***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: Abstract . Rationale : A large proportion of patients with major depression do not respond sufficiently to any first-line treatment . Objectives : The aim of this study was to compare a strategy of sertraline dose increase with a strategy of adding mianserin in patients with major depression insufficiently responding to 6 weeks of open treatment with sertraline  , controlling for the effect of an extended duration of treatment . Methods : One thous and six hundred and twenty-nine patients , 18–65 years of age , with major depression scoring at least 18 on the 17-item Hamilton depression scale ( HDS ) were treated openly with 50 mg/day sertraline , and patients who after 4 weeks had not responded ( achieving at least a 50 % reduction in score on the HDS ) were treated with 100 mg/day sertraline for an additional 2-week period . The patients who had still not responded were then r and omised to double-blind treatment for an additional 5 weeks with either 100 mg/day sertraline plus placebo , 200 mg/day sertraline plus placebo or 100 mg/day sertraline plus 30 mg/day mianserin . Results : After 6 weeks of open treatment , 60 % had responded and 22 % had dropped out , leaving 295 non-responding patients ( 18 % ) for r and omisation . In the intention-to-treat- analysis , continuing the treatment with 100 mg/day sertraline result ed in response in 70 % of the non-responders , similar to the response rate ( 67 % ) obtained in the patients who had mianserin added . However , increasing the sertraline dose to 200 mg/day result ed in a lower response rate at 56 % ( P<0.05 ) . Similar results were seen in the completers . A substantial increase in the accumulated response rate from week 6 to week 8 was seen . There was no influence of baseline variables , including the presence of melancholic features on the overall post-r and omisation response rate . Conclusion : After 6 weeks of insufficient antidepressant treatment with 50–100 mg/day sertraline , a continued treatment with 100 mg/day sertraline can be considered until at least week 8 before considering changing strategy , unless the condition deteriorates Treatment effects are often evaluated by comparing change over time in outcome measures . However , valid analyses of longitudinal data can be problematic , particularly when some data are missing for reasons related to the outcome . In choosing the primary analysis for confirmatory clinical trials , regulatory agencies have for decades favored the last observation carried forward ( LOCF ) approach for imputing missing values . Many advances in statistical methodology , and also in our ability to implement those methods , have been made in recent years . The characteristics of data from acute phase clinical trials can be exploited to develop an appropriate analysis for assessing response profiles in a regulatory setting . These data characteristics and regulatory considerations will be review ed . Approaches for h and ling missing data are compared along with options for modeling time effects and correlations between repeated measurements . Theory and empirical evidence are utilized to support the proposal that likelihood-based mixed-effects model repeated measures ( MMRM ) approaches , based on the missing at r and om assumption , provide superior control of Type I and Type II errors when compared with the traditional LOCF approach , which is based on the more restrictive missing completely at r and om assumption . It is further reasoned that in acute phase clinical trials , unstructured modeling of time trends and within-subject error correlations may be preferred BACKGROUND There is a mismatch between the wish of a patient with depression to have counselling and the prescription of antidepressants by the doctor . AIMS To determine whether counselling is as effective as antidepressants for depression in primary care and whether allowing patients to choose their treatment affects their response . METHOD A partially r and omised preference trial , with patients r and omised to either antidepressants or counselling or given their choice of either treatment . The treatment and follow-up were identical in the r and omised and patient preference arms . RESULTS There were 103 r and omised and 220 preference patients in the trial . We found : no differences in the baseline characteristics of the r and omised and preference groups ; that the two treatments were equally effective at 8 weeks , both for the r and omised group and when the r and omised and patient preference groups for a particular treatment were combined ; and that expressing a preference for either treatment conferred no additional benefit on outcome . CONCLUSIONS These data challenge several assumptions about the most appropriate treatment for depression in a primary care setting CONTEXT Extracts of St John 's wort are widely used to treat depression . Although more than 2 dozen clinical trials have been conducted with St John 's wort , most have significant flaws in design and do not enable meaningful interpretation . OBJECTIVE To compare the efficacy and safety of a st and ardized extract of St John 's wort with placebo in out patients with major depression . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States . PARTICIPANTS Two hundred adult out patients ( mean age , 42.4 years ; 67.0 % female ; 85.9 % white ) diagnosed as having major depression and having a baseline Hamilton Rating Scale for Depression ( HAM-D ) score of at least 20 . INTERVENTION Participants completed a 1-week , single-blind run-in of placebo , then were r and omly assigned to receive either St John 's wort extract ( n = 98 ; 900 mg/d for 4 weeks , increased to 1200 mg/d in the absence of an adequate response thereafter ) or placebo ( n = 102 ) for 8 weeks . MAIN OUTCOME MEASURES The primary outcome measure was rate of change on the HAM-D over the treatment period . Secondary measures included the Beck Depression Inventory ( BDI ) , Hamilton Rating Scale for Anxiety ( HAM-A ) , the Global Assessment of Function ( GAF ) scale , and the Clinical Global Impression-Severity and -Improvement scales ( CGI-S and CGI-I ) . RESULTS The r and om coefficient analyses for the HAM-D , HAM-A , CGI-S , and CGI-I all showed significant effects for time but not for treatment or time-by-treatment interaction ( for HAM-D scores , P<.001 , P = .16 , and P = .58 , respectively ) . Analysis of covariance showed nonsignificant effects for BDI and GAF scores . The proportion of participants achieving an a priori definition of response did not differ between groups . The number reaching remission of illness was significantly higher with St John 's wort than with placebo ( P = .02 ) , but the rates were very low in the full intention-to-treat analysis ( 14/98 [ 14.3 % ] vs 5/102 [ 4.9 % ] , respectively ) . St John 's wort was safe and well tolerated . Headache was the only adverse event that occurred with greater frequency with St John 's wort than placebo ( 39/95 [ 41 % ] vs 25/100 [ 25 % ] , respectively ) . CONCLUSION In this study , St John 's wort was not effective for treatment of major depression This study examined cross-sectional and prospect i ve associations of exercise with depressed mood in a community-based sample of older men and women ( aged 50 - -89 years in 1984 - -1987 ) in southern California .  Regular strenuous exercise and exercise > or =3 times per week were reported ; depressed mood was assessed by using the Beck Depression Inventory ( BDI ) . After exclusion of persons with categorical depression and those rating themselves largely or extremely physically limited during the previous month , data on 932 men and 1,097 women were available for cross-sectional analysis .  Exercise  and depressed mood were reassessed for 404 men and 540 women in 1992 - -1995 ; these data were the focus of prospect i ve analyses . In 1984 - -1987 ,  exercise rates were high ( > 80 % ) , and average BDI scores were low . Cross-sectional analyses indicated that before and after adjustment for covariates , exercise was significantly associated with less depressed mood . However , prospect i ve analyses of the 944 persons who attended both clinic visits indicated no association between baseline exercise  and either follow-up BDI score ( p > 0.10 ) or change in BDI score between baseline and follow-up ( p > 0.10 ) . Results confirm that exercisers have less depressed mood . However , exercise does not protect against future depressed mood for those not clinical ly depressed at baseline CONTEXT Extracts of Hypericum perforatum ( St John 's wort ) are widely used for the treatment of depression of varying severity . Their efficacy in major depressive disorder , however , has not been conclusively demonstrated . OBJECTIVE To test the efficacy and safety of a well-characterized H perforatum extract ( LI-160 ) in major depressive disorder . DESIGN AND SETTING Double-blind , r and omized , placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States . PARTICIPANTS Adult out patients ( n = 340 ) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale ( HAM-D ) of at least 20 . INTERVENTIONS Patients were r and omly assigned to receive H perforatum , placebo , or sertraline ( as an active comparator ) for 8 weeks . Based on clinical response , the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg . Responders at week 8 could continue blinded treatment for another 18 weeks . MAIN OUTCOME MEASURES Change in the HAM-D total score from baseline to 8 weeks ; rates of full response , determined by the HAM-D and Clinical Global Impressions ( CGI ) scores . RESULTS On the 2 primary outcome measures , neither sertraline nor H perforatum was significantly different from placebo . The r and om regression parameter estimate for mean ( SE ) change in HAM-D total score from baseline to week 8 ( with a greater decline indicating more improvement ) was -9.20 ( 0.67 ) ( 95 % confidence interval [ CI ] , -10.51 to -7.89 ) for placebo vs -8.68 ( 0.68 ) ( 95 % CI , -10.01 to -7.35 ) for H perforatum ( P = .59 ) and -10.53 ( 0.72 ) ( 95 % CI , -11.94 to -9.12 ) for sertraline ( P = .18 ) . Full response occurred in 31.9 % of the placebo-treated patients vs 23.9 % of the H perforatum-treated patients ( P = .21 ) and 24.8 % of sertraline-treated patients ( P = .26 ) . Sertraline was better than placebo on the CGI improvement scale ( P = .02 ) , which was a secondary measure in this study . Adverse-effect profiles for H perforatum and sertraline differed relative to placebo . CONCLUSION This study fails to support the efficacy of H perforatum in moderately severe major depression . The result may be due to low assay sensitivity of the trial , but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy BACKGROUND The necessity of antidepressant continuation-phase therapy following acute-phase response has result ed in the need to characterize the longer-term efficacy and safety of all new medications . Previous studies using " extension " protocol s suggest that mirtazapine has sustained antidepressant effects . The current study was performed to evaluate the efficacy and safety of up to 1 year of mirtazapine therapy , using a more rigorous , r and omized , placebo-controlled discontinuation design . METHOD An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine ( flexibly titrated , 15 - 45 mg/day ) . Thereafter , 156 fully remitted patients ( according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores ) were r and omly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo . RESULTS Mirtazapine therapy reduced the rate of depressive relapse by more than half , with 43.8 % of patients relapsing on treatment with placebo as compared with 19.7 % of the mirtazapine-treated patients . The discontinuation rate due to adverse events was 11.8 % for active mirtazapine therapy versus 2.5 % for placebo . Although weight gain was significantly greater in the group receiving active medication during the double-blind phase ( p = .001 ) , patients taking mirtazapine gained only 1.4 kg ( 3.1 lb ) across the 40 weeks of continuation therapy , and there was no difference in the rates of weight gain as a newonset adverse event . CONCLUSION Continuation-phase therapy with mirtazapine is effective and well tolerated BACKGROUND This was the first controlled continuation phase study ( up to 1-year total treatment ) to evaluate the safety and efficacy of bupropion SR for decreasing the risk for relapse of depression in patients who responded to bupropion SR .  METHODS Patients with recurrent major depression were treated with bupropion SR 300 m 
    Output:
    
For patients who do not respond to initial medication treatment , treatments such as psychotherapy , exercise , light therapy , alternative medicines , and counselling have demonstrated benefits over placebo and may enhance remission rates when used in combination with antidepressants .
R and omized controlled clinical trials conducted in the last 5 years provide very good evidence to show that achieving and sustaining the fully remitted state is an attainable goal in the management of patients with depression