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Atypical Antipsychotics (atypical + antipsychotics)
Selected AbstractsFACTS ABOUT ATYPICAL ANTIPSYCHOTICSJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2006FASHP, Marshall E. Cates PharmD No abstract is available for this article. [source] Synthesis and Biological Evaluation of New Quinazoline and Cinnoline Derivatives as Potential Atypical Antipsychotics,CHEMISTRY & BIODIVERSITY, Issue 1 2006Mario Alvarado Abstract Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained aminobutyrophenone derivatives QF0104B (5) and QF0108B (6) were synthesized (Schemes,2 and 3), and evaluated for their binding affinities (Table) towards the serotonin 5-HT2A and 5-HT2C, and the dopamine D2 receptors. Among the new compounds, the quinazoline derivative 15 (=7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydroquinazolin-5-one) exhibited the highest affinities towards the serotonin 5-HT2A and dopamine D2 receptors, and it is in the borderline of potential atypical antipsychotics. The cinnoline derivative 23 (=7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydro-3-methylcinnolin-5-one) displayed high selectivity in its binding profile towards the 5-HT2C compared to both the 5-HT2A and D2 receptors. [source] Atypical antipsychotics and weightgain , a systematic reviewACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2000D. M. Taylor Objective: To review systematically data relating to weight changes with atypical antipsychotics. Method: We conducted a Medline search on October 29 1999 and covered the period 1980,99. All recovered papers were examined for further relevant reports. In addition, we wrote to pharmaceutical manufacturers and 10 practising clinicians to ask them to provide other relevant reports known to them. Results: Eighty reports mentioning change in body weight were retrieved. Data relating to weight changes were of variable quality. Weight changes were indicated by a variety of measures. The majority of reports related to short-term changes. Conclusion: All atypical drugs, with the exception of ziprasidone, have been associated with weight increases. Clozapine seems to have the highest risk of weight gain, followed by olanzapine and quetiapine. There is probably a lower risk with risperidone, sertindole and zotepine and a still lower risk with amisulpride. Ziprasidone appears not to be associated with weight gain. In the absence of more compelling data, these rankings must be considered approximate and preliminary. Longer, more robust trials are needed. [source] Atypical antipsychotics and anorexia nervosa: A reviewEUROPEAN EATING DISORDERS REVIEW, Issue 1 2010Rebecca F. McKnight Abstract Background There is currently mixed opinion regarding the value of using atypical antipsychotics to treat anorexia nervosa (AN). Aims To evaluate the literature on the use of atypical antipsychotics in AN. Method A review of all studies and clinical guidelines published before September 2009 involving use of an atypical antipsychotic in patients with AN. Analysis is by narrative synthesis. Results Forty-three publications or study protocols were found, including four randomized-controlled trials, five open-label trials and 26 case reports. The most studied drugs were olanzapine, quetiapine and risperidone. Atypical antipsychotics appear safe and there is some evidence of positive effects on depression, anxiety and core eating disordered psychopathology in patients with anorexia nervosa. Currently there is insufficient evidence to confirm atypical antipsychotics enhance weight gain in this setting. Conclusions Further high quality evidence is needed in this area in order to provide practical guidance to clinicians. However, the main challenge is to persuade adequate numbers of AN patients to participate in research trials. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2006Pinkhas Sirota Abstract Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637,mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16,mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (,7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia. Copyright © 2006 John Wiley & Sons, Ltd. [source] Genomic Influences on Schizophrenia-Related Neurotransmitter SystemsJOURNAL OF NURSING SCHOLARSHIP, Issue 4 2005Norman L. Keltner Purpose: (a) to summarize genomic influences in schizophrenia, (b) to review the molecular genetic profile associated with schizophrenia, (c) to summarize the genetic factors affecting dopamine and serotonin neurotransmitter systems, and (d) to list nursing implications for this knowledge. Organizing Framework: Schizophrenia and schizophrenia-spectrum disorders, both clustered in families, arise from both genetic and environmental influences. Schizophrenia does not develop from a single genetic mutation but rather from many genetic alterations acting together. Conclusions: Studies focused on genetic polymorphisms of neurotransmitter systems pique nurses' interest because pharmacological interventions affecting those systems remain the primary approach to treatment. Atypical antipsychotics have in common the ability to antagonize dopaminergic and serotonergic receptors. This review includes the recent discoveries regarding genetic modifications affecting dopamine and serotonin neurotransmitter systems and their potential as a basis for treatment. [source] Latest news and product developmentsPRESCRIBER, Issue 21 2008Article first published online: 2 DEC 200 Osteoporosis guideline A new guideline on the management of osteoporosis in men over 50 and post-menopausal women has been published by the National Osteoporosis Guideline Group (www.shef.ac.uk/NOGG), a group of organisations representing health professionals and patients, with funding from several pharmaceutical companies. The guideline recommends using the FRAX tool (www.shef.ac.uk/FRAX) to assess the 10-year fracture risk in individuals with risk factors to facilitate targeting DXA scans to measure bone mineral density. Patients who have already sustained a fragility fracture should be treated without risk assessment. Treatment recommendations are similar to those published in draft NICE guidance on primary and secondary prevention, selecting alendronate as the drug of first choice for most patients. Efalizumab efficacy A multicentred postapproval trial has demonstrated long-term efficacy and a favourable safety profile for efalizumab (Raptiva) in moderate to severe chronic plaque psoriasis. The CONTROL II study, presented in September at the 17th EADV congress in Paris, was conducted at 170 sites in 18 European countries and involved 1255 patients who had failed to respond to traditional systemic therapies. In this non-blinded study, 68 per cent of participants achieved the primary efficacy end-point and showed improvement within the first 12 weeks; control was maintained in responding patients who continued treatment. Adverse effects were graded as mild or moderate and similar to those reported in earlier studies. There was no evidence of an increase in malignancies or infections. New oral anticoagulant Rivaroxaban (Xarelto), an oral factor Xa inhibitor, has been introduced for the prevention of venous thrombo-embolism in patients undergoing elective hip or knee replacement surgery. Compared with the low molecular weight heparin enoxaparin (Clexane), rivaroxaban has been shown to reduce the risk of venous thrombosis by 70 per cent after hip replacement and by 49 per cent after knee replacement; the risk of bleeding was similar. At the recommended dose of 10mg once daily, prophylaxis after hip surgery lasts five weeks and costs £157; prophylaxis after knee surgery lasts two weeks and costs £63. New products UCB Pharma has introduced lacosamide (Vimpat) as adjunctive treatment of partial-onset epilepsy with or without secondary generalisation in patients aged 16 and over. A month's treatment at the recommended maintenance dose of 100-200mg twice daily costs approximately £73-£140. A new non-nucleoside reverse transcriptase inhibitor (NNRI) is available for the treatment of HIV-1 infection in combination with a boosted protease inhibitor (PI) and other antiretrovirals in treatment-experienced adults. Etravirine (Intelence) costs approximately £320 for one month's treatment at the recommended dose of 200mg twice daily. Voltarol Pain-Eze (diclofenac) 12.5mg tablets are now available without prescription; a pack of 18 tablets costs £5.99. Atypicals and EPS risk Atypical antipsychotics are not associated with a significantly lower risk of extra-pyramidal symptoms than first-generation agents such as perphenazine (Fentazin), a new analysis of the CATIE study has shown (Br J Psychiatry 2008;193:279,88). CATIE was a large trial comparing the efficacy and safety of antipsychotics in the treatment of schizophrenia in which perphenazine was a representative first-generation agent (Am J Psychiatry 2006;163:611,22). This analysis found no differences in the risk of parkinsonism, dystonia, akathisia or tardive dyskinesia between perphenazine and the newer antipsychotics; use of antiparkinsonian medication was higher with risperidone and lower with quetiapine (Seroquel). Mental health website A new website offering information about mental illnesses and drug treatment has been launched by the United Kingdom Psychiatric Pharmacy Group (UKPPG), the College of Mental Health Pharmacists (CMHP), the Pharmaceutical Schizo-phrenia Initiative (PSI) and the National Institute for Mental Health in England (NIMHE). www.choiceandmedication.org.uk includes information about 17 mental illnesses and a large number of drug treatments. It offers links to other sites offering information and downloadable leaflets, help to identify the local mental health trust and downloadable charts comparing treatments for each indication. [source] Atypical antipsychotics in the treatment of deliriumPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 5 2009Vaios Peritogiannis md Delirium is common in all medical settings. Atypical antipsychotics are increasingly used for the management of delirium symptomatology but their effectiveness has not been systematically studied. The aim of the present study was therefore to provide an up-to-date review on the use of atypical antipsychotics in the treatment of delirium. A search was conducted of the databases of MEDLINE, PsycINFO and EMBASE from 1997 to 2008 for English-language articles using the key words ,delirium' and the names of all the atypical antipsychotics. A total of 23 studies were used for this review. Fifteen of the studies were single-agent trials. Four studies were comparison trials, including one double-blind trial, and four studies were retrospective, including three comparison studies. All studies reported improvement of delirium symptomatology after the administration of atypical antipsychotics. No study included a placebo group. Other limitations included sample heterogeneity, small sample size, different rating scales for delirium, and lack of adequate controls. The improvement in delirium was observed within a few days after treatment initiation and the doses given were relatively low. Atypical antipsychotics were well tolerated, but safety was not evaluated systematically. Atypical antipsychotics appear to be effective and safe in symptomatic treatment of delirium but the evidence is limited and inconclusive. There are no double-blind, placebo-controlled studies assessing the efficacy and safety of these agents in delirium. Further research is needed with well-designed studies. [source] Switching atypical antipsychotics: a reviewACTA NEUROPSYCHIATRICA, Issue 6 2004Pierre Chue Background:, Atypical antipsychotics are increasingly used in the treatment of diverse psychiatric disorders; however, there is little information on the ,why, when, and how' of switching between the different atypical antipsychotics currently available. Objective:, To review the data on switching and atypical antipsychotics. Methods:, A literature search was initially conducted using the key words followed by a search of relevant articles including conference abstracts; relevant pharmaceutical companies were also contacted. Results:, Clinical trial data are limited in terms of parameters measured, and case reports describe specific problems. Few studies are based on real world populations of psychiatric patients over the long-term. Careful patient and drug selections matched to a carefully supervised and appropriate cross titration based upon the pharmacodynamic and pharmacokinetic properties of all of the drugs involved is important to avoid potential complications such as re-emergence or worsening of psychosis and withdrawal, rebound, and emergent phenomena including new or uncovered side-effects. Psychoeducation and involvement of patients and caregivers in the process are also necessary for a successful switch. Conclusion:, Despite the prevalence of switching in real world clinical practice, there is a paucity of data to guide clinicians with respect to effective and safe strategies. There are no criteria defining a successful switch. With the increasing range and formulations of atypical antipsychotics available, there is a rationale for their early use to avoid the practical problems associated with switching from conventional antipsychotics as well as the opportunity to maintain patients on an optimal atypical antipsychotic monotherapy. [source] The prefrontal cortex: a target for antipsychotic drugsACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010F. ArtigasArticle first published online: 14 DEC 200 Objective:, At therapeutic doses, classical antipsychotic drugs occupy a large proportion of subcortical dopamine D2 receptors, whereas atypical antipsychotics preferentially occupy cortical 5-HT2 receptors. However, the exact cellular and network basis of their therapeutic action is not fully understood. Method:, To review the mechanism of action of antipsychotic drugs with a particular emphasis on their action in the prefrontal cortex (PFC). Results:, The PFC controls a large number of higher brain functions altered in schizophrenia. Histological studies indicate the presence of a large proportion of PFC neurons expressing monoaminergic receptors sensitive to the action of atypical- and to a lesser extentclassical antipsychotic drugs. Functional studies also indicate that both drug families act at PFC level. Conclusion:, Atypical antipsychotic drugs likely exert their therapeutic activity by a preferential action on PFC neurons, thus modulating the PFC output to basal ganglia circuits. Classical antipsychotics also interact with these PFC targets in addition to blocking massively striatal D2 receptors. [source] Which comes first: atypical antipsychotic treatment or cardiometabolic risk?ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2009S. M. Stahl Objective:, To provide an overview for practicing clinicians on the pharmacological basis of cardiometabolic risk induced by antipsychotic drugs in patients with serious mental illness, to propose hypotheses to explain these risks and to give tips for managing cardiometabolic risk during antipsychotic treatment. Method:, A MEDLINE search using terms for atypical antipsychotics (including individual drug names), metabolic, cardiovascular, weight gain and insulin resistance, cross-referenced with schizophrenia was performed on articles published between 1990 and May 2008. Results:, Strong evidence exists for significant cardiometabolic risk differences among several antipsychotic agents. Histamine H1 and serotonin 5HT2C antagonism are associated with risk of weight gain, but receptor targets for dyslipidemia and insulin resistance have not yet been identified. Convincing data indicate that hypertriglyceridemia and insulin resistance may occur in the absence of weight gain with certain antipsychotics. Conclusion:, Although lifestyle and genetics may contribute independent risks of cardiometabolic dysfunction in schizophrenia and other serious mental illness, antipsychotic treatment also represents an important contributor to risk of cardiometabolic dysfunction, particularly for certain drugs and for vulnerable patients. Mental health professionals must learn to recognize the clinical signposts indicating antipsychotic-related cardiometabolic problems to forestall progression to type II diabetes, cardiovascular events and premature death. [source] The case for long-acting antipsychotic agents in the post-CATIE eraACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2007H. A. Nasrallah Objective:, Long-acting antipsychotic agents were developed to promote treatment compliance in patients requiring maintenance treatment for schizophrenia. Method:, An analysis of the impact of non-compliance on treatment outcomes in schizophrenia and the advantages and disadvantages of long-acting antipsychotics. Results:, Partial or total non-compliance with oral antipsychotics remains widespread and is associated with significant increases in the risk of relapse, rehospitalization, progressive brain tissue loss and further functional deterioration. Long-acting agents have the potential to address issues of all-cause discontinuation and poor compliance. The development of the first long-acting atypical antipsychotic, which appears to be effective and well tolerated, should further improve the long-term management of schizophrenia. Conclusion:, Long-acting agents represent a valuable tool for the management of schizophrenia and merit wider use, especially in light of emerging literature regarding the neuroprotective advantages of atypical antipsychotics over conventional agents in terms of regenerating brain tissue during maintenance therapy. [source] Behavioural management of antipsychotic-induced weight gain: a reviewACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2003U Werneke Objective: Although psychiatrists are aware of weight gain induced by atypical antipsychotics, only few studies on behavioural interventions in this patient group are published. This review aims to summarize the evidence on effectiveness of behavioural interventions for weight gain in the general population and in-patients treated with atypical antipsychotics. Method: Medline and Cochrane databases search for evidence on effectiveness of behavioural interventions. Results: In general, behavioural approaches including, diet, exercise and drug treatments may be effective. There were only 13 studies of behavioural interventions for patients taking antipsychotic medication. No study met the criteria for a RCT. Calorie restriction in a controlled ward environment, structured counselling combined with cognitive behavioural therapy and counselling on life style and provision of rewards may potentially lead to weight loss. Conclusion: Currently only limited, methodologically flawed, evidence is available that behavioural interventions in overweight patients treated with antipsychotics, although intuitively appealing, actually work. [source] Atypical antipsychotics and weightgain , a systematic reviewACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2000D. M. Taylor Objective: To review systematically data relating to weight changes with atypical antipsychotics. Method: We conducted a Medline search on October 29 1999 and covered the period 1980,99. All recovered papers were examined for further relevant reports. In addition, we wrote to pharmaceutical manufacturers and 10 practising clinicians to ask them to provide other relevant reports known to them. Results: Eighty reports mentioning change in body weight were retrieved. Data relating to weight changes were of variable quality. Weight changes were indicated by a variety of measures. The majority of reports related to short-term changes. Conclusion: All atypical drugs, with the exception of ziprasidone, have been associated with weight increases. Clozapine seems to have the highest risk of weight gain, followed by olanzapine and quetiapine. There is probably a lower risk with risperidone, sertindole and zotepine and a still lower risk with amisulpride. Ziprasidone appears not to be associated with weight gain. In the absence of more compelling data, these rankings must be considered approximate and preliminary. Longer, more robust trials are needed. [source] Neuroprotection in emerging psychotic disordersEARLY INTERVENTION IN PSYCHIATRY, Issue 2 2007Gregor Berger Abstract Aim:, The emerging phase of psychotic disorders is pleomorphic and fluctuates in presentation. Hence, from a clinical perspective, treatment modalities are often unclear. This paper investigates the rational and potential use of neuroprotective agents in emerging psychotic disorders. Methods:, Medline databases were searched from 1966 to 2006 followed by the cross-checking of references using following keywords: neuroprotection, apoptosis, natural cell death, neurodevelopment, plasticity, neurogenesis, combined with brain and schizophrenia. Results:, Agents such as atypical antipsychotics, antidepressants, omega-3 fatty acids, modulators of glutamateric neurotransmission (e.g. ampakines, glycine, memantine), erythropoietin, N -acetylcysteine, COX-2 inhibitors or antioxidants have neuroprotective (anti-apoptotic) properties and may therefore be able to protect brain maturational processes disturbed in emerging psychotic disorders. Clinical trials suggest that atypical antipsychotics, antidepressants, omega-3 fatty acids and low-dose lithium as sole treatments were able to improve symptoms and functioning, and delay or in some cases even prevent the onset of frank psychosis. Initially these substances have been chosen because they have been used either as sole or augmentation treatments in established psychotic disorders. However, chronicity and already effective treatments may overshadow their potential clinical use in emerging (prodromal) psychosis. Conclusion:, Neuroprotection as a new treatment paradigm for at-risk mental states seems to be promising and pilot data are suggestive that more benign interventions may already be sufficient to delay or even prevent the onset of frank psychosis. A coordinated research effort will be necessary to address the question which agents should be used under which circumstances. [source] Atypical antipsychotics and anorexia nervosa: A reviewEUROPEAN EATING DISORDERS REVIEW, Issue 1 2010Rebecca F. McKnight Abstract Background There is currently mixed opinion regarding the value of using atypical antipsychotics to treat anorexia nervosa (AN). Aims To evaluate the literature on the use of atypical antipsychotics in AN. Method A review of all studies and clinical guidelines published before September 2009 involving use of an atypical antipsychotic in patients with AN. Analysis is by narrative synthesis. Results Forty-three publications or study protocols were found, including four randomized-controlled trials, five open-label trials and 26 case reports. The most studied drugs were olanzapine, quetiapine and risperidone. Atypical antipsychotics appear safe and there is some evidence of positive effects on depression, anxiety and core eating disordered psychopathology in patients with anorexia nervosa. Currently there is insufficient evidence to confirm atypical antipsychotics enhance weight gain in this setting. Conclusions Further high quality evidence is needed in this area in order to provide practical guidance to clinicians. However, the main challenge is to persuade adequate numbers of AN patients to participate in research trials. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2006Daniela Noaķn Abstract The dopamine D4 receptor (D4R) has received considerable interest because of its higher affinity for atypical antipsychotics, the extremely polymorphic nature of the human gene and the genetic association with attention deficit and hyperactivity disorder (ADHD). Several efforts have been undertaken to determine the D4R expression pattern in the brain using immunohistochemistry, binding autoradiography and in situ hybridization, but the overall published results present large discrepancies. Here, we have explored an alternative genetic approach by studying bacterial artificial chromosome (BAC) transgenic mice that express enhanced green fluorescent protein (EGFP) under the transcriptional control of the mouse dopamine D4 receptor gene (Drd4). Immunohistochemical analysis performed in brain sections of Drd4 -EGFP transgenic mice using an anti-EGFP polyclonal antibody showed that transgenic expression was predominant in deep layer neurons of the prefrontal cortex, particularly in the orbital, prelimbic, cingulate and rostral agranular portions. In addition, discrete groups of Drd4 -EGFP labelled neurons were observed in the anterior olfactory nucleus, ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD. [source] Metabolic drug interactions with new psychotropic agentsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2003Edoardo Spina Abstract New psychotropic drugs introduced in clinical practice in recent years include new antidepressants, such as selective serotonin reuptake inhibitors (SSRI) and ,third generation' antidepressants, and atypical antipsychotics, i.e. clozapine, risperidone, olanzapine, quetiapine, ziprasidone and amisulpride. These agents are extensively metabolized in the liver by cytochrome P450 (CYP) enzymes and are therefore susceptible to metabolically based drug interactions with other psychotropic medications or with compounds used for the treatment of concomitant somatic illnesses. New antidepressants differ in their potential for metabolic drug interactions. Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19, while nefazodone is a potent inhibitor of CYP3A4. These antidepressants may be involved in clinically significant interactions when coadministered with substrates of these isoforms, especially those with a narrow therapeutic index. Other new antidepressants including sertraline, citalopram, venlafaxine, mirtazapine and reboxetine are weak in vitro inhibitors of the different CYP isoforms and appear to have less propensity for important metabolic interactions. The new atypical antipsychotics do not affect significantly the activity of CYP isoenzymes and are not expected to impair the elimination of other medications. Conversely, coadministration of inhibitors or inducers of the CYP isoenzymes involved in metabolism of the various antipsychotic compounds may alter their plasma concentrations, possibly leading to clinically significant effects. The potential for metabolically based drug interactions of any new psychotropic agent may be anticipated on the basis of knowledge about the CYP enzymes responsible for its metabolism and about its effect on the activity of these enzymes. This information is essential for rational prescribing and may guide selection of an appropriate compound which is less likely to interact with already taken medication(s). [source] Neurocognition and its influencing factors in the treatment of schizophrenia,effects of aripiprazole, olanzapine, quetiapine and risperidoneHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2010M. Riedel Abstract Background To examine influencing variables of neurocognition in patients with schizophrenia and to predict cognition during antipsychotic treatment. Methods Data were obtained from patients with an acute episode of schizophrenia participating in two double-blind and one open label trial comparing the effects of different atypical antipsychotics on cognition. In total, 129 patients were enrolled in this analysis. Cognitive function was assessed at admission, week 4 and 8. Efficacy and tolerability were assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Simpson Angus Sale (SAS). Patients were treated with aripirazole, olanzapine, quetiapine and risperidone. Regression analysis including mixed effect models was performed. Results A significant improvement in all cognitive domains was observed from baseline to week 8. Regarding the antipsychotic treatment applied quetiapine seemed to achieve the most favourable cognitive improvement. Negative and depressive symptoms, the patient's age and the concomitant and antipsychotic treatment applied were observed to significantly influence and predict neurocognition. Conclusion The results may indicate that schizophrenia is a static disorder with trait and state dependent cognitive components especially in the memory domains. The influence of negative and depressive symptoms should be considered in daily clinical routine. Copyright © 2010 John Wiley & Sons, Ltd. [source] The effect of dopamine partial agonists on the nicotine dependency in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2010Se Hee Kim Abstract Objective We compared the effects of haloperidol and three atypical antipsychotics (risperidone, olanzapine, and aripiprazole) on nicotine dependence in schizophrenic patients. Methods One hundred and thirty nine schizophrenic patients, who began using antipsychotic medication, were assessed for severity of nicotine dependence and for cigarette craving at baseline and following 8 weeks of treatment using the Fagerström Tolerance Questionnaire (FTQ) and a Likert-style, seven point, visual-analogue rating scale. Results Nicotine dependence increased in the haloperidol group, but not in atypical antipsychotics groups. Patients treated with aripiprazole showed a reduction both in nicotine dependence and cigarette craving. Conclusions The effects of aripiprazole, a partial agonist of the dopamine D2 receptor, may reduce the severity of nicotine dependence in schizophrenic patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] Improvement in social competence in patients with schizophrenia: a pilot study using a performance-based measure using virtual reality,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2009Kyung-Min Park Abstract Objective The objective of this study was to explore the possibility of the use of Virtual Reality Functional Skills Assessment (VRFSA) in a future regular clinical trial, as well as to report a preliminary result about effectiveness of atypical antipsychotics to social competence in schizophrenia. Methods We developed the VRFSA that measured subjects' performances automatically and used analogue scale rather than Likert scale. Twenty-four female patients with paranoid schizophrenia and 15 healthy females were recruited. This was a 6-week, randomized, open-label, and flexible dose study, and 2 treatments (baseline versus post-treatment),×,2 skills phases (receptive versus expressive),×,2 patient groups (aripiprazole versus risperidone) analysis of variance was used in the final analysis. Results There was a significant difference in the VRFAS between the patients and the healthy subjects (p,<,0.05). Eighteen patients were included in the final analysis. We found larger treatment effect than those found in previous studies, and significant treatment,×,skills phase,×,group interaction effect on the VRFAS. Conclusions Our results suggest that the VRFAS is strongly sensitive to changes in social competence and thus especially beneficial in short-term clinical trials. In addition, atypical antipsychotics can improve social competence and differentially improve receptive skills and expressive skills in schizophrenia. Copyright © 2009 John Wiley & Sons, Ltd. [source] Augmentation of atypical antipsychotics with valproic acid.HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2009An open-label study for most difficult patients with schizophrenia Abstract Objective Most difficult inpatients with schizophrenia are in serious needs but obviously underrepresented in clinical trials. Methods Very challenging patients received open-label treatment with atypical antipsychotics concurrently augmented with valproic acid. The primary outcome was the newly developed Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz). Patients improving more than 20 points were classified as responders. Results Mean age and illness duration of 28 participants (22male) were 42 y.o. and 20 years, respectively. They had spent a half of their life admitted after the onset. The average Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity (CGI-S) were very severe at 79 and 6.1, respectively, with the baseline Global Assessment of Functioning (GAF) of as low as 21. As a result of augmentation, there were nine responders, 12 partial responders, and seven non-responders including only two patients who got worse. The main antipsychotics were mostly either risperidone or olanzapine. Mean maximum oral dose and blood level of valproic acid were 1907,mg and 91.7,µg/ml, respectively. Overall significant improvements whilst to an inadequate degree were noted in clinical parameters. Valproate augmentation was generally well tolerated but serious adverse effects included thrombocytopenia, anaemia and sedation/falls. Conclusions While these preliminary results need to be tested against tenacious monotherapy or polypharmacy involving clozapine, augmenting atypical antipsychotics with valproic acid can be useful for very severe schizophrenia. Copyright © 2009 John Wiley & Sons, Ltd. [source] Cardiac side effects of psychiatric drugs,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2008Paul Mackin Abstract This review describes the common effects of psychotropic drugs on the cardiovascular system and offers guidance for practical management. Selected reports from the literature describing common side effects associated with psychotropic drugs are reviewed, and suggestions for further reading are given throughout the text. Orthostatic hypotension is the most common adverse autonomic side effect of antipsychotic drugs. Among the atypical antipsychotics the risk of orthostatic hypotension is highest with clozapine and among the conventional drugs the risk is highest with low potency agents. Rarely, orthostatic hypotension may result in neurocardiogenic syncope. QTc prolongation can occur with all antipsychotics but an increased risk is seen with pimozide, thioridazine, sertindole and zotepine. QTc prolongation is a marker of arrhythmic risk. Torsade de pointe, a specific arrhythmia, may lead to syncope, dizziness or ventricular fibrillation and sudden death. Heart muscle disease presents most commonly in the elderly as chronic heart failure, but myocarditis and cardiomyopathy, although relatively rare, are devastating, but potentially reversible complications of psychotropic drug therapy have been particularly linked to clozapine treatment. Patients with severe mental illness (SMI) are a ,high risk' population with regard to cardiovascular morbidity and mortality. It is probable that many patients accumulate an excess of ,traditional' risk factors for the development of cardiovascular disease, but other mechanisms including psychotropic drugs may also be influential in increasing risk in this vulnerable group. These risks need to be seen in the context of the undoubted therapeutic efficacy of the psychotropic armamentarium and the relief that these drugs bring to those suffering from mental disorder. Copyright © 2007 John Wiley & Sons, Ltd. [source] Neurological complications of psychiatric drugs: clinical features and management,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2008Peter M. Haddad Abstract This paper reviews the main neurological complications of psychiatric drugs, in particular antipsychotics and antidepressants. Extrapyramidal syndromes include acute dystonia, parkinsonism, akathisia, tardive dyskinesia and tardive dystonia. Extrapyramidal symptoms (EPS) are less frequent with atypical than with conventional antipsychotics but remain common in clinical practice partly due to lack of screening by health professionals. Neuroleptic malignant syndrome (NMS) consists of severe muscle rigidity, pyrexia, change in conscious level and autonomic disturbance but partial forms also occur. NMS is particularly associated with the initiation and rapid increase in dose of high-potency antipsychotics but it has been reported with all the atypical antipsychotics and rarely with other drugs including antidepressants. Serotonin toxicity comprises altered mental state (agitation, excitement, confusion), neuromuscular hyperactivity (tremor, clonus, myoclonus, hyper-reflexia) and autonomic hyperactivity and occurs on a spectrum. Severe cases, termed serotonin syndrome, usually follow the co-prescription of drugs that increase serotonergic transmission by different pathways, for example a monoamine oxidase inhibitor (MAOI) and a selective serotonin reuptake inhibitor (SSRI). Most antipsychotics and antidepressants lower the seizure threshold and can cause seizures; the risk is greater with clozapine than with other atypical antipsychotics and greater with tricyclic antidepressants (TCAs) than with SSRIs. In randomised controlled trials in elderly patients with dementia atypical antipsychotics are associated with a higher risk of stroke and death than placebo. Cohort studies suggest that conventional drugs carry at least the same risk. Cessation of treatment with antipsychotics and antidepressants can lead to a wide range of discontinuation symptoms which include movement disorders and other neurological symptoms. Clinicians need to be familiar with strategies to reduce the risk of these adverse events and to manage them when they arise. Their occurrence needs to be balanced against the benefits of psychiatric drugs in terms of efficacy and improved quality of life in a range of disorders. Copyright © 2007 John Wiley & Sons, Ltd. [source] Retrospective database analysis on the effectiveness of typical and atypical antipsychotic drugs in an outpatient clinic settingHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2007Cengiz Akkaya Abstract Objective To report the outcomes of a retrospective database analysis to compare the effectiveness of atypical and typical antipsychotic drugs. Methods Medical records of patients admitted to the psychiatry outpatient clinic between January 1998 and October 2005 were retrospectively reviewed. Data obtained from patient records were noted on a special form assessing four aspects of the treatment history: socio-demographic features, disease characteristics, initial treatment at the time of admission, and course of treatment. Patient groups (typical/atypical and Risperidone/Haloperidol/Olanzapine) were compared for time to all-cause medication discontinuation and rate of discontinuation. Results There was no statistically significant difference in the duration of treatment between patients using atypical (n,=,150) and typical (n,=,124) antipsychotics. The duration of treatment was significantly longer in patients on Haloperidol (n,=,91) compared with those on Risperidone (n,=,63). Rates of discontinuation over 18 months were 59.3% for patients on atypical antipsychotics and 57.3% for those on typical antipsychotics, and 68.3% for patients on Risperidone, 51.6% for patients on Haloperidol and 54.3% for patients on Olanzapine. Conclusion Despite our hypothesis patients with chronic schizophrenia discontinued their atypical and typical antipsychotics, at a high rate with no significant difference indicating substantial limitations in the effectiveness of these drugs. Copyright © 2007 John Wiley & Sons, Ltd. [source] Effect of risperidone on plasma catecholamine metabolites and brain-derived neurotrophic factor in patients with bipolar disordersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2006Reiji Yoshimura Abstract A combination treatment with a mood stabilizer and an antipsychotic drug is often used in as many as 90% of subjects with acute mania. Recently, augmentation therapy with atypical antipsychotics has been investigated in both the acute and long-term treatment of bipolar disorder with or without psychosis. In the present study, the authors investigated the efficacy of risperidone treatment for both acute manic and depressive episodes in bipolar disorder. Eighteen patients (M/F: 8/10, age: 34,±,15,yr) who met the DSM-IV criteria for bipolar I disorder (12 cases of manic episodes, 6 cases of depressive episodes) with risperidone treatment were evaluated regarding their clinical improvement using the Young Mania rating Scale (YMRS) and the Hamilton rating Scale for Depression (Ham-D). Plasma concentrations of HVA and MHPG were analyzed by HPLC-ECD and plasma brain-derived neurotrophic factor (BDNF) levels were detected by sandwich ELISA. The mean scores of the YMRS were 22, 18, 12, 8, and 5 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The mean scores of the Ham-D were 24, 25, 21, 21, and 19 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The plasma levels of HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed to have decreased 4 weeks after risperidone administration in manic patients. The levels did not change in depressive patients. The plasma levels of BDNF were decreased in depressive patients compared with manic patients or healthy controls. However, the administration of risperidone did not alter plasma BDNF levels. Copyright © 2006 John Wiley & Sons, Ltd. [source] Heterogeneity of violence in schizophrenia and implications for long-term treatmentINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2008J. Volavka Summary Aims:, Most patients with schizophrenia are not violent. However, persistent violent behaviour in a minority of patients presents a therapeutic challenge. Published treatment guidelines and most pharmacological and epidemiological literature on violence in schizophrenia treat overt physical aggression as a homogeneous phenomenon. The aim of this review is to address the subtyping of violent behaviour in schizophrenia, and to relate the subtypes to treatment. Method:, Literature describing subtypes of violence in schizophrenia and the treatment of this problem was reviewed. ,Schizophrenia', ,violence', ,aggression', ,hostility' and ,personality disorders' were the principal search terms describing behaviours. Generic names of individual atypical antipsychotics and mood stabilisers were used in treatment searches. Results:, There are at least three aetiological subtypes of violence in schizophrenia (i) that related directly to positive psychotic symptoms, (ii) impulsive violence and (iii) violence stemming from comorbidity with personality disorders, particularly psychopathy. Current treatment of violence in schizophrenia relies on antipsychotics and mood stabilisers. The evidence of effectiveness is relatively strong for clozapine, but inconsistent for other treatments. No systematic recommendations relating the treatment to aetiological subtypes of violence were found. Discussion:, The inconsistent effectiveness of the current treatments of violent behaviour in schizophrenia is due, at least in part, to the aetiological heterogeneity of that behaviour. We should not expect that any given pharmacological treatment will be equally effective in reducing violent behaviour caused by psychosis, impaired impulse control or personality disorder. Conclusion:, Violence in schizophrenia is aetiologically heterogeneous. This heterogeneity has therapeutic implications that impact clinical practice today and should be further explored in future studies. [source] Determinants of antipsychotic medication use among older people living in aged care homes in AustraliaINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2010Prasad S. Nishtala Abstract Objective To investigate determinants of antipsychotic medication use among older people living in aged care homes in Australia. Design Retrospective study of a random sample of de-identified medication reports using cross-sectional data gathered between 1 January 2008 and 30 June 2008 in Australia. Subjects The mean (SD) age of the residents was 84.0 (9.0) years. Seventy-five per cent were females. Measures Resident demographics, clinical characteristics, medical diagnoses and prescribed medication were systematically recorded. Logistic regression (LR) models were used to determine predictors for any antipsychotic, atypical and conventional antipsychotic use. Results Twenty-three per cent of the residents were prescribed one or more antipsychotics. In the LR model, factors for predicting the odds ratio and 95% confidence interval (CI) for any antipsychotic medication use were agitation (7.11, 95% CI 3.15,16.03), challenging behaviours (7.47, 95% CI 2.53,22.10), dementia (2.35, 95% CI 1.36,4.06), dementia with mood disorder (0.39, 95% CI 0.16,0.92), paranoia (6.70, 95% CI 1.08,41.55), psychosis (14.79, 95% CI 3.64,60.00) and any psychiatric diagnosis (3.30, 95% CI 1.82,6.00). Use of atypical antipsychotic medication was significant for agitation (4.58, 95% CI 2.05,10.23), aggression (2.25, 95% CI 1.05,4.78), challenging behaviours (8.01, 95% CI 2.76,23.24), dementia (3.64, 95% CI 1.99,6.67), dementia with mood disorder (0.16, 95% CI 0.06,0.43), psychosis (16.51, 95% CI 4.28,63.66) and any psychiatric diagnosis (4.44, 95% CI 2.33,8.46). Conclusions Psychiatric diagnosis, psychosis and dementia were associated with significantly greater odds for the use of antipsychotic medications. Older people suffering from dementia and comorbid mood disorders treated with antidepressants were less likely to be prescribed atypical antipsychotics. Copyright © 2009 John Wiley & Sons, Ltd. [source] Treatment of Dementia in Community-Dwelling and Institutionalized Medicare BeneficiariesJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2007Ann L. Gruber-Baldini PhD OBJECTIVES: To establish nationally representative estimates of the use of agents to treat Alzheimer's disease and related dementias (ADRDs) and related behavioral symptoms in Medicare beneficiaries and to describe medication use according to residential status and other patient characteristics. DESIGN: Cross-sectional prevalence study. SETTING: Community and various long-term care (LTC) settings. PARTICIPANTS: Twelve thousand six hundred ninety-seven beneficiaries from the 2002 Medicare Current Beneficiary Survey (MCBS), of whom 11,593 were community dwelling and 1,104 resided in various LTC settings. MEASUREMENTS: ADRDs were identified according to International Classification of Diseases, Ninth Revision, codes in Medicare claims and self- and proxy reports. Medication use was derived from self-reports (community) and extracts of facility medication administration records (LTC). RESULTS: In 2002, an estimated 3.4 million Medicare beneficiaries were diagnosed with ADRDs (8.1%), of whom 58.9% resided in the community (prevalence rate=5.1%) and 41.1% resided in LTC facilities (prevalence rate=57.2%). Use of antidementia drugs was similar across settings, with 24.7% of subjects with dementia in the community and 26.3% of those in LTC receiving prescriptions for donepezil, galantamine, or rivastigmine. Use of haloperidol was comparable (and low) in both settings. Use of atypical antipsychotics, especially risperidone, olanzapine, and quetiapine, was much higher in LTC residents (21.0%, 11.9%, and 7.1%, respectively) than in the community (5.1%, 4.0%, and 2.3%). CONCLUSION: The prevalence of ADRDs in LTC settings is much larger than in the community, but there is little difference in the proportions receiving antidementia drugs, although LTC residents are more likely to be treated with atypical antipsychotics (risperidone, olanzapine, and quetiapine), presumably for behavioral symptoms. [source] Hyperprolactinemia and amenorrhea associated with olanzapine normalized after addition of aripiprazoleJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2007J. Wolf MD Summary Hyperprolactinemia is a frequent side-effect in the use of atypical antipsychotics. The propensity to induce hyperprolactinemia is highly substance dependent and hyperprolactinemia is not always associated with clinical side-effects. We report a case in which hyperprolactinemia and amenorrhea under the treatment with olanzapine gets normalized after the addition of aripiprazole. [source] | |||||||||||||||||||||||||||||||