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International audience ; Recent studies analysing the trends in antipsychotic (AP) prescriptions for children and adolescents have raised concerns regarding the influence of socioeconomic status. Previous findings have also shown variable prescription rates for first-generation (FG) and second-generation (SG) APs. Method Our objectives were to assess the proportion of patients from low-income families receiving APs and the most commonly prescribed APs in France. We conducted a descriptive analysis of AP drugs dispensed during a 1-year period (July 1, 2013–June 30, 2014) in a northwestern region of France with 941,857 subjects less than 18 years old. All data were extracted from an exhaustive, individual and anonymous social security database. We obtained each subject's socioeconomic status (by identifying their affiliation with a specific social security program) and also collected sociodemographic data, drug type, prescribing and dispensing dates and amount, and prescriber type (e.g., hospital physician, general practitioner, psychiatrist, paediatrician). Results There were two main novel findings. First, we found that the proportion of patients with AP prescriptions was nearly ten times higher in low-income families than in the general population: 35.9% of CMU-C patients compared to 3.7% in all of Pays de la Loire (X 2 = 7875.1, p < 0.001). Additionally, we found a higher rate of FGAP than SGAP prescriptions (65% vs. 57%). Conclusions Our study suggests two types of AP misuse that could provide interesting targets for public healthcare interventions. First, our results strongly suggest an over-representation of patients from low-income families. Low-income families primarily resided in areas with low physician density and appeared to receive drugs to treat their conditions more frequently than other individuals. This increased prescription rate is a public health issue, potentially requiring political action. Second, the use of FGAPs did not adhere to the latest recommendations for drug use in this ...

International audience ; Recent studies analysing the trends in antipsychotic (AP) prescriptions for children and adolescents have raised concerns regarding the influence of socioeconomic status. Previous findings have also shown variable prescription rates for first-generation (FG) and second-generation (SG) APs. Method Our objectives were to assess the proportion of patients from low-income families receiving APs and the most commonly prescribed APs in France. We conducted a descriptive analysis of AP drugs dispensed during a 1-year period (July 1, 2013–June 30, 2014) in a northwestern region of France with 941,857 subjects less than 18 years old. All data were extracted from an exhaustive, individual and anonymous social security database. We obtained each subject's socioeconomic status (by identifying their affiliation with a specific social security program) and also collected sociodemographic data, drug type, prescribing and dispensing dates and amount, and prescriber type (e.g., hospital physician, general practitioner, psychiatrist, paediatrician). Results There were two main novel findings. First, we found that the proportion of patients with AP prescriptions was nearly ten times higher in low-income families than in the general population: 35.9% of CMU-C patients compared to 3.7% in all of Pays de la Loire (X 2 = 7875.1, p < 0.001). Additionally, we found a higher rate of FGAP than SGAP prescriptions (65% vs. 57%). Conclusions Our study suggests two types of AP misuse that could provide interesting targets for public healthcare interventions. First, our results strongly suggest an over-representation of patients from low-income families. Low-income families primarily resided in areas with low physician density and appeared to receive drugs to treat their conditions more frequently than other individuals. This increased prescription rate is a public health issue, potentially requiring political action. Second, the use of FGAPs did not adhere to the latest recommendations for drug use in this ...

OBJECTIVE: Partial compliance with antipsychotic medication increases relapse and rehospitalization rates in patients with schizophrenia. The aim of the present study was to assess the frequency of and factors contributing to partial compliance. METHOD: During a 10 day period in June 2004 psychiatrists working in hospitals or in private practices in Germany were asked to participate in a compliance survey. Physicians were requested to evaluate the compliance in 10 patients with schizophrenia using a questionnaire consisting of 10 questions. The frequency of unintentional and intentional partial compliance as well as patient-related contributing factors were assessed. Unintentional partial compliance was defined as the lack of drug intake on any day during the past month. Demographic data of participants were collected. Responses were analysed using descriptive statistics and generalized estimation equation models. RESULTS: The psychiatrists (n=699) regarded 68% of the evaluated patients (n=5729) as unintentionally partially compliant within the last month. Sixty-nine per cent of the patients were considered intentionally partially compliant in the past. The most frequently assessed patient-related factors contributing to the partial compliance were lack of insight into the need for prophylactic medication (68%), lack of insight/denial of illness (66%/63%), feeling embarrassed at taking medication every day (62%), needing someone to remind them to take their medication (62%), cognitive problems (55%), and living conditions inappropriate for compliance (46%). CONCLUSIONS: Partial compliance is a common problem in schizophrenia. Strategies to improve partial compliance derived from the contributing factors identified in the present study may include regular telephone reminders by case managers or families, adequate support in the patients' environment, use of dosette boxes, rationalizing drug regimens (e.g. once-daily dosage, monotherapy, depot medication), and psychoeducation.

PharmD ; Risperidone and aripiprazole (RiAr) are the only approved drugs by the FDA for the treatment of irritability associated with Autism Spectrum Disorder (ASD) in children and adolescents. The regulatory bodies in Europe (European Medicines Agency) and India (The Central Drugs Standard Control Organization) have not approved the drugs for the indication of ASD. Cultural, economic and regulatory variations may impact the approach towards the treatment of ASD in India and Malta. The objectives of the research are to 1) develop and administer a questionnaire to psychiatrists in India and Malta 2) evaluate and compare the accessibility and affordability of RiAr and 3) detect adverse drug reactions (ADRs) not listed in the approved Summary of Product Characteristics (SmPC) in children and adolescents treated with RiAr for ASD through Eudravigilance. The methodology included 1) a questionnaire, entitled ASD-Q (IND-MT) which was developed, validated (by 10 experts) and disseminated to psychiatrists (N=47) in India (n=31) and Malta (n=16). ASD-Q(IND-MT) consisted of 6 sections and 28 close ended Likert scale questions ranging from 1 (strongly disagree) to 5 (strongly agree) and gathered opinions on the perception of ASD, influence of culturally developed screening tools, Childhood Autism Rating Scale (CARS) in Malta and the Indian Scale of Assessment (ISAA) in India, prescribing behaviour of RiAr and role of pharmacists in managing ASD, 2) a comparison of the price of RiAr against the Monthly Per Capita Expenditure (MPCE) in India and Malta to obtain an indication of the affordability of the treatment, 3) Eudravigilance signal detection and French causality assessment was carried out and ADRs received duringNovember 2001 to September 2017 were extracted in the age group 6-17 years (risperidone) and 5-16 years (aripiprazole). Statistical analysis of the ASD-Q (IND-MT) indicated a significant difference (p<0.05) between the prescribing behaviour of RiAr. A significant difference (p=0.040) was noted between the psychiatrists when asked about the interpretation of the screening tools (ISAA/CARS) score. Thirteen Indian psychiatrists out of 31 and 2 Maltese psychiatrists out of 16 agreed that they prescribe RiAr to patients with mild to moderate autism. Eighteen Indian psychiatrists out of 31 and 14 Maltese psychiatrists out of 16 agreed that they would prescribe antipsychotics to patients who have severe autism. A statistically significant difference (p<0.001) is noted between psychiatrists when asked about the influence of screening tools (ISAA/CARS) on the prescribing behaviour of antipsychotics. The Likert mean score was 4.45±0.506 by Indian psychiatrists and 2.56±1.153 by Maltese psychiatrists indicating higher agreement by the Indian psychiatrists. The Cost analysis of RiAr revealed that RiAr would cost €3.5 and €3.9 in India and €26.7 and €28.8 in Malta monthly. The percentage of MPCE required for one month of treatment with RiAr is 11.30% and 12.60% in India and 3.30% and 3.56% in Malta respectively. Five ADR signals were assessed for risperidone and three signals for aripiprazole. The French causality assessment concluded "uncertain" or "unlikely" relation between the ADR signals and the drugs. Culturally developed screening tools have a different influence on the prescribing behaviour of drugs in India and Malta. The cost of medicines is low in India compared to Malta but the treatment is more affordable in Malta. The SmPC of RiAr includes all the ADRs indicated through the EudraVigilance signal detection in this study. ; N/A

Pu Zhi,1,* Yanqiong Wang,1,* Wei Quan,1,2 Yanli Su,1 Hui Zhang1 1Department of Psychiatry, Xi'an Mental Health Center, Institute of Mental Health, Xi'an Medical University, Xi'an, China; 2Department of Natural Medicine, Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an, China *These authors contributed equally to this work Abstract: Hyperprolactinemia is a common side effect of antipsychotic drugs. Although changes of antipsychotic drugs or reduction of their doses can solve this problem, a modification of the treatment regimen can lead to instability in patients. Herein, we followed up a patient with elevated prolactin caused by paliperidone and found that the prolactin level was decreased after the administration of a combination with a low-dose aripiprazole. In addition, we summarized and analyzed the findings from the case and the literature review conducted. Keywords: aripiprazole, schizophrenia, prolactin

Background  Concerns about the pharmacological management of the behaviour of individuals with intellectual disability have resulted in the development of legislative and procedural controls.Method  This Australian study provided a comparison of 873 reported cases where drugs were administered to manage behaviour in March 2000, with 762 cases reported in March 1993. Drug use in individuals who remained medicated across time (n = 316: recurrent sample) was also compared with those who were reported only in 1993 (n = 329: limited sample).Results  A small decrease in the proportion of individuals who were reported to have received medication was evident over time (from 5% to 4.5% of total population). However, this was accompanied by an increase in drug diversity and interclass polypharmacy. An increase in antidepressant use was evident (from 7.4% to 13.8% of reported drugs), and there was a trend towards greater reporting of medication for acute behavioural problems and medication use with children. Greater use of antipsychotic drugs was evident in individuals who remained medicated across time compared with those who did not.Conclusions  The findings suggest the need for continuous research into practice. The fact that many individuals receive medication over long periods makes it incumbent on service providers to engage in regular, comprehensive and individualized review and evaluation of medication regimes.

© 2015 Elsevier Ltd. 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen, acting as a non-selective serotonin 5-HT1A/5-HT2A-R agonist. Psychotomimetic agents such as the non-competitive NMDA-R antagonist phencyclidine and serotonergic hallucinogens (DOI and 5-MeO-DMT) disrupt cortical synchrony in the low frequency range (<4 Hz) in rat prefrontal cortex (PFC), an effect reversed by antipsychotic drugs. Here we extend these observations by examining the effect of 5-MeO-DMT on low frequency cortical oscillations (LFCO, <4 Hz) in PFC, visual (V1), somatosensory (S1) and auditory (Au1) cortices, as well as the dependence of these effects on 5-HT1A-R and 5-HT2A-R, using wild type (WT) and 5-HT2A-R knockout (KO2A) anesthetized mice. 5-MeO-DMT reduced LFCO in the PFC of WT and KO2A mice. The effect in KO2A mice was fully prevented by the 5-HT1A-R antagonist WAY-100635. Systemic and local 5-MeO-DMT reduced 5-HT release in PFC mainly via 5-HT1A-R. Moreover, 5-MeO-DMT reduced LFCO in S1, Au1 and V1 of WT mice and only in V1 of KO2A mice, suggesting the involvement of 5-HT1A-R activation in the 5-MeO-DMT-induced disruption of V1 activity. In addition, antipsychotic drugs reversed 5-MeO-DMT effects in WT mice. The present results suggest that the hallucinogen action of 5-MeO-DMT is mediated by simultaneous alterations of the activity of sensory (S1, Au1, V1) and associative (PFC) cortical areas, also supporting a role of 5-HT1A-R stimulation in V1 and PFC, in addition to the well-known action on 5-HT2A-R. Moreover, the reversal by antipsychotic drugs of 5-MeO-DMT effects adds to previous literature supporting the usefulness of the present model in antipsychotic drug development. ; This work was supported by grants from Instituto de Salud Carlos III (PI09/1245 (P.C.), PI12/00156 (P.C.) and PI13/01390 (A.B.) (PN de I+D+I 2008-2011, ISCIII-Subdirección General de Evaluación y Fomento de la Investigación cofinanced by the European Regional Development Fund. "Una manera de hacer Europa"), SAF 2012-35183 (Spanish Ministry of Economy and Competitiveness, co-financed by European Regional Development Fund (ERDF), Centro de Investigación Biomédica en Red de Salud Mental, (CIBERSAM P82, 11INT3) and the Innovative Medicines Initiative Joint Undertaking (IMI) under Grant Agreement N° 115008 (NEWMEDS). IMI is a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations. Support from the Generalitat de Catalunya (2014 SGR798) is also acknowledged. MR was supported by a IDIBAPS fellowship ; Peer Reviewed

Background Despite of its global underuse, clozapine is still the golden standard antipsychotic for patients with treatment-resistant schizophrenia (TRS). Objective To evaluate the patterns of clozapine and other antipsychotic drugs prescription in TRS in community mental health centers in São Paulo, Brazil. Methods A multiple-choice questionnaire was applied to fifteen psychiatrists at five centers inquiring about patients' clinical condition, adherence to oral treatment and current antipsychotic treatment. History of previous and current antipsychotic treatment was collected through medical chart review. Results Out of 442 schizophrenia patients, 103 (23.3%) fulfilled the criteria for TRS. Fifty-eight patients (56.3%) were receiving polypharmacy; 30 (29.1%) were on atypical antipsychotic monotherapy, 14 (13.6%) were on typical antipsychotic monotherapy, 25 (24.3%) were taking depot antipsychotic medication and only 22 (21.4%) were receiving clozapine. Discussion As well as in other parts of the world, many TRS patients (78.6%) receive other drugs instead of clozapine in São Paulo, the best evidence-based medication for patients with TRS. The government should make every effort to provide medical training and the equipment and logistic support to adequately serve those who could benefit from clozapine treatment at the community health centers.

Treatment resistant schizophrenia (TRS) is a severely disabling disorder, which decreases dramatically the quality of life and overall functionality, while it increases the rate of hospital admissions and overall healthcare costs. The main objective of this research was to evaluate the risk factors for TRS in a group of patients based on a retrospective analysis. The secondary objective was to design an algorithm for initial evaluation in patients with schizophrenia, in order to detect the candidates at risk for developing TRS. Medical charts and consultation records of all patients aged between 18 and 30, diagnosed with TRS, evaluated during 1-year in our department, were selected for analysis. The most significant risk factors for TRS found in univariate model were younger age at schizophrenia onset, male gender, living in rural areas, co-morbid drug dependence, lower therapeutic adherence, and premorbid personality disorder. Marginally significant were higher Positive and Negative Syndrome Scale (PANSS) scores at previous admissions, higher scores on PANSS negative symptoms sub-scale, and lower educational background. In the multivariate model, TRS was still significantly predicted.

Antipsychotic drugs are considered a critical component in the treatment of schizophrenia, one of the most debilitating mental illnesses. Social workers need sophisticated, up-to-date knowl edge about these medications to more fully embrace their roles as collaborators and consultants with clients, families, physicians, and other providers in the clinical arena. This article provides an overview of the efficacy of antipsychotic medications and a brief review of their common side effects and then details the current research and treatment practices with the so-called conven tional and atypical antipsychotics on the market or in development, as well as commonly used adjunctive and side-effect medications. The article concludes by discussing trends in psycho pharmacological research in schizophrenia of special relevance to social work

Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n = 25/condition), relative to typical controls (n = 100). This revealed alterations in the expression of these proteins that were specific to schizophrenia. Further characterization of metabolic alterations in an extended cohort of first-onset antipsychotic drug-naïve schizophrenia patients (n = 58) and controls (n = 63) revealed that the relationship between insulin receptor expression in monocytes and physiological insulin sensitivity was disrupted in schizophrenia and that altered expression of the insulin receptor was associated with whole genome polygenic risk scores for schizophrenia. Finally, longitudinal follow-up of the schizophrenia patients over the course of antipsychotic drug treatment revealed that peripheral metabolic markers predicted changes in psychopathology and the principal side effect of weight gain at clinically relevant time points. These findings suggest that peripheral blood cells can provide an accessible surrogate model for metabolic alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic complications following antipsychotic therapy. ; This work was supported by grants from the Stanley Medical Research Institute (SMRI); the Engineering and Physical Sciences Research Council UK (EPSRC); the Dutch Government-funded Virgo consortium (ref. FES0908); the Netherlands Genomics Initiative (ref. 050-060-452); the European Union FP7 funding scheme: Marie Curie Actions Industry Academia Partnerships and Pathways (ref. 286334, PSYCH-AID project); SAF2016-76046-R and SAF2013-46292-R (MINECO) and PI16/00156 (ISCIII and FEDER).

Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n = 25/condition), relative to typical controls (n = 100). This revealed alterations in the expression of these proteins that were specific to schizophrenia. Further characterization of metabolic alterations in an extended cohort of first-onset antipsychotic drug-naïve schizophrenia patients (n = 58) and controls (n = 63) revealed that the relationship between insulin receptor expression in monocytes and physiological insulin sensitivity was disrupted in schizophrenia and that altered expression of the insulin receptor was associated with whole genome polygenic risk scores for schizophrenia. Finally, longitudinal follow-up of the schizophrenia patients over the course of antipsychotic drug treatment revealed that peripheral metabolic markers predicted changes in psychopathology and the principal side effect of weight gain at clinically relevant time points. These findings suggest that peripheral blood cells can provide an accessible surrogate model for metabolic alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic complications following antipsychotic therapy. ; This work was supported by grants from the Stanley Medical Research Institute (SMRI); the Engineering and Physical Sciences Research Council UK (EPSRC); the Dutch Government-funded Virgo consortium (ref. FES0908); the Netherlands Genomics Initiative (ref. 050-060-452); the European Union FP7 funding scheme: Marie Curie Actions Industry Academia Partnerships and Pathways (ref. 286334, PSYCH-AID project); SAF2016-76046-R and SAF2013-46292-R (MINECO) and PI16/00156 (isciii and FEDER).

The right of an accused in a criminal trial to due process is, in essence, the right to a fair opportunity to defend against the State's accusations. Those who have experienced the full thrust of the power of government when leveled against them know that the only protection the citizen has is in the requirement for a fair trial. [I]nvoluntary medication with antipsychotic drugs poses a serious threat to a defendant's right to a fair trial. On July 24, 1998, Russell Weston shot and killed two police officers, and wounded a third, near a security checkpoint in the United States Capitol building. Reportedly, Weston's goal was to gain access to the "override console" of the "ruby satellite system," a time machine located in the "great safe of the U.S. Senate," so that he could prevent "cannibals" from taking over and spreading "black heva," a deadly plague. A federal prison psychiatrist diagnosed Weston as suffering from schizophrenia, and the D.C. District Court found him incompetent to stand trial. A person is competent to stand trial so long as he has "sufficient present ability to consult with his lawyer with a reasonable degree of rational understanding" and "a rational as well as factual understanding of the proceedings against him." This competency requirement is based on the recognition that in an adversary system of justice, it is unfair to convict someone who is unable to defend himself. Although treatment with psychotropic medications? can sometimes render an in- competent detainee competent,' Weston refused to take these medications voluntarily. For more than three years, the federal courts in the District of Columbia struggled with the question of whether Weston could be compelled to take psychotropic medications involuntarily.

Meiling Lu,1,* Jinghua Li,1,* Zaili Luo,2,3,* Shuai Zhang,3 Shaobo Xue,1 Kesheng Wang,1 Yan Shi,4 Cunzhen Zhang,3 Haiyang Chen,3 Zhong Li1,5 1Central Laboratory, The 10th People's Hospital, Tongji University, Shanghai, People's Republic of China; 2International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, Shanghai, People's Republic of China; 3Institution of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China; 4Department of Gastroenterology, The 10th People's Hospital, Tongji University, Shanghai, People's Republic of China; 5Zhangjiang Center for Translational Medicine, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: Tumor metastasis is the most common cause of death and poor prognosis for cancer patients. Therapeutics that prevent tumor metastasis are the key to prolonging the lifespan of cancer patients. Cancer stem cells are believed to be critical in the metastatic process. Recently, drug screening for cancer stem cells reports that antipsychotic drugs displayed potential anticancer activity. Thioridazine, one of the antipsychotic drugs for dopamine receptors (DRs), is shown to induce the differentiation of cancer stem cells in leukemic disease and breast cancer, but it is not known if this drug would affect liver cancer. In this study, expression of DR5 was higher in tumors than in nontumor adjacent tissues, while DR1 was lower in human hepatocellular carcinoma (HCC) than those in the adjacent tissues. Other DRs were very low or undetectable. Treatment of HCC cells with thioridazine displays a dose-dependent response in HCC cell lines SNU449, LM3, and Huh7. Thioridazine treatment reduced cell viability and sphere formation of HCC cell lines through induction of G0/G1 cell cycle arrest and suppression of stemness genes CD133, OCT4, and EpCam. It also inhibited cell migration via suppression of epithelial–mesenchymal transition (EMT)-related genes such as twist2 and E-cadherin. Thioridazine-pretreated LM3 cells decreased the capacity of tumorigenesis in nude mice. Taken together, our data suggest that thioridazine may have the potential role in treatment of HCC. Keywords: antipsychotic, thioridazine, HCC, dopamine receptors, metastasis

This paper reviews history of new drug development in Korea as well as researchs on development of new psychotherapeutic drug from traditional medicines or natural products in Korea. Korea has a long history of traditional medicine and accumulated knowledge of natural resources. However, only a few new drug have been developed from those natural products. Now many researchers in Korea are devoting themselves to test the possibility of natural products as antipsychotic drugs, antidepressants, anxiolytic drugs and cognitive enhancers. However, only a few graduates from traditional medical schools in Korea are engaging in research on developing new drug from natural products and they are not familiar to research methods of western medicine and pharmacology. For research and development of new drug from natural products or traditional medicines, many researchers should be trained for methodology of basic medicine, pharmacology, pharmacognosy, and oriential pharmacy. Government and pharmaceutical companies need to provide more investment for R & D for new drug from natural products including establishment of data base for component of traditional medicines and natural products, system development integrating information technology, bio-technology and nanotechnology, and international collaboration with advanced countries which have common interest in new drug development from natural products. ; open