Showing papers on "Psychotropic drug published in 2011"

β-Blockers and Survival among Danish Patients with Malignant Melanoma: A Population-Based Cohort Study

Abstract: Background: To study whether use of β-blockers increases survival in patients with malignant melanoma because experimental data suggest that catecholamine hormones may be involved in stimulating the aggressiveness of malignant melanoma. Methods: A total of 4,179 patients diagnosed with malignant melanoma in Denmark with a median follow-up of 4.9 years and identified in the Danish Cancer Registry participated. Data on β-blocker use, comorbidity, and survival were obtained from medical and administrative databases. Cox proportional hazards models were used to estimate HRs for all-cause mortality with 95% CIs with adjustment for prognostic factors. Results: A total of 372 (8.9%) patients with malignant melanoma were treated with β-blockers within 90 days of melanoma diagnosis. The median β-blocker duration for exposure within 90 days of melanoma diagnosis, more than 90 days, and no prior exposure was 7.6, 1.4, and 0 years, respectively. The patients receiving β-blockers were older, had more comorbidities, and more cardiovascular and psychotropic drug user than the patients receiving no β-blockers prior to melanoma diagnosis. After adjustment for age and comorbidity index, the HR for melanoma death was 0.87 (95% CI: 0.64–1.20) and for all-cause mortality was 0.81 (95% CI: 0.67–0.97). Conclusion: Increased survival time of patients with melanoma receiving β-blockers suggests that this class of drugs may hold promise in treatment strategy for these patients. Impact: The observations described here suggest that catecholamines may retard melanoma progression and that β-blockers may have unrecognized potential as a therapeutic intervention for melanoma. Cancer Epidemiol Biomarkers Prev; 20(10); 2273–9. ©2011 AACR .

Gender-related mental-health differences between refugees and non-refugee immigrants - a cross-sectional register-based study

Abstract: Being an immigrant in a high-income country is a risk factor for severe mental ill health. Studies on mental ill health among immigrants have found significant differences in mental health outcome between immigrants from high income countries and low-income countries. Being an asylum seeker or a refugee is also associated with mental ill health. This study aimed to assess if there is a difference in mental ill health problems between male and female refugee and non-refugee immigrants from six low-income countries in Sweden. A cross-sectional, population-based study design was used comparing refugees with non-refugees. The study size was determined by the number of persons in Sweden fulfilling the inclusion criteria at the time of the study during 2006. Outcome: Mental ill health, as measured with the proxy variable psychotropic drugs purchased. Refugee/Non-refugee: Sweden grants asylum to refugees according to the Geneva Convention and those with a well-grounded fear of death penalty, torture or who need protection due to an internal or external armed conflict or an environmental disaster. The non-refugees were all family members of those granted asylum in Sweden. Covariates: Gender and origin. Potential confounders: Age, marital status, education and duration of stay in Sweden. Background variables were analysed using chi square tests. The association between outcome, exposure and possible confounders was analysed using logistic regression analyses. Multiple logistic regression analysis was used to adjust for potential confounders. The study population comprised 43,168 refugees and non-refugees, of whom 20,940 (48.5%) were women and 24,403 (56.5%) were refugees. Gender, age, origin, marital status and education were all associated with the outcome. For female, but not male, refugees there was a significantly higher likelihood of purchasing psychotropic drugs than non-refugees (OR = 1.27, 95% CI = 1.15 - 1.40). Female refugees from low-income countries seem to be a risk group among immigrant women from low-income countries, whereas male refugees had the same risk patterns as non-refugee immigrants from low-income countries. This underlines the need for training of clinicians in order to focus on pre-migration stress and the asylum process, among female newcomers.

Healthcare and social services resource use and costs of self-harm patients.

Abstract: Patients who have self-harmed have increased morbidity across a wide range of health outcomes, but there is no evidence on their pattern of health and social service use, and its relationship with repetition of self-harm Previous studies have shown that resource use and costs in the short-term hospital management of self-harm is associated with certain patient and service characteristics but their impact in the longer term has not been demonstrated The aim of this study is to test the association between changing levels of costs of health and social care with further episodes of self-harm and to identify the clinical and social factors associated with this This was a cost-analysis incidence study of a sample of patients from a cohort of self-harm patients who remained within one region over the course of their follow-up Resource use was retrospectively observed from their first episode of self-harm (dating back on some occasions to the 1970’s), and costs applied Panel data analyses were used to identify factors associated with observed costs over time Patients with five or more episodes of self-harm had the highest levels of resource costs Health and social care costs reduced with time from last episode of self-harm In the year following the first episode of self-harm, psychiatric care accounted for 69% and psychotropic drug prescriptions 1% of the mean resource costs The management of self-harm occurs within a complex system of health and social care Major self-harm repeaters place the greatest cost burden on the system Better understanding of the impact of risk assessment models and consequent service provision on clinical outcome may help in the design of effective services for this patient group

Prescribing pattern of psychotropic drugs in nursing home residents with dementia.

Abstract: BACKGROUND: The goal of this study is to determine patterns of psychotropic drug use (PDU), the association with neuropsychiatric symptoms (NPS), and the variability across dementia types in nursing home residents with dementia. In addition, PDU was analyzed across multiple indications. METHODS: This was a prospective cohort study over a two-year period from 2006 to 2008, which involved 14 dementia special care units in nine nursing homes. A total of 117 residents with dementia participated in the study, of whom 35% had Alzheimer's dementia (AD) and 11% vascular dementia (VaD). PDU was classified according to anatomical therapeutic chemical-classification as either "present" or "absent". RESULTS: The majority of residents had moderately severe to severe dementia. At all successive assessments, almost two-thirds of residents received any psychotropic drug (PD) and almost one-third continued to receive any PD. Of all PDs, antipsychotics (APs) were prescribed most frequently. Fewer residents started with antidepressants, but continued to receive antidepressants at higher percentages. Anxiolytics showed an intermittent course, but a subgroup of 9% showed two-year continuation. Once started on PDs at baseline, residents continued to use PDs at high percentages: three-quarters continued to receive APs for at least six months. Half of residents received at least one PD; one-fifth received at least two PDs simultaneously. Residents with AD received more hypnotics and antidementia drugs; residents with VaD received more antipsychotics, antidepressants, anxiolytics and anticonvulsants. CONCLUSIONS: PDs have different utilization patterns, but overall, consistently high continuation rates were found. These results warrant scrutiny of continuous PDU.

Using the Zebrafish Photomotor Response for Psychotropic Drug Screening

Abstract: Because psychotropic drugs affect behavior, we can use changes in behavior to discover psychotropic drugs. The original prototypes of most neuroactive medicines were discovered in humans, rodents and other model organisms. Most of these discoveries were made by chance, but the process of behavior based drug discovery can be made more systematic and efficient. Fully automated platforms for analyzing the behavior of embryonic zebrafish capture digital video recordings of animals in each individual well of a 96-well plate before, during, and after a series of stimuli. To analyze systematically the thousands of behavioral recordings obtained from a large-scale chemical screen, we transform these behavioral recordings into numerical barcodes, providing a concise and interpretable summary of the observed phenotypes in each well. Systems-level analysis of these behavioral phenotypes generate testable hypotheses about the molecular mechanisms of poorly understood drugs and behaviors. By combining the in vivo relevance of behavior-based phenotyping with the scale and automation of modern drug screening technologies, systematic behavioral barcoding represents a means of discovering psychotropic drugs and provides a powerful, systematic approach for unraveling the complexities of vertebrate behavior.

Psychotropic drug prescription in nursing home patients with dementia: influence of environmental correlates and staff distress on physicians' prescription behavior

Abstract: Background: The aim of the study was to examine whether staff distress and aspects of the nursing home environment were associated with psychotropic drug use (PDU) in patients with dementia.Methods: This was a cross-sectional study of 1289 nursing home patients with dementia from 56 Dementia Special Care Units (SCUs) in the Netherlands. The primary outcome was PDU. Potential correlates of PDU were staff distress, environmental correlates (the number of patients per unit or per living room, staff/patient ratio, and the presence of a walking circuit), and patient factors (gender, age, dementia severity, and neuropsychiatric symptoms (NPS)). Multilevel logistic regression analysis was used to estimate the relative contributions of predictor variables in explaining PDU.Results: Staff distress, aspects of the physical nursing home environment and patients' neuropsychiatric symptoms were independently associated with PDU. Staff distress at patients' agitation was associated with antipsychotic and anxiolytic drug use (OR 1.66, 95% CI (1.16-2.36) and 1.62 (1.00-2.61), respectively). SCUs with more patients per living room had higher hypnotic drug use (OR 1.08, 95% CI (1.02-1.14)). Low staff/patient ratio was associated with high antidepressant drug use (OR 0.13, 95% CI (0.04-0.47)). The effects of nursing home environment on study outcome were smallest for antidepressant use (intra-SCU correlation 0.005) and highest for hypnotic use (intra-SCU correlation 0.171).Conclusion: Staff distress and other environmental aspects are independently associated with PDU. These findings raise questions about the appropriateness of psychoactive drug prescriptions for nursing home patients with dementia.

Thyroid adverse effects of psychotropic drugs: a review.

Abstract: Objectives Because many patients with mental illness take more than one psychotropic drug, an understanding of the effects of every class of these drugs is very important to manage any thyroid abnormalities that can happen with these patients. Methods A systematic review of all the published literature was made via Medline. Keywords used for the search were "thyroid side effects" in association with one of the following: "antipsychotics," "antidepressants," "lithium," "anticonvulsants," "benzodiazepines," "anticholinergics," "antihistaminergics," "cholinesterase inhibitors," "stimulants," "methadone," and "naltrexone." Results Phenothiazines, which are antipsychotics, mainly alter iodine capture, complex and deactivate it, as well as decrease thyroid-stimulating hormone's (TSH's) response to thyroid-releasing hormone (TRH). Nonphenothiazines, typical antipsychotics, can induce the formation of thyroid autoantibodies and can elevate TSH levels. Atypical antipsychotics may decrease TRH-stimulated TSH. Tricyclic antidepressant drugs complex with iodine and thyroid peroxidase and deactivate them, induce deiodinase activity and interfere with the hypothalamo-pituitary-thyroid (HPT) axis by decreasing TSH response to TRH. The main effect with other antidepressant drugs is a decrease in circulating thyroid hormone levels. Lithium inhibits thyroid hormone release and increases TRH-stimulated TSH, inducing goiter, clinical and subclinical hypothyroidism, and hyperthyroidism. Carbamazepine mainly reversibly decreases serum thyroid hormone levels. Other psychotropic drugs such as valproic acid, benzodiazepines, opiates, anticholinergic and antihistaminergic drugs, and stimulants have minor interferences with thyroid functions. Conclusion Patients receiving lithium, phenothiazines, and tricyclic antidepressants TCA should be closely monitored for the development of thyroid function abnormalities. Only patients at risk for developing thyroid function abnormalities should be monitored when they receive typical and/or atypical antipsychotic drugs, nontricyclic antidepressant drugs, and carbamazepine. No specific recommendations are proposed as toward thyroid function monitoring for patients receiving any other psychopharmacologic drug.

The interrelation between premenstrual syndrome and major depression: results from a population-based sample.

Abstract: Research about the relationship between premenstrual syndrome (PMS) and major depression is limited. This study examined the relationship between moderate to severe PMS and major depression in a population-based sample of women of reproductive age. The objectives of the study were to assess the association between premenstrual syndrome and major depression, to analyse how PMS and major depression differ and to characterise the group of women who report both PMS and major depression. Data were obtained from the Swiss Health Survey 2007. Included in the analysis was data from women under the age of 55 without hysterectomy and who answered the questions on PMS symptoms. The population-based sample consisted of 3518 women. Weighted prevalence rates were calculated and relative risk ratios for PMS, major depression and women who reported both PMS and major depression, were calculated with logistic multinominal logit regression. The prevalence of major depression was 11.3% in women screening positive for moderate PMS and 24.6% in women screening positive for severe PMS. Compared to women without any of these conditions, women who reported moderate to severe alcohol consumption had a lower risk for PMS. Women reporting use of antidepressants, and use of oral contraceptives had a higher risk for major depression compared to women without any of these conditions. Women reporting work dissatisfaction had a higher risk for PMS. A higher relative risk to report both PMS and major depression compared to women without PMS or major depression was related to factors such as high psychological distress, low mastery, psychotropic drug consumption, and low self-rated health. The results suggested that women who suffer from both PMS and major depression are more impaired compared to women with only one disorder. The results further indicated that PMS and major depression are different disorders that can, however, co-occur.

Adverse drug reaction monitoring in psychiatry out-patient department of an Indian teaching hospital.

Abstract: Objectives : Adverse drug reactions (ADRs) to psychotropic agents are common and can lead to noncompliance or even discontinuation of therapy. There is paucity of such data in the Indian context. We deemed it worthwhile to assess the suspected ADR profile of psychotropic drugs in an ambulatory setting in a public teaching hospital in Kolkata. Materials and Methods : A longitudinal observational study was conducted in the outpatient department (OPD) of the concerned psychiatry unit. Twenty consecutive patients per day, irrespective of their psychiatric diagnosis, were screened for suspected ADRs, 2 days in a week, over 15 months. Adverse event history, medication history and other relevant details were captured in a format as adopted in the Indian National Pharmacovigilance Programme. Causality was assessed by criteria of World Health Organization-Uppsala Monitoring Center (WHO-UPC). Results : We screened 2000 patients (68.69% males, median age 34.4 years), of whom 429 were suspected of having at least one ADR; 84 cases had insufficient evidence about causality (WHO-UMC causality status unlikely) and were excluded from further analysis. Thus, 17.25% (95% confidence interval: 15.59-18.91%) of our study population reported ADRs with at least possible causality. Of 352 events recorded, 327 (92.90%) were probable and the rest possible. None was labeled certain as rechallenge was not performed. Patients received a median of 3.2 psychotropic drugs each. Thirty-three different kinds of ADRs were noted, including tremor (19.60%), weight gain (15.34%) and constipation (14.49%). Among the incriminated drugs, antipsychotics represented the majority (57.10%), with olanzapine topping the list. Conclusions : This study offers a representative profile of ADRs to be expected in psychiatry out-patients in an Indian public hospital. Establishment of a psychotropic drug ADR database can be a worthy long-term goal in the Indian context.

Zebrafish neurobehavioral protocols

Abstract: 1. Video-Aided Analysis of Zebrafish Locomotion and Anxiety-Related Behavioral Responses Jonathan M. Cachat, Peter R. Canavello, Salem I. Elkhayat, Brett K. Bartels, Peter C. Hart, Marco F. Elegante, Esther C. Beeson, Autumn L. Laffoon, Whitlee A.M. Haymore, David H. Tien, Anna K. Tien, Sopan Mohnot, and Allan V. Kalueff 2. Videograms: A Method for Repeatable Unbiased Quantitative Behavioral Analysis Without Scoring or Tracking Russell C. Wyeth, Oliver R. Braubach, Alan Fine, and Roger P. Croll 3. Automated Imaging of Avoidance Behavior in Larval Zebrafish Ruth M. Colwill and Robbert Creton 4. Quantifying Anti-Predator Responses to Chemical Alarm Cues Brian D. Wisenden 5. Modified Associative Learning T-Maze Test for Zebrafish (Danio rerio) and Other Small Teleost Fish Georgianna G. Gould 6. Zebrafish Conditioned Place Preference Models of Drug Reinforcement and Relapse to Drug Seeking Amit Parmar, Miral Parmar, and Caroline H. Brennan 7. A Simple and Effective Method to Condition Olfactory Behaviors in Groups of Zebrafish Oliver R. Braubach, Russell C. Wyeth, Andrew Murray, Alan Fine, and Roger P. Croll 8. Aquatic Light/Dark Plus Maze Novel Environment for Assessing Anxious Vs. Exploratory Behavior in Zebrafish (Danio rerio) and Other Small Teleost Fish Georgianna G. Gould 9. A Novel Test Battery to Assess Drug-Induced Changes in Zebrafish Social Behavior David J. Echevarria, Christine Buske, Christina N. Toms, and David J. Jouandot 10. Measuring Agonistic Behavior in Zebrafish Henning Schneider 11. Measuring Endocrine (Cortisol) Responses of Zebrafish to Stress Peter R. Canavello, Jonathan M. Cachat, Esther C. Beeson, Autumn L. Laffoon, Chelsea Grimes, Whitlee A.M. Haymore, Marco F. Elegante, Brett K. Bartels, Peter C. Hart, Salem I. Elkhayat, David H. Tien, Sopan Mohnot, Hakima Amri, and Allan V. Kalueff 12. Phenotyping of Zebrafish Homebase Behaviors in Novelty-Based Tests Adam Stewart, Jonathan M. Cachat, Keith Wong, Nadine Wu, Leah Grossman, Christopher Suciu, Jason Goodspeed, Marco F. Elegante, Brett K. Bartels, Salem I. Elkhayat, David H. Tien, Siddharth Gaikwad, Ferdous Kadri, Kyung Min Chung, Julia Tan, Ashley Denmark, Thomas Gilder, John DiLeo, Katie Chang, Kevin Frank, Eli Utterback, Patrick Viviano, and Allan V. Kalueff 13. Neurophenotyping of Adult Zebrafish Using the Light/Dark Box Paradigm Adam Stewart, Caio Maximino, Thiago Marques de Brito, Anderson Manoel Herculano, Amauri Gouveia Jr., Silvio Morato, Jonathan M. Cachat, Siddharth Gaikwad, Marco F. Elegante, Peter C. Hart, and Allan V. Kalueff 14. Intraperitoneal Injection as a Method of Psychotropic Drug Delivery in Adult Zebrafish Adam Stewart, Jonathan M. Cachat, Christopher Suciu, Siddharth Gaikwad, Eli Utterback, John DiLeo, and Allan V. Kalueff 15. Assessing the Maximum Predictive Validity for Neuropharmacological Anxiety Screening Assays Using Zebrafish Amanda Linker, Adam Stewart, Siddharth Gaikwad, Jonathan M. Cachat, Marco F. Elegante, Allan V. Kalueff, and Jason E. Warnick 16. Deconstructing Adult Zebrafish Behavior with Swim Trace Visualizations Jonathan M. Cachat, Adam Stewart, Eli Utterback, Siddharth Gaikwad, Molly Hook, Kathryn Rhymes, and Allan V. Kalueff

Behavioral Genetics of Affective and Anxiety Disorders

Abstract: As shown by clinical genetic studies, affective and anxiety disorders are complex genetic disorders with genetic and environmental factors interactively determining their respective pathomechanism. Advances in molecular genetic techniques including linkage studies, association studies, and genome-wide association studies allow for the detailed dissection of the genetic influence on the development of these disorders. Besides the molecular genetic investigation of categorical entities according to standardized diagnostic criteria, intermediate phenotypes comprising neurobiological or neuropsychological traits (e.g., neuronal correlates of emotional processing) that are linked to the disease of interest and that are heritable, have been proposed to be closer to the underlying genotype than the overall disease phenotype. These intermediate phenotypes are dimensional and more precisely defined than the categorical disease phenotype, and therefore have attracted much interest in the genetic investigation of affective and anxiety disorders. Given the complex genetic nature of affective and anxiety disorders with an interaction of multiple risk genes and environmental influences, the interplay of genetic factors with environmental factors is investigated by means of gene-environment interaction (GxE) studies. Pharmacogenetic studies aid in the dissection of the genetically influenced heterogeneity of psychotropic drug response and may contribute to the development of a more individualized treatment of affective and anxiety disorders. Finally, there is some evidence for genetic factors potentially shared between affective and anxiety disorders pointing to a possible overlapping phenotype between anxiety disorders and depression.

One-year prospective follow-up of pharmacological treatment in children with attention-deficit/hyperactivity disorder

Abstract: To delineate the safety and tolerability profile of methylphenidate and atomoxetine in children and adolescents with attention deficit hyperactivity disorder (ADHD) monitored for more than 1 year. A cohort study analyzing data from the national ADHD register on patients from the Lombardy Region treated with MPH or atomoxetine. A total of 229 children (median age 11 years, range 6–17), enrolled in 15 regional centers between June 2007 and May 2010. The prevalence rate of pharmacological treatment for ADHD was 0.23%, whereas the estimated ADHD prevalence in the population was 0.95%. In total, 73.8% of patients had been treated with atomoxetine (10–90 mg daily) or MPH (10–75 mg daily); 22% of patients also received an additional psychotropic drug. Of the treated children, 26.9% discontinued the drug prior to 1 year of treatment, mostly because of adverse effects (28.6%). No new or unexpected adverse events (rate 39.2%) were encountered. Decreased appetite, headache, and unstable mood were the leading events. The most severe events occurred in two boys: one experienced absence seizures for the first time with MPH, the other experienced hallucinations with atomoxetine. Therapy was discontinued in ten male patients (7.7%) because of adverse events. All patients with adverse effects recovered well. A very low rate of ADHD prevalence was estimated in Italian children compared to that reported in other countries. Although the medications for ADHD are generally well tolerated, with only mild or minor adverse effects in most cases, their rational use can only be guaranteed by disseminating and monitoring evidence-based practices and by monitoring the safety and efficacy of treatments in both the short and long terms with appropriate tools and approaches.

Childhood Under Siege: How Big Business Targets Children

Abstract: This book is a shocking venture behind the scenes of the widespread manipulation of children by profit-seeking corporations – and of society’s failure to protect them.Childhood Under Siege reveals big business’s discovery of a new resource to be mined for profit – our children. A journey through a world of unabashed exploitation, clued-out parents, and governments that look the other way, it tells the chilling and at times darkly humorous story of business’s plans to turn kids into obsessive and narcissistic mini-consumers, media addicts, cheap and pliable workers, and chemical industry guinea pigs. Not to mention pharmaceutical pill poppers – psychotropic drug consumption by children has increased fivefold since 1980.It’s a winner-takes-all battle for children’s hearts, minds and bodies as corporations pump billions into rendering parents and governments powerless to protect children from their calculated commercial assault and its disturbing toll on their health and well-being.

Neurochemical effects of buspirone, a novel psychotropic drug, on the central cholinergic system

Abstract: Buspirone, a novel psychotropic anxioselective agent, produced a dose-dependent decrease in the level of acetylcholine in the striatum of the rat. The maximum effect of about 25-30% was produced at the dose of 20 mg kg-1. A smaller decrease of 10% was also found in the n. accumbens-olfactory tubercle while other brain regions were unaffected. The drug did not alter striatal choline acetyltransferase or acetylcholinesterase activities and was feeble in displacing [3H]dexetimide from its specific muscarinic binding sites. The effect of buspirone in lowering acetylcholine content was more marked and longer lasting in the striatum of female than male rats. Buspirone proved to be weak as a blocker of the dopamine receptor agonist, apomorphine, and it appears that only a small proportion of the decrease in striatal acetylcholine content can be attributed to the blockade of dopamine receptors. Rapid homologous tolerance to an acute challenge with buspirone on striatal acetylcholine was achieved within seven days of its chronic administration, and, unlike clozapine, a cross tolerance of buspirone to chronic haloperidol treatment was also observed. Other data indicating that the drug differed from haloperidol both qualitatively and quantitatively on dopaminergic neurochemical parameters, and the fact that it is not cataleptogenic, suggest that buspirone cannot be considered a typical neuroleptic agent. The possibility that buspirone may act as an agonist at certain presynaptic dopamine receptors, which could translate into a fall in striatal acetylcholine content, is discussed.

Lipogenic effects of psychotropic drugs: focus on the SREBP system.

Abstract: Antipsychotics, antidepressants and mood stabilizers are psychotropic drugs widely used in the treatment of psychiatric disorders, such as schizophrenia, bipolar disorder and major depressive disorder. Such drugs have been used since the early 1950s, and it is now well established that they target neurotransmitter receptors and/or transporters located on central nervous system (CNS) neurons. However, their mechanism of action is still not fully understood, and there is large inter-individual variation in therapeutic response. Psychotropic drugs are also associated with numerous adverse effects, of which weight gain and metabolic disturbances have gained increased focus during the last decade. Based on studies in cultured cells, we have demonstrated that several psychotropic drugs upregulate the expression of genes involved in cellular fatty acid and cholesterol biosynthesis, controlled by the SREBP transcription factors. Lipogenic effects were also observed in vivo, in rat liver and in lymphocytes from drug-treated patients. These results provide new insight into the molecular mechanisms of psychotropic drug action and could be relevant both for their therapeutic action and metabolic adverse effects.

Sedative Load among Community-Dwelling People Aged 75 Years and Older: A Population-Based Study

Abstract: Background: Drugs with sedative properties are among the most widely used drugs in community-dwelling older people. Use of sedative drugs has been associated with falls and fractures, cognitive and memory impairment and impaired physical function among older people. The sedative load model has been developed to quantify the cumulative effect of taking multiple drugs with sedative properties. Objective: The objective of the study was to investigate factors associated with sedative load among community-dwelling older people, using data collected as part of the Finnish Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (GeMS) study. Methods: The GeMS study was a randomized, comparative study that evaluated a model for geriatric assessment, care and rehabilitation using a study sample of 1000 persons aged ≥75 years who were living in Kuopio, Finland. Of these, 700 people consented to participate and were community-dwelling. Demographic, diagnostic and drug use data (both regular and when-required drugs) were elicited during nurse interviews. For the current analysis, sedative load was computed using a previously published model, in which drugs taken on a regular and when-required basis were classified into one of four groups according to their sedative potential. Group 1 included primary sedatives (sedative rating 2) and group 2 included drugs with sedation as a prominent side effect (sedative rating 1). Each participant’s sedative load was calculated by summing the sedative ratings of group 1 and 2 drugs. Logistic regression models were used to investigate factors associated with sedative load. Results: Twenty-nine percent of participants (n = 205) had a sedative load of ≥1 (i.e. used one or more drugs with sedative properties), and 22% (n = 158) had a sedative load of ≥2 (i.e. used either one primary sedative or two drugs with sedation as a prominent adverse effect or preparations with a sedating component) when considering regularly used drugs. A sedative load of ≥2 that related to regularly used drugs was associated with female sex (odds ratio [OR] 1.65; 95% CI 1.02, 2.67), poor self-perceived health (OR 2.06; 95% CI 1.25, 3.38), impaired instrumental activities of daily living [IADL] (OR 1.89; 95% CI 1.18, 3.01) and often feeling lonely (OR 4.72; 95% CI 2.15, 10.40). The same factors remained significantly associated with a sedative load of ≥2 after drugs used on a when-required basis were included in the analyses. Conclusions: The advantages of the sedative load model were that it included drugs with sedative properties prescribed for somatic diseases, described cumulative exposure to drugs that exert sedative effects through multiple mechanisms in the CNS, and incorporated a sedative rating for each drug. In an older population, female sex, impaired IADL, poor self-perceived health, and loneliness were associated with higher sedative load. Clinicians should remain cognizant of these factors when reviewing drug regimens and targeting interventions to optimize sedative use.

Genomics and pharmacogenomics of schizophrenia.

Abstract: Schizophrenia (SCZ) is among the most disabling of mental disorders. Several neurobiological hypotheses have been postulated as responsible for SCZ pathogenesis: polygenic/multifactorial genomic defects, intrauterine and perinatal environment-genome interactions, neurodevelopmental defects, dopaminergic, cholinergic, serotonergic, gamma-aminobutiric acid (GABAergic), neuropeptidergic and glutamatergic/N-Methyl-D-Aspartate (NMDA) dysfunctions, seasonal infection, neuroimmune dysfunction, and epigenetic dysregulation. SCZ has a heritability estimated at 60-90%. Genetic studies in SCZ have revealed the presence of chromosome anomalies, copy number variants, multiple single-nucleotide polymorphisms of susceptibility distributed across the human genome, aberrant single nucleotide polymorphisms (SNPs) in microRNA genes, mitochondrial DNA mutations, and epigenetic phenomena. Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variation in specific candidate genes and the positive and adverse effects of drug treatment. Approximately, 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are major substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are major substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. About 10-20% of Western populations are defective in genes of the CYP superfamily. Only 26% of Southern Europeans are pure extensive metabolizers for the trigenic cluster integrated by the CYP2D6+CYP2C19+CYP2C9 genes. The pharmacogenomic response of SCZ patients to conventional psychotropic drugs also depends on genetic variants associated with SCZ-related genes. Consequently, the incorporation of pharmacogenomic procedures both to drugs in development and drugs on the market would help to optimize therapeutics in SCZ and other central nervous system (CNS) disorders.

Organisational merger and psychiatric morbidity: a prospective study in a changing work organisation

Abstract: Background Prospective studies on the relationship between organisational merger and mental health have been conducted using subjective health indicators. The objective of this prospective occupational cohort study was to examine whether a negative change during an organisational merger is an independent predictive factor of psychiatric morbidity. Method Survey data on organisational characteristics, health and other factors were collected prior to (1996) and after the merger (2000); register data on psychiatric morbidity were collected at baseline (1/1/1994–30/9/2000) and during the follow-up (1/10/2000–31/12/2005). Participants were 6511 (77% men) industrial employees aged 21–65 years with no register-based diagnosed psychiatric events prior to the follow-up (the Still Working Study). During the follow-up, 252 participants were admitted to the hospital due to psychiatric disorders, were prescribed a psychotropic drug or attempted or committed suicide. Results A negative self-reported change in the work organisation during the merger was associated with increased risk of postmerger psychiatric event (HR 1.60, 95% CI 1.19 to 2.14). This association was independent of mental health-related factors measured before the merger announcement, such as demographic characteristics, occupational status, personal orientation to life, self-rated health, self-reported psychiatric morbidity or chronic disease. Conclusion A negative change in work organisation during an organisational merger may elevate the risk for postmerger psychiatric morbidity.

Pattern of psychotropic drug use among older adults having a depression or an anxiety disorder: results from the longitudinal ESA study.

Abstract: Objective:To document the use of psychotropic drugs in Quebec older adult population with a depressive or anxiety disorder.Method:Data from the Enquete sur la Sante des Aines (ESA) study conducted ...

Intraperitoneal Injection as a Method of Psychotropic Drug Delivery in Adult Zebrafish

Abstract: Zebrafish behavioral phenotypes are often evaluated in response to pharmacological modulation by various psychotropic drugs. An important step in this process is the method of drug administration. While the most popular drug administration technique in zebrafish research is by immersion, systemic intraperitoneal injection is another effective alternative. This method is useful for drugs that are difficult to dissolve in water, or which require a better control over the amount of drug delivered to an individual animal. Here we outline a simple protocol for the intraperitoneal injection of drugs in adult zebrafish.

Sub-threshold depression and antidepressants use in a community sample: searching anxiety and finding bipolar disorder.

Abstract: To determine the use of antidepressants (ADs) in people with sub-threshold depression (SD); the lifetime prevalence of mania and hypomania in SD and the link between ADs use, bipolarity and anxiety disorders in SD. Study design: community survey. Study population: samples randomly drawn, after stratification from the adult population of municipal records. Sample size: 4999 people from seven areas within six Italian regions. Tools: Questionnaire on psychotropic drug consumption, prescription; Structured Clinical Interview NP for DSM-IV modified (ANTAS); Hamilton Depression Rating Scale (HAM-D); Mood Disorder Questionnaire (MDQ); Short Form Health Survey (SF-12). SD definition: HAM-D > 10 without lifetime diagnosis of Depressive Episode (DE). SD point prevalence is 5.0%. The lifetime prevalence of mania and hypomania episodes in SD is 7.3%. Benzodiazepines (BDZ) consumption in SD is 24.1%, followed by ADs (19.7%). In SD, positive for MDQ and comorbidity with Panic Disorder (PD) or Generalized Anxiety Disorders (GAD) are associated with ADs use, whereas the association between a positive MDQ and ADs use, without a diagnosis of PD or GAD, is not significant. Only in people with DE the well-being (SF-12) is higher among those using first-line antidepressants compared to those not using any medication. In people with SD no significant differences were found in terms of SF-12 score according to drug use. This study suggests caution in prescribing ADs to people with SD. In people with concomitant anxiety disorders and SD, it should be mandatory to perform a well-designed assessment and evaluate the presence of previous manic or hypomanic symptoms prior to prescribing ADs.

Psychotropic drug competition for [3H]imipramine binding further indicates the presence of only one high‐affinity drug binding site on human α1‐acid glycoprotein

Abstract: The role of orl-acid glycoprotein (q-AGP) as a high affinity, but low capacity, binding component in human plasma was recognized only a few years ago and al-AGP has since received increasing attention from clinical pharmacologists as a parameter of the pharmacokinetics of many basic drugs (De Leve & Piafsky 1981: Piafsky 1980). In attempts to characterize molecular aspects of the interaction of drugs with this protein only one high-affinity binding site has been reported for nearly all drugs so far investigated, e.g. for dipyridamole (El-Gamal et al 1982), perazine (Brinkschulte & Breyer-Pfaff 1980; Schley et a1 1980), chlorpromazine (El-Gamal et a1 1983), imipramine (Kornguth et a1 1981), thioridazine (Nyberg & Martensson 1982), quinidine (Fremstad et al 1976), disopyramide (Lima et al 1981); propranolol (Glasson et al 1980; Sager et a1 1979), pindolol and other @-blockers (Lemaire & Tillement 1982) nicergolin (Robert et a1 1983), methadone (Abramson 1982), and even some acidic drugs like warfarin and phenylbutazone (Urien et al 1982). Moreover, during some of these studies mutual displacement reactions have been observed for some Of these drugs. All these findings are in agreement with our recent conclusion about the presence of only one single drug binding site at the arl-AGP molecule which is common for nearly all drugs investigated so far (Miiller & Stillbauer 1983). This conclusion is further substantiated by the data reported herein indicating that this site is also important for the binding of several tricyclic antidepressants as well as for a variety of other psychotropic drugs.

Antidepressant and antipsychotic use in an Italian pediatric population.

Abstract: The safety and effectiveness of psychotropic drug use in the paediatric population is widely debated, in particular because of the lack of data concerning long term effects. In Italy the prevalence of psychotropic drug prescriptions increased in the early 2000s and decreased afterwards. In such a context, a study with the aim to estimate the incidence and prevalence of psychotropic drug prescription in the paediatric population and to describe diagnostic and therapeutic approaches was performed. The study population was composed of 76,000 youths less than 18 years and living in the area covered by the local health unit of Verona, Italy. The data source was the Verona local health unit's administrative prescription database. Prevalence and incidence of antidepressant and/or antipsychotic drug prescriptions in the 2004-2008 period were estimated. Children and adolescents receiving antidepressant and/or antipsychotic drug prescriptions between 1 January 2005 and 31 December 2006 were identified and questionnaires were sent to the prescribers with the aim to collect data concerning diagnostic and therapeutic approaches, and care strategies. The prevalence of psychotropic drug prescriptions did not change in the 2004-2008 period, while incidence slightly increased (from 7.0 in 2005 to 8.3 per 10,000 in 2008). Between 1 January 2005 and 31 December 2006, 111 youths received at least one psychotropic drug prescription, 91 of whom received antidepressants. Only 28 patients attended child and adolescent psychiatry services. Information concerning diagnostic and therapeutic approaches, and care strategies was collected for 52 patients (47%). Anxiety-depressive syndrome and attention disorders were the diseases for which psychotropic drugs were most commonly prescribed. In all, 75% youths also received psychological support and 20% were prescribed drugs for 2 or more years. Despite the low drug prescription prevalence, the finding that most children were not cared for by child and adolescent psychiatric services is of concern and calls for a systematic, continuous monitoring of psychopharmacological treatments.

Pharmacoepidemiological characterization of psychotropic drugs consumption using a latent class analysis.

Abstract: France has one of the highest recorded rates of psychotropic use of drugs compared with other European countries, especially for anxiolytics, hypnotics and antidepressants. The aim of this study was to characterize the use of three psychotropic drugs among the most prescribed in France (bromazepam, paroxetine, zolpidem) using reimbursement databases in real-life conditions. Individuals from a region affiliated to the French General Health Insurance Scheme, who had received at least two dispensings of bromazepam, paroxetine or zolpidem reimbursed between 1 January and 30 June 2008, were included. We used a latent class analysis to identify different subgroups of users for these three psychotropic drugs. A total of 40,644 patients were included for bromazepam, 36,264 for zolpidem and 31,235 for paroxetine. Using latent class analysis, four clinical subtypes of users of bromazepam and zolpidem were identified: nonproblematic users, at-risk users, users with a probable mental disorder and compulsive users. Three subgroups were identified for paroxetine that differed rather by the prescription patterns. Users of anxiolytics and hypnotics with at-risk behaviours represented a significant proportion in the studied population. This original method could be extended to other prescription databases to identify populations at risk of abuse or dependence to psychotropic drugs.