Focus on aripiprazole: a review of its use in child and adolescent psychiatry. Effectiveness of atypical antipsychotic medications in reducing violent behavior among persons with schizophrenia in community-based treatment. Antipsychotic medication for childhood-onset schizophrenia. Antipsychotic prescribing practices in Connecticut's public mental health system: rates of changing medications and prescribing styles. International multisite double-blind trial of the atypical antipsychotics risperidone and olanzapine in 175 elderly patients with chronic schizophrenia. Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment. Atypical (second generation) antipsychotic treatment response in very late-onset schizophrenia-like psychosis. A Consecutive Series of Treated Affected Offspring of Parents with Bipolar Disorder: Is Response Associated with the Clinical Profile? Medical-claims databases in the design of a health-outcomes comparison of quetiapine (`Seroquel') and usual-care antipsychotic medication Changes in cognitive functioning with risperidone and olanzapine treatment: a large-scale, double-blind, randomized study Atypical Antipsychotic Usage-Related Higher Serum Leptin Levels and Disabled Lipid Profiles in Euthymic Bipolar Patients First generation antipsychotics switch with Risperidone in the treatment of chronic schizophrenic patients. An assessment of emergent tardive dyskinesia and existing dyskinesia in patients receiving long-acting, injectable risperidone: Results from a long-term study Lower incidence of tardive dyskinesia with risperidone compared with haloperidol in older patients. Prescribing for inpatients with schizophrenia: an international multi-center comparative study. Effectiveness of maintenance treatments with atypical and typical antipsychotics in stable schizophrenia with early stage: 1-year naturalistic study Quetiapine is not associated with increase in prolactin secretion in contrast to haloperidol. Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder Is flunarizine a long-acting oral atypical antipsychotic? A randomized clinical trial versus haloperidol for the treatment of schizophrenia. [Measures to reduce high-dose multiple antipsychotics in Japan]. Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study Switching to olanzapine from previous antipsychotics: a regional collaborative multicenter trial assessing 2 switching techniques in Asia Pacific. Treatment adherence associated with conventional and atypical antipsychotics in a large state Medicaid program.
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 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 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 We characterized prescribing in Connecticut 's State public mental health system to assess the feasibility of implementing an evidence -based medication algorithm . Medication records for a r and om sample of out patients with diagnoses of schizophrenia spectrum disorders showed prescribing patterns similar to the entire United States . The base rate of changing antipsychotic medications was moderate . Over half of patients received decanoate  medications  , polypharmacy was nontrivial , and there was variability in prescribing patterns across physicians . Caucasian patients were more likely to receive an atypical antipsychotic  and less likely to have a decanoate medication  , and Latino patients were less likely to change medications . Because the base rate of changing medications was moderate and a considerable proportion of patients were prescribed newer antipsychotic medications , introducing a research -derived medication algorithm with newer atypical antipsychotics as first line agents may fit well with current practice . Further , implementing such an algorithm may reduce racial and ethnic disparities in prescribing patterns OBJECTIVE The authors compared the effects of the two most commonly used atypical antipsychotics , risperidone and olanzapine , in elderly patients with schizophrenia . METHODS In an 8-week , international , double-blind study , patients ( out patients , hospital in patients , and residents of nursing or boarding homes ) were r and omly assigned to receive risperidone ( 1 mg to 3 mg/day ) or olanzapine ( 5 mg to 20 mg/day ) . The main outcome measures were changes in Positive and Negative Syndrome Scale ( PANSS ) total scores and rates of extrapyramidal symptoms ( EPS ) . RESULTS Subjects were 175 patients age 60 years or over with schizophrenia or schizoaffective disorder . The mean duration of illness was 36.5 years . Median doses were 2 mg/day of risperidone and 10 mg/day of olanzapine .  PANSS total scores and four of the five PANSS factor scores ( positive symptoms , negative symptoms , disorganized thoughts , and anxiety/depression ) improved significantly at all time-points and at endpoint in both groups ; between-treatment differences were not significant . EPS-related adverse events were reported by 9.2 % of patients in the risperidone group and 15.9 % in the olanzapine group ; the between-treatment difference was not significant . Total scores on the Extrapyramidal Symptom Rating Scale were reduced in both groups at endpoint ; between-treatment differences were not significant . Clinical ly relevant weight gain was seen in both groups , but was significantly less frequent in risperidone patients than in olanzapine patients . CONCLUSIONS Stable elderly patients with chronic schizophrenia receiving appropriate doses of risperidone or olanzapine over an 8-week period experienced significant reductions in the severity of psychotic and extrapyramidal symptoms , with a relatively low risk of side effects OBJECTIVES To determine the clinical and cost-effectiveness of different classes of antipsychotic drug treatment in people with schizophrenia responding inadequately to , or having unacceptable side-effects from , their current medication . DESIGN Two pragmatic , r and omised controlled trials ( RCTs ) were undertaken . The first RCT ( b and 1 ) compared the class of older , inexpensive conventional drugs with the class of new atypical drugs in people with schizophrenic disorders , whose current antipsychotic drug treatment was being changed either because of inadequate clinical response or owing to side-effects . The second RCT ( b and 2 ) compared the new ( non-clozapine ) atypical drugs with clozapine in people whose medication was being changed because of poor clinical response to two or more antipsychotic drugs . Both RCTs were four-centre trials with concealed r and omisation and three follow-up assessment s over 1 year , blind to treatment . SETTING Adult mental health setting s in Engl and . PARTICIPANTS In total , 227 participants aged 18 - 65 years ( 40 % of the planned sample ) were r and omised to b and 1 and 136 ( 98 % of the planned sample ) to b and 2 . INTERVENTIONS Participants were r and omised to a class of drug . The managing clinician selected the individual drug within that class , except for the clozapine arm in b and 2 . The new atypical drugs included risperidone , olanzapine , quetiapine and amisulpride . The conventional drugs included older drugs , including depot preparations . As in routine practice , clinicians and participants were aware of the identity of the prescribed drug , but clinicians were asked to keep their participating patient on the r and omised medication for at least the first 12 weeks . If the medication needed to be changed , the clinician was asked to prescribe another drug within the same class , if possible . MAIN OUTCOME MEASURES The primary outcome was the Quality of Life Scale ( QLS ) . Secondary clinical outcomes included symptoms [ Positive and Negative Syndrome Scale ( PANSS ) ] , side-effects and participant satisfaction . Economic outcomes were costs of health and social care and a utility measure . RESULTS Recruitment to b and 1 was less than anticipated ( 40 % ) and diminished over the trial . This appeared largely due to loss of perceived clinical equipoise ( clinicians progressively becoming more convinced of the superiority of new atypicals ) . Good follow-up rates and a higher than expected correlation between QLS score at baseline and at follow-up meant that the sample as recruited had 75 % power to detect a difference in QLS score of 5 points between the two treatment arms at 52 weeks . The recruitment to b and 2 was approximately as planned . Follow-up assessment s were completed at week 52 in 81 % of b and 1 and 87 % of b and 2 participants . B and 1 data showed that , on the QLS and symptom measures , those participants in the conventional arm tended towards greater improvements . This suggests that the failure to find the predicted advantage for new atypicals was not due to inadequate recruitment and statistical power in this sample . Participants reported no clear preference for either class of drug . There were no statistically significant differential outcomes for participants entering b and 1 for reasons of treatment intolerance to those entering because of broadly defined treatment resistance . Net costs over the year varied widely , with a mean of 18,850 pounds sterling in the conventional drug group and 20,123 pounds sterling in the new atypical group , not a statistically significant difference . Of these costs , 2.1 % and 3.8 % were due to antipsychotic drug costs in the conventional and atypical group , respectively . There was a trend towards participants in the conventional drug group scoring more highly on the utility measure at 1 year . The results for b and 2 showed an advantage for commencing clozapine in quality of life ( QLS ) at trend level ( p = 0.08 ) and in symptoms ( PANSS ) , which was statistically significant ( p = 0.01 ) , at 1 year . Clozapine showed approximately a 5-point advantage on PANSS total score and a trend towards having fewer total extrapyramidal side-effects . Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals ( p < 0.05 ) . Net costs of care varied widely , but were higher than in b and 1 , with a mean of 33,800 pounds sterling in the clozapine group and 28,400 pounds sterling in the new atypical group . Of these costs , 4.0 % and 3.3 % , respectively , were due to antipsychotic drug costs . The increased costs in the clozapine group appeared to reflect the licensing requirement for inpatient admission for commencing the drug . There was a trend towards higher mean participant utility scores in the clozapine group . CONCLUSIONS For b and 1 , there is no disadvantage in terms of quality of life and symptoms , or associated costs of care , over 1 year in commencing conventional antipsychotic drugs rather than new atypical drugs . Conventional drugs were associated with non-significantly better outcomes and lower costs . Drug costs represented a small proportion of the overall costs of care ( < 5 % ) . For b and 2 , there is a statistically significant advantage in terms of symptoms but not quality of life over 1 year in commencing clozapine rather than new atypical drugs , but with increased associated costs of care . The results suggest that conventional antipsychotic drugs , which are substantially cheaper , still have a place in the treatment of patients unresponsive to , or intolerant of , current medication . Further analyses of this data set are planned and further research is recommended into areas such as current antipsychotic treatment guidance , valid measures of utility in serious mental illness , low-dose ' conventional ' treatment in first episode schizophrenia , QLS validity and determinants of QLS score in schizophrenia , and into the possible financial and other mechanisms of rewarding clinician participation in trials 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 : In adults with established bipolar disorder ( BD ) , differential response to  mood stabilizers  has been associated with the clinical profile . Long-term treatment studies of youth with BD are lacking . This paper provides longitudinal observations of response to  mood stabilizers  early in the course of illness in youth with BD . Method : We report on 15 research patients who , as adolescents , met DSM-IV lifetime criteria for a bipolar spectrum disorder and required long-term treatment . These youths derived from families with one parent having BD whose course and long-term treatment response were determined in accordance with research criteria . The patients were offered lithium , and if they failed to respond or refused it , they were treated with either an anticonvulsant or an atypical antipsychotic . Using a vali date d scale , an independent rater retrospectively blindly scored the response to long-term treatment . Results : Those patients who stabilized on  lithium  derived from lithium-responsive families , whereas those who stabilized on an  antipsychotic  derived from lithium-nonresponsive families . The clinical course in the youths stabilized by lithium differed from that in the youths stabilized by an atypical antipsychotic . Conclusions : Our findings suggest that the clinical profile may help in selecting effective stabilizing treatment and that a proportion of youth can be stabilized on monotherapy . This is a small case series with nonr and om treatment assignment , and the findings should be considered tentative Treating schizophrenia is expensive . Preventing rehospitalization of patients with schizophrenia provides an attractive opportunity for cost savings , especially for patients with ' revolving-door ' or multiple-episode schizophrenia . Reducing the occurrence of extrapyramidal symptoms and other adverse events associated with st and ard antipsychotic agents may increase compliance and reduce the rate of rehospitalization of patients with schizophrenia .  Quetiapine ( ' Seroquel ' , ICI 204,636 , Zeneca Pharmaceuticals ) is a new dibenzothiazepine antipsychotic agent with a low propensity for extrapyramidal symptoms . We describe here a unique methodology to compare quetiapine with usual-care medications in real-world treatment setting s. The trial objective is to determine if therapy with this new atypical antipsychotic agent can reduce the rate of rehospitalization and , therefore , treatment costs . Using two secondary medical-cl aims data bases , we defined the minimal threshold for revolving-door status as 1.0 admission per year ; this definition allows our trial to focus on the sub population of schizophrenic patients with the greatest potential for cost savings by either the new atypical antipsychotic quetiapine or usual-care therapy . We describe here the approach used in our trial Objective The effects of risperidone and olanzapine on cognitive functioning in patients with schizophrenia were compared in a r and omized , double-blind trial . Method Three hundred and seventy-seven patients were r and omly assigned to receive 2–6 mg/day of risperidone or 5–20 mg/day of olanzapine for 8 weeks . Cognitive function was assessed with a focused cognitive assessment battery ; in addition , extrapyramidal symptoms were assessed using the extrapyramidal symptom rating scale ( ESRS ) , and the positive and negative syndrome scale ( PANSS ) was rated for all patients . Results Treatment with these two atypical antipsychotic medications was associated with improved performance on the Wisconsin card sorting test , the trail-making test , the California verbal learning test , the continuous performance test , and some aspects of verbal fluency and spatial working memory . No differences in the effects of the drugs on any of the cognitive tests were noted . Correcting for the effects of anticholinergic treatment did not alter the magnitude of cognitive effects . Conclusions Atypical antipsychotic treatment is associated with wide-ranging benefits on cognitive functioning . Previous reports of greater benefits of olanzapine over risperidone in a small- sample pilot study were not substantiated . These results are not due in general to changes in clinical symptoms or movement disorders , suggesting a direct effect of atypical antipsychotic medications on cognitive deficits in schizophrenia Atypical antipsychotics (AA)-induced  weight gain is associated with increased leptin levels . AA have been increasingly used in the treatment of bipolar disorders . This cross-sectional study aim ed to evaluate the association between serum leptin and lipid profiles considering the drug treatments in euthymic bipolar out patients .  Leptin and lipid profiles were compared , and no differences were noted in leptin , cholesterol , and low-density lipoprotein levels among the patients and controls . Glucose , very-low-density lipoprotein , and triglyceride levels in patients were higher than in controls , while high-density lipoprotein levels were low . Patients were divided into three groups according to their type of drug usage : AA users , AA + mood stabilizer users , and mood stabilizer users .  Each group of patients was compared with a healthy control group for mentioned biochemical parameters . Lipid profiles were disordered by using both AA and mood stabilizers , but higher leptin levels are associated with AA usage . However , leptin does not seem to be responsible for dyslipidemia caused by AA or mood stabilizers in euthymic bipolar patients BACKGROUND Schizophrenia is a severe chronic psychiatric disorder for which treatment compliance is important in the prevention of relapse .  Second generation antipsychotics ( SGA ) , such as Risperidone , have been found to be more effective in the treatment of such patients than the high potency first generation antipsychotics ( FGA ) . This is an open study where the same group of patients was first treated with FGA and then were switched to Risperidone , in controlled hospital conditions , after a wash- out period . The aim of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with FGA  would further benefit from a switch to an atypical antipsychotic drug . SUBJECTS AND METHODS Eighty hospitalized patients suffering from Schizophrenia or Schizoaffective disorder ( male 54 , female 26 ) were first treated with Haloperidol ( N=60 ) or Fluphenazine ( N=20 ) , and then were switched to Risperidone . Their clinical state was monitored using the PANSS scale for Schizophrenia , measuring the Total PANSS score . The KLAWANS scale for assessment of extrapyramidal syndrome ( EPS ) was also used . Administration and dosage of Trihexiphenidil ( THF ) was recorded . The study lasted for 8 weeks , with 4 screenings ( Visit 0-baseline- FGA , Visits 1 - 3 Risperidone on Day 14 , 28 and 56 , respectively ) . RESULTS The average age was 38 . Patients usually suffered the paranoid form of Schizophrenia ( 55 % ) . The duration of illness was more than 5 years ( 38.8 % ) . During the eight- week trial on Risperidone , using the PANSS total scores , we observed clinical improvement where the therapy switch had caused an initial worsening ( p<0.05 ) . Also , the compared baseline ( FGA ) and last visit showed a low , but statistically significant benefit in favor of Risperidone ( t=5.45 , df=79 , p<0.005 ) . Intensity of EPS measured by KLAWANS scores significantly decreased during time ( F=4.115 ; p=0.016 ; Partial Eta Square=0.058 ) . Average Trihexiphenidil doses followed Risperidone in a dose dependent manner ( r=0.748 , r=0.661 , respectively , p<0.01 ) with the consequent decrease of patients needing THF corrective therapy ( 68.8 % at the baseline toward 22.5 % on last visit ) . CONCLUSION Switch to Risperidone medication provided significant additional improvement in symptom severity , extrapyramidal side effects and need for anticholinergic medication . This suggests that one might expect better compliance in future treatment in this population of chronic schizophrenic patients INTRODUCTION Treatment-emergent tardive dyskinesia ( TD ) can be a serious side effect of antipsychotic treatment . Atypical antipsychotics are associated with a lower risk for TD than are conventional agents . A long-acting atypical antipsychotic , with more stable blood levels and lower peak blood levels than an oral formulation , may provide differential benefit regarding side effects , including movement disorders . This analysis assessed TD by defined research criteria in patients receiving long-acting , injectable risperidone .  METHODS Clinical ly stable subjects with schizophrenia or schizoaffective disorder participated in a 50-week , open-label trial of long-acting , injectable risperidone . TD was studied by defined research criteria ( Schooler , N.R. , Kane , J.M. , 1982 . Research diagnosis for tardive dyskinesia . Arch . Gen. Psychiatry . 39 , 486 - 487 ; Americal Psychiatric Association , 2000 . Diagnostic and Statistical Manual of Mental Disorders , fourth ed . American Psychiatric Association , Washington , DC ) . The severity of dyskinesia and other movement disorders were rated by the Extrapyramidal Symptom Rating Scale ( ESRS ) . RESULTS ESRS dyskinesia data were available for 662 patients . Five of 530 subjects without dyskinesia at baseline ( 0.94 % ) met the predefined criteria for emergent persistent TD during therapy . Based on either exposure to study medication or Kaplan-Meier analysis , the 1-year rate was 1.19 % . Among the 132 subjects with dyskinesia at baseline , the mean score on the ESRS physician 's exam for dyskinesia improved significantly at endpoint ( -2.77 ; P<0.0001 ) , regardless of anticholinergic drug use . ( P=0.243 for patients with versus without anticholinergic drug use . ) CONCLUSIONS In this open-label study , treatment with long-acting risperidone was associated with a low rate of emergent persistent TD . Significant improvement in existing dyskinesias was noted . The TD rate reported here is consistent with other reports of atypical antipsychotics and substantially lower than with conventional antipsychotics OBJECTIVE To compare the 9-month cumulative incidence of tardive dyskinesia ( TD ) with risperidone to that with haloperidol in older patients . DESIGN A prospect i ve longitudinal study . SETTING An outpatient psychiatric clinic . PARTICIPANTS Subjects were middle-aged and older ( mean age 66 years ) patients with schizophrenia , dementia , mood disorders , or other conditions with psychotic symptoms or severe behavioral disturbances . Sixty-one patients on risperidone were matched with 61 patients from a larger sample of haloperidol-treated patients in regard to age , diagnosis , and length of pre-enrollment neuroleptic intake to create clinical ly comparable groups . The median daily dose of each medication was 1.0 mg . MEASUREMENTS Abnormal Involuntary Movement Scale , modified Simpson-Angus ' scale for extrapyramidal symptoms , Brief Psychiatric Rating Scale , and Mini-Mental State Examination were administered at baseline , 1 month , and 3 , 6 , and 9 months . The diagnosis of TD was based on specific research criteria . The raters were blind to the patient 's medication status . RESULTS Life table analysis revealed that patients treated with haloperidol were significantly more likely to develop TD than patients treated with risperidone ( P < .05 , Peto-Prentice ) . CONCLUSIONS The atypical antipsychotic risperidone is significantly less likely to result in TD than the conventional neuroleptic haloperidol in a high-risk group of older patients , at least over a 9-month period BACKGROUND This study compares prescription practice s for acute in patients with schizophrenia among six academic departments located in China , Japan , Hungary , and the U.S. METHODS Prescription data for a sample of 429 in patients from six academic departments were collected on a r and omly chosen census day . All patients met criteria for schizophrenia according to DSM-IV and had a length of illness of at least two years . RESULTS While patients at the different centers varied in their demographic and clinical characteristics , i. e. , age , sex , and length of illness , a great variation in prescription patterns for antipsychotic and other psychotropic drugs among centers was observed even within the same country for all the variables studied ( i. e. , number and dose antipsychotics , atypical and depot antipsychotics , other psychotropic drugs , multiple antipsychotics , and daily dose ) except antidepressant use . In most cases these differences persisted even after adjusting for demographic and clinical characteristics ( age , sex , and length of illness ) of the subjects . Antipsychotics were usually prescribed in divided daily doses in combination with one or more other psychotropic drugs , including anticholinergics , anticonvulsants , benzodiazepines , and non-benzodiazepine hypnotics .  Anticholinergic use was more common with typical antipsychotics . Rates of atypical antipsychotic drug use were lowest in the Japanese center . The Japanese center had by far the highest mean daily dose of antipsychotics .  CONCLUSIONS The results indicate that prescription patterns in different centers do not follow any specific guidelines for the treatment of schizophrenia . The results also confirm previous findings that prescribing practice s for schizophrenia vary greatly among centers and countries . A common prescribing pattern found was the use of atypical antipsychotic drugs in combination with psychotropic drugs , such as anticholinergics , hypnotics , anticonvulsants , and benzodiazepines , administered in multiple daily doses Rationale The relative effectiveness of the atypical antipsychotic drugs and conventional agents in patients with early-stage schizophrenia has not been comprehensively determined . Objectives The aim of our study was to evaluate the efficacy and safety of seven antipsychotic drugs for the maintenance treatment in patients with early-stage schizophrenia . Methods In a 12-month open-label , prospect i ve observational , multicenter study , 1,133 subjects with schizophrenia or schizophreniform disorder within 5 years of onset were monotherapy with chlorpromazine , sulpiride , clozapine , risperidone , olanzapine , quetiapine , or aripiprazole . The primary measure was the rate of treatment discontinuation for any reason . Secondary outcomes included measures for clinical and functional outcomes and tolerability . Results The percentage of patients discontinued treatment within 12 months was 41.4 % for chlorpromazine , 39.5 % for sulpiride , 36.7 % for clozapine , 40.2 % for risperidone , 39.6 % for olanzapine , 46.9 % for quetiapine , and 40.2 % for aripiprazole , a nonsignificant difference ( p = 0.717 ) ; there were no significant differences among these seven treatments on discontinuation due to relapse , intolerability , patient decision , or nonadherence ( all p values ≥ 0.260 ) . Extrapyramidal symptoms were more prominent in chlorpromazine and sulpiride treatment groups . Anticholinergic side effects were most common with clozapine and chlorpromazine . Weight gain was most common with olanzapine and clozapine . Conclusions The efficacy of seven antipsychotic medications for the maintenance treatment appeared similar in early-stage schizophrenia . With regard to the high dropout rate and side effects , special programs are needed to keep efficacy and safety of antipsychotics maintenance treatment for schizophrenia with early BACKGROUND Typical antipsychotic drugs frequently cause hyperprolactinemia and even galactorrhea . In addition , these side effects may result in noncompliance with antipsychotic treatment . Capacity to avoid hyperprolactinemia has been accepted as one atypical criterion . The aim of the present study was to compare effects of haloperidol , the most commonly used antipsychotic , and quetiapine , a novel antipsychotic agent used in Turkey , on serum prolactin ( PRL ) levels . METHODS The study consisted of 35 females diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders , 4(th ) ed . ( DSM-IV ) . Thirty-five patients in a drug-free period for at least 2 weeks were included to r and omized quetiapine ( n = 18 ) and haloperidol ( n = 17 ) treatment group . All patients were assessed by Brief psychiatric rating scale ( BPRS ) , Positive and negative syndrome scale ( PANSS ) , and Extrapyramidal symptoms rating scale ( ESRS ) . PRL levels were measured both at the beginning and at the sixth week of the study . RESULTS Both treatment groups exhibited significant improvements in clinical signs as evaluated by BPRS and PANSS . While there was no significant difference in PRL level between groups at the beginning of the study , control prolactin ( PRL ) levels were significantly lower in quetiapine compared to haloperidol group . While no quetiapine group patients exhibited galactorrhea , we observed that two patients from the haloperidol group had galactorrhea related to hyperprolactinemia . CONCLUSIONS The present study revealed that quetiapine is not associated with increase in PRL secretion in contrast to the conventional antipsychotic haloperidol There is evidence that major psychiatric discords such as schizophrenia ( SZ ) and bipolar disorder ( BD ) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins . Brain-derived neurotrophic factor ( BDNF ) is the most widely distributed neurotrophin in the central nervous system ( CNS ) , and performs many biological functions such as promoting the survival , differentiation , and plasticity of neurons . Variants in the BDNF gene increase the risk of SZ and bipolar disorder . Chronic administration of drugs used to treat SZ and BD , such as lithium , valproate , quetiapine , clozapine , and olanzapine , increases BDNF expression in rat brain . To examine serum BDNF , three groups of chronically medicated DSM-IV SZ patients , on treatment with clozapine ( n=27 ) , typical ( n=14 ) , and other atypical antipsychotics ( n=19 ) , 30 euthymic BD patients , and 26 healthy control had 5 ml blood sample s collected by venipuncture . Serum BDNF levels were significantly higher in SZ patients ( p<0.001 ) when compared to either controls or euthymic BD patients . Increased BDNF in SZ patients might be related to the course of illness or to treatment variables . Prospect i ve studies are warranted BACKGROUND Flunarizine is known as a nonspecific calcium channel blocker that has been used for decades for the treatment of migraine , vertigo , and cognitive deficits related to cerebrovascular disorders . Flunarizine also has dopamine D2 receptor blocking properties and was effective in animal models of predictive validity for antipsychotics . However , its clinical antipsychotic efficacy has never been investigated . OBJECTIVE To evaluate the therapeutic efficacy and tolerability of flunarizine compared to haloperidol in out patients with stable and chronic DSM-IV-defined schizophrenia and schizoaffective disorder . METHOD Seventy patients from 2 centers were r and omly assigned and participated in a double-blind , parallel-group , flexible-dose study comparing flunarizine ( 10 - 50 mg/day ) and haloperidol ( 2.5 - 12.5 mg/day ) for 12 weeks . Patients were assessed with the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impressions-Improvement ( CGI-I ) scale , the Extrapyramidal Symptom Rating Scale ( ESRS ) , a battery for cognitive performance , and laboratory examinations . The study was conducted from September 2004 to May 2007 . RESULTS Mean doses at endpoint were 29.7 mg/day for flunarizine and 6.4 mg/day for haloperidol . Both groups showed significant symptom improvement during the study , with a reduction of 21 % in the flunarizine group and 19 % in the haloperidol group in PANSS total scores ( p < .05 ) . There were no significant differences in PANSS overall score and all subscales , CGI-I score , or cognitive performance . Dropout rates , ESRS scores , and prolactin levels were not different between groups , but significantly more patients reported emergence of akathisia in the haloperidol group ( p = .04 ) , and weight gain was significantly higher with flunarizine ( 1.2 kg ) than with haloperidol ( -0.8 kg ) ( p < .05 ) . CONCLUSION This is the first study evaluating the antipsychotic properties of flunarizine , which showed good efficacy and tolerability for the treatment of schizophrenia , with a possible atypical profile . Its unique pharmacokinetic profile as an oral drug with long half-life ( 2 - 7 weeks ) , low cost , and low induction of extrapyramidal symptoms warrants further investigation , particularly in psychiatric patients with low adherence to treatment In Japan , multiple antipsychotic drugs are administered at a high dose to schizophrenia patients , which is rare in other countries . Many of such patients suffer from side effects , among which extrapyramidal and autonomic side effects frequently occur . Many anticholinergic agents and cathartics are concomitantly used for schizophrenia patients , and their vital prognoses are likely to be poor . With this background , we suggest a method in which antipsychotic drugs are slowly reduced as follows : for low potency drugs , the dose is decreased with 25 mg or lower of chlorpromazine equivalent dose per week , and , for high potency ones , the dose is decreased with 50 mg or lower of chlorpromazine equivalent dose per week . In February 2009 , the author 's patients with schizophrenia , who had been undergoing the slow reduction of antipsychotic drugs for a few years , showed an average number of antipsychotics  being 1.26 ( SD : 0.50 ) , with the average dose being equivalent to 527 mg of chlorpromazine ( SD : 297 mg ) , and the rate of achieving monotherapy was 70 % . A r and omized controlled trial involving the National Mental Sanatoriums and a private hospital demonstrated that  antipsychotic drugs  can be reduced with relative safety according to our method . Currently , prescription reform is being conducted in many hospitals , while prescription as practice d in the previous century still continues in some hospitals . It is considered that the problems regarding high-dose administration of multiple drugs can possibly be solved if many centers employ our method Subjects at their first psychotic episode show an enlarged volume of the pituitary gl and , but whether this is due to hypothalamic – pituitary – adrenal ( HPA ) axis hyperactivity , or to stimulation of the prolactin-secreting cells by antipsychotic treatment , is unclear . We measured pituitary volume , using 1.5-mm , coronal , 1.5 T , high-resolution MRI images , in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls . In all , 18 patients were antipsychotic-free ( 12 of these were antipsychotic-naïve ) , 26 were receiving atypical antipsychotics , and 33 were receiving typical antipsychotics .  As hypothesized , patients had a larger pituitary volume than controls ( + 22 % , p<0.001 ) . When divided by antipsychotic treatment , and compared to controls , the pituitary volume was 15 % larger in antipsychotic-free patients ( p=0.028 ) , 17 % larger in patients receiving atypicals ( p=0.01 ) , and 30 % larger in patients receiving typicals ( p<0.001 ) . Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together ( + 11 % , p=0.08 ) . When divided by diagnosis , and compared to controls , the pituitary volume was 24 % larger in patients with schizophrenia/schizophreniform disorder ( n=40 , p<0.001 ) , 19 % larger in depressed patients ( n=13 , p=0.022 ) , 16 % larger in bipolar patients ( n=16 , p=0.037 ) , and 12 % larger in those with other psychoses ( n=9 , p=0.2 ) . In conclusion , the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment , and this could be due to activation of the HPA axis . Typical antipsychotics exert an additional enlarging effect on pituitary volume , likely to be related to activation of prolactin-secreting cells . This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis BACKGROUND This open-label , multicenter , r and omized study compared the efficacy and safety of switching moderately ill Asian patients with schizophrenia from their current regimen of antipsychotic medication to the atypical antipsychotic olanzapine using either a direct switch method or a start-taper switch method . METHOD Asian in patients and out patients with DSM-IV schizophrenia ( N = 108 ) currently treated with predominantly typical antipsychotics were switched to olanzapine ( initial dose of 10 mg/day ) for 6 weeks . Patients were r and omly assigned to 1 of 2 groups : the direct switch group ( N = 54 ) received only olanzapine , while the start-taper switch group ( N = 54 ) received olanzapine and their usual antipsychotic in decreasing doses for the first 2 weeks . A successful switch was defined as completing 6 weeks of therapy without worsening of symptoms ( Clinical Global Impressions-Severity of Illness scale [ CGI-S ] ) or extrapyramidal side effects ( Simpson-Angus Scale ) . Overall efficacy was assessed using the Positive and Negative Syndrome Scale ( PANSS ) , and safety was assessed by recording adverse events and measuring vital signs . RESULTS Statistically significant ( p < .001 ) improvements from baseline to endpoint occurred in both switch groups in the CGI-S score and the PANSS total score and subscores . However , no significant differences were observed between the switch groups for any efficacy measure . Both techniques had comparable rates of successful switching ( direct switch , 74.1 % vs. start-taper switch , 67.9 % ) . The frequency of treatment-emergent adverse events was similar between switch groups with no clinical ly significant differences in any laboratory value or vital sign . Weight gain occurred in both switch groups ( p < .001 ) , but the groups were not statistically different from each other . Both switch groups showed statistically significant ( p < .01 ) improvements from baseline to endpoint on the Simpson-Angus Scale and Barnes Akathisia Scale . CONCLUSION Moderately ill Asian patients with schizophrenia may experience a decrease in symptom severity and improvement in extrapyramidal symptoms when switched from their current medication to olanzapine therapy 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
In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator .
Conclusion Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo , and as effective as established drug therapies .
Atypical antipsychotics produce fewer extrapyramidal symptoms , but weight gain is more common ( with olanzapine ) .
There is insufficient data confidently to distinguish between different atypical antipsychotics
Background Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder , and considered to have fewer extrapyramidal effects than older antipsychotics .