Atypical (second generation) antipsychotic treatment response in very late-onset schizophrenia-like psychosis. Nonlinear Complexity and Spectral Analyses of Heart Rate Variability in Medicated and Unmedicated Patients with Schizophrenia1 Antipsychotic medication for childhood-onset schizophrenia. Elevated prolactin in pediatric patients on typical and atypical antipsychotics. Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia Determinants of antipsychotic medication use among older people living in aged care homes in Australia. Antipsychotic Drug Use and Mortality in Older Adults with Dementia Clinical symptom responses to atypical antipsychotic medications in Alzheimer's disease: phase 1 outcomes from the CATIE-AD effectiveness trial. Differences of satisfaction with medication between patients with schizophrenia treated with typical antipsychotics and atypical antipsychotics. Different Effects of Typical and Atypical Antipsychotics on Grey Matter in First Episode Psychosis: the ÆSOP Study Focus on aripiprazole: a review of its use in child and adolescent psychiatry. Effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care. Cognitive effects of atypical antipsychotic medications in patients with Alzheimer's disease: outcomes from CATIE-AD. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Psilocybin induces schizophrenia‐like psychosis in humans via a serotonin‐2 agonist action Neuroleptic-related dyskinesias in children and adolescents. Treatment adherence associated with conventional and atypical antipsychotics in a large state Medicaid program. Adherence and persistence to typical and atypical antipsychotics in the naturalistic treatment of patients with schizophrenia Attitude toward antipsychotic medication as a predictor of antipsychotic treatment discontinuation in first-episode early-onset psychosis. Atypical antipsychotic monitoring in the Kilkenny Mental Health Services. Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug Olanzapine and haloperidol in first episode psychosis: Two-year data Effectiveness of atypical antipsychotic medications in reducing violent behavior among persons with schizophrenia in community-based treatment.
INTRODUCTION Symptom amelioration in older patients with very late onset schizophrenia-like psychosis ( VLOSLP ) is often difficult , with limited psychotropic response reports yielding variable findings . Information about atypical ( second generation ) antipsychotic use in this population is scant . METHODS A consecutive sample of geriatric psychiatry out patients and in patients with psychotic disorders were retrospectively identified over a 31-month period based on systematic information abstract ion from an electronic medical record ( e-record ) . After exclusion criteria were applied , 8/138 out patients and 13/362 in patients met inclusion criteria for VLOSLP and had been naturalistically treated with an atypical antipsychotic during hospitalization or nine months of outpatient care . M and atorily completed e-record st and ardized symptom severity response ratings were converted into positive treatment response thresholds . RESULTS 38 % of out patients and 77 % of in patients ( mean age = 76 years for both groups ; mean age of onset of psychosis = 70 years for out patients and 74 years for in patients ) met criteria for positive treatment response to an atypical antipsychotic ( either aripiprazole , olanzapine , quetiapine , or risperidone ) with sign/symptom amelioration , rather than eradication . CONCLUSIONS Various atypical antipsychotics at geriatric doses yielded a positive treatment response in nearly two-thirds of VLOSLP patients . Patients with less chronic , more severe symptoms responded at a higher rate . Prospect i ve , double-blind , placebo-controlled trials with representative subject sample s are needed to vali date these preliminary findings Objective : Heart rate variability ( HRV ) reflects functioning of the autonomic nervous system and possibly also regulation by the neural limbic system , abnormalities of which have both figured prominently in various etiological models of schizophrenia , particularly those that address patients ’ vulnerability to stress in connection to psychosis onset and exacerbation . This study provides data on cardiac functioning in a sample of schizophrenia patients that were either medication free or on atypical antipsychotics  , as well as cardiac data on matched healthy controls . We included a medication-free group to investigate whether abnormalities in HRV previously reported in the literature and associated with atypical antipsychotics were solely the effect of medications or whether they might be a feature of the illness ( or psychosis ) itself . Method : We collected  24-hour ECGs on 19 patients and 24 controls . Of the patients , 9 were medication free and 10 were on atypical antipsychotics .  All subject groups were matched for age and gender . Patient groups showed equivalent symptom severity and type , as well as duration of illness . We analyzed the data using nonlinear complexity ( symbolic dynamic ) HRV analyses as well as st and ard and relative spectral analyses . Results : For the medication-free patients as compared to the healthy controls , our data show decreased R – R intervals during sleep , and abnormal suppression of all frequency ranges , but particularly the low frequency range , which persisted even after adjusting the spectral data for the mean R – R interval . This effect was exacerbated for patients on atypical antipsychotics . Likewise , nonlinear complexity analysis showed significantly impaired HRV for medication-free patients that was exacerbated in the patients on atypical antipsychotics . Conclusions : Altogether , the data suggest a pattern of significantly decreased cardiac vagal function of patients with schizophrenia as compared to healthy controls , apart from and beyond any differences due to medication side effects . The data additionally confirm earlier reports of a deleterious effect of atypical antipsychotics on HRV , which may exacerbate an underlying vulnerability in patients . These results support previous evidence that autonomic abnormalities may be a core feature of the illness ( or psychosis ) , and that an even more conservative approach to cardiac risk in schizophrenia than previously thought may therefore be clinical ly appropriate BACKGROUND : Childhood-onset schizophrenia is schizophrenia with onset prior to the age of 13 years . Although it is rare , people who suffer from schizophrenia at an early age appear to have a clinical ly severe form of the illness with poor long-term prognosis . Antipsychotic medication is one way of managing this rare but serious mental illness . OBJECTIVES : To examine the effects of antipsychotic medication for childhood-onset schizophrenia . SEARCH STRATEGY : We search ed the Cochrane Schizophrenia Group Trials Register ( November 2006 and February 2007 ) , inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors of trials for additional information . SELECTION CRITERIA : We included all r and omised clinical trials involving children and young people with a diagnosis of childhood onset schizophrenia ( i.e. with a diagnosis of schizophrenia before the age of 13 ) comparing any antipsychotic drug with another antipsychotic or placebo . DATA COLLECTION AND ANALYSIS : We reliably selected , quality assessed and extracted data from trials . We excluded data where more than 50 % of participants in any group were lost to follow up . For homogenous dichotomous data we calculated r and om effects , relative risk ( RR ) and its 95 % confidence interval ( CI ) and , where appropriate , number needed to treat ( NNT ) on an intention-to-treat basis . For normal continuous data we calculated the weighted mean difference ( WMD ) . MAIN RESULTS : From a total of 2062 citations , we identified six relevant trials . We categorised trials into three comparisons : atypical versus typical , atypical versus atypical and typical versus typical antipsychotic drugs . The only comparison to find any differences between treatment groups was atypical versus typical antipsychotic drugs . A few results from one study favoured the atypical antipsychotic clozapine over haloperidol in treating treatment resistant childhood-onset schizophrenia ( n=21 , WMD CGAS 17.00 CI 7.74 to 26.26 ; n=21 , WMD Bunney-Hamburg Psychosis Rating Scale -3.60 CI -6.64 to -0.56 ) . Participants on clozapine , however , were three times more likely to have drowsiness ( 1 RCT , n=21 , RR 3.30 CI 1.23 to 8.85 , NNH 2 CI 2 to 17 ) and half of the children receiving clozapine had neutropenia ( 1 RCT , n=21 , RR 12 , CI 0.75 to 192.86 ) . AUTHORS ' CONCLUSIONS : There are few relevant trials and , presently , there is little conclusive evidence regarding the effects of antipsychotic medication for those with early onset schizophrenia . Some benefits were identified in using the atypical antipsychotic clozapine compared with haloperidol but the benefits were offset by an increased risk of serious adverse effects . Larger , more robust , trials are required As part of systematic treatment trials of haloperidol , clozapine , and olanzapine with a total of 35 children and adolescents with early onset psychosis , prolactin was measured at baseline and week 6 of treatment . The National Institute of Mental Health patients --13 females , 22 males ( mean age , 14.1+/-2.3 years ; range , 9.1 - 19 years ) with childhood onset schizophrenia ( n = 32 ) , or Psychotic Disorder not otherwise specified ( NOS ) ( n = 3 ) with onset of psychosis before age 13 - -were recruited for open or double-blind trials of haloperidol , clozapine , or olanzapine .  Baseline serum prolactin was measured after a 3-week washout period and after 6 weeks of treatment . Mean prolactin concentration after 6 weeks of treatment was significantly elevated on all three drugs ; however , on clozapine , mean prolactin remained within the normal range . Prolactin was increased above the upper limit of normal for 100 % of 10 patients on haloperidol , 70 % of 10 patients on olanzapine , and 0 % of 15 patients on clozapine ( chi2 analyses : H > C , p = 0.004 ; O > C , p = 0.001 ) . Given the potential endocrine and possible cardiac correlates of hyperprolactinemia , these more robust prolactin elevations in pediatric patients after short-term exposure to olanzapine than those reported for adults justify longer observation intervals with bigger sample s to establish treatment safety of atypical antipsychotics in adolescents Background There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia . This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation , a recognized index of medication effectiveness in the treatment of schizophrenia . Methods We used data from a large , 3-year , observational , non-r and omized , multisite study of schizophrenia , conducted in the U.S. between 7/1997 and 9/2003 . Patients who were initiated on oral atypical antipsychotics ( clozapine , olanzapine , risperidone , quetiapine , or ziprasidone ) or oral typical antipsychotics ( low , medium , or high potency ) were compared on time to all-cause medication discontinuation for 1 year following initiation . Treatment group comparisons were based on treatment episodes using 3 statistical approaches ( Kaplan-Meier survival analysis , Cox Proportional Hazards regression model , and propensity score-adjusted bootstrap resampling methods ) . To further assess the robustness of the findings , sensitivity analyses were performed , including the use of ( a ) only 1 medication episode for each patient , the one with which the patient was treated first , and ( b ) all medication episodes , including those simultaneously initiated on more than 1 antipsychotic . Results Mean time to all-cause medication discontinuation was longer on atypical ( N = 1132 , 256.3 days ) compared to typical antipsychotics ( N = 534 , 197.2 days ; p < .01 ) , and longer on atypicals compared to typicals of high potency ( N = 320 , 187.5 days ; p < .01 ) , medium potency ( N = 140 , 213.5 days ; p < .01 ) , and low potency ( N = 74 , 208.7 days ; p < .01 ) . Among the atypicals , only clozapine , olanzapine , and risperidone had significantly longer time to all-cause medication discontinuation compared to typicals , regardless of potency level , and compared to haloperidol with prophylactic anticholinergic treatment . When compared to perphenazine , a medium-potency typical antipsychotic , only clozapine and olanzapine had a consistently and significantly longer time to all-cause medication discontinuation . Results were confirmed by sensitivity analyses . Conclusion In the usual care of schizophrenia patients , time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level . Findings were primarily driven by clozapine and olanzapine , and to a lesser extent by risperidone . Furthermore , only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine , a medium-potency typical antipsychotic OBJECTIVE To investigate determinants of antipsychotic medication use among older people living in aged care homes in Australia . DESIGN Retrospective study of a r and om 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 systematic ally 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 Context Recent reports suggest that antipsychotics are associated with increased risk for death in patients with dementia . Contribution This large , population -based study from Canada assessed the risk for death after dispensation of antipsychotics in older adults with dementia . New use of antipsychotics compared with nonuse was associated with increased risk for death at 30 days . Conventional agents were associated with higher risks than were atypical agents . Caution Sensitivity analyses showed that unmeasured confounders might diminish or erase observed associations . Implication Both conventional and atypical antipsychotics may be associated with an increased risk for death in elderly persons with dementia . The Editors Various challenging behavioral and psychological symptoms commonly develop in older adults with dementia and predispose them and their caregivers to poor outcomes ( 1 ) . Nonpharmacologic strategies are recommended as first-line management for these symptoms ( 2 ) , but they may be difficult to implement in clinical practice ( 3 ) . For many reasons , antipsychotic medications are routinely prescribed in this setting ( 4 , 5 ) . Conventional antipsychotics , such as haloperidol , have been available since the 1950s . Meta-analyses of clinical trials evaluating conventional antipsychotics to treat agitation in dementia show that these agents have modest efficacy and important adverse effects compared with placebo ( 6 , 7 ) . In the past decade , use of newer atypical antipsychotics has been rapidly increasing in clinical practice because these agents were thought to produce fewer adverse effects than conventional agents ( 2 ) . A Canadian study found that the prevalence of antipsychotic use in older adults increased from 2.2 % in 1993 to 3.0 % at the end of 2002 . In that study , atypical antipsychotics , which were unavailable in 1993 , accounted for 82.5 % of all antipsychotics dispensed in 2002 ( 8) . Short-term r and omized , controlled trials ( RCTs ) have studied the role of atypical antipsychotics in the management of behavioral and psychological symptoms of dementia ( 2 , 9 ) . An RCT involving 421 out patients with Alzheimer disease and psychosis , aggression , or agitation concluded that the adverse effects of these newer drugs offset their advantages ( 10 ) . As a result , improvements in behavioral symptoms with antipsychotic drug treatment do not necessarily lead to improvements in overall quality of life for patients or their caregivers ( 11 ) . In April 2005 , the U.S. Food and Drug Administration ( FDA ) issued a public health advisory that the use of atypical antipsychotics to treat elderly patients with dementia was associated with an increased risk for death compared with placebo ( 12 ) . In June 2005 , Health Canada issued a similar warning and additional data ( 13 ) . These warnings stem from review s of RCTs that involve the atypical agents risperidone , olanzapine , quetiapine , and aripiprazole . The mortality rate was approximately 1.6 to 1.7 times higher than with placebo and was greater with antipsychotics than with placebo in 15 of the 17 trials review ed by the U.S. FDA ( 12 ) . The warnings extend to all currently available atypical antipsychotics . Other publications have provided support for these warnings and have raised further safety concerns about older conventional antipsychotics ( 1416 ) . Important questions remain unanswered . Although RCTs provide the best evidence of treatment efficacy and harm , the individual RCTs in this case had low event rates . Reliable estimates of the mortality risk were generated only when data were combined by meta- analysis ( 14 ) . Furthermore , these RCTs were generally short in duration and could not provide information about the long-term effect of antipsychotics on mortality ( 14 , 17 ) . Finally , these trials provide estimates of harm primarily for atypical antipsychotics . Relatively few data are available on harms associated with older conventional antipsychotics . Studies suggest that important differences may exist in the safety profiles of conventional and atypical agents ( 15 , 16 , 18 , 19 ) . Using population -based data , we sought to determine the risk for all-cause mortality in older adults with dementia who received atypical antipsychotics , conventional antipsychotics , or no antipsychotic .  Because important baseline differences exist among these groups , we used propensity score matching to improve their comparability . We also evaluated the effect of duration of treatment with antipsychotics on the risk for death . Methods Data Sources Ontario is Canada 's most populous province . During our study , Ontario had a population of approximately 12 million people , of whom 1.4 million were 65 years of age or older . A universally funded health program covers nearly all physician services , medications , and hospital services for patients 65 years of age or older in Ontario . Information from 4 administrative health care data bases was linked to develop the study cohort : pharmacy records from the Ontario Drug Benefit program , hospitalization records from the Canadian Institute for Health Information Discharge Abstract Data base , physician billing information for inpatient and outpatient services from the Ontario Health Insurance Plan , and basic demographic information and vital statistics from the Registered Persons Data base . We used encrypted unique identifiers that are common among data bases to link anonymous information on demographic characteristics and health services utilization for patients in our study . Little basic information on patients is missing in these data bases . For example , the coding accuracy of drug cl aims in the Ontario Drug Benefit program data base is excellent , with an error rate of only 0.7 % ( 20 ) . The study was approved by the ethics review board of Sunnybrook and Women 's College Health Sciences Centre , Toronto , Ontario , Canada . Dementia Cohort We identified a cohort of all Ontario residents 66 years of age or older with a diagnosis of dementia ( in the Ontario Health Insurance Plan or Discharge Abstract Data base ) between 1 April 1997 and 31 March 2002 . To focus on antipsychotic drug treatment for behavioral and psychological symptoms of dementia , we excluded patients who had evidence of other psychotic disorders ( such as schizophrenia ) or were receiving palliative care services . To reduce the potential for selection bias , we studied only new users of antipsychotics and excluded those who had received antipsychotics in the year before cohort entry ( 21 ) . Exposure to Antipsychotics We identified new use of antipsychotics if any agent available through the Ontario Drug Benefit program was dispensed after cohort entry . Cohort entry ( that is , the index date ) was defined as the date of the first dispensed antipsychotic drug . Available atypical drugs included olanzapine , quetiapine , and risperidone , and available conventional drugs included chlorpromazine , flupenthixol , fluphenazine , haloperidol , loxapine , pericyazine , perphenazine , pimozide , thioridazine , and trifluoperazine . Clozapine was rarely used in Ontario during the study period , and we therefore excluded patients who were receiving this medication . Other atypical antipsychotics ( such as aripiprazole and ziprasidone ) are not licensed for use in Canada . We decided that exposure to an antipsychotic was discontinued ( and we censored follow-up ) if the patient did not refill his or her antipsychotic prescription within an interval composed of the days of drug supply plus a grace period of 20 % . For example , we censored follow-up for a patient who did not refill his or her 60-day antipsychotic prescription within 72 days . We also censored follow-up for patients who switched from atypical to conventional antipsychotics ( or vice versa ) . However , we continued follow-up for patients who switched from 1 atypical antipsychotic to another , because data suggest no statistically significant difference in the risk for death associated with individual drugs in this class ( 13 , 14 , 16 ) . We applied the same rules to conventional antipsychotics .  All-Cause Mortality The primary outcome was all-cause mortality , as recorded in the Registered Persons Data base ( for patients who were not hospitalized at the time of death ) or the Discharge Abstract Data base ( for patients who died while hospitalized ) . To assess the influence of the duration of antipsychotic exposure on the outcome , we evaluated the risk for death at 30 , 60 , 120 , and 180 days after the initial dispensing of antipsychotic medication . Cohort Matching We stratified the dementia cohort to support separate analyses among persons living in the community and those residing in long-term care at cohort entry . Studies have demonstrated that rates of antipsychotic prescribing are substantial among older adults newly admitted to long-term care facilities ( 4 ) . Furthermore , long-term care residents typically carry a greater burden of comorbid disease and are more vulnerable to adverse drug events than are their counterparts in the community ( 22 , 23 ) . Our first objective was to determine the risk for death among older adults with dementia who received atypical antipsychotics compared with those who were not exposed to any antipsychotic .  Because antipsychotic use was not r and omly assigned in the study cohorts , we addressed potential confounding and selection biases by developing a propensity score for antipsychotic use . We then applied this score to match users of atypical antipsychotics with nonusers in the dementia cohort . The rationale and methods underlying the use of a propensity score for a proposed causal exposure variable are described elsewhere ( 24 ) . Recent studies provide guidance on the selection of variables to include in the propensity score ( 25 , 26 ) . We developed a logistic regression model by using 42 covariates describing patient characteristics . Tables 1 and 2 list many of the characteristics included in the propensity score . After a structured and iterative assessment of the balance of measured covariates OBJECTIVE The study measured the effects of atypical antipsychotics on psychiatric and behavioral symptoms in patients with Alzheimer 's disease and psychosis or agitated behavior . METHOD The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer 's Disease ( CATIE-AD ) Alzheimer 's disease effectiveness study included 421 out patients with Alzheimer 's disease and psychosis or agitated/aggressive behavior . Patients were assigned r and omly to masked , flexible-dose treatment with olanzapine , quetiapine , risperidone , or placebo for up to 36 weeks . Patients could be r and omly reassigned to a different medication at the clinician 's discretion , which ended phase 1 . Psychiatric and behavioral symptoms , functioning , cognition , care needs , and quality of life were measured at regular intervals . RESULTS In relation to placebo , the last observation in phase 1 showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score , risperidone on the Clinical Global Impression of Changes , olanzapine and risperidone on the Brief Psychiatric Rating Scale ( BPRS ) hostile suspiciousness factor , and risperidone on the BPRS psychosis factor . There was worsening with olanzapine on the BPRS withdrawn depression factor . Among patients continuing phase 1 treatment at 12 weeks , there were no significant differences between antipsychotics and placebo on cognition , functioning , care needs , or quality of life , except for worsened functioning with olanzapine compared to placebo . CONCLUSION In this descriptive analysis of out patients with Alzheimer 's disease in usual care setting s , some clinical symptoms improved with atypical antipsychotics . Antipsychotics may be more effective for particular symptoms , such as anger , aggression , and paranoid ideas . They do not appear to improve functioning , care needs , or quality of life Many studies have demonstrated that atypical antipsychotics are superior to typical antipsychotics in that they have fewer side-effects and produce better improvement of cognitive deficits and quality of life in patients with schizophrenia . However , most of these studies dealt with objective indices assessed by research ers rather than subjective indices that are indeed important to patients themselves . In 126 patients with schizophrenia , annoyance of side-effects and psychotic symptoms , satisfaction with medication , wish to change medication , and knowledge of atypical antipsychotics  were assessed using question naires . Patients treated with typical antipsychotics complained less of annoyance of poor attention and concentration than those treated with atypical antipsychotics , which can be explained by increased awareness of these symptoms by the patients due to the improvement of cognitive function . There were no significant differences between the two groups in other variables . The present results that satisfaction and annoyance were similar between patients treated with typical antipsychotics and those with atypical antipsychotics , may partly explain why patients hesitated and rejected changing or shifting from typical to atypical antipsychotics . But because 98 of 126 patients did not know about atypical antipsychotics , it is important to educate the patients on the merits of atypical antipsychotics Typical antipsychotic drugs act on the dopaminergic system , blocking the dopamine type 2 ( D2 ) receptors . Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors , and a high degree of occupancy of the serotoninergic receptors 5-HT2A . Whether these different pharmacological actions produce different effects on brain structure remains unclear . We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based , nonr and omized sample of patients at the first psychotic episode . Subjects were recruited as part of a large epidemiological study ( ÆSOP : aetiology and ethnicity in schizophrenia and other psychoses ) . We evaluated 22 drug-free patients , 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics .  We used high-resolution MRI and voxel-based methods of image analysis . The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes . However , typicals seem to affect more extensively the basal ganglia ( enlargement of the putamen ) and cortical areas ( reductions of lobulus para central is , anterior cingulate gyrus , superior and medial frontal gyri , superior and middle temporal gyri , insula , and precuneus ) , while atypical antipsychotics seem particularly associated with enlargement of the thalami . These changes are likely to reflect the effect of antipsychotics on the brain , as there were no differences in duration of illness , total symptoms scores , and length of treatment among the groups . In conclusion , we would like to suggest that even after short-term treatment , typical and atypical antipsychotics may affect brain structure differently OBJECTIVE To review published literature regarding aripiprazole in child and adolescent psychiatry . METHOD A literature review was conducted using the medline search term : ' aripiprazole ' with limits : Human trials , English language , All Child ( aged 0 - 18 years ) . Additional articles were identified from reference information and poster presentation data . RESULTS Aripiprazole is an atypical antipsychotic which was recently approved for use in Canada , but has been available for several years in the United States . Pharmacologically , aripiprazole is a partial agonist at D(2 ) and 5-HT(1A ) receptors and an antagonist at 5-HT(2A ) receptors . R and omized controlled trial data is available showing efficacy for aripiprazole in the treatment of children and adolescents with schizophrenia , bipolar disorder and behavioural problems associated with autism . Open-label evidence is also available for use of aripiprazole in other disorders such as tic disorders , aggression and disruptive behavior disorders . Unlike some other available atypical antipsychotics , there does not appear to be any effect on QTc interval on the electrocardiogram . Adverse effects including extrapyramidal symptoms ( EPS ) , akathisia , sedation , headache , nausea were significant in clinical trials in children and adolescents . The possibility of aripiprazole causing tardive dyskinesia can not be excluded . In this population , aripiprazole appears to have minimal impact on the metabolic profile compared to most other atypical antipsychotics , with minimal changes in weight or body mass index , no significant changes in glucose or lipid metabolism , and a decrease in serum prolactin . CONCLUSION Aripiprazole may represent an important alternative for some children and adolescents who have experienced poor efficacy or significant metabolic adverse effects with their current antipsychotic treatment regimen BACKGROUND In two recent r and omised clinical trials , a meta- analysis and in an effectiveness study analysing routine data from the U.S. Veterans Administration the superiority of the newer atypical drugs over typical antipsychotic drugs , concerning both their efficacy and their side-effect profile , has been question ed . AIMS OF THE STUDY To analyse the effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care . METHODS Cohort study using routine care data from a statutory sickness fund with 5.4 million insured in Germany . To be included , patients had to be discharged with a diagnosis of schizophrenia in 2003 and fulfil membership criteria . Main outcome measures were rehospitalisation rates , mean hospital bed days , mean length of stay , cost of inpatient and pharmaceutical care to the sickness fund during follow-up and medication used to treat side-effects . RESULTS 3121 patients were included into the study . There were no statistically significant differences in the effectiveness of atypical and typical antipsychotics on rehospitalisation during follow-up ( rehospitalisation rate ratio 1.07 , 95 % confidence interval 0.86 to 1.33 ) . However , there were consistent observations of atypical antipsychotics being more effective for severe cases of schizophrenia ( 14.6 % of study population ; > 61 prior bed days per year in 2000 - 2002 ) in the follow-up period , whereas for the other severity strata typical antipsychotics seemed more effective in reducing various rehospitalisation outcomes .  Patients treated with atypical antipsychotics  received significantly less prescriptions for anticholinergics or tiaprid ( relative risk 0.26 , 95 % confidence interval 0.18 to 0.38 ) . DISCUSSION The effectiveness of atypical antipsychotics for schizophrenia on rehospitalisation measures appeared similar to that of typical antipsychotics . With the exception of severe cases , the higher costs for atypical antipsychotics were not offset by savings from reduced inpatient care . Major limitations include the lack of statistical power for subgroup analyses , the lack of clinical severity scale data and of life-course medical history data which both increase the risk of residual confounding by disease severity . CONCLUSIONS This study provides evidence that the effectiveness of atypical and typical antipsychotics measured in terms of hospital readmissions appears to be similar in routine care . IMPLICATION S FOR HEALTH CARE PROVISION AND USE From a clinical perspective , this study provides evidence that the effectiveness of atypical and typical antipsychotics measured in terms of hospital readmissions appears to be similar in routine care . IMPLICATION S FOR HEALTH POLICIES Routine data studies can yield valuable information for policy decision-makers on the costs and the effectiveness of pharmaceuticals in routine care , complementing efficacy data from r and omised clinical trials currently used for licensing and reimbursement decisions . IMPLICATION S FOR FURTHER RESEARCH The non-significant differences in the effectiveness of atypical compared to typical antipsychotics according to severity of disease should be investigated in a prospect i ve observational study or in a r and omised clinical trial OBJECTIVE The impact of the atypical antipsychotics olanzapine , quetiapine , and risperidone on cognition in patients with Alzheimer 's disease is unclear . The authors assessed the effects of time and treatment on neuropsychological functioning during the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer 's Disease study ( CATIE-AD ) . METHOD CATIE-AD included 421 out patients with Alzheimer 's disease and psychosis or agitated/aggressive behavior who were r and omly assigned to receive masked , flexible-dose olanzapine , quetiapine , risperidone , or placebo . Based on their clinicians ' judgment , patients could discontinue the originally assigned medication and receive another r and omly assigned medication . Patients were followed for 36 weeks , and cognitive assessment s were obtained at baseline and at 12 , 24 , and 36 weeks . Outcomes were compared for 357 patients for whom data were available for at least one cognitive measure at baseline and one follow-up assessment that took place after they had been on their prescribed medication or placebo for at least 2 weeks . RESULTS Overall , patients showed steady , significant declines over time in most cognitive areas , including in scores on the Mini-Mental State Examination ( MMSE ; -2.4 points over 36 weeks ) and the cognitive subscale of the Alzheimer 's Disease Assessment Scale ( -4.4 points ) . Cognitive function declined more in patients receiving antipsychotics than in those given placebo on multiple cognitive measures , including the MMSE , the cognitive subscale of the Brief Psychiatric Rating Scale , and a cognitive summary score summarizing change on 18 cognitive tests . CONCLUSIONS In CATIE-AD , atypical antipsychotics were associated with worsening cognitive function at a magnitude consistent with 1 year 's deterioration compared with placebo . Further cognitive impairment is an additional risk of treatment with atypical antipsychotics that should be considered when treating patients with Alzheimer 's disease OBJECTIVE Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder . This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large , controlled clinical trial . METHOD Patients with first-episode psychosis ( N=263 ) were r and omly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks . Domains measured included psychopathology , psychosocial variables , neurocognitive functioning , and brain morphology and metabolism . This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase . RESULTS Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity , which did not differ significantly in last-observation-carried-forward analyses . However , in a mixed-model analysis , olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating .  Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain , compared with the haloperidol-treated patients . Overall , significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study ( 67 % versus 54 % ) . CONCLUSIONS As expected on the basis of previous studies , both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis . However , olanzapine had several relative advantages in therapeutic response . Although the nature of adverse events differed between the two agents , retention in the study was greater with olanzapine . Retention in treatment is important in this patient population , given their risk of relapse . Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia PSILOCYBIN , an indoleamine hallucinogen , produces a  psychosis-like syndrome in humans that resembles first episodes of schizophrenia . In healthy human volunteers , the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone , but were increased by the dopamine antagonist and typical antipsychotic haloperidol . These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation , independently of dopamine stimulation . Thus , serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics BACKGROUND Few studies have investigated the comparative risk of neuroleptic-related dyskinesias in children and adolescents receiving typical versus newer , atypical antipsychotics .  This prospect i ve study was completed to test whether clinical use of atypical antipsychotics is associated with less risk for developing neuroleptic-related dyskinesias than clinical use of typical neuroleptics in an unselected heterogeneous population of seriously emotionally disturbed youths admitted to acute residential treatment . We also tested a novel model of predictive risk for neuroleptic-related dyskinesias in children and adolescents . METHOD 102 children and adolescents receiving typical neuroleptics , atypical antipsychotics , or the combination were studied . Youths developing neuroleptic-related dyskinesias were compared with youths free of dyskinesias over a 3-month study period on demographic , diagnostic , and treatment variables . Logistic regression was utilized to develop a novel model of predictive risk . RESULTS Of neuroleptic-treated youths , 5.9 % had probable tardive dyskinesia , a rate less than the prevalence of tardive dyskinesia in chronic neuroleptic-treated adults . Use of typical neuroleptics was significantly ( p = .03 ) associated with dyskinesia compared with use of atypical antipsychotics . Four variables including IQ , initial Abnormal Involuntary Movement Scale score , type of antipsychotic , and cumulative number of risk factors accounted for 35.8 % of the variance when predicting dyskinetic status . CONCLUSION Use of atypical antipsychotics appears to be associated with less dyskinesia risk than typical neuroleptics in an unselected group of seriously emotionally disturbed children and adolescents . Results support a cumulative risk model of neuroleptic-related dyskinesia in youths OBJECTIVES Rates of medication adherence over a one-year period were assessed among out patients with schizophrenia who initiated therapy with conventional or atypical antipsychotic agents .  METHODS Data were drawn from paid medical and pharmacy cl aims for a r and om sample of 10 percent of all California Medicaid ( " Medi-Cal " ) recipients . Out patients with schizophrenia who were aged 18 years or older and who initiated monotherapy with a conventional or atypical antipsychotic medication in the last quarter of 1997 were identified . The percentages of patients who discontinued antipsychotic therapy or who had a switch in medications over a one-year period were determined . The use of selected concomitant medications was also assessed . Data were analyzed by means of chi square tests and multivariate statistics that adjusted for demographic and clinical differences between medication groups . RESULTS A total of 298 patients who initiated therapy with a conventional ( N=93 ) or atypical ( N=205 ) antipsychotic medication were identified . The groups were similar in mean age ( about 42 years ) and gender distribution ( about 54 percent were male ) . Compared with patients who received conventional antipsychotics , those receiving atypical antipsychotics were significantly less likely to have a switch in medication and to use concomitant anticholinergic and anxiolytic medications . In each group , antipsychotic medication was available for about 60 percent of days over one year of follow-up . CONCLUSIONS Compared with the use of conventional antipsychotics , the use of atypical antipsychotic medications was associated with significantly less treatment switching and less use of concomitant medications . However , undertreatment , evidence d by a lack of prescription refills , occurred among patients taking both medication classes , which highlights the need for further research on nonadherence Objective To compare adherence and persistence to typical versus atypical antipsychotics and between specific atypical agents in the usual care of schizophrenia and to examine the association between adherence and persistence . Method Data were drawn from a 3-year prospect i ve , nonr and omized , noninterventional study of schizophrenia conducted during 1997–2003 . Initiators on haloperidol , risperidone , olanzapine , quetiapine , and clozapine with at least 1 year of follow-up were included ( n = 878 ) .  Adherence ( Medication Possession Ratio , MPR ) and persistence ( time to all-cause medication discontinuation ) were assessed using medical record prescription information . Analyses employed multivariate statistics adjusted for group differences . Results Overall , 58 % of the patients were deemed adherent ( MPR > 80 % ) . Adherence rates were higher : for atypical ( 59.4 % ) than typical antipsychotics ( 34.5 % , p < 0.001 ) , for clozapine ( 77 % ) than each comparator excluding olanzapine ( p < 0.01 ) , and for olanzapine ( 64 % ) than risperidone ( 57 % , p = 0.027 ) and quetiapine ( 52 % , p = 0.019 ) . Differences between risperidone and quetiapine were not statistically significant . Adherence and persistence were highly correlated ( r = 0.957 , p < 0.001 ) . Conclusion In the usual care of schizophrenia , medication adherence and persistence appear to be highly correlated and to significantly differ between typical and atypical antipsychotics and among atypical agents . The choice of antipsychotic may play a meaningful role in patients ’ adherence to and persistence with antipsychotic medications BACKGROUND Antipsychotic drug discontinuation is a key risk factor in psychotic relapses . Clinical relapse is related to poor outcome , especially in the earlier stages of psychotic illness . The attitude toward treatment during the acute phase of a first episode of psychosis has been proposed as one of the main determinants of treatment discontinuation . However , the relationship between attitude toward antipsychotic medication and treatment discontinuation in the adolescent population has not been properly assessed . METHODS Adolescents , aged 12 - 18 years old , consecutively admitted to an adolescent unit with a first lifetime admission for a first episode of psychosis were asked to participate in a r and omized , flexible-dose , 6-month controlled trial of olanzapine vs. quetiapine .  Attitude toward antipsychotic medication  was assessed using the 10-item Drug Attitude Inventory ( DAI ) . The outcome variable was all-cause treatment discontinuation over the 6-month follow- up . The study sample was composed of 42 patients [ 34 boys ( 82.9 % ) , eight girls ( 17.1 % ) , mean age ± SD : 16.1±1.3 ] . RESULTS Of the 42 patients , only 29 ( 69 % ) continued the medication throughout the entire 6-month follow-up , while 13 ( 31 % ) discontinued the medication . DAI scores were greater than zero at all assessment s , indicating that the general attitude of the patients toward medication was positive . Higher DAI scores at baseline were related to lower all-cause treatment discontinuation [ adjusted hazard ratio ( HR ) = 0.81 ( 95 % CI : 0.68 - 0.96 ) , P=0.016 ] , while DAI scores at 15 days were unrelated to treatment discontinuation [ adjusted HR=1.0 ( 95 % CI : 0.82 - 1.23 ) , P=0.998 ] . CONCLUSIONS A better attitude toward antipsychotic medication at a first lifetime psychiatric admission for a first early-onset psychotic episode was significantly related to lower all-cause antipsychotic treatment discontinuation OBJECTIVES To examine baseline testing and ongoing monitoring of cardiovascular and other risk factors in individuals prescribed atypical antipsychotic medications . METHODS We derived a list of baseline and ongoing monitoring tests from the literature ( Weight , BMI , blood pressure , U&E , LFTs , glucose , HbA1C , FBC , TFTs , prolactin , lipids & ECG ) and then review ed a r and om sample of 80 records of patients prescribed atypical antipsychotics and currently attending an Irish public catchment area service , for evidence of testing . RESULTS Levels of testing for baseline tests ranged from 45 % for blood pressure to 0 % for BMI . Levels of ongoing monitoring tests ranged from 42.5 % for U&E to 0 % for BMI . Patients admitted to hospital were much more likely to have had testing . CONCLUSIONS The need for baseline and ongoing monitoring of certain tests in patients prescribed atypical antipsychotics is increasingly accepted . Levels of such testing are currently quite low and need to increase The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound . Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and 19 matched controls participated . Patients were r and omly assigned to treatment with either low doses of the typical antipsychotic drug , zuclopenthixol , or the atypical compound , risperidone . High-resolution magnetic resonance imaging ( MRI ) scans were obtained in patients before and after 12 weeks of exposure to medication and in controls at baseline . Cau date nucleus , nucleus accumbens , and putamen volumes were measured . Compared with controls , absolute volumes of interest ( VOIs ) were smaller in patients at baseline and increased after treatment . However , with controls for age , gender and whole brain or intracranial volume , the only significant difference between patients and controls was a Hemisphere x Group interaction for the cau date nucleus at baseline , with controls having larger left than right cau date nuclei and patients having marginally larger right than left cau date volumes . Within patients , the two medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs . Nevertheless , when medication groups were examined separately , a significant volume increase in the putamen was evidence d in the risperidone group . The altered asymmetry in cau date volume in patients suggests intrinsic basal ganglia pathology in schizophrenia , most likely of neurodevelopmental origin Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis . This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period . Two hundred and sixty-three patients were r and omized to olanzapine or haloperidol in a doubleblind , multisite , international 2-year study . Clinical symptoms and side effects were assessed at baseline and longitudinally following r and omization for the duration of the study . Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity ( the primary outcome measure ) over the course of the study . However , the treatment groups differed on two secondary efficacy measures . Patients were less likely to discontinue treatment with olanzapine than with haloperidol :  mean time ( in days ) in the study was significantly greater for those treated with olanzapine compared to haloperidol ( 322.09 vs. 230.38 , p<0.0085 ) . Moreover , remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol ( 57.25 % vs. 43.94 % , p<0.036 ) . While extrapyramidal side effects were greater in those treated with haloperidol , weight gain , cholesterol level and liver function values were greater in patients treated with olanzapine . The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients , which must be weighed against those adverse effects that are more likely with olanzapine This study prospect ively compared the effectiveness of atypical antipsychotic medications to that of conventional neuroleptics in reducing violent behavior  among patients with schizophrenia under " usual care " conditions in the community . Participants ( n = 229 ) were adults with schizophrenia spectrum disorders receiving inpatient or outpatient services in public sector mental health systems in North Carolina . Subjects were followed for 2 years in an observational study using multiple methods of data collection at 6-month intervals to assess treatment , sociodemographic characteristics , clinical features , and violence outcomes . Treatment with atypical antipsychotic medications ( clozapine , risperidone , or olanzapine ) was found to significantly reduce the risk of violent behavior , whereas treatment with conventional neuroleptics did not have this same beneficial effect . A cumulative effect on reduced violence was attributable to consistent compliance with atypical antipsychotic medications over a 2-year period . Concurrent reductions in psychotic symptoms , substance abuse , and adverse medication side effects were found to mediate the association between adherence with atypicals and lower violence risk . Treatment with atypical antipsychotic medications should be considered as an important component of violence risk management for schizophrenia patients at risk for violent behavior
No convincing evidence suggests that atypical antipsychotic medications are superior to typical medications for the treatment of adolescents with psychosis .
However , atypical antipsychotic medications may be more acceptable to young people because fewer symptomatic adverse effects are seen in the short term .
Little evidence is available to support the superiority of one atypical antipsychotic medication over another , but side effect profiles are different for different medications .
Treatment with olanzapine , risperidone and clozapine is often associated with weight gain .
Aripiprazole is not associated with increased prolactin or with dyslipidaemia .
Adolescents may respond better to st and ard-dose as opposed to lower-dose risperidone , but for aripiprazole and ziprasidone , lower doses may be equally effective .
BACKGROUND Schizophrenia often presents in adolescence , but current treatment guidelines are based largely on studies of adults with psychosis .
Over the past decade , the number of studies on treatment of adolescent-onset psychosis has increased .
The current systematic review collates and critiques evidence obtained on the use of various atypical antipsychotic medications for adolescents with psychosis .
OBJECTIVES To investigate the effects of atypical antipsychotic medications in adolescents with psychosis .
We review ed in separate analyses various comparisons of atypical antipsychotic medications with placebo or a typical antipsychotic medication or another atypical antipsychotic medication or the same atypical antipsychotic medication but at a lower dose .