***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: BACKGROUND It is uncertain whether higher doses of selective serotonin reuptake inhibitors have greater efficacy in  generalised anxiety disorder .  AIMS To assess the efficacy of different doses of escitalopram in generalised anxiety disorder . METHOD R and omised , double-blind , placebo-controlled , fixed-dose , parallel-group , 12-week study , with 681 patients : placebo ( n=139 ) ; escitalopram  , 5 mg/day , ( n=134 ) ; 10 mg/day ( n=136 ) ; 20 mg/day ( n=133 ) ; paroxetine , 20 mg/day ( n=139 ) . RESULTS Mean change in the primary efficacy measure was greater with escitalopram 10 and 20 mg than with placebo ; 10 mg was more efficacious than paroxetine . Paroxetine was superior to placebo on some secondary measures , at some time points . Compared with placebo , more patients withdrew because of adverse events with escitalopram 20 mg and paroxetine . CONCLUSIONS Escitalopram was efficacious in generalised anxiety disorder , 20 was not significantly superior to 10 mg/day . Escitalopram 10 mg was more efficacious than paroxetine BACKGROUND Pregabalin inhibits release of excess excitatory neurotransmitters , presumably by binding to the alpha2-delta subunit protein of widely distributed voltage-dependent calcium channels in the brain and spinal cord . OBJECTIVE To assess the anxiolytic efficacy of pregabalin in patients with generalized anxiety disorder . DESIGN Double-blind , placebo-controlled , active-comparator trial . Patients were r and omized to 4 weeks of treatment with pregabalin , 300 mg/d ( n = 91 ) , 450 mg/d ( n = 90 ) , or 600 mg/d ( n = 89 ) ; alprazolam , 1.5 mg/d ( n = 93 ) ; or placebo ( n = 91 ) . SETTING Psychiatry research and clinic setting s. PATIENTS Out patients meeting the DSM-IV criteria for generalized anxiety disorder , with a baseline Hamilton Anxiety Rating Scale ( HAM-A ) total score of 20 or greater . MAIN OUTCOME MEASURES Change from baseline to end point in total HAM-A score in the  pregabalin and alprazolam groups compared with the placebo group . The end point response criterion was 50 % or greater reduction in the HAM-A total score . RESULTS Pregabalin and alprazolam produced a significantly greater reduction in mean + /- SE HAM-A total score at last-observation-carried-forward end point compared with placebo ( -8.4 + /- 0.8 ) : pregabalin , 300 mg ( -12.2 + /- 0.8 , P<.001 ) , 450 mg ( -11.0 + /- 0.8 , P = .02 ) , and 600 mg ( -11.8 + /- 0.8 , P = .002 ) , and alprazolam ( -10.9 + /- 0.8 , P = .02 ) . By week 1 and at last-observation-carried-forward end point , the 3 pregabalin groups and the alprazolam group had significantly ( P<.01 ) improved HAM-A psychic anxiety symptoms compared with the placebo group . Compared with the placebo group , HAM-A somatic anxiety symptoms were also significantly ( P<.02 ) improved by the 300- and 600-mg pregabalin groups , but not by the 450-mg pregabalin ( week 1 , P = .06 ; week 4 , P = .32 ) and the alprazolam groups ( week 1 , P = .21 ; week 4 , P = .15 ) . Of the 5 treatment groups , the 300-mg pregabalin group was the only medication group that differed statistically in global improvement at treatment end point not only from the placebo group but also from the alprazolam group . CONCLUSION Pregabalin was significantly more efficacious than placebo for the treatment of psychic and somatic symptoms of generalized anxiety disorder and was well tolerated by most study patients This multicenter , double-blind , placebo-controlled , parallel-group , r and omized study assessed the efficacy , safety , and tolerability of a novel CCK-B antagonist CI-988 in the treatment of  generalized anxiety disorder ( GAD ) . Patients received placebo or CI-988 ( 300 mg/day , thrice daily ) for 4 weeks . Patients with a primary diagnosis of GAD according to DSM-III-R criteria were r and omized . The study design included a 1- to 2-week single-blind placebo baseline phase , followed by a 4-week double-blind treatment phase . Efficacy was measured weekly by Hamilton Rating Scale for Anxiety ( HAM-A ) , Clinical Global Impressions of Severity and Change , UCLA-Multi Dimensional Anxiety Scale , and Hamilton Rating Scale for Depression .  Patients were also evaluated to determine whether they met criteria for irritable bowel syndrome ( IBS ) at screening and were evaluated with a gastrointestinal visual analog scale at each visit . Eighty-eight patients were r and omized to CI-988 ( N = 45 ) and  placebo ( N = 43 ) at three centers . CI-988 did not demonstrate an anxiolytic effect superior to placebo in this clinical trial . There was no significant difference in mean change in HAM-A total between placebo ( -7.73 ) and CI-988 ( -8.64 ) . However , a significant treatment-by-center interaction and a highly variable placebo response rate among the three centers limit the interpretation of the results . CI-988 did not have an effect on symptoms of IBS other than diarrhea , which worsened in patients with IBS . Other than a higher incidence of some gastrointestinal symptoms ( diarrhea , dyspepsia , flatulence , and nausea ) , CI-988 was well tolerated . Results suggest that testing higher oral doses of CI-988 may be warranted Background : Agomelatine is a novel agent that acts on melatonergic ( MT1 , MT2 ) receptors and serotonergic ( 5-HT2C ) receptors . Pre clinical data and data from clinical trials in major depression suggest that agomelatine may have anxiolytic properties . A r and omized , double-blind , placebo-controlled trial was design ed to assess the efficacy of agomelatine in generalized anxiety disorder ( GAD ) . Methods : One hundred twenty-one patients with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition GAD and no comorbid disorders were r and omized to agomelatine ( 25 - 50 mg/d ) or placebo for 12 weeks . The primary outcome measure was the Hamilton Anxiety Rating Scale , whereas secondary outcome measures included the Clinical Global Impression scales , the Leeds Sleep Evaluation Question naire , and the Sheehan Disability Scale . Safety measures included assessment of spontaneously reported adverse events , laboratory monitoring , and the Discontinuation Emergent Signs and Symptoms Scale to evaluate discontinuation symptoms . Results : Analysis of covariance of change in the last Hamilton Anxiety Rating Scale total score from baseline demonstrated significant superiority of agomelatine 25 to 50 mg as compared with placebo ( E [ SE ] = −3.28 [ 1.58 ] ; 95 % confidence interval = −6.41 to −0.15 ; P = 0.040 ) . Data on secondary outcome measures , including clinical response , symptoms of insomnia , and improvement in associated disability , were consistent with the efficacy of agomelatine . Safety analysis indicated that agomelatine was tolerated as well as placebo and was devoid of discontinuation emergent symptoms . Conclusions : This study suggests that agomelatine is effective in the treatment of GAD and is well tolerated . Additional trials , using an active comparator and extending over a longer period , are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for anxiety disorders OBJECTIVE This study assessed the efficacy and safety of sertraline in the treatment of generalized anxiety disorder ( GAD ) . METHOD The study was conducted from April 2000 to May 2002 . Out patients with DSM-IV GAD ( N = 326 ) who satisfied inclusion /exclusion criteria and completed a 1-week screening phase were r and omly assigned to 10-week double-blind treatment with flexible dosing of sertraline ( 50 - 200 mg/day ) or placebo . The primary efficacy measure was change from baseline in Hamilton Rating Scale for Anxiety ( HAM-A ) total score . Response was defined as a 50 % or greater decrease in HAM-A total score at endpoint . RESULTS Sertraline produced a statistically significant reduction in anxiety symptoms , as measured by HAM-A total change scores ( p = .032 ) , HAM-A psychic anxiety subscale ( p = .011 ) , and Hospital Anxiety and Depression Scale-anxiety subscale ( p = .001 ) . Response rates were significantly higher ( p = .05 ) for the sertraline group ( 59.2 % ) compared to the placebo group ( 48.2 % ) . Sertraline was well tolerated , with only sexual side effects reported significantly more often by subjects receiving sertraline than those receiving placebo . CONCLUSION Despite the relatively small between-group differences , study findings suggest a role for sertraline in the acute treatment of GAD Deramciclane , a camphor derivative , is a novel anxiolytic agent with a unique mechanism of action . It acts as a potent and specific antagonist at serotonin 5-HT2A/2C receptors , and exhibits anxiolytic efficacy in animal models . The aim of this double-blind , placebo-controlled , parallel-group study was to evaluate the efficacy , safety , and tolerability of a range of doses of deramciclane in patients with generalized anxiety disorder ( GAD ) . Adult patients with a diagnosis of GAD ( DSM-IV ) and a Hamilton Anxiety Rating Scale ( HAM-A ) total score > or=18 ; a score > or=2 for the HAM-A items ' Anxious Mood ' and ' Tension ' ; a score > or=4 on the Clinical Global Impression of Severity of Illness ( CGI-S ) Scale ; and a score < or=20 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) were enrolled in the study . Following a 1 - 2 week placebo run-in period , patients were r and omized to receive deramciclane ( 10 , 30 , or 60 mg/day in two divided doses ) or placebo for 8 weeks , followed by a 2-week placebo wash-out period . The primary efficacy measure was change in HAM-A score from baseline to week 8 . Adverse events were monitored throughout the study . Withdrawal reactions were assessed at the end of the study ( week 8) and during the placebo wash-out period using the Physician 's Withdrawal Checklist ( 34 items ) . In the intent-to-treat population ( n=208 ) , both the deramciclane 30 mg/day and 60 mg/day doses provided clinical ly relevant improvements in HAM-A total score after 8 weeks of treatment , reaching statistical significance compared with placebo in the 60 mg/day dose group ( p=0.024 ) and a clear trend in the 30 mg/day group ( p=0.059 ) . On the HAM-A psychic anxiety factor , significant improvements were seen in patients in the deramciclane 30 mg/day and 60 mg/day treatment groups compared with those in the placebo group ( p<0.05 ) . Adverse events were reported at a similar frequency across all four treatment groups ; the most commonly reported adverse event was headache . No withdrawal reactions were observed on abrupt discontinuation of deramciclane . In conclusion , deramciclane 60 mg/day showed significant evidence of efficacy for the treatment of GAD in adult patients . The efficacy for the 30 mg/day dose was close to the larger dose although not significant in the primary analysis , and there was no significant evidence of efficacy for the 10 mg/day dose . Deramciclane was safe and well-tolerated up to the 60 mg/day dose over an 8-week period OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) appear to be an effective class of medications for the treatment of  generalized anxiety disorder .  Within the SSRI class , however , there have been no comparative treatment studies for this disorder . Therefore , in the present study , we compared the efficacy and tolerability of 2 SSRIs , paroxetine and sertraline , in the treatment of generalized anxiety disorder . METHOD In this parallel-group , double-blind , flexible-dose study , 55 patients with primary generalized anxiety disorder ( DSM-IV criteria ) were r and omly assigned to receive either paroxetine or sertraline treatment for 8 weeks . Primary efficacy measures were the mean changes in Hamilton Rating Scale for Anxiety ( HAM-A ) scores as well as responder and remission rates based on the Clinical Global Impressions scale . Secondary efficacy measures consisted of the Indiana University Generalized Anxiety Measurement Scale and self-report ratings of anxiety , and quality -of-life outcome . Tolerability 
    Output:
    
Though the frequentist analysis was inconclusive because of a high level of uncertainty in effect sizes ( based on the relatively small number of comparative trials ) , the probabilistic analysis , which did not rely on significant outcomes , showed that fluoxetine ( in terms of response and remission ) and sertraline ( in terms of tolerability ) seem to have some advantages over other treatments .
Among five UK licensed treatments , duloxetine , escitalopram , and pregabalin might offer some advantages over venlafaxine and paroxetine