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Antipsychotics
Kinds of 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] 5-HT1A RECEPTOR AGONIST PROPERTIES OF ANTIPSYCHOTICS DETERMINED BY [35S]GTP,S BINDING IN RAT HIPPOCAMPAL MEMBRANESCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2007Yuji Odagaki SUMMARY 15-Hydroxytryptamine 1A (5-HT1A) receptors have attracted increasing attention as a promising target for antipsychotic therapy. Although many atypical antipsychotic drugs, including the prototype clozapine, have been reported to be partial agonists at 5-HT1A receptors, these results are often fragmental and derived mainly from experiments that used cultured cells. 2In the present study, [35S]guanosine 5,- O -(3-thiotriphosphate) ([35S]GTP,S) binding assay in rat hippocampal membranes was applied to a series of antipsychotic drugs, especially atypical antipsychotics. 3Most, but not all, of atypical antipsychotic drugs and the classical antipsychotic drug nemonapride behaved as partial agonists at 5-HT1A receptors with varied potencies and relative efficacies. The most potent compound was perospirone with a mean EC50 of 27 nmol/L, followed by aripiprazole (45 nmol/L) > ziprasidone (480 nmol/L) > nemonapride (790 nmol/L) > clozapine (3900 nmol/L) > quetiapine (26 000 nmol/L). The maximal percentage increases over the basal binding (%Emax) for these antipsychotic drugs were 30,50%, with the exception of perospirone (, 15%), whereas 5-HT stimulated the binding to a mean %Emax of 105%. 4Increasing concentrations of the selective and neutral 5-HT1A antagonist WAY100635 shifted the concentration,response curve of nemonapride-stimulated [35S]GTP,S binding to the right and in parallel. 5The relative efficacy or intrinsic activity of a compound was affected differently by the differing concentrations of guanosine diphosphate (GDP) in the assay buffer, which should be taken into consideration when determining the relative efficacies of these antipsychotics as 5-HT1A receptor agonists. 6These results provide important information concerning the relevance of 5-HT1A receptor partial agonist properties in the treatment for schizophrenic patients with most, if not all, of atypical antipsychotic drugs. [source] Are All Commonly Prescribed Antipsychotics Associated with Greater Mortality in Elderly Male Veterans with Dementia?JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2010Rebecca C. Rossom MD OBJECTIVES: To estimate mortality risk associated with individual commonly prescribed antipsychotics. DESIGN: Five-year retrospective study. SETTING: Veterans national healthcare data. PARTICIPANTS: Predominantly male, aged 65 and older, with a diagnosis of dementia and no other indication for an antipsychotic. Subjects who received an antipsychotic were compared with randomly selected controls who did not. Exposed and control cohorts were matched according to their date of dementia diagnosis and time elapsed from diagnosis to the start of antipsychotic therapy. MEASUREMENTS: Mortality during incident antipsychotic use. RESULTS: Cohorts who were exposed to haloperidol (n=2,217), olanzapine (n=3,384), quetiapine (n=4,277), or risperidone (n=8,249) had more comorbidities than their control cohorts. During the first 30 days, there was a significant increase in mortality in subgroups prescribed a daily dose of haloperidol greater than 1 mg (hazard ratio (HR)=3.2, 95% confidence interval (CI)=2.2,4.5, P<.001), olanzapine greater than 2.5 mg (HR=1.5, 95% CI=1.1,2.0, P=.01), or risperidone greater than 1 mg (HR=1.6, 95% CI=1.1,2.2, P=.01) adjusted for demographic characteristics, comorbidities, and medication history using Cox regression analyses. Greater mortality was not seen when a daily dose of quetiapine greater than 50 mg (HR=1.2, 95% CI=0.7,1.8, P=.50) was prescribed, and there was no greater mortality associated with a dose less than 50 mg (HR=0.7, 95% CI=0.5,1.0, P=.03). No antipsychotic was associated with greater mortality after the first 30 days. CONCLUSION: Commonly prescribed doses of haloperidol, olanzapine, and risperidone, but not quetiapine, were associated with a short-term increase in mortality. Further investigations are warranted to identify patient characteristics and antipsychotic dosage regimens that are not associated with a greater risk of mortality in elderly patients with dementia. [source] Latest news and product developmentsPRESCRIBER, Issue 10 2008Article first published online: 3 JUN 200 Glitazones more than double fracture risk An analysis of the UK General Practice Research Database has found that both glitazones increase the risk of fracture more than two-fold (Arch Intern Med 2008;168:820-5). Compared with nonusers, the odds ratio for fracture (mostly hip and wrist) was 2.59 for pioglitazone and 2.38 for rosiglitazone. The risk increased with dose but was unrelated to age and sex. Reduce antipsychotics in dementia patients Antipsychotics should be prescribed for patients with dementia only as a last resort at times of severe distress or critical need, the All-Party Parliamentary Group on Dementia has concluded. Its inquiry (available at www.alzheimers.org.uk) found that antipsychotics are being prescribed for patients with mild behavioural symptoms and for prolonged periods despite the limited benefits they offer and the risk of serious adverse effects such as stroke. Contributory factors include lack of training for staff, inadequate leadership and exclusion of family and friends from decisions about treatment. High-dose atorvastatin in chronic kidney disease High-dose atorvastatin (Lipitor) reduces cardiovascular events in patients with chronic kidney disease (CKD) more than a low dose , despite similar reductions in LDL-C (J Am Coll Cardiol 2008;51:1448-54). A post hoc subgroup analysis of the Treating-to-New-Targets study involving 10 001 patients with CHD, with or without CKD, found that atorvastatin 10 and 80mg per day reduced LDLC and triglycerides to similar levels; there was no change in HDL-C. After a median follow-up of five years, the incidence of cardiovascular events in patients with CKD was 9.3 per cent at 80mg per day and 13.4 per cent at 10mg per day (number needed to treat to prevent one event, NNT, 24). In patients with no CKD, the corresponding figures were 7.9 vs 9.2 per cent (NNT 74). There was no difference in all-cause mortality; adverse events were more frequent at the higher dose. COX-2 NSAIDs not more cost-effective An economic analysis of COX-2 selective NSAIDs has concluded that they are not more cost effective than older agents plus a proton pump inhibitor (PPI) in the treatment of osteoarthritis and rheumatoid arthritis (Health Technology Assessment 2008;12:No. 11). The analysis concluded that selective and nonselective NSAIDs were similarly effective but selective agents were associated with a lower risk of upper GI events and a higher risk of cardiovascular events. However, the available evidence includes only low numbers of events and further studies are needed. Compared with ibuprofen or diclofenac plus a PPI, the COX-2 selective NSAIDs look ,generally unattractive from a cost effectiveness point of view', even in high-risk patients with a history of peptic ulcer. There were insufficient data to allow a reliable comparison within the COX-2s. Naftidrofuryl helps intermittent claudication Naftidrofuryl increases pain-free walking distance (PFWD) in patients with intermittent claudication, a new Cochrane review has shown (Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD001368. DOI: 10.1002/ 14651858.CD001368.pub3; also see page 49 in this issue). The meta-analysis of six trials involving a total of 1083 patients found that, compared with placebo, naftidrofuryl increased PFWD by over a third with a proportion successfully treated of 20 per cent (NNT 4.5). Coversyl Arginine To clarify any confusion following our recent news item (Perindopril brand switch, 19 April issue, page 12), Servier has asked us to reiterate that the new formulations Coversyl Arginine 2.5, 5 and 10mg are equivalent to 2, 4 and 8mg of the discontinued Coversyl formulation. Coversyl Arginine contains perindopril arginine, a salt that offers greater stability and a longer shelf-life. Prescriptions for the Coversyl brand of perindopril must in future be written as Coversyl Arginine in its revised strengths. Coversyl Plus has also been replaced by Coversyl Arginine Plus and the same revised dosages apply. Generic formulations of perindopril remain unaffected. Copyright © 2008 Wiley Interface Ltd [source] Use of Antipsychotics to Treat Cocaine Toxicity?ACADEMIC EMERGENCY MEDICINE, Issue 1 2008Stanley Wu MD 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] Medication use and risk of fallsPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2002C. Ineke Neutel PhD, FACE Abstract Purpose Injuries due to falls are an important public health concern, particularly for the elderly, and effective prevention is an ongoing endeavour. The present study has two related objectives: (1) to describe associations between drug use and falls in an institutionalized population, and (2) to identify a high risk subgroup within the larger population. Methods The initial analysis was based on a population of 227 residents who were followed over a 1-year period. Logistic regression techniques were used to estimate odds ratios (ORs) of the association of falls and drug use. The study of potential ,high-risk' groups employed a case,crossover design to estimate the risk of falling associated with starting a new drug course. Results Relatively weak ORs for risk of falling were observed for various drug classes; the highest OR was for benzodiazepines (BZD) at OR=1.8, (unadjusted). Residents taking multiple drugs were at particular risk for falling, e.g. an OR of 6.1, for those using 10+ drugs. The case,crossover analysis indicated that residents starting a new BZD/antipsychotic were at very high risk (OR,=,11.4,) for experiencing a fall. Conclusions Residents who took many different types of medications, as well as residents starting a new BZD/antipsychotics were at greatly increased risk of falling. These are high risk groups where increased monitoring or adjustments to drug regimens could lead to prevention of falls. Copyright © 2002 John Wiley & Sons, Ltd. [source] QTc-interval abnormalities in a forensic populationCRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 2 2007Sobhi Girgis Background,Antipsychotic drugs have been linked to sudden death among psychiatric patients, with a suggestion that prolongation of the QT-interval detectable on a standard electrocardiogram may be linked to fatal cardiac arrhythmias in these circumstances. Patients in secure forensic psychiatric facilities may be particularly likely to be on high-dose antipsychotic medication, and yet, as far as the authors are aware, no study of QT-intervals among such patients has been reported. Aim,To investigate the prevalence of QT-interval abnormalities and associated known risk factors for fatal cardiac arrhythmias in a sample of forensic patients. Method,Participants had a 12-lead electrocardiogram taken at 50 mm/s. Information was collected on their age, gender, psychiatric diagnosis, history of cardiovascular, liver and kidney diseases, and smoking, on all medications and on history of seclusion over the previous 12 months. Analysis was carried out using binary logistic regression. Results,Lower rates of QT-interval abnormalities than might be expected for this population were found. It was also found that a high dose of antipsychotics was associated with QTc prolongation (Adjusted OR = 9.5, 95% CI 2.6,34.2), a result consistent with previous literature. Conclusion,Forensic patients need not be at increased risk of QTc abnormality provided risk factors are properly managed. A high dose of antipsychotic medication increases the risk of QTc prolongation. Copyright © 2007 John Wiley & Sons, Ltd. [source] 10-Year trends in the treatment and outcomes of patients with first-episode schizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010J. Nielsen Nielsen J, le Quach P, Emborg C, Foldager L, Correll CU. 10-Year trends in the treatment and outcomes of patients with first-episode schizophrenia. Objective:, The first episode of schizophrenia is a critical period for illness course and outcomes. We aimed to investigate treatments and outcomes during the first year after the diagnosis of schizophrenia. Method:, Pharmacoepidemiologic inception cohort study of all newly diagnosed patients with schizophrenia in Denmark (n = 13 600) 1996,2005. Results:, From 1996 to 2005, the mean age at first diagnosis decreased significantly (29.2,26.1 years), more patients received antipsychotics (67.2,80.7%, annual OR = 1.07, CI: 1.06,1.09, P < 0.001) and antipsychotic polypharmacy for >4 months (16.7,37.1%, OR = 1.14, CI: 1.12,1.57, P < 0.001). The antipsychotic defined daily dosage (DDD) doubled (150,332 DDD, P < 0.001), use of antidepressants (24.3,40.6%, P < 0.001). Bed days [89.9 days (CI: 81.8,98.8) to 71.8 days, CI: 63.7,80.8, P < 0.0001] decreased, whereas outpatient contacts [10.2 (CI: 9.5,11.0) to 21.4 (CI: 19.9,21.0), P < 0.0001] doubled. Conclusion:, Between 1996 and 2005, there was an earlier recognition of schizophrenia, intensified outpatient treatment, increased use and dosing of antipsychotics and antidepressants, but also more antipsychotic polypharmacy. [source] Treatment of major depressive disorder in the Finnish general populationDEPRESSION AND ANXIETY, Issue 11 2009Juha Hämäläinen M.D.M.A. Abstract Background: Few general population studies of the treatment of major depressive disorder (MDD) have included the whole spectrum of treatments. We estimated the rates of different treatments and the effect of individual and disorder characteristics plus provider type on treatment received. Methods: In the Health 2000 Study, a representative sample (n=6,005) from the adult Finnish population (,30 years) were interviewed (CIDI) in 2000,2001 for the presence of DSM-IV mental disorders during the past 12 months. Logistic regression models were used to examine factors influencing the type of treatment: either pharmacotherapies (antidepressants, anxiolytics, sedatives/hypnotics, antipsychotics) or psychological treatment. Results: Of the individuals with MDD (n=288), currently 24% used antidepressants, 11% anxiolytics, 16% sedatives/hypnotics, 5% antipsychotics, and 17% reported having received psychological treatment. Overall, 31% received antidepressants or psychological treatment or both; 18% received minimally adequate treatment. Of those 33% (n=94) using health care services for mental reasons, 76% received antidepressants or psychological treatment or both; 54% received minimal adequate treatment. In logistic regression models, the use of antidepressants was associated with female sex, being single, severe MDD, perceived disability, and comorbid dysthymic disorder; psychological treatment with being divorced, perceived disability, and comorbid anxiety disorder. Conclusions: Due to the low use of health services for mental reasons, only one-third of subjects with MDD use antidepressants, and less than one-fifth receives psychological treatment. The treatments provided are determined mostly by clinical factors such as severity and comorbidity, in part by sex and marital status, but not education or income. Depression and Anxiety 26:1049,1059, 2009. © 2009 Wiley-Liss, Inc. [source] Antipsychotic prescribing trends: a review of pharmaco-epidemiological studiesACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010H. Verdoux Objective:, To review findings from pharmaco-epidemiological studies exploring antipsychotic (AP) drugs prescribing trends. Method:, We retrieved original studies that explored AP prescribing trends in general population samples since 2000. For each study, we extracted information on sampling method, period, assessment of AP use and corresponding estimates (incidence rates, prevalence rates, pharmacy sales, prescription data) and diagnostic assessment. Results:, Nearly all studies meeting the inclusion criteria (n = 17) showed an increase in AP prescriptions, mainly because of a dramatic rise in second-generation antipsychotics (SGAP) prescriptions. APs are often prescribed for non-psychotic disorders in adults as well as in children and adolescents. Conclusion:, Considering the growing number of persons from the general population exposed to APs, population studies assessing the risk/benefit ratio of SGAP use in disorders other than psychosis are necessary, particularly in children and adolescents. [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] Treatment of schizoaffective disorder , a challenge for evidence-based psychiatryACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010M. Jäger Objective:, Schizoaffective disorder is a common diagnosis in mental health services. The aim of the present article was to review treatment studies for schizoaffective disorder and draw conclusions for clinical decision making. Method:, We searched MEDLINE and Cochrane Library for relevant clinical trials and review articles up to the year 2008. Results:, Thirty-three studies using standardized diagnostic criteria, 14 of which were randomized controlled trials, could be identified. The comparability of studies is limited by the use of different diagnostic criteria. The studies reviewed do not permit consistent recommendations as to whether schizoaffective disorder should be treated primarily with antipsychotics, mood stabilizers or combinations of these drugs. The relevance of diverse subtypes of schizoaffective disorder for treatment recommendations is unclear. Conclusion:, The pertinent empirical database is small and heterogeneous. The lack of conclusive recommendations is related to issues of nosological status, plurality of diagnostic criteria and validity of the concept of schizoaffective disorder. [source] Treatment-resistant bipolar depression: towards a new definitionACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2009I. Pacchiarotti Objective:, To summarize the conceptual and operational definitions of treatment-resistant bipolar depression and to review the evidence-based therapeutic options. Method:, Structured searches of PubMed, Index Medicus, Excerpta Medica and Psyclit conducted in December 2008. Results:, Criteria for treatment resistance in bipolar depression are commonly based on concepts stemming from treatment resistance as defined for unipolar depression, an approach that proved to be inadequate. In fact, the addition of an ad hoc criterion based on lithium and other mood stabilizer unresponsiveness after reaching adequate plasma levels appears to be a patch that attempts to take into account the uniqueness of bipolar depression but fails to become operational. Recent data from randomized clinical trials of new anticonvulsants and second-generation antipsychotics should lead to the development of a modern definition of treatment-resistant bipolar depression, and specific therapeutic algorithms. Conclusion:, We suggest a redefinition of resistant bipolar I and II depression. We propose different degrees of severity within bipolar depression in a stepwise manner. [source] The subjective experience of taking antipsychotic medication: a content analysis of Internet dataACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2009J. Moncrieff Objective:, We explored the subjective effects associated with olanzapine, risperidone and older antipsychotics. Method:, We conducted a content analysis of an Internet database of comments about prescribed medications. Results:, We analysed 223 comments on risperidone, 170 on olanzapine and 46 relating to three older antipsychotics. The predominant subjective effects produced by all drugs consisted of sedation, cognitive impairment and emotional flattening or indifference. Connections appeared between these effects and Parkinsonian-like symptoms with the older drugs, sexual impairment with risperidone and metabolic effects with olanzapine. The experience of akathisia was frequently linked to suicidal thoughts. Some respondents described how the drugs' subjective effects helped to reduce symptoms of mania, psychosis and anxiety. Conclusion:, The generalisability of Internet data is uncertain. However, the data suggest that adverse subjective effects play a central role in the experience of taking antipsychotic drugs and may be related to the drugs' desired benefits. [source] How psychiatrists inform themselves and their patients about risks and benefits of antipsychotic treatmentACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2009R. Mendel Objective:, In order to choose the best treatment option, physicians have to inform themselves and their patients about both the benefits and risks of available treatment options equally. Our study aims to investigate whether psychiatrists actually do conduct such a balanced information search and presentation. Method:, Psychiatrists' information search and information presentation to a patient with schizophrenia were studied using two separate experiments. In both, participants were presented with hypothetical case vignettes and descriptions of fictitious antipsychotics. Results:, When searching for information, psychiatrists looked more for risks than benefits of antipsychotic treatment options (t = ,3.4, df = 74, P = 0.001). However, when informing a patient, they named more benefits than risks (t = 17.1, df = 224, P < 0.001). Conclusion:, The risk-biased information search presumably follows the principle of ,primum non nocere'. The benefit-biased information presentation might be motivated by the wish to persuade patients to accept the proposed therapy. [source] Neurocognitive functions in euthymic bipolar patientsACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2009K. Jamrozinski Objective:, Meta-analytic findings support the hypothesis of specific neurocognitive deficits for bipolar patients in the domains of attention, processing speed, memory and executive functions. This study aims to show neurocognitive impairment in euthymic patients with bipolar I disorder compared with healthy controls while detailing the impact of medication side-effects or illness characteristics on neuropsychological test performance. Method:, Forty euthymic patients with bipolar I disorder were compared with 40 healthy controls in a cross-sectional design. Clinical features and neuropsychological measures of IQ, psychomotor speed, verbal fluency, learning and memory, executive functions and attention were assessed. Results:, Patients without antipsychotic drug use did not differ significantly from healthy controls in any neuropsychological measure. Yet patients treated with antipsychotics showed significant underperformance in the domains of semantic fluency, verbal learning and recognition memory as well as executive functions related to planning abilities, even when clinical features were controlled for. Conclusion:, The impact of antipsychotic medication needs to be further clarified for euthymic bipolar patients and should be considered when neuropsychological test performance is interpreted. [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] Prospective comparison of course of disability in antipsychotic-treated and untreated schizophrenia patientsACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2009J. Thirthalli Objective:, To compare the course of disability in schizophrenia patients receiving antipsychotics and those remaining untreated in a rural community. Method:, Of 215 schizophrenia patients identified in a rural south Indian community, 58% were not receiving antipsychotics. Trained raters assessed the disability in 190 of these at baseline and after 1 year. The course of disability in those who remained untreated was compared with that in those who received antipsychotics. Results:, Mean disability scores remained virtually unchanged in those who remained untreated, but showed a significant decline (indicating decrement in disability) in those who continued to receive antipsychotics and in those in whom antipsychotic treatment was initiated (P < 0.001; group × occasion effect). The proportion of patients classified as ,disabled' declined significantly in the treated group (P < 0.01), but remained the same in the untreated group. Conclusion:, Disability in untreated schizophrenia patients remains unchanged over time. Treatment with antipsychotics in the community results in a considerable reduction in disability. [source] The metabolic syndrome and schizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2009J. M. Meyer Objective:, To summarize the accumulated data on metabolic syndrome prevalence in patients with schizophrenia, examine evidence for a biological contribution of the mental illness to metabolic risk and review novel options available for management of prediabetic states. Method:, A Medline search using metabolic syndrome, insulin resistance and insulin sensitivity cross-referenced with schizophrenia was performed on articles published between 1990 and May 2008. Results:, Recent evidence indicates that schizophrenia increases predisposition towards metabolic dysfunction independent of environmental exposure. Both fasting and non-fasting triglycerides have emerged as important indicators of cardiometabolic risk, while metformin, thiazolidinediones and GLP-1 modulators may prove promising tools for managing insulin resistance. Conclusion:, Because of lifestyle, disease and medication effects, schizophrenia patients have significant risk for cardiometabolic disease. Routine monitoring, preferential use of metabolically neutral antipsychotics and lifestyle education are critical to minimizing risk, with a possible role for antidiabetic medications for management of insulin resistant states that do not respond to other treatment strategies. [source] Social functioning as an outcome measure in schizophrenia studiesACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2007T. Burns Objective:, Deficits in social functioning are a core feature of schizophrenia. Method:, A literature search of English language articles published between January 1990 and December 2006 was undertaken to identify: i) scales used most frequently to assess social functioning in schizophrenia; and ii) the most frequently used social functioning scales in randomized, controlled trials of antipsychotics. A further search (without time limits) examined their psychometric properties. Results:, A total of 301 articles employed social functioning scales in the assessment of schizophrenia. These contained 87 potentially relevant measures. Only 14 randomized, controlled studies of antipsychotic agents were identified that examined social functioning. Scales varied greatly in terms of measurement approach, number and types of domains covered and scoring systems. A striking lack of data on psychometric properties was observed. Conclusion:, Limited consensus on the definition and measurement of social functioning exists. The Personal and Social Performance Scale is proposed as a useful tool in future research. [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] Pharmacological treatment of negative symptoms of schizophrenia: therapeutic opportunity or Cul-de-sac?ACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2007P. F. Buckley Objective:, Negative symptoms of schizophrenia are debilitating and they contribute to poor outcome in schizophrenia. Initial enthusiasm that second-generation antipsychotics would prove to be powerful agents to improve negative symptoms has given way to relative pessimism that the effects of current pharmacological treatments are at best modest. Method:, A review of the current ,state-of-play' of pharmacological treatments for negative symptoms in schizophrenia. Results:, Treatment results to date have been largely disappointing. The evidence for efficacy of second-generation antipsychotics is reviewed. Conclusion:, The measurement and treatment trials methodology for the evaluation of negative symptoms need additional refinement before therapeutic optimism that better treatments for negative symptoms can be realized. [source] Negative symptoms of schizophrenia: a problem that will not go awayACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2007S. M. Stahl Objective:, Negative symptoms of schizophrenia are a common, enduring, and debilitating component of the psychopathology of schizophrenia. Although efforts thus far to elucidate a distinct schizophrenia subtype based upon negative symptoms have yielded mixed results, there are nevertheless neurobiological correlates of the negative symptom typology. Method:, A review of nosology, typology, and assessment tools for determining core negative symptoms in schizophrenia. Results:, Negative symptoms can be difficult to evaluate objectively. Current rating scales ,capture' key domains of negative symptoms, in spite of considerable overlap between these domains. However, each objective assessment trades off methodological rigor and detail against brevity of assessment and ease of use. Conclusion:, The description of new methods for measuring these devastating symptoms, coupled with the ongoing development of novel antipsychotics and agents that augment antipsychotics have fuelled renewed interest in the evaluation of negative symptoms and optimism that better treatments for negative symptoms can be found. [source] Obesity, serious mental illness and antipsychotic drugsDIABETES OBESITY & METABOLISM, Issue 7 2009Richard I. G. Holt The prevalence of overweight and obesity is higher in people with mental illness than in the general population. Body weight is tightly regulated by a complex system involving the cortex and limbic system, the hypothalamus and the gastrointestinal tract. While there are justifiable concerns about the weight gain associated with antipsychotic medication, it is too simplistic to ascribe all obesity in people with serious mental illness (SMI) to their drug treatment. The development of obesity in SMI results from the complex interaction of the genotype and environment of the person with mental illness, the mental illness itself and antipsychotic medication. There are dysfunctional reward mechanisms in SMI that may contribute to poor food choices and overeating. While it is clear that antipsychotics have profound effects to stimulate appetite, no one receptor interaction provides an adequate explanation for this effect, and many mechanisms are likely to be involved. The complexity of the system regulating body weight allows us to start to understand why some individuals appear much more prone to weight gain and obesity than others. [source] Novel antipsychotics in bipolar and schizoaffective maniaACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2004G. J. R. Mensink Objective:, Novel antipsychotics are increasingly used in the treatment of bipolar and schizoaffective mania. This paper presents an overview of the controlled studies in this field. Method:, Using cross-references, a computerized search was performed on MEDLINE and EMBASE psychiatry covering the period 1990,2002. Results:, Olanzapine and risperidone, added to mood stabilizers, and olanzapine as monotherapy enjoy the most evidential support in terms of efficacy and side-effect profile for their use in acute bipolar mania. The use of modern antipsychotics in bipolar prophylaxis and in both the short- and long-term treatment of schizomania has not been widely studied yet. Conclusion:, More controlled trials are still needed comparing modern antipsychotics as monotherapy and adjunctive to mood stabilizers with conventional antipsychotics, lithium, anticonvulsants and with each other in short-term and, especially, maintenance treatment of (schizo)mania. Partly based on controlled studies, olanzapine, risperidone and other modern antipsychotics could become preferable for these indications. [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] Antipsychotic combination therapy in schizophrenia.ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2002A review of efficacy, risks of current combinations Objective:, To review the literature on efficacy and risks of combining antipsychotics (atypical with atypical or conventional) and suggest a rationale and strategies for future clinical trials. Method:, A computerized Medline search supplemented by an examination of cross-references and reviews was performed. Results:, Empirical evidence for the efficacy of combining antipsychotics is too limited to draw firm conclusions. The practice of augmenting clozapine with more ,tightly bound' D2 receptor antagonists as exemplified by risperidone augmentation of clozapine has some empirical and theoretical support. The risks of augmentation strategies have not been studied systematically. No study has examined the economic impact of combination treatment. Conclusion:, Further trials of antipsychotic combination therapies are needed before this currently unsupported practice can be recommended. Rationales for combination treatment include a broadening of the range of receptor activity or an increase in D2 receptor occupancy with certain atypical agents. Trial methodology needs to take into account subject characteristics, duration of treatment, optimization of monotherapy comparators, and appropriate outcome measures. [source] Augmentation with sulpiride for a schizophrenic patient partially responsiveto clozapineACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2000Jean H. Stubbs Objective:,Schizophrenic patients who are only partially responsive to clozapine pose a therapeutic challenge. In these circumstances some clinicians would consider adding in a second antipsychotic. We present a case report and review evidence for the efficacy of such augmentation strategies. Method:,Single case report and literature review. Results:,The total number of patients in studies and case reports of combining clozapine with other antipsychotics is small. There has been only one randomized controlled trial. This found the addition of sulpiride to clozapine resulted in clinical improvement in some patients. Conclusion:,Further randomized controlled studies of augmentation of clozapine therapy are needed to provide scientific justification for this clinical practice. [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] | |||||||||||||||||||||||||||||||||||||