***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Mirtazapine added to antipsychotics appears to improve the clinical picture of schizophrenia , including both negative and positive symptoms . This study explored the effect of adjunctive mirtazapine on neurocognition in patients with schizophrenia who had shown an insufficient response to first-generation antipsychotics ( FGAs ) . Thirty-seven schizophrenia patients , who were at least moderately ill despite their FGA treatment , received add-on mirtazapine ( n=19 ) or placebo ( n=18 ) in a 6-wk double-blind , r and omized trial . Widely used neuropsychological tests were performed to explore visual-spatial functions , verbal and visual memory , executive functions , verbal fluency and general mental and psychomotor speed . The data were analysed on the modified intent-to-treat basis with last observation carried forward . False discovery rate was applied to correct for multiple testing . Mirtazapine outperformed placebo in the domains of visual-spatial ability and general mental speed/attentional control as assessed by , correspondingly , Block Design and Stroop dots . The difference in the degree of change ( i.e. change while on mirtazapine minus that on placebo ) was 18.6 % ( p=0.044 ) and 11.1 % ( p=0.044 ) , respectively . Adjunctive mirtazapine might offer a safe , effective and cost-saving option as a neurocognitive enhancer for FGA-treated schizophrenia patients . Mirtazapine+FGA combinations may become especially useful in light of the currently increasing attention towards FGAs . Larger and longer studies that incorporate functional outcomes , as well as comparisons with second-generation antipsychotics are , however , still needed for more definite conclusions 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 BACKGROUND Preliminary evidence indicates a beneficial effect of serotonin 2A ( 5-HT(2A ) ) receptor antagonists in antipsychotic-induced akathisia ( AIA ) . We investigated the antiakathisia effect , safety , and tolerability of low-dose mirtazapine , an agent with marked 5-HT(2A ) antagonism . METHODS In a 7-day double-blind trial , 90 antipsychotic-treated patients meeting DSM-IV criteria for AIA were r and omly assigned to mirtazapine ( n = 30 ; 15 mg ) , propranolol ( n = 30 ; 80 mg ) , or placebo ( n = 30 ) . Primary outcome measures were between-group differences in Barnes Akathisia Scale ( BAS ) global scores and in the proportion of responders ( reduction of > or = 2 points on BAS ) . Analysis was by intention to treat . RESULTS Twenty-four patients ( 26.6 % ) who were assigned treatment did not complete the study ( 7 mirtazapine , 8 propranolol , 9 placebo ) , due to lack of response ( n = 19 ) and adverse events ( n = 5 ) . Both mirtazapine and propranolol significantly reduced AIA severity ( BAS : -34 % mirtazapine and -29 % propranolol vs. placebo -11 % ; p = .012 and p = .023 , respectively ) . Thirteen ( 43.3 % ) mirtazapine and 9 ( 30.0 % ) propranolol-treated patients versus 2 ( 6.7 % ) placebo-treated patients responded ( the corresponding odds ratios 10.7 [ 95 % confidence interval ( CI ) , 2.1 - 53.3 ] and 6.0 [ 95 % CI , 1.1 - 30.7 ] ) . Five ( 16.7 % ) of 30 propranolol-treated patients and none in the mirtazapine and placebo groups ( p = .0195 for both ) prematurely discontinued the study due to clinical ly significant hypotension or bradycardia . CONCLUSIONS The comparable efficacy and better tolerability of low-dose mirtazapine versus propranolol , the current first-line treatment for AIA , position mirtazapine as a favorable c and i date for the treatment of acute AIA and may improve current therapeutic practice The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more .  ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Objective Some patients with schizophrenia may need mirtazapine augmentation to improve negative and cognitive symptoms . However there have been a few studies about the tolerability of mirtazapine augmentation to antipsychotics such as akathisia , extrapyramydal symptoms , weight gain , and body mass index ( BMI ) . Methods This study was an eight-week double-blind , r and omized controlled trial ( RCT ) of mirtazapine augmentation to risperidone .  Twenty-one stabilized participants diagnosed with schizophrenia and undergoing treatment with risperidone  were r and omized to adjunctive treatment with mirtazapine ( 15 mg/day for the first two weeks , 30 mg/day for the next six weeks ) or placebo . Eleven patients were assigned to the mirtazapine group , and nine patients were given placebo . Results There was no significant difference between the mirtazapine and placebo groups with respect to Barnes Akathisia rating Scale ( BAS ) and Sympsom-Angus Scale ( SAS ) . However , the mirtazapine group exhibited a statistically significant increase in weight and BMI ( p<0.05 ) . Conclusion These results suggest that mirtazapine augmentation can be tolerable in schizophrenic patients treated with risperidone ; however , we should pay attention to the weight gain with mirtazapine . Our results should be replicated in a large-scale lengthy trial The development of therapeutic strategies to effectively treat negative symptoms remains one of the primary goals in the treatment of schizophrenia .  Mirtazapine is the first of a new class of dual action compounds , the noradrenergic and specific serotonergic antidepressants ( NaSSa ) , whose activity is related to the enhancement of noradrenergic and serotonergic transmission by a presynaptic & agr;2 antagonism and postsynaptic 5-HT2 and 5-HT3 antagonism , respectively . This study was a 8-week double-blind , r and omized , placebo-controlled trial of 30 mg adjunctive mirtazapine to clozapine therapy in 24 patients with DSM-IV schizophrenia . The main finding at the end of the trial was a significant reduction on the Scale for the Assessment of Negative Symptoms ( SANS ) total scores in the mirtazapine group compared to placebo ( P<0.01 ) with a significant improvement on the SANS subscales avolition/apathy and anhedonia/asociality . The Brief Psychiatric Rating Scale total score at week 8 showed superiority of mirtazapine over placebo . These findings suggest a potential role for mirtazapine as an augmentation strategy in the treatment of negative symptoms of schizophrenia It has been reported that mirtazapine would be helpful for treating negative symptoms in schizophrenia . Nevertheless , the results are contradictory so far . This study was design ed to investigate the effect of mirtazapine added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and r and omized clinical trial . Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 19 to 49 years . All patients were in patients and were in the active phase of the illness , and met DSM-IV-TR criteria for schizophrenia . Patients were allocated in a r and om fashion 20 to risperidone 6 mg/day plus mirtazapine 30 mg/day and 20 to risperidone 6 mg/day plus placebo . The principal measure of the outcome was Positive and Negative Syndrome Scale ( PANSS ) . The mirtazapine group had significantly greater improvement in the negative symptoms and PANSS total scores over the eight-week trial . Therapy with 30 mg/day of mirtazapine was well tolerated and no clinical ly important side effects were observed . The present study indicates mirtazapine as a potential combination treatment strategy for chronic schizophrenia particularly for negative symptoms 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 The negative symptoms of  schizophrenia  remain a major clinical challenge . Mirtazapine is an antidepressant with antagonist properties at 5-HT2A , 5-HT3 and alpha 2 receptors as well as indirect 5-HT1a agonist effects . Many of these pharmacological actions have clinical or pre clinical evidence of efficacy in schizophrenia . This study was a 6-week r and omized placebo-controlled trial of mirtzepine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia . The primary finding of the trial was a 42 % reduction in Positive and Negative Syndrome Scale ( PANSS ) negative symptom scores in the mirtazapine group compared to placebo at the end of 6 weeks ( mirtazapine 13.9 , SD 1.56 ; placebo 23.9 , SD 1.56 ; P = 0.000 , F = 20.31 , d.f . = 1 ) . The PANNS total scores , Clinical Global Impression severity and improvement scales in addition showed superiority of mirtazapine over placebo . There was no difference between the groups on the Hamilton depression scale at endpoint , suggesting that the improvement in negative symptoms was not an artifact of mood improvement . These results suggest a potential role for mirtazapine in the negative symptoms of schizophrenia Depression is common in schizophrenia and worsens its course . The role of antidepressants for schizophrenic depression remains unclear . In this study , the efficacy of add-on mirtazapine on depression in schizophrenia was explored in a subsidiary arm of a recent r and omized controlled trial . Patients ( n = 41 ) with chronic but stable schizophrenia and inadequate response to stable doses of different first-generation antipsychotics  were 
    Output:
    
The available evidence is primarily of very low quality and indicates that mirtazapine adjunct is not clearly associated with an effect for negative symptoms , but there is some indication of a positive effect on overall mental state and akathisia .
No effect was found for global state or leaving the study early and data were not available for quality of life or service use .
Due to limitations of the quality and applicability of the evidence it is not possible to make any firm conclusions , the role of mirtazapine adjunct in routine clinical practice remains unclear .