Second Generation Antipsychotics Improve Sexual Dysfunction in Schizophrenia: A Randomised Controlled Trial Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth. 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). Comparison of SGA oral medications and a long-acting injectable SGA: the PROACTIVE study. Employment Outcomes in a Randomized Trial of Second-Generation Antipsychotics and Perphenazine in the Treatment of Individuals with Schizophrenia Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. Subcortical modulation of attentional control by second-generation antipsychotics in first-episode psychosis Cerebral Cortical Gray Expansion Associated with Two Second-Generation Antipsychotics The Effectiveness of Guideline Implementation Strategies on Improving Antipsychotic Medication Management for Schizophrenia 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 Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms. More evidence on additive antipsychotic effect of adjunctive mirtazapine in schizophrenia: an extension phase of a randomized controlled trial Cognitive-behavioral therapy as an adjunct to second-generation antipsychotics in the treatment of schizophrenia. An Evaluation of Monitoring Practices in Patients on Second Generation Antipsychotics Prescribing second-generation antipsychotics and the evolving standard of care in Italy. Add-on mirtazapine enhances antipsychotic effect of first generation antipsychotics in schizophrenia: A double-blind, randomized, placebo-controlled trial
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 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 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 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 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 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 Psychotic disorders are characterized by significant deficits in attentional control , but the neurobiological mechanisms underlying these deficits early in the course of illness prior to extensive pharmacotherapy are not well understood . Moreover , little is known regarding the symptom and brain changes associated with amelioration of attentional impairments through antipsychotic pharmacotherapy . In this study 14 male patients experiencing a first-episode of psychosis with minimal prior antipsychotic treatment completed an  attentional control task while undergoing functional magnetic resonance imaging at the onset of treatment with a second generation antipsychotic ( risperidone or aripiprazole ) in a double blind r and omized clinical trial and then again following approximately 12 weeks of treatment . In addition , 14 age- , and performance-matched healthy male volunteers who were not treated completed the same task at a baseline timepoint and then again following 12 weeks . Patients showed significantly greater activation than healthy volunteers in the right globus pallidus , left thalamus , and right thalamus at the time of the baseline scan . Among patients there was a significant reduction in right globus pallidus blood-oxygen level dependent ( BOLD ) response following antipsychotic treatment that correlated significantly with improvement in response accuracy and reductions in thought disturbance . No changes in globus pallidus activation were observed in healthy volunteers over this time period . These preliminary findings suggest that improvement in attentional control and concomitant reductions in thought disturbance in first-episode psychosis may be associated with reductions in subcortical activity following administration of second-generation antipsychotics early in the course of illness . These findings have implication s for underst and ing how changes in basal ganglia activity may be linked to improvements in attentional control through antipsychotics 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 : 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 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 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 Adjunctive mirtazapine improved negative symptoms of schizophrenia  in several studies . Recently , we found an improvement also in positive symptoms when mirtazapine was added to first generation antipsychotics ( FGAs ) in a 6 week r and omized controlled trial ( RCT ) . The short duration of that trial was its limitation . This study aim ed to explore whether longer treatment is worthwhile OBJECTIVE This study determined whether adding cognitive-behavioral therapy to treatment for out patients with schizophrenia  would be more effective than the use of second-generation antipsychotics alone . Thirty-three patients were r and omly assigned to receive either  second-generation antipsychotics alone  ( N=18 ) or  second-generation antipsychotics plus cognitive-behavioral therapy  ( N=15 ) . METHODS All patients received pharmacotherapy from a single provider and in a predetermined st and ard manner . Psychopathology ratings were done at baseline , at the end of treatment ( 12 weeks ) and three months after completion of treatment ( 24 weeks ) . RESULTS Twenty-five ( 76 % ) patients completed baseline and 12-week evaluations , and 17 ( 68 % ) patients who finished treatment also completed evaluations at 24 weeks . At the end of treatment persons in the second-generation antipsychotics plus cognitive-behavioral therapy group were rated as having less severe delusions than patients in the group receiving second-generation antipsychotics only , and this difference was maintained three months after treatment ended . CONCLUSIONS Adding cognitive-behavioral therapy may help with reducing the severity of delusions among patients with schizophrenia 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 The present study was carried out to investigate the routine use of second-generation antipsychotic drugs in the Italian psychiatric care system . Seven outpatient psychiatric services enrolled a consecutive case series of patients who were being treated , or had started treatment , with clozapine , olanzapine , risperidone , or quetiapine .  Information on sociodemographic and clinical variables , current psychotropic drug use , side-effects and past use of typical drugs was collected . In addition , patient symptoms and functional status were evaluated by the Health of the Nation Outcome Scale . Patients receiving off-label prescribing of second-generation antipsychotics were identified . A total of 209 patients were collected . In comparison with patients receiving other second-generation antipsychotics , living in residential facilities , unemployment , long psychiatric histories , and problems with activities of daily living and living conditions were more common in clozapine-treated patients . Nearly 80 % of patients receiving clozapine had schizophrenia compared to less than 50 % of those receiving other second-generation antipsychotics . Overall , 109 patients ( 52 % ) received off-label prescriptions of second-generation antipsychotic drugs . This survey indicates that clozapine was mostly reserved for severe cases and poor responders ; the high rate of off-label prescriptions highlights the gap existing between recommendations derived from r and omised clinical trials and the current use of drugs BACKGROUND Mirtazapine , an antidepressant with a broad spectrum of receptor affinity may , if combined with first generation antipsyhotics ( FGAs ) , improve clinical profile of the FGAs . However , potentiation of the antipsychotic effect by mirtazapine has not been reported thus far . We explored the efficacy of adjunctive mirtazapine on symptoms of schizophrenia in patients having an insufficient response to different FGAs . METHODS Schizophrenia-diagnosed patients with a prolonged disease and a history of a poor response to numerous antipsychotics , who were at least moderately ill despite their FGAs treatment , received add-on mirtazapine ( n=20 ) or placebo  ( n=19 ) in a 6-week double-blind r and omized controlled trial ( RCT ) . The analysis was made on a Modified Intent-to-Treat ( MITT ) basis with Last Observations Carried Forward ( LOCF ) . RESULTS Mirtazapine outranged placebo on almost all measures . The clear-cut clinical relevance of this finding was demonstrated by a large effect size of 1.00 ( 95 % CI 0.23 - 1.67 , p=0.003 ) on the total Positive and Negative Syndrome Scale ( PANSS ) scores ( the primary outcome ) . The PANSS positive subscale scores decreased by 17.2 % with mirtazapine vs. 1.6 % with placebo ( p<0.001 ) , and the PANSS negative subscale scores by 12 % and 3 % ( p<0.001 ) , correspondingly . CONCLUSIONS This is the first RCT reporting a robust additive antipsychotic effect of an adjunctive antidepressant . Mirtazapine-FGAs combination appears to be a safe , well-tolerated and efficacious treatment option in this challenging population . These findings are important due to the current re-emerging attention to FGAs . The focus of further studies should be exp and ed to include combinations with or switching to novel antipsychotics , different sub population s of patients with schizophrenia , finding of optimal doses , and comparison with clozapine
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 .