Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth. Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study. Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. TNF-α −308 G>A polymorphism and weight gain in patients with schizophrenia under long-term clozapine, risperidone or olanzapine treatment Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics. Effectiveness of second-generation antipsychotics with acute-phase schizophrenia Cognitive Improvement in Schizophrenic Patients does not Require a Serotonergic Mechanism: Randomized Controlled Trial of Olanzapine vs Amisulpride Antipsychotic switching: results from a one-year prospective, observational study of patients with schizophrenia Second Generation Antipsychotics Improve Sexual Dysfunction in Schizophrenia: A Randomised Controlled Trial A randomized, double-blind, placebo-controlled study of ziprasidone monotherapy in bipolar disorder with co-occurring lifetime panic or generalized anxiety disorder. Cerebral Cortical Gray Expansion Associated with Two Second-Generation Antipsychotics The expert consensus guideline series. Treatment of behavioral emergencies 2005. Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms. Social cognition and visual perception in schizophrenia inpatients treated with first-and second-generation antipsychotic drugs. The Effectiveness of Guideline Implementation Strategies on Improving Antipsychotic Medication Management for Schizophrenia Employment Outcomes in a Randomized Trial of Second-Generation Antipsychotics and Perphenazine in the Treatment of Individuals with Schizophrenia Long-term (3-year) effectiveness of haloperidol, risperidone and olanzapine: results of a randomized, flexible-dose, open-label comparison in first-episode nonaffective psychosis Influence of resting energy expenditure on weight gain in adolescents taking second-generation antipsychotics. Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians Randomized, placebo-controlled trial of risperidone for acute treatment of bipolar anxiety. Heart rate and heart rate variability in panic, social anxiety, obsessive-compulsive, and generalized anxiety disorders at baseline and in response to relaxation and hyperventilation. An Evaluation of Monitoring Practices in Patients on Second Generation Antipsychotics
BACKGROUND The use of antipsychotics , especially second-generation antipsychotics ( SGAs ) , for children with mental health disorders in Canada has increased dramatically over the past five years . These medications have the potential to cause major metabolic and neurological complications with chronic use . OBJECTIVE To synthesize the evidence for specific metabolic and neurological side effects associated with the use of SGAs in children , and provide evidence -based recommendations for the monitoring of these side effects . METHODS A systematic review of controlled clinical trials of SGAs involving children was performed . Recommendations for monitoring SGA safety were made according to a classification scheme based on the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) system . When there was inadequate evidence , recommendations were based on consensus and expert opinion . A multidisciplinary consensus group review ed all relevant evidence and reached consensus on the recommendations . RESULTS The present guidelines provide evidence -based recommendations for monitoring SGA safety . The strength of recommendations for specific physical examination manoeuvres and laboratory tests are provided for each SGA medication at specific time points . CONCLUSION Multiple r and omized controlled trials evaluated the efficacy of many of the SGAs in paediatric mental health disorders . These benefits , however , are not without risks - both metabolic and neurological side effects occur in children treated with SGAs . The risk of weight gain , increased body mass index and abnormal lipid levels is greatest with olanzapine , followed by clozapine and quetiapine . The risk of neurological side effects of the treatment is greatest with risperidone , olanzapine and aripiprazole . Appropriate monitoring procedures for adverse effects will improve the quality of care of children treated with these medications Until relatively recently , long-acting injectable ( LAI ) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics ( SGA ) increased . Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice , this is not seen in recent r and omized clinical trials . PROACTIVE ( Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy ) relapse prevention study incorporated efficacy and effectiveness features . At 8 US academic centers , 305 patients with schizophrenia or schizoaffective disorder were r and omly assigned to LAI risperidone ( LAI-R ) or physician 's choice oral SGAs . Patients were evaluated during the 30-month study by masked , central ized assessors using 2-way video , and monitored biweekly by on-site clinicians and assessors who knew treatment assignment . Relapse was evaluated by a masked Relapse Monitoring Board . Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant . Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group . In contrast , the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores . There were no other between-group differences in symptoms or functional improvement . Despite the advantage for psychotic symptoms , LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization . Biweekly monitoring , not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm , may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials CONTEXT Second-generation ( atypical ) antipsychotics ( SGAs ) are more expensive than first-generation ( typical ) antipsychotics ( FGAs ) but are perceived to be more effective , with fewer adverse effects , and preferable to patients . Most evidence comes from short-term efficacy trials of symptoms . OBJECTIVE To test the hypothesis that in people with schizophrenia requiring a change in treatment , SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs . DESIGN A noncommercially funded , pragmatic , multisite , r and omized controlled trial of antipsychotic drug classes , with blind assessment s at 12 , 26 , and 56 weeks using intention-to-treat analysis . SETTING Fourteen community psychiatric services in the English National Health Service . PARTICIPANTS Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects . INTERVENTIONS R and omized prescription of either FGAs or SGAs ( other than clozapine ) , with the choice of individual drug made by the managing psychiatrist . MAIN OUTCOME MEASURES Quality of Life Scale scores , symptoms , adverse effects , participant satisfaction , and costs of care . RESULTS The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded . Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores . Participants reported no clear preference for either drug group ; costs were similar . CONCLUSIONS In people with schizophrenia whose medication is changed for clinical reasons , there is no disadvantage across 1 year in terms of quality of life , symptoms , or associated costs of care in using FGAs rather than nonclozapine SGAs . Neither inadequate power nor patterns of drug discontinuation accounted for the result There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia .  It is less clear if clozapine is more effective than the other second-generation antipsychotic ( SGA ) drugs . A noncommercially funded , pragmatic , open , multisite , r and omized controlled trial was conducted in the United Kingdom National Health Service ( NHS ) . Participants were 136 people aged 18 - 65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs . Participants were r and omly allocated to clozapine or to one of the class of other SGA drugs ( risperidone , olanzapine , quetiapine , amisulpride ) as selected by the managing clinician . Outcomes were assessed blind to treatment allocation . One-year assessment s were carried out in 87 % of the sample . The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score ( 3.63 points ; CI : 0.46 - 7.71 ; p = .08 ) but did show an advantage in Positive and Negative Syndrome Scale ( PANSS ) total score that was statistically significant ( -4.93 points ; CI : -8.82 to -1.05 ; p = .013 ) during follow-up . Clozapine showed a trend toward having fewer total extrapyramidal side effects . At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs . In conclusion , in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs , there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year Atypical or second-generation antipsychotics ( SGAs ) are associated with excessive body weight gain ( BWG ) and other components of metabolic syndrome . Among all SGAs , clozapine and olanzapine are known to cause the most significant weight gain , followed by risperidone and quetiapine . The genetic variant of tumor necrosis factor α ( TNF-α ) , -308 G > A polymorphism ( rs1800629 ) , has been implicated in clozapine-induced BWG in several studies . We hypothesized that TNF-α -308 G > A polymorphism has a general effect on SGA-induced BWG . The present study was conducted to examine the association between TNF-α -308 G > A polymorphism and BWG during treatment for schizophrenia using a variety of second generation antipsychotics ( SGAs ) . A total of 500 patients with schizophrenia treated with clozapine ( n=275 ) , olanzapine ( n=79 ) or risperidone ( n=146 ) for an average of 49.9 months were recruited . Subjects with an increase in weight of more than 7 % from the baseline before the current SGA treatment to the weight at the survey point were defined as having BWG . The association between TNF-α -308 G > A polymorphism and BWG was studied , and the effect of non-genetic factors such as baseline BMI , SGA treatment duration and SGA type on the association was controlled by logistic regression . The results revealed that there was no significant association between BWG and TNF-α -308 G > A polymorphism ( GG/GA/AA or GG/GA+AA ) in each separate SGA group or collectively . These findings suggest that TNF-α -308 G > A polymorphism does not play a major role in SGA-induced weight gain OBJECTIVE Second-generation antipsychotic ( SGA ) effects in youth were monitored to quantify extrapyramidal side effects ( EPS ) and to identify risk profiles for treatment-emergent EPS . METHOD Data were analyzed for the nonr and omized , prospect i ve Second-generation Antipsychotic Treatment Indications , Effectiveness and Tolerability in Youth ( SATIETY ) inception cohort study . EPS were assessed at baseline and 4 , 8 , and 12 weeks after naturalistic SGA initiation for schizophrenia , mood , disruptive behavior , and autism spectrum disorders using the Simpson-Angus Scale ( SAS ) , Barnes Akathisia Scale , Abnormal Involuntary Movement Scale ( AIMS ) , and Treatment Emergent Side Effect Scale . Drug-induced parkinsonism was defined by incident mean SAS score > 0.33 , anticholinergic initiation , or increasing total SAS score ≥2 in patients with baseline EPS . RESULTS In 342 youth aged 13.6 ± 3.5 years ( male = 58.2 % , antipsychotic-naive = 65.8 % ) , 15.2 % developed drug-induced parkinsonism .  Raw SGA-grouped drug-induced parkinsonism rates were as follows : quetiapine = 1.5 % , olanzapine = 13.8 % , risperidone = 16.1 % , ziprasidone = 20.0 % , and aripiprazole = 27.3 % . SGA type , dose , higher age , and lower baseline functioning were jointly associated with drug-induced parkinsonism ( R(2 ) = 0.18 ; p < .0001 ) . Controlling for these factors , drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine . Subjectively reported EPS ( 5 % ) , EPS-related treatment discontinuation ( 3.3 % ) , and anticholinergic initiation ( 3 % ) were infrequent . Anticholinergic initiation was most frequent with risperidone ( 10.2 % ; p = .0004 ) . Treatment-emergent dyskinesia ranged from 4.5 % ( aripiprazole ) to 15.5 % ( olanzapine ) . SGA type , younger age , white race/ethnicity , and baseline AIMS were jointly associated with treatment-emergent dyskinesia ( R(2 ) = 0.31 ; p < .0001 ) . Controlling for these factors , treatment-emergent dyskinesia rates differed among SGA subgroups , with higher rates with olanzapine and ziprasidone . At baseline , psychostimulant use was associated with dyskinesia , and number of psychotropic comedications was associated with subjective EPS . CONCLUSION In youth , SGA-related EPS rates did not generally exceed those reported in adults , with particularly low rates with quetiapine and olanzapine PURPOSE Although olanzapine may have advantages over other second-generation antipsychotics ( SGAs ) regarding longer time to treatment discontinuation among chronically ill patients , little evidence has been provided for the comparative effectiveness of SGAs in the acute phase . We aim ed to determine if any of four SGAs were more effective in treating newly admitted acute schizophrenic patients . We performed a rater-blinded , r and omized controlled trial of four SGAs in 15 psychiatric emergency sites . Eligible patients were 18 - 64 years old and met diagnostic criteria for schizophrenia , acute schizophrenia-like psychotic disorder , or schizoaffective disorder . A final total of 78 patients were r and omly assigned by means of sealed envelopes to receive risperidone ( 3 - 12 mg/day ; n=20 ) , olanzapine ( 10 - 20 mg/day ; n=17 ) , quetiapine ( 300 - 750 mg/day ; n=20 ) , or aripiprazole ( 12 - 30 mg/day ; n=21 ) , with follow-up at 8 weeks . The primary outcome measure was all-cause treatment discontinuation . RESULTS Overall , 37 % ( 29/78 ) of patients discontinued the study medication before 8 weeks : 25 % for risperidone ; 12 % for olanzapine ; 55 % for quetiapine ; and 52 % for aripiprazole .  Time to treatment discontinuation for any cause was significantly longer in the olanzapine group than in the quetiapine ( p=0.006 ) or aripiprazole ( p=0.008 ) groups , but not compared to the risperidone group ( p=0.32 ) . Time to treatment discontinuation was significantly longer in the risperidone group than in the quetiapine group ( p=0.048 ) , but not compared to the aripiprazole group ( p=0.062 ) . However , the rate of p.r.n . intramuscular haloperidol use was significantly higher in the aripiprazole group than in other groups ( p=0.029 ) . CONCLUSION Olanzapine and risperidone are superior to quetiapine and aripiprazole for the acute treatment of psychosis in hospitalized patients Combined serotonin-2A ( 5-HT2A ) and dopamine-2 ( D2 ) receptor blockade has been proposed as a c and i date mechanism by which second-generation antipsychotics ( SGAs ) improve both cognition and negative symptoms in schizophrenic patients , in contrast to antipsychotics of the first generation . The SGA amisulpride , however , only binds to D2/D3 receptors , which makes it an interesting tool to test this assumption . In a r and omized controlled trial , 52 schizophrenic patients were allocated to treatment with either olanzapine ( 10–20 mg/day ) or amisulpride ( 400–800 mg/day ) . A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks . Cognitive improvements of moderate size were observed , with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs . Importantly , amisulpride was not inferior to olanzapine for any cognitive domain . Combined 5-HT2A/D2 receptor blockade is probably not necessary for cognitive improvement by SGAs ABSTRACT Objective : The Health Outcomes of a Canadian Community Cohort ( HOCCC ) study is a 1-year prospect i ve observational study of out patients with schizophrenia or related psychotic disorders . The purpose of the study was to compare effectiveness of antipsychotic treatment as measured by 1-year treatment completion rates . Design and methods : Patients ( N = 929 ) were enrolled if in the course of usual clinical practice they switched to a second-generation antipsychotic ( SGA ) . Observational data were collected for up to 1 year . The primary analysis compared 1-year treatment-completion rates for the olanzapine cohort with the other SGA cohort ( quetiapine , risperidone , clozapine ) , using a chi-squared test . Results : Of 929 patients enrolled , 64.8 % ( 516/796 ) of evaluable patients completed 1 year of treatment . There was no statistically significant difference in the proportion of treatment completers between the olanzapine cohort ( 67.4 % , 256/380 ) and the other SGA cohort ( 62.5 % , 260/416 ) . Treatment-completion rates were risperidone 62.0 % ( 127/205 ) , quetiapine 63.7 % ( 123/193 ) and clozapine 55.6 % ( 10/18 ) . Antipsychotic polypharmacy was common . Patients treated with olanzapine or risperidone had significantly higher increases in BMI than quetiapine-treated patients . There were no major differences between olanzapine monotherapy and pooled other SGA monotherapy groups in status of extrapyramidal symptoms from baseline to endpoint . Conclusions : Olanzapine and other SGAs exhibited similar rates of 1-year treatment completion . Further study of medication combinations is needed , given their perceived clinical value , and the high frequency of antipsychotic polypharmacy in clinical practice . Limitations : As most patients received several psychotropics and power was reduced in monotherapy analyses , comparisons between cohorts must be interpreted cautiously . Comparisons between individual antipsychotics were post hoc and not powered a priori . Accuracy and completeness of adverse event information for drugs other than olanzapine is limited The impact of antipsychotic drug treatment on sexual function was investigated during a r and omised trial comparing first generation antipsychotics ( FGAs ) to ( nonclozapine ) second generation antipsychotics ( SGAs ) .  Sexual function and quality of life were ( rater-blind ) assessed in 42 patients with DSM-IV schizophrenia ( aged 18–65 ) using the self-report version of the Derogatis Interview for Sexual Function ( DISF-SR ) and the Heinrichs Quality of Life Scale ( QLS ) , prior to , and 12 weeks following , a change in medication from an FGA drug to either an FGA or SGA drug . SGAs significantly improved sexual function compared to FGAs . Change in sexual function was associated with change in quality of life . Where impaired sexual functioning is a distressing adverse effect of treatment with an FGA agent , consideration should be given to switching to an SGA OBJECTIVE Bipolar disorder often co-occurs with anxiety disorders . Evidence suggests that second-generation antipsychotics ( SGAs ) may be useful in treating both conditions . This study examined the efficacy of ziprasidone in the treatment of these disorders . METHOD This 3-site , r and omized , double-blind , placebo-controlled , parallel group , 8-week trial of ziprasidone monotherapy examined 49 subjects with bipolar disorder and lifetime panic disorder ( with or without agoraphobia ) or generalized anxiety disorder ( GAD ) experiencing moderately severe anxiety symptoms at entrance into the study . Both bipolar disorder and anxiety diagnoses were based on DSM-IV-TR criteria . Patients were screened and r and omized from June 25 , 2010 , through August 23 , 2011 . Primary outcome measures were the Clinical Global Impressions-21 Anxiety Scale ( CGI-21 Anxiety ) and the Sheehan Disability Scale ( SDS ) , with secondary measures monitoring anxiety and mood symptoms . RESULTS Last-observation-carried-forward analyses demonstrated that patients in the ziprasidone group did not improve significantly more than those in the placebo group on the CGI-21 Anxiety ( F1 = 0.34 ; P = .564 ) or SDS ( F1 = 0.26 ; P = .611 ) . Secondary analysis using hierarchical linear modeling found similar results ( CGI-21 Anxiety : F1 = 1.82 ; P = .178 ; and SDS : F1 = 0.70 ; P = .408 ) . Regardless of group , time in the study was associated with significant decrease in anxiety ( F1 = 11.08 ; P = .001 ) and total disability ( F1 = 26.16 ; P < .001 ) . Patients in the ziprasidone group showed a greater increase in abnormal involuntary movement , and 81.8 % ( n = 9 ) of the subjects who withdrew from the study due to adverse events , serious adverse events , or side effects were in the ziprasidone group . CONCLUSIONS Results suggest that ziprasidone monotherapy was not associated with a clinical ly significant improvement in anxiety symptoms or improved function for patients with bipolar disorder , lifetime panic disorder or GAD , and concurrent moderately severe anxiety symptoms , and it was associated with a more negative side-effect profile relative to placebo . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01172652 BACKGROUND Second-generation antipsychotics ( SGAs ) differ from first-generation antipsychotics ( FGAs ) with respect to induction of less extrapyramidal morbidity , partially reducing negative symptoms , and causing modest improvement in neurocognitive functioning in patients with schizophrenia . SGAs demonstrate 5-HT2a antagonism . Differential effects of SGAs and FGAs on cortical gray volumes are explored herein . METHODS Cerebral cortical gray was examined volumetrically in 19 patients with schizophrenia before and following 28 days of treatment with two SGAs ( risperidone and ziprasidone ; n = 13 ) or a FGA ( haloperidol ; n = 6 ) . Seven ( untreated ) control subjects were also assessed at a similar interval . RESULTS During treatment with the SGAs risperidone and ziprasidone , cerebral cortical gray of 13 patients with schizophrenia exp and ed 20.6 + /- 11.4 cc ( p < .0005 ) . Six patients receiving the FGA haloperidol , as well as 7 control subjects , showed no change in cortical gray volumes ( p = .983 and p = .932 , respectively ) at the time of re assessment . CONCLUSIONS Volumetric increase of cerebral cortical gray occurred early in the course of treatment with the SGAs ziprasidone and risperidone , but not with the FGA haloperidol . Such cortical gray expansion may be relevant to the reported enhanced neurocognition and quality of life associated with SGA treatment OBJECTIVES Due to inherent dangers and barriers to research in emergency setting s , few data are available to guide clinicians about how best to manage behavioral emergencies . Key constructs such as agitation are poorly defined . This lack of empirical data led us to undertake a survey of expert opinion , results of which were published in the 2001 Expert Consensus Guidelines on the Treatment of Behavioral Emergencies . Several second-generation ( atypical ) antipsychotics ( SGAs ) are now available in new formulations for treating behavioral emergencies ( e.g. , intramuscular [ i.m . ] olanzapine and ziprasidone ; rapidly dissolving tablets of olanzapine and risperidone ) . Critical questions face the field . The SGAs are significantly different from the FGAs and from each other and have not been studied in unselected patients as were the FGAs . Can the SGAs can be thought of as a class , do all antipsychotics have similar anti-agitation effects in different conditions , and , if equally effective , what limits might their safety profiles impose ? Should antipsychotics be used more specifically to treat psychotic conditions , while benzodiazepines ( BNZs ) alone are used nonspecifically ? Few data are available concerning combinations of SGAs and BNZs , and findings concerning the traditional combination of haloperidol plus a BNZ may not be relevant to combinations with SGAs . The culture is also evolving with more emphasis on patient involvement in treatment decisions . An international consensus has been developing that calming rather than sedation is the appropriate endpoint of behavioral emergency interventions . We undertook a new survey of expert opinion to up date recommendations from the earlier survey . METHOD A written survey of 61 questions ( 1,020 options ) was mailed to 50 experts in the field , 48 ( 96 % ) of whom completed it . The survey sought to define level of agitation at which emergency interventions are appropriate , scope of assessment depending on urgency and patients ' ability to cooperate , guiding principles for selecting interventions , and appropriate physical and medication strategies at different levels of diagnostic confidence for a variety of provisional diagnoses and complicating conditions . A modified version of the R AND Corporation 's 9-point scale for rating appropriateness of medical decisions was used to score most options . Consensus was defined as a non-r and om distribution of scores by chi-square " goodness-of-fit " test . We assigned a categorical rank ( first line/preferred , second line/alternate , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean . Ratings were used to develop guidelines for preferred strategies in key clinical situations . This study received financial support from multiple sponsors , with the panel kept blind to sponsorship to reduce possible bias . Medication ratings were based on responses of only those respondents with direct experience with each drug . In reporting practice patterns , the panel was asked to respond based on actual data rather than estimates . RESULTS The expert panel reached consensus on 78 % of the options rated on the 9-point scale . The responses suggest that physicians can make provisional diagnoses with some confidence and that pharmacological and nonpharmacological interventions are selected differentially based on diagnosis and other salient demographic and medical features . BNZs are recommended when no data are available , when there is no specific treatment ( e.g. , personality disorder ) , or when they may have specific benefits ( e.g. , intoxication ) . No single SGA emerges as a nonspecific replacement for haloperidol ; instead , different SGAs are preferred in various circumstances consistent with current evidence . To the degree that haloperidol is recommended , it is almost always in combination with a BNZ ; haloperidol alone is preferred only in the medically compromised . In contrast , the SGAs are more often recommended for use alone , and the panel would avoid combining BNZs with some SGAs . Oral risperidone alone or combined with a BNZ receives strong support in a variety of situations . Oral olanzapine was rated very similarly to risperidone , with slightly higher ratings than risperidone in situations where it has been studied ( e.g. , schizophrenia , mania ) and slightly lower ratings where it has not been studied or safety may be a concern ; there was less support for combining oral olanzapine with a BNZ . For oral treatment of agitation related to schizophrenia or mania , olanzapine alone , risperidone alone or combined with a BNZ , and haloperidol plus a BNZ are first line , with strong support also for combining divalproex with the antipsychotic for presumed mania . Oral ziprasidone and quetiapine generally received similar second-line ratings in most situations . If a parenteral agent is needed , i.m . olanzapine alone received somewhat more support than i.m . ziprasidone alone ; however , there was more support for i.m . ziprasidone alone or combined with a BNZ than for i.m . olanzapine plus a BNZ , probably reflecting safety concerns . For example , for a provisional diagnosis of schizophrenia , first-line parenteral options are i.m . olanzapine or ziprasidone alone or i.m . haloperidol or ziprasidone combined with a BNZ . Neither of the new parenteral formulations received as much support as traditional agents ( i.m . BNZs , i.m . haloperidol ) when no data are available or the diagnosis involves medical comorbidity or intoxication . When initial intervention with risperidone , ziprasidone , or haloperidol is unsuccessful , the panel recommended adding a BZD to the antipsychotic . However , when initial treatment with olanzapine or quetiapine is unsuccessful , increasing the dosage is recommended . Perphenazine was consistently rated second line and droperidol and chlorpromazine received third-line ratings throughout . CONCLUSIONS Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines suggest that the SGAs are now preferred for agitation in the setting of primary psychiatric illnesses but that BNZs are preferred in other situations First-generation antipsychotics have been associated with striatal volume increases . The effects of second-generation antipsychotics ( SGAs ) on the striatum are unclear . Moreover , SGAs may have neuroprotective effects on the hippocampus . Dose-dependent volumetric effects of individual SGAs have scarcely been investigated . Here we investigated structural brain changes in  antipsychotic-naive , first-episode schizophrenia patients after 6 months treatment with the SGA , quetiapine .  We have recently reported on baseline volume reductions in the cau date nucleus and hippocampus . Baseline and follow-up T1-weighted images ( 3 T ) from 22 patients and 28 matched healthy controls were analysed using tensor-based morphometry . Non-parametric voxel-wise group comparisons were performed . Small volume correction was employed for striatum , hippocampus and ventricles . Dose-dependent medication effects and associations with psychopathology were assessed . Patients had significant bilateral striatal and hippocampal loss over the 6-month treatment period . When compared to controls the striatal volume loss was most pronounced with low quetiapine doses and less apparent with high doses . Post-hoc analyses revealed that the striatal volume loss was most pronounced in the cau date and putamen , but not in accumbens . Conversely , hippocampal volume loss appeared more pronounced with high quetiapine doses than with low doses . Clinical ly , higher baseline positive symptoms were associated with more striatal and hippocampal loss over time . Although patients ' ventricles did not change significantly , ventricular increases correlated with less improvement of negative symptoms . Progressive regional volume loss in quetiapine-treated , first-episode schizophrenia patients may be dose-dependent and clinical ly relevant . The mechanisms underlying progressive brain changes , specific antipsychotic compounds and clinical symptoms warrant further research PURPOSE Social cognition captures affect recognition , social cue perception , " theory of mind , " empathy , and attributional style . The aim of our study was to assess social cognition in schizophrenia in patients being treated with first-generation antipsychotic drugs ( FGAs ) , n=28 ( perphenazine and haloperidol , FGAs ) or with second-generation antipsychotic drugs ( SGAs ) , n=56 ( olanzapine and clozapine , SGAs ) . SUBJECTS AND METHODS Eighty-four patients completed the Facial Expression Recognition Test , the Voice Emotion Recognition Test , the Short Recognition Memory Test for Faces , and the Reading the Mind in the Eyes Test . Patients also completed the  Visual Object and Space Perception Test ( VOSP ) as a control task , which would not engage social cognition . The patients were compared with fifty healthy controls matched for age and gender . RESULTS There were no significant differences on social cognitive performance between the FGA- and SGA-treatment groups . Nor was olanzapine superior to clozapine , FGAs or both . However , patients treated with FGAs performed significantly worse on VOSP compared to both groups treated with SGAs , a 10 % difference . CONCLUSIONS We can not conclude that SGAs were associated with better social cognition than FGAs . However , there were small but significant advantages for SGAs in non-social visual processing function , as evaluated with the VOSP Objectives : To compare the effectiveness of a conceptually-based , multicomponent “ enhanced ” strategy with a “ basic ” strategy for implementing antipsychotic management recommendations of VA schizophrenia guidelines . Methods : Two VA medical centers in each of 3 Veterans Integrated Service Networks were r and omized to either a basic educational implementation strategy or the enhanced strategy , in which a trained nurse promoted provider guideline adherence and patient compliance . Patients with acute exacerbation of schizophrenia were enrolled and assessed at baseline and 6 months and their medical records were abstract ed ; 291 participants were included in analyses . Logistic regression models were developed for rates of : ( 1 ) switching patients from first-generation antipsychotics ( FGA ) to second-generation antipsychotics ( SGA ) , and ( 2 ) guideline -concordant antipsychotic dose . Results : Of participants prescribed FGAs at baseline , those at enhanced sites were significantly more likely than participants at basic sites to have an SGA added to the FGA during the study ( 29 % vs. 8 % ; adjusted OR = 7.7 ; 95 % CI : 2.0–30.1 ) , but were not significantly more likely to be switched to monotherapy with an SGA ( 29 % vs. 23 % ) . Guideline -concordant antipsychotic dosing was not significantly affected by the intervention . Conclusions : The enhanced guideline implementation strategy increased addition of SGAs to FGA therapy , but did not significantly increase guideline -recommended switching from FGA to SGA monotherapy . Antipsychotic dosing was not significantly altered . The study illustrates the challenges of changing clinical behavior . Strategies to improve medication management for schizophrenia are needed , and must incorporate recommendations likely to emerge from recent research suggesting comparable effectiveness of SGAs and FGAs Employment has been increasingly recognized as an important goal for individuals with schizophrenia . Previous research has shown mixed results on the relationship of specific antipsychotic medications to employment outcomes , with some studies finding greater benefits for second-generation antipsychotic medications ( SGAs ) over first-generation antipsychotic medication ( FGAs ) . A r and omized controlled trial ( CATIE ) examined medication assignment and both employment outcomes and participation in psychosocial rehabilitation ( PSR ) among 1,121 individuals with a diagnosis of schizophrenia r and omized to SGAs ( olanzapine , quetiapine , risperidone , ziprasidone ) or one FGA ( perphenazine ) .  Service use and employment were assessed at quarterly interviews . There were no differences between medication groups on employment outcomes or participation in PSR . Consistent with other CATIE results , there were no differences in employment or participation in PSR among these five medications , including the FGA perphenazine Rationale To enhance the effectiveness of antipsychotics  in first-episode psychosis is crucial in order to achieve the most favourable prognosis . Difference in effectiveness between antipsychotics is still under debate . Objective The purpose of this study is to determine the long-term ( 3-year ) effectiveness and efficacy of haloperidol , risperidone and olanzapine in first-episode schizophrenia-spectrum disorders . Method This is a prospect i ve , r and omized , open-label study . Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention programme of first-episode psychosis . One hundred seventy-four patients were r and omly assigned to haloperidol ( N = 56 ) , olanzapine ( N = 55 ) , or risperidone ( N = 63 ) and followed up for 3 years . The primary effectiveness measure was all-cause of treatment discontinuation . In addition , an analysis based on per- protocol population s was conducted in the analysis for clinical efficacy . Results The treatment discontinuation rate for any cause differed significantly between treatment groups ( χ2 = 10.752 ; p = 0.005 ) , with a higher rate in haloperidol than in risperidone and olanzapine . The difference in the discontinuation rate between risperidone and olanzapine showed a tendency towards significance ( χ2 = 3.022 ; p = 0.082 ) . There was a significant difference in the mean time to all-cause discontinuation between groups ( log-rank χ2 = 12.657;df = 2 ; p = 0.002 ) . There were no significant advantages to any of the three treatments in reducing the psychopathology severity . Conclusions After 3 years of treatment , a lower effectiveness was observed in haloperidol compared to second-generation antipsychotics ( SGAs ) . The use of SGAs for the treatment of early phases of nonaffective psychosis may enhance the effectiveness of antipsychotics BACKGROUND & AIMS Weight gain is an undesirable side effect of second-generation antipsychotics ( SGAs ) . We performed this study to examine the influence of SGAs on resting energy expenditure ( REE ) and the relationship of REE to weight gain in adolescent patients . METHODS Antipsychotic-naïve or quasi-naïve ( < 72 h of exposure to antipsychotics ) adolescent patients taking olanzapine , quetiapine , or risperidone in monotherapy were followed up for one year . We performed a prospect i ve study ( baseline , 1 , 3 , 6 , and 12 months after treatment ) based on anthropometric measurements , bioelectrical impedance analysis , and indirect calorimetry ( Deltatrac ™ II MBM-200 ) to measure REE . We also analyzed metabolic and hormonal data and adiponectin concentrations . RESULTS Forty-six out of the 54 patients that started treatment attended at least 2 visits , and 16 completed 1 year of follow-up . Patients gained 10.8 ± 6.2 kg ( 60 % in the form of fat mass ) and increased their waist circumference by 11.1 ± 5.0 cm after 1 year of treatment . The REE/kg body mass ratio decreased ( p = 0.027 ) , and the REE/percentage fat-free mass ( FFM ) ratio increased ( p = 0.007 ) following the fall in the percentage of FFM during treatment . Weight increase was significantly correlated with the REE/percentage FFM ratio at all the visits ( 1 - 3 - 6 - 12 months ) ( r = 0.69 , p = 0.004 at 12 months ) . CONCLUSIONS SGAs seem to induce a hypometabolic state ( reflected as decreased REE/kg body mass and increased REE/percentage FFM ) . This could explain , at least in part , the changes in weight and body composition observed in these patients Depressive disorders are a major health care issue and one of the foremost causes of disability in adults around the world , result ing in significant costs to society and health care systems ( 1 ) . The estimated economic burden associated with depression was $ 83.1 billion in 2000 and is probably higher today ( 2 ) . Depressive disorders include major depressive disorder ( MDD ) ; dysthymia ; and subsyndromal depression , including minor depression . Major depressive disorder is the most prevalent depressive disorder , with an estimated lifetime prevalence of 16 % in the United States ( 3 ) . An average of 8 million ambulatory care visits per year result in a primary diagnosis of MDD ( 4 ) . The American Psychiatric Association ( 5 ) defines MDD as depressed mood or loss of pleasure or interest along with other symptoms , including significant change in weight or appetite , insomnia or hypersomnia , psychomotor agitation or retardation nearly every day , fatigue or loss of energy , feelings of worthlessness or excessive or inappropriate guilt , indecisiveness or decreased ability to concentrate , and recurrent thoughts of death or suicide , that last for at least 2 weeks and affect normal functioning . Dysthymia is less severe , but symptoms last for 2 or more years . In contrast , subsyndromal depression is associated with less severe symptoms of depression that do not qualify for MDD or dysthymia diagnoses . The treatment of depression can be characterized by 3 phases ( Figure 1 ) : acute ( 6 to 12 weeks ) , continuation ( 4 to 9 months ) , and maintenance ( 1 year ) ( 7 ) . Relapse is defined as the return of depressive symptoms during the acute or continuation phases and is therefore considered part of the same depressive episode , whereas recurrence is defined as the return of depressive symptoms during the maintenance phase and is considered a new , distinct episode . Response to treatment ( typically defined as 50 % reduction in measured severity ) can be quantified using various tools , such as the Patient Health Question naire-9 ( PHQ-9 ) ( 7 ) or the Hamilton Depression Rating Scale ( HAM-D ) ( 8) . Figure 1 . Phases of treatment of major depression . Adapted from reference 6 . TX = treatment . Various treatment approaches can be used to manage MDD , such as psychotherapy , complementary and alternative medicine ( CAM ) , exercise , and pharmacotherapy . The psychological interventions used to treat depression include acceptance and commitment therapy , cognitive therapy , cognitive behavioral therapy ( CBT ) , interpersonal therapy , and psychodynamic therapies ( Table 1 ) . The CAM treatments include acupuncture , meditation , -3 fatty acids , S-adenosyl-l-methionine ( SAMe ) , St. John 's wort , and yoga . Exercise includes a broad range of activities that can be done for varying duration s , in classes , individually , or in informal groups . For pharmacologic therapy , the scope of this guideline is limited to second-generation antidepressants ( SGAs ) ( selective serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , and selective serotonin norepinephrine reuptake inhibitors ) . First-generation antidepressants ( tricyclic antidepressants and monoamine oxidase inhibitors ) are very rarely used because SGAs have lower toxicity in overdose than first-generation antidepressants and similar efficacy . Table 1 . Common Psychological Interventions to Treat Depression Guideline Focus and Target Population The purpose of this guideline from the American College of Physicians ( ACP ) is to summarize and grade the evidence on the comparative effectiveness and safety of nonpharmacologic treatments and SGAs ( including serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , bupropion , mirtazapine , nefazodone , and trazodone ) , alone or in combination , for MDD . The target audience for this guideline includes all clinicians , and the target patient population includes all adults with MDD . These recommendations are based on a background evidence article ( 9 ) and a systematic evidence review sponsored by the Agency for Healthcare Research and Quality ( AHRQ ) ( 6 ) . Methods Systematic Review of the Evidence The systematic evidence review was conducted by the AHRQ 's RTI InternationalUniversity of North Carolina at Chapel Hill Evidence -based Practice Center ( 6 ) . Additional method ological details can be found in the Appendix ) , accompanying background evidence article ( 9 ) , and full report ( 6 ) . Review ers search ed several data bases for studies published in English , German , or Italian from 1 January 1990 through September 2015 . Studies on efficacy were limited to r and omized , controlled trials and systematic review s and meta-analyses , although evidence on harms included observational studies . Review ers combined data when possible using meta- analysis and assessed the risk of bias and quality of studies according to established methods . The study population included adult out patients ( aged 18 years ) with MDD during either an initial or a second treatment attempt who did not remit after an initial adequate trial with an SGA . The review evaluated the following classes of interventions : depression-focused psychotherapy , CAM , exercise , and SGAs . Outcomes assessed included benefits in response ( often defined as 50 % improvement in HAM-D scores ) , remission ( often defined as a HAM-D score 7 ) , speed of response , speed of remission , relapse , quality of life , functional capacity ( as assessed by various scales ) , reduction of suicidality , or reduction of hospitalization . Harms assessed included overall adverse events , withdrawals because of adverse events , serious adverse events , and specific adverse events . Quality of life , functional status , suicidality , and hospitalizations were rarely reported . Grading the Evidence and Developing Recommendations This guideline was developed by the ACP Clinical Guidelines Committee according to the ACP guideline development process , which has been described ( 10 ) . The Clinical Guidelines Committee used the evidence tables in the accompanying systematic review and full report ( 9 ) when reporting the evidence and grade d the recommendations using ACP 's guideline grading system ( Table 2 ) . Table 2 . The American College of Physicians ' Guideline Grading System * Peer Review The AHRQ evidence review was sent to invited peer review ers and posted on the AHRQ Web site for public comments . The guideline was peer- review ed through the journal and was posted online for comments from ACP Governors and Regents . Comparative Benefits of Pharmacologic Versus Nonpharmacologic Treatment Options for Initial Management Refer to Appendix Table 1 and the accompanying systematic review ( 9 ) for additional details of the evidence . Appendix Table 1 . First-Line Treatment for MDD : SGAs Versus Nonpharmacologic Therapies * SGA Versus Psychological Interventions SGA Versus CBT Monotherapy . Moderate- quality evidence from 5 trials ( 1115 ) showed no difference in response when comparing SGAs ( fluoxetine , fluvoxamine , paroxetine , or sertraline ) with CBT in patients with MDD after 8 to 52 weeks of treatment . Low- quality evidence from 3 trials ( 11 , 14 , 15 ) showed no difference between remission rates ( fluoxetine , fluvoxamine , and paroxetine ) and functional capacity ( 14 ) ( fluvoxamine and paroxetine ) for SGAs compared with CBT . Combination Therapy . Low- quality evidence from 2 trials ( 14 , 16 ) showed no difference in response or remission when comparing monotherapy using SGAs ( escitalopram , fluvoxamine , or paroxetine ) with combination therapy using SGAs plus CBT ( problem-solving therapy or telephone-based CBT ) in patients with MDD after 12 to 52 weeks of treatment . Low- quality evidence from 2 trials ( 14 , 16 ) assessed function , and 1 trial showed that patients who received the combination therapy reported more improvement on 3 of 5 work-functioning measures than those who received SGA monotherapy , although clinical ly important differences on these measures are uncertain . SGA Versus Interpersonal Therapy Monotherapy . Low- quality evidence showed no difference in response ( 1 trial ; escitalopram ) ( 17 ) or remission ( 2 trials ; citalopram , escitalopram , or sertraline ) ( 17 , 18 ) for SGAs compared with interpersonal therapy for patients with MDD after 12 weeks of treatment . Combination Therapy . Low- quality evidence from 1 trial ( 19 ) showed increased remission for SGA monotherapy compared with SGA combined with interpersonal therapy ( with nefazodone ) in patients with MDD after 12 weeks of treatment . SGA Versus Psychodynamic Therapies Monotherapy . Low- quality evidence from 1 trial ( 20 ) showed no difference in remission for fluoxetine compared with psychodynamic monotherapy in patients with MDD after 16 weeks of treatment . Low- quality evidence from 2 trials ( 20 , 21 ) showed few differences in functional capacity between the treatments . Combination Therapy . Low- quality evidence from 1 trial ( 21 ) showed no difference in functional capacity for SGA monotherapy compared with SGA plus psychodynamic combination therapy . SGA Versus CAM Interventions SGA Versus Acupuncture Monotherapy . Low- quality evidence from 2 trials ( 22 , 23 ) showed no difference in treatment response when comparing fluoxetine with acupuncture monotherapy for patients with MDD after 6 weeks of treatment . Combination Therapy . Low- quality evidence from 2 trials ( 24 , 25 ) showed that combination therapy of SGAs with acupuncture improved treatment response compared with monotherapy with SGAs ( fluoxetine or paroxetine ) in patients with MDD after 6 weeks of treatment . However , low- quality evidence from 1 trial ( 24 ) showed no difference in remission when comparing paroxetine monotherapy with paroxetine plus acupuncture combination therapy . SGA Versus -3 Fatty Acids Monotherapy . Low- quality evidence from network meta- analysis showed that SGAs ( fluoxetine ) were associated with a greater response than -3 fatty acids in patients with MDD .  SGA Versus SAMe Monotherapy . Low- quality evidence from network meta- analysis showed no difference in response between treatment with escitalopram BACKGROUND The treatment of bipolar disorder is often complicated by the presence of a co-occuring anxiety disorder . Although second generation antipsychotics are being used with increasing frequency in bipolar patients , their anxiolytic effects have not been well studied in this population . METHODS The anxiolytic effect of risperidone 0.5 - 4 mg/day was tested in an 8-week , double-blind , placebo-controlled , r and omized clinical trial in 111 patients with bipolar disorder and a co-occuring panic disorder or generalized anxiety disorder ( GAD ) . The primary outcome measure was the Clinician Global Improvement-21 Anxiety scale ( CGI-21 Anxiety ) . Secondary measures included the Hamilton Anxiety Scale ( HAM-A ) and the Sheehan Panic Disorder Scale . RESULTS On the last-observation-carried forward analysis of repeated measures analysis of variance ( ANOVA ) , risperidone was not more effective than placebo for the CGI-21 Anxiety score or the other anxiety outcome measures .  Risperidone was well tolerated , with only two patients withdrawing because of adverse events . LIMITATIONS The  risperidone treated group had more patients with mixed states and lifetime panic disorder at r and omization than the placebo group . The study was limited to 8 weeks and to individuals with bipolar and comorbid panic disorder or GAD . The results may not be applicable to risperidone as an add-on treatment to mood stabilizers , or to bipolar disorder comorbid with anxiety disorders other than panic disorder or GAD . CONCLUSIONS Risperidone monotherapy was not an effective anxiolytic for bipolar patients with comorbid panic disorder or GAD in doses of 0.5 - 4 mg/day over 8 weeks of treatment . The efficacy of other second generation antipsychotics and mood stabilizers on anxiety in patients with bipolar disorder and a co-occuring anxiety disorder should be investigated in double-blind , placebo-controlled studies It remains unclear if diminished high frequency heart rate variability ( HF-HRV ) can be found across anxiety disorders .  HF-HRV and heart rate ( HR ) were examined in panic ( PD ) , generalized anxiety ( GAD ) , social anxiety ( SAD ) , and obsessive-compulsive disorder ( OCD ) relative to healthy controls at baseline and during anxiety stressors . All disorders evidence d diminished baseline HF-HRV relative to controls . Baseline HRV differences were maintained throughout relaxation . For hyperventilation , PD and GAD demonstrated greater HR than controls . Psychotropic medication did not account for HF-HRV differences except in OCD . Age and sex evidence d multiple main effects . Findings suggest that low baseline HF-HRV represents a common index for inhibitory deficits across PD , GAD , and SAD , which is consistent with the notion of autonomic inflexibility in anxiety disorders . Elevated HR responses to hyperventilation , however , are specific to PD and GAD Objective : Treatment with second generation antipsychotics ( SGAs ) can increase the risk of patients with schizophrenia developing obesity , hyperlipidaemia and diabetes . Routine monitoring is recommended , but clinical practice suggests monitoring is not conducted at a rate necessary for these comorbidities . The aim was to audit what proportion of patients were having their weight , height , girth , body mass index , lipids and blood sugar levels monitored and recorded . Method : An audit of patients with schizophrenia , discharged from three psychiatric wards , was conducted . Two data sheets were recorded for every patient and inter-rater reliability was calculated . Data were then entered into SPSS and statistical significance calculated . Results : The sample consisted of 93 patients ; SGAs were taken by 31 % of admitted and 88 % of discharged patients . Of these , 65 % had their weight recorded , 61 % height , 31 % r and om blood sugar levels , 3 % postpr and ial blood sugar levels , 2 % glycosylated haemoglobin , and 7.5 % cholesterol and triglycerides . Girth and BMI were not recorded . Abnormalities were detected in 29 % of recorded BSL and 2 % of recorded cholesterol . Conclusions : Patients with schizophrenia on antipsychotics  have an alarmingly low rate of monitoring of these common adverse effects and comorbidities . Clinicians need to be aware of this , so that they can improve their practice
Overall , a general lack of efficacy of SGAs on panic symptoms was observed .
Except for ziprasidone , SGAs were well tolerated in these short-term trials
A role for second-generation antipsychotics ( SGAs ) in the treatment of  panic disorders ( PD ) has been proposed , but the actual usefulness of SGAs in this disorder is unclear .