, N = 742; anxious/nonanxious population, N = 740; atypical/nonatypical population, N = 737). RESULTS: Completion rates were between 84% and 90% and comparable across all subgroups, with low discontinuations due to adverse events. Patients receiving adjunctive aripiprazole demonstrated significantly greater improvement in MADRS total score versus patients receiving adjunctive placebo, starting at week 1 or week 2 and continuing through to endpoint (anxious: -8.72 vs. -6.17, p < or = .001; nonanxious: -8.61 vs. -4.97, p < or = .001; atypical: -9.31 vs. -5.15, p < or = .001; nonatypical: -8.08 vs. -6.22, p < .05). At endpoint, remission rates were also significantly higher with adjunctive aripiprazole versus adjunctive placebo (p < .05) in all subgroups. Treatment emergent adverse event profile was similar in all subgroups and comparable to the total population. Reporting of akathisia and weight gain on aripiprazole treatment did not differ between subgroups. CONCLUSION: Adjunctive aripiprazole is an effective treatment for patients with major depression presenting with either anxious or atypical features. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758. Copyright 2008 Physicians Postgraduate Press, Inc.

2008 Dec;69(12):1928-36. Epub 2008 Dec 2

Efficacy, safety and tolerability of quetiapine augmentation in treatment resistant depression: An open-label, pilot study.

Manchester Mental Health and Social Care Trust/University of Manchester M13 9WL, United Kingdom.

BACKGROUND: Atypical antipsychotics may have efficacy as augmentation therapy in treatment resistant depression (TRD) but evidence is limited. METHODS: An open label study of quetiapine augmentation in 24 patients (mean age: 46.3 years) with a DSM-IV major depressive episode resistant to at least 2 trials of antidepressant medication, and currently taking a monoamine reuptake inhibitor. An 8-week treatment phase was followed by an 18-week extension in patients who showed clinical benefit. RESULTS: Eighteen patients (75%) completed the 8-week treatment phase with seven patients (29%) being responders on the Montgomery Asberg Depression Rating Scale and 13 (54%) on the CGI-I. Fewer patients responded if they had previously received olanzapine in the current episode but this was not statistically significant (0% v 37%, p=0.27). Of the eleven patients entering the extension phase, 3 patients (27%) experienced a significant worsening of mood. The most common adverse events were sedation (54%), dry mouth (38%) and dizziness (29%). Significant weight gain was found in 40% of patients treated for 26 weeks. Average quetiapine doses were 245 mg at 8 weeks and 346 mg at 26 weeks. CONCLUSIONS: Quetiapine may be a helpful adjunctive agent for some patients with TRD but placebo-controlled trials are needed to establish its place in management. LIMITATIONS: The trial was open-label and the numbers were small.

2009 Jan 24. [Epub ahead of print]

Beneficial acute antidepressant effects of aripiprazole as an adjunctive treatment or monotherapy in bipolar patients unresponsive to mood stabilizers: results from a 16-week open-label trial.

Catholic University of Sacred Heart of Rome, Institute of Psychiatry and Psychology, Bipolar Disorders Unit, Via Ugo De Carolis, 48 00136 Roma, Italy. mariannamazza@hotmail.com

OBJECTIVE: Several lines of research suggested that aripiprazole might be a useful treatment for acute bipolar depression. The aim of this open-label trial is to give more evidence of the clinical effectiveness and tolerability of aripiprazole in acute bipolar depression. RESEARCH DESIGN AND METHODS: Aripiprazole response was prospectively assessed for 16 weeks using the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression Severity Scale (CGI-S), and the Young Mania Rating Scale in 85 bipolar patients with acute depression inadequately responsive to one mood stabilizer. MAIN OUTCOME MEASURES: Aripiprazole was well tolerated. Only three (3.5%) patients discontinued the study for side effects. The most common side effect was akathisia, occurring in 17/80 (21.2%) patients. Patients showed statistically insignificant weight gain (0.9 +/- 2.64 kg) over the 16-week trial. RESULTS: Patients showed a significant decrease in mean MADRS and CGI-S, and 80 (94.1%) patients completed the 16-week trial. Thirty-nine (45.8%) patients received aripiprazole as monotherapy and 46 received the drug adjunctively (54.1%). Fifty-two (65%) patients met criteria for response (>/= 50% reduction in MADRS total score), 30 (37.5%) patients met criteria for remission (final MADRS total score </= 12). CONCLUSIONS: Aripiprazole was associated with beneficial effects on mood in patients with bipolar depression, and appears well tolerated with very small changes in mean body weight. These results highlight the potential benefits of aripiprazole for bipolar disorder patients. However, double-blind, placebo-controlled studies are necessary to confirm aripiprazole's efficacy, tolerability and safety in bipolar depression.

2008 Dec;9(18):3145-9

Quality improvement in long term care: the psychotropic assessment tool (PAT).

Washington University, Barnes Jewish Hospital, St. Louis, MO, USA.

BACKGROUND: There are already a substantial number of individuals with dementia in long-term care. Many nursing home patients have difficult behaviors and are currently managed with psychotropic medications. Medications for behavior need to be titrated and monitored over time for efficacy and safety, and subsequently tapered if ineffective. Some of these medications are not without risk, and that risk-benefit ratio should be discussed and documented with the family. Currently, we are not aware of any quality improvement process that has been developed in long-term care to address these issues. OBJECTIVES: To describe the process of a novel quality improvement intervention that was designed to improve documentation in the medical record and interdisciplinary communication of the usefulness and possible side effects of psychotropic agents used in the management of difficult behaviors for dementia. DESIGN: Retrospective review of the chart and quality improvement records in a long-term care facility. SETTING: An academic long-term care facility that specializes in dementia care in St. Louis, MO. METHODS: The quality improvement team created a process and a form named the Psychotropic Assessment Tool (PAT) to document current behavioral symptoms of the residents; determine whether the resident was on psychotropic agents; identify whether agents had been initiated, titrated, and/or tapered if appropriate; and whether there were any side effects related to the behavioral medications. A letter was created and provided to the surrogate decision maker that described the risk-benefit ratio of the use of antipsychotic agents when these drugs were prescribed. Recommendations from the quality improvement team were provided to the primary care physician. After 1 year of this process, we reviewed the medical charts and quality improvement PAT forms of all residents. We documented the use of psychotropic agents before and after initiating the PAT process, the presence of current behavioral symptoms, the presence of possible side effects, and the recommendations of the interdisciplinary team that met after the monthly quality improvement meetings. RESULTS: A total of 110 patients were included in this study, which reviewed psychotropic drug use between July 2005 and July 2006. The mean age of the residents was 83.8 +/- 7.5 years. All residents had a diagnosis of dementia. Mean MMSE score was 13.5 +/- 7.3. The prevalence of potential problems that could have been associated with psychotropic drug use was not insignificant and included falls (45%), weight loss (16%), weight gain (7%), dizziness (9%), and sedation (5%). However, behaviors that might warrant psychotropic drug use were not uncommon and included active depression (12%), anxiety (24%), hallucinations (11%), disruptive behavior (21%) and delusions (21%). The percentage of residents on antipsychotics changed from 26.5% pre-PAT process to 25.2% post-PAT process; those on anxiolytics changed from 6.0% to 4.0%. There was a change in hypnotics from 2.6% to 3.4%. Antidepressant usage remained the same at 55%. The PAT CHAT discussion resulted in recommendation of medication changes in 25% of residents. CONCLUSIONS: The initiation of this quality improvement process using the PAT led to improved chart documentation and interdisciplinary communication between the team, primary care physicians, and families. Further studies are needed to determine whether this process can impact use of psychotropic agents, improve quality of life, decrease adverse drug events, and/or reduce medical-legal risk.

2008 Nov;9(9):676-83. Epub 2008 Sep 27

Psychotropic prescription practices in east Asia: looking back and peering ahead.

Department of Pharmacology, National University of Singapore, Singapore. phctanch@nus.edu.sg

PURPOSE OF REVIEW: The present review focuses on the pharmacoepidemiological issues of psychotropic drug use in countries within east Asia, with special emphasis on antipsychotic, antidepressant and benzodiazepine prescriptions. Pharmacogenetic studies in different ethnic groups are also reviewed. RECENT FINDINGS: Recent studies have revealed the prevalence of antipsychotic polytherapy (defined as the use of more than one antipsychotic; up to 45.7%), less conservative antipsychotic use (defined as the use of more than 1000 mg/day chlorpromazine equivalents; up to 17.9%) and depot antipsychotic use (up to 15.3%) in different populations in east Asia. Clozapine is commonly prescribed (up to 60%) in China. There is a trend of increasing second-generation antipsychotic use in east Asian countries. Up to 67.5% of patients received newer antidepressants such as selective serotonin reuptake inhibitors. Benzodiazepine medications are used in up to 29.9% of study populations. Socioeconomic factors appear to be one of the major common factors that affect the prescription of antipsychotics and newer antidepressants. Pharmacogenetic factors associated with antipsychotic response, weight gain and extrapyramidal side effects have been examined. Treatment adherence and pharmacoeconomic factors are relatively understudied. SUMMARY: Future studies on prescribing trends of antipsychotics and antidepressants need to focus on children, adolescent and elderly patient populations, the impact of changing prescription trends and the long-term effects on patients and their caregivers, as well as pharmacogenetic factors, which can potentially pave the way for better and more individualized prescription of psychotropic drugs in east Asia.

2008 Nov;21(6):645-50

Changing trends in pediatric antipsychotic use in Florida's Medicaid program.

Department of Mental Health Law and Policy, Louis de la Parte Florida Mental Health Institute, University of South Florida, Tampa, FL 33647, USA. rconstantine@fmhi.usf.edu

OBJECTIVE: This study describes the changing trends in antipsychotic use among youths aged 18 years and younger and in age subgroups (zero to five, six to 12, and 13 to 18 years) in the Florida Medicaid program. METHODS: The study used Florida Medicaid claims data associated with approximately 1.2 million children and adolescent enrollees per year to describe monthly antipsychotic use from July 2002 to December 2005. A preliminary examination of trends indicated that antipsychotic use might be different for the periods before May 2004 and after April 2004. For this reason, piecewise regression was used to compare the trends for these two periods. RESULTS: This study found significant increases in the use of antipsychotic medications for all three age groups from July 2002 to April 2004. The greatest rate of growth was for the 13- to 18-year age group, and the least rate of growth was for the zero- to five-year age group. From May 2004 to December 2005 antipsychotic utilization trends were flat for youths age 18 years and younger and for the six- to 12-year and the 13- to 18-year age groups. For preschool-age children (the zero- to five-year age group), there was a slight but significant decline in antipsychotic use. Significant changes were also observed in the specific second-generation antipsychotic agents prescribed. Although risperidone remained the most frequently prescribed antipsychotic, its use declined significantly from May 2004 to December 2005. Olanzapine use also declined during this period. On the other hand, aripiprazole use increased significantly throughout the study period, with usage among the 13- to 18-year age group almost equaling that of risperidone by December 2005. CONCLUSIONS: The lack of growth in antipsychotic prescribing after the spring of 2004 represents a significant departure from historical trends. Although some in-state policies may have affected these trends, it appears that the timing and extent of the changes occurred shortly after the Food and Drug Administration required warnings on second-generation antipsychotic medications related to weight gain, glucose levels, and diabetes. They appeared immediately after the black box warning for pediatric antidepressant medications, and they appeared shortly after the Joint American Diabetes and American Psychiatric Association Consensus Statement. These factors suggest the existence of a prescribing community that is responsive to evidence and to professional and regulatory actions based on it.

2008 Oct;59(10):1162-8

Probiotics Improve Outcomes After Roux-en-Y Gastric Bypass Surgery: A Prospective Randomized Trial.

Department of Surgery, Surgery Center for Outcomes Research and Evaluation (SCORE), Stanford University School of Medicine, Stanford, CA, USA.

INTRODUCTION: Roux-en-Y gastric bypass (RNYGB) surgery offers an effective and enduring treatment for morbid obesity. Gastric bypass may alter gastrointestinal (GI) flora possibly resulting in bacterial overgrowth and dysmotility. Our hypothesis was that daily use of probiotics would improve GI outcomes after RNYGB. METHODS: Forty-four patients undergoing RNYGB were randomized to either a probiotic or control group; 2.4 billion colonies of Lactobacillus were administered daily postoperatively to the probiotic group. The outcomes of H(2) levels indicative of bacterial overgrowth, GI-related quality of life (GIQoL), serologies, and weight loss were measured preoperatively and at 3 and 6 months postoperatively. Categorical variables were analyzed by chi (2) test and continuous variables were analyzed by t test with a p < 0.05 for significance. RESULTS: At 6 months, a statistically significant reduction in bacterial overgrowth was achieved in the probiotic group with a preoperative to postoperative change of sum H( 2 ) part per million (probiotics = -32.13, controls = 0.80). Surprisingly, the probiotic group attained significantly greater percent excess weight loss than that of control group at 6 weeks (controls = 25.5%, probiotic = 29.9%) and 3 months (38.55%, 47.68%). This trend also continued but was not significant at 6 months (60.78%, 67.15%). The probiotic group had significantly higher postoperative vitamin B12 levels than the control group. Both probiotic and control groups significantly improved their GIQoL. CONCLUSION: In this novel study, probiotic administration improves bacterial overgrowth, vitamin B12 availability, and weight loss after RNYGB. These data may provide further evidence that altering the GI microbiota can influence weight loss.

Probiotic administration alters the gut flora and attenuates colitis in mice administered dextran sodium sulfate.

Department of Gastrointestinal Sciences, The Wellcome Trust Research Laboratory, Christian Medical College, Vellore, India.

BACKGROUND: Probiotics are used in the therapy of inflammatory bowel disease. This study aimed to determine whether prior administration of probiotic lactobacilli and bifidobacteria would prevent disease and change gut flora in an animal model of colitis. METHODS: Swiss albino mice received a probiotic mixture (four Lactobacillus and four Bifidobacterium species) or medium (control) for a week prior to induction of colitis by oral 4% dextran sodium sulfate (DSS) for seven days. Appropriate non-colitis controls were used. Histological damage was assessed (n = 5 per group), as was expression of mRNA for tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, transforming growth factor (TGF)-beta1 and SOCS-1 in the colonic mucosa (n = 6 per group). Secretion of TNF-alpha was measured in distal colon organ culture (n = 5-6 per group). Levels of Bacteroides, Bifidobacterium, and Lactobacillus acidophilus in feces were quantified by real time polymerase chain reaction (PCR) targeting 16S rDNA. RESULTS: Compared to untreated DSS colitis, probiotic treatment significantly reduced weight loss (P < 0.05), shifted histological damage to lesser grades of severity (P < 0.001), reduced mRNA expression of TNF-alpha and TGF-beta1 (P < 0.05), and down-regulated production of TNF-alpha from distal colon explants (P < 0.05). Colitis induced a significant reduction in the relative proportions of Bifidobacterium, Bacteroides and Lactobacillus acidophilus group bacteria in feces, and these levels were significantly increased in probiotic-treated mice compared to DSS mice (P < 0.001). CONCLUSION: Prior administration of probiotic bacteria reduced mucosal inflammation and damage in DSS-induced colitis. DSS colitis was associated with significant changes in the fecal anaerobic bacterial flora and these changes were modulated by administration of probiotic bacteria.

Biotherapeutic effects of Bifidobacterium spp. on orogastric and systemic candidiasis in immunodeficient mice.

Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin, USA. balish@surgery.wisc.edu.

Two commercially available Bifidobacterium spp. (Bifidobacterium infantis and Bifidobacterium lactis) were compared for their capacities to protect immunodeficient bg/bg-nu/nuand bg/bg-nu/+mice from orogastric and lethal candidiasis. Both Bifidobacterium spp. prolonged the survival of Candida albicans-colonized adult and neonatal bg/bg-nu/numice. The bifidobacteria affected the production of antibodies to C. albicans, inhibited disseminated candidiasis, suppressed weight loss associated with C. albicans infection, inhibited the growth of C. albicans in the alimentary tract, inhibited systemic candidiasis of endogenous origin, and decreased the severity of gastric candidiasis in both mouse strains. B. infantis inhibited systemic candidiasis of endogenous origin better than B. lactis; however, B. lactis was significantly more effective at inhibiting C. albicans colonization of the alimentary tract, suppressing gastric candidiasis, and protecting bg/bg-nu/numice from lethal candidiasis than B. infantis. These results show that Bifidobacterium spp. can protect immunodeficient mice from candidiasis but different species manifest quantitative and qualitative differences in their probiotic and biotherapeutic effects.

Saccharomyces boulardii ameliorates Citrobacter rodentium-induced colitis through actions on bacterial virulence factors.

Div. of Gastroenterology, BC Children's Hospital, 4480 Oak St., Rm. K4-181, Vancouver, BC, Canada V6H 3V4.

Saccharomyces boulardii has received increasing attention as a probiotic effective in the prevention and treatment of infectious and inflammatory bowel diseases. The aim of this study was to examine the ameliorating effects of S. boulardii on Citrobacter rodentium colitis in vivo and identify potential mechanisms of action. C57BL/6 mice received 2.5 x 10(8) C. rodentium by gavage on day 0, followed by S. boulardii (25 mg; 5 x 10(8) live cells) gavaged twice daily from day 2 to day 9. Animal weights were monitored until death on day 10. Colons were removed and assessed for epithelial barrier function, histology, and myeloperoxidase activity. Bacterial epithelial attachment and type III secreted proteins translocated intimin receptor Tir (the receptor for bacterial intimin) and EspB (a translocation apparatus protein) required for bacterial virulence were assayed. In infected mice, S. boulardii treatment significantly attenuated weight loss, ameliorated crypt hyperplasia (234.7 +/- 7.2 vs. 297.8 +/- 17.6 microm) and histological damage score (0.67 +/- 0.67 vs. 4.75 +/- 0.75), reduced myeloperoxidase activity (2.1 +/- 0.4 vs. 4.7 +/- 0.9 U/mg), and attenuated increased mannitol flux (17.2 +/- 5.0 vs. 31.2 +/- 8.2 nm.cm(-2).h(-1)). The ameliorating effects of S. boulardii were associated with significantly reduced numbers of mucosal adherent C. rodentium, a marked reduction in Tir protein secretion and translocation into mouse colonocytes, and a striking reduction in EspB expression and secretion. We conclude that S. boulardii maintained colonic epithelial barrier integrity and ameliorated inflammatory sequelae associated with C. rodentium infection by attenuating C. rodentium adherence to host epithelial cells through putative actions on the type III secretion system.

Maturation of the mucosal immune system underlies colitis susceptibility in interleukin-10-deficient (IL-10-/-) mice.

Departments of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4952, USA.

Elevated mucosal IL-12/23p40 and IFN-gamma accompany early inflammation in IL-10-deficient (IL-10(-/-)) mice and then later decline while inflammation persists. This report addresses whether this cytokine profile reflects disease progression or inherent, age-related changes in mucosal immunity. IL-10(-/-) and wild-type (WT) mice were maintained in an ultrabarrier facility or transferred to conventional housing at 3, 12, or 30 weeks of age. Weight, stool changes, and histologic features were followed. Lamina propria mononuclear cells were cultured for cytokine analysis by ELISA. Ultrabarrier-housed IL-10(-/-) mice are statistically indistinguishable from WT mice by weight, disease activity index, and histologic inflammation. IL-10(-/-) mice but not WT, transferred at 3 weeks, develop colitis gradually, reaching a significant, sustained maximum by 15 weeks of age. Transfer at 12 weeks induces rapid disease onset in both strains, maximal at 15 weeks of age. Inflammation persists in IL-10(-/-), and WT recover. IL-10(-/-) and WT mice transferred at 30 weeks demonstrate transient diarrhea and weight loss but no chronic inflammation. Probiotics delay symptom onset only in the 12-week-old group. IFN-gamma production from ultrabarrier-housed IL-10(-/-) mice is elevated at 12 weeks of age, and older animals have decreased IFN-gamma and increased IL-4. IL-10 is important for suppressing inflammation after transfer at 3 weeks of age and limiting inflammation after transfer at 12 weeks but has little influence at 30 weeks of age. Colitis onset, progression, and response to probiotic therapy vary with immune system age, suggesting that a distinct, Th1-driven, age-dependent cytokine profile may contribute to increased colitis susceptibility in otherwise healthy mice.

Effect of oral administration of Butyrivibrio fibrisolvens MDT-1 on experimental enterocolitis in mice.

Department of Life Science, College of Agriculture, Meiji University, Higashimita, Tama-ku, Kawasaki 214-8571, Japan.