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Non-competitive NMDA receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to evoke the symptoms of the illness. Likewise, serotonergic hallucinogens, acting on 5-HT2A receptors, induce perceptual and behavioural alterations possibly related to psychotic symptoms. The neurobiological basis of these alterations is not fully elucidated. Data obtained in recent years revealed that the NMDA receptor antagonist phencyclidine (PCP) and the serotonergic hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane; DOI) produce a series of common actions in rodent prefrontal cortex (PFC) that may underlie psychotomimetic effects. Hence, both agents markedly disrupt PFC function by altering pyramidal neuron discharge (with an overall increase) and reducing the power of low frequency cortical oscillations (LFCO; < 4 Hz). In parallel, PCP increased c-fos expression in excitatory neurons of various cortical areas, the thalamus and other subcortical structures, such as the amygdala. Electrophysiological studies revealed that PCP altered similarly the function of the centromedial and mediodorsal nuclei of the thalamus, reciprocally connected with PFC, suggesting that its psychotomimetic properties are mediated by an alteration of thalamocortical activity (the effect of DOI was not examined in the thalamus). Interestingly, the observed effects were prevented or reversed by the antipsychotic drugs clozapine and haloperidol, supporting that the disruption of PFC activity is intimately related to the psychotomimetic activity of these agents. Overall, the present experimental model can be successfully used to elucidate the neurobiological basis of schizophrenia symptoms and to examine the potential antipsychotic activity of new drugs in development. ; Supported by the Innovative Medicines Initiative Joint Undertaking (IMI) under Grant Agreement No. 115008 (NEWMEDS). IMI is a public–private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations. Support from the following grants is also acknowledged: SAF 2012-35183 (Ministry of Economy and Competitiveness and European Regional Development Fund), PI09/1245 and PI12/00156 (PN de I+D+I 2008-2011, ISCIII-Subdireccion General de Evaluación y Fomento de la Investigación cofinanced by the European Regional Development Fund. 'Una manera de hacer Europa') and Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM (P82, 11INT3). Support from the Generalitat de Catalunya (SGR20093) is also acknowledged. P.C. is supported by the Researcher Stabilization Program of the Health Department of the Generalitat de Catalunya. M.R. is recipient of an IDIBAPS fellowship. ; Peer reviewed

<i>Background/Aim:</i> In recent years, there has been a growing interest in developing adequate treatments for patients with a diagnosis of schizophrenia and a comorbid substance use disorder (SUD). In the present paper we aim to critically review published reports on the use of conventional and second-generation antipsychotics in the treatment of patients with schizophrenia and comorbid SUD, to provide clinicians with a clearer view of the pharmacological treatment of this highly prevalent dual diagnosis based upon the evidence arising from the scientific literature. <i>Methods:</i> A search of the relevant literature from Medline, PsycLIT and EMBASE databases, included in the Science Citation Index, and available up to November 2006 was conducted using the terms: 'schizophrenia', 'substance use disorder' and 'antipsychotics'. <i>Results:</i> While research on the use of conventional antipsychotics has remained limited, the majority of studies suggest the effectiveness of second-generation antipsychotics, particularly clozapine, for patients with schizophrenia and a comorbid substance use disorder. <i>Conclusion:</i> In the absence of randomized controlled trials that could provide more reliable information, clinical decisions may need to rely on indirect data provided by the increasing number of case reports, open trials and retrospective studies showing a decrease in cigarette smoking, alcohol, cocaine or cannabis use and an improvement of overall psychiatric symptoms.

[EN] In this work, a molecular hydrogel made of gelator (S)-4-((3-methyl-1-(nonylamino)-1-oxobutan-2-yl)amino)-4-oxobutanoic acid (SVN) has been employed as soft container to modify the photochemical and photophysical behavior of the antipsychotic drug cyamemazine (CMZ). The interaction of CMZ with the gel network has been evidenced by fluorescence spectroscopy through a hypsochromic shift of the emission band (from lambda(max) = 521 nm in solution to lambda(max) = 511 nm in the gel) and an increase of the fluorescence lifetime (5.6 ns in PBS vs. 7.2 ns in the gel). In the laser flash photolysis experiments on CMZ/SVN systems, the CMZ triplet excited state ((3)CMZ*), monitored at lambda = 320 nm, has been more efficiently generated and became much longer-lived than in solution (2.7 mu s vs. 0.7 mu s); besides, photochemical ionization leading to the radical cation CMZ(+center dot) was disfavored. In the steady-state experiments, photooxidation of CMZ to afford the N,S-dioxide derivative CMZ-SONO has been retarded in the gel, which provides a more lipophilic and constrained microenvironment. Both the photophysical properties and the photoreactivity are in agreement with CMZ located in a less polar domain when entrapped in the supramolecular gel, as result of the interaction of the drug with the fibers of the supramolecular SVN gel. ; Financial support from the Spanish Government (CTQ2016-78875-P and CTQ2015-71004-R), the Generalitat Valenciana (PROMETEO/2017/075) and the European Union is gratefully acknowledged. ; Vendrell-Criado, V.; Angulo-Pachón, CA.; Miravet, JF.; Galindo, F.; Miranda Alonso, MÁ.; Jiménez Molero, MC. (2020). Photobehavior of the antipsychotic drug cyamemazine in a supramolecular gel protective environment. Journal of Photochemistry and Photobiology B Biology. 202:1-4. https://doi.org/10.1016/j.jphotobiol.2019.111686 ; S ; 1 ; 4 ; 202 ; Bourin, M., Dailly, E., & Hascöet, M. (2006). Preclinical and Clinical Pharmacology of Cyamemazine: Anxiolytic Effects and Prevention of Alcohol and ...

1 4 202 ; S ; [EN] In this work, a molecular hydrogel made of gelator (S)-4-((3-methyl-1-(nonylamino)-1-oxobutan-2-yl)amino)-4-oxobutanoic acid (SVN) has been employed as soft container to modify the photochemical and photophysical behavior of the antipsychotic drug cyamemazine (CMZ). The interaction of CMZ with the gel network has been evidenced by fluorescence spectroscopy through a hypsochromic shift of the emission band (from lambda(max) = 521 nm in solution to lambda(max) = 511 nm in the gel) and an increase of the fluorescence lifetime (5.6 ns in PBS vs. 7.2 ns in the gel). In the laser flash photolysis experiments on CMZ/SVN systems, the CMZ triplet excited state ((3)CMZ*), monitored at lambda = 320 nm, has been more efficiently generated and became much longer-lived than in solution (2.7 mu s vs. 0.7 mu s); besides, photochemical ionization leading to the radical cation CMZ(+center dot) was disfavored. In the steady-state experiments, photooxidation of CMZ to afford the N,S-dioxide derivative CMZ-SONO has been retarded in the gel, which provides a more lipophilic and constrained microenvironment. Both the photophysical properties and the photoreactivity are in agreement with CMZ located in a less polar domain when entrapped in the supramolecular gel, as result of the interaction of the drug with the fibers of the supramolecular SVN gel. Financial support from the Spanish Government (CTQ2016-78875-P and CTQ2015-71004-R), the Generalitat Valenciana (PROMETEO/2017/075) and the European Union is gratefully acknowledged. Vendrell-Criado, V.; Angulo-Pachón, CA.; Miravet, JF.; Galindo, F.; Miranda Alonso, MÁ.; Jiménez Molero, MC. (2020). Photobehavior of the antipsychotic drug cyamemazine in a supramolecular gel protective environment. Journal of Photochemistry and Photobiology B Biology. 202:1-4. https://doi.org/10.1016/j.jphotobiol.2019.111686 Bourin, M., Dailly, E., & Hascöet, M. (2006). Preclinical and Clinical Pharmacology of Cyamemazine: Anxiolytic Effects and Prevention of Alcohol and Benzodiazepine ...

A letter report issued by the General Accounting Office with an abstract that begins "The Department of Veterans Affairs (VA) provides health care services to veterans who have been diagnosed with psychosis--primarily schizophrenia, a disorder that can substantially limit their ability to care for themselves, secure employment, and maintain relationships. These veterans also have a high risk of premature death, including suicide. Effective treatment, especially antipsychotic drug therapy, has reduced the severity of their illnesses and increased their ability to function in society. VA's guideline for prescribing atypical antipsychotic drugs is sound and consistent with published clinical practice guidelines used by public and private health care systems. VA's prescribing guideline, recommends that physicians use their best clinical judgment, based on clinical circumstances and patients' needs, when choosing among the atypical drugs. Most Veterans Integrated Service Networks and facilities use VA's prescribing guideline; however, five VISNs have additional policies and procedures for prescribing atypical antipsychotic drugs. Although these procedures help manage pharmaceutical cost, they also have the potential to result in more weight given to cost than clinical judgment which is not consistent with the prescribing guideline."

WOS: 000390418700002 ; Objective: Schizophrenia involves white matter abnormalities that might have a central role in the pathophysiology. Abnormal brain connectivity especially in prefrontal and temporal heteromodal cortex has been suggested as the leading structural impairment in patients with schizophrenia. In this study we examined the relationship between potential white matter changes and clinical response, as well as associations with antipsychotic treatment follow-up. Methods: 18 first-episode schizophrenia (FES) patients were recruited from the outpatient unit of the GATA (Gulhane Military Medical Academy) Haydarpasa Research and Training Hospital, between June 2009-February 2010. Fourteen patients with FES were recruited, and 16 healthy control subjects were recruited from the community. Diffusion tensor MRI (DT-MRI) was obtained from participants at baseline and after 4 weeks of standard antipsychotic treatment. A color-coded fractional anisotropy map for each 11 patient was extracted from the 4-week follow-up and the baseline splenium and genu FA measurements. According to Basser and others major eigenvector linear maps were transformed into the color-coded maps. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Brief Psychiatric Rating Scale (BPRS) scores between baseline and follow up were also evaluated. Results: In this study; in the FES patients, both genu FA (p=0.001) and the splenium FA (p=0.013) values were statistically significantly lower than the healthy control group. There were mild FA increases respectively genu and splenium (p=0.533, p=0.318) in the FES patients after the treatment. But the FA changes did not correlate with the changes in clinical symptoms. A negative, moderate, statistically significant correlation (Pearson's r=-0.569, p=0.034) was found between baseline splenium FA values and BPRS scores. The duration of illness prior to treatment was negatively, weak, statistically non-significantly correlated (r=-0.066; p=0.846) between baseline and follow-up splenium FA changes. Conclusions: The reduced mean Callosal FA (CFA) values might indicate myelination defects and problems in axonal transport. The existence of white matter changes even in first episode drug-naive schizophrenia patients supports the view that these problems occurs in earlier stages of development. Although the callosal FA changes did not correlate with symptom improvement or the dose of antipsychotic medication, there was a mild increase in follow-up FA measurements. These findings show that CC which is the main conduit of interhemispheric connection is affected distinctly in patients with schizophrenia. Further collaborative studies are needed to clarify the potential long-term effects of antipsychotics on white matter microstructure and also its reversibility.

Background: Patients taking atypical antipsychotics are in danger of antipsychotic-induced weight gain. Weight increases rapidly in the initial period after starting antipsychotics. Cardiovascular and cerebrovascular morbidity and mortality and reduced quality of. Both nonpharmacologic prevention and intervention strategies have shown modest effects on weight. Changes in physical appearance can lead to body image issues and problems with self-esteem, which in turn could lead to poor compliance with medication. Purpose: This study aimed to evaluate the effectiveness of an exercise program that can benefit patients who are gaining weight related to atypical antipsychotic agent intake.Methods: A quasi-experimental research design was undertaken. The research setting was held in a general tertiary medical teaching/training medical facility owned by the Philippine government. There are 31 respondents for this study 12 were males and 19 were females who were chosen from the list of the in-patients utilizing the universal sampling technique. Data were gathered using a self-formulated tool to collect mostly demographic data which is adopted from the National Alliance for Mental Health.Results: Patients' diagnosis tends to have a positive relationship with weight loss. Respondents diagnosed with bipolar with psychotic features showed to have loss weight more than the diagnosed with schizophrenia. The results of this study showed that patient's adhering to the exercise program had lost weight after the course. Conclusion: Activity and exercise are especially important for people living with mental illness. Furthermore, physical activity does not only help patients manage their weight but to serve as diversional activity that adds vitality for patients in the facility

Patients receiving psychiatric medication, like the antipsychotic drug haloperidol, are at an increased risk of sudden cardiac death (SCD). Haloperidol blocks the cardiac rapidly-activating delayed rectifier potassium current, thereby increasing electrical dispersion of repolarization which can potentially lead to arrhythmias. Whether these patients are also at a higher risk to develop SCD during an acute myocardial infarction (AMI) is unknown. AMI locally shortens action potential duration, which might further increase repolarization dispersion and increase the risk of arrhythmia in the presence of haloperidol compared to without. Our aim was to test whether treatment with haloperidol implies an increased risk of SCD when eventually experiencing AMI. Twenty-eight female Danish Landrace pigs were randomized into three groups: low dose haloperidol (0.1 mg/kg), high dose (1.0 mg/kg) or vehicle-control group. One hour after haloperidol/vehicle infusion, AMI was induced by balloon-occlusion of the mid-left anterior descending coronary artery and maintained for 120 min, followed by 60 min of reperfusion. VF occurred during occlusion in 7/11 pigs in the control group, 3/11 in the low dose (p = 0.198) and 2/6 in the high dose group (p = 0.335). High dose haloperidol significantly prolonged QT, and reduced heart rate, vascular resistance and blood pressure before and during AMI. Premature ventricular contractions in phase 1b during AMI were reduced with high dose haloperidol. AMI-induced arrhythmia was not aggravated in pigs with haloperidol treatment. Our results do not suggest that AMI is contributing to the excess mortality in patients treated with antipsychotic drugs seen in epidemiological studies. ; This work was funded by Novo Nordisk Foundation Synergy program (to TJ and JTH); European Union's Horizon 2020 research and innovation programme under acronym ESCAPE-NET, registered under grant agreement No. 733381 (JTH); Hjertecentrets Forskningsudvalg (to SMS).

Background: Attitudes towards antipsychotic medication play an important part in the treatment for schizophrenia and related disorders. We aimed measuring general practitioners' attitudes to antipsychotic drugs and their adverse side effects and comparing these with the attitudes of the general population. Methods: Analysis and comparison of two representative samples, one comprising 100 General Practitioners (GPs), the other 791 individuals randomly selected from the general population. The setting was the German speaking cantons of Switzerland. Results: General practitioners have significantly more positive attitudes towards anti-psychotic drugs than the general public. They reject widespread prejudices about the use of anti-psychotic medication significantly more than the general population. In particular the risk of dependency was assessed as 'low' by GP's (80%), in contrast to only 18% of the general population sample. In no instance did a majority of the GPs advise not tolerating any of the 10 possible adverse effects presented in this study. This is in marked contrast to the general population sample, where a majority recommended discontinuation for movement disorder (63%), strong tremor (59%), risk of dependency (55%) and feelings of unrest (54%). Conclusion: As well as effective management of side-effects being a vital aspect of patient and carer education, prescribing doctors need to be aware that their mentally ill patients are likely to be confronted with extremely negative public attitudes towards antipsychotic medication and with strong pressures to stop taking their medication in the event of side-effects.