***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: Two hundred and forty neurotic out- patients were allocated to no diagnostic category but were rated in terms of observer and self ratings of both depression and anxiety at weekly intervals during a 4-week trial of amitriptyline , diazepam , amitriptyline and diazepam , and placebo . The sample could not be divided into anxious and depressed groups on the basis of the clinical picture . The outcome tended to be good irrespective of medication but the significant drug effects found were due to amitriptyline and concerned measures of anxiety as well as depression . It is concluded that a distinction between anxiety and depression in neurotic out- patients is of no practical value with regard to drug treatment 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 CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data This study examines the scientific basis for mental health intervention programs in primary care . The validity of five underlying assumptions is evaluated , using the results of a naturalistic study covering a representative sample of 25 Dutch family practice s and data from the literature . Our findings corroborate the validity of the assumptions . Firstly , our study indicates that mental disorders are indeed very prevalent in primary care setting s. Secondly , we find that a substantial proportion of mental disorders is not recognized by the general practitioner ( GP ) . Thirdly , our data show that mental disorders in primary care are not transient or self-limiting . Fourthly , it is shown that only half of the GP attenders with a mental disorder receive some form of  mental health treatment in the 14 months after their index consultation . Finally , our data suggest that mental disorders , when identified , can be treated effectively in primary care . These findings are in general agreement with the literature . In the discussion we underscore the need for public health intervention programs targeted at primary care providers . Training programs for general physicians must be directed at improving recognition and diagnosis and at enhancing the availability and quality of mental health interventions . The effectiveness of these programs has to be tested in r and omized trials Four hundred and thirty-four patients suffering from mild to moderate depression were recruited into a double-blind multicentre general practice study and r and omly received either Limbitrol ( 25 mg amitriptyline and 10 mg chlordiazepoxide ) or amitriptyline 25 mg in matching white capsules given as a single night-time dose . The dose was titrated to a maximum of four capsules per night . Patients were assessed on entry and at 7-day intervals for depressive state ( Hamilton Rating Scale for Depression ) , cardiovascular effect and side-effects for 28 days . Self- assessment s of depression and anxiety using the Leeds Scale were made in the form of a patient question naire . Both groups showed significant improvement at each visit and significantly more patients improved after 7 days in the Limbitrol group . There was no significant difference in treatment over all between groups , in the incidence of side-effects , or in the effects on the heart Objective : To assess , in depressed patients , the clinical benefit of mianserin augmentation of fluoxetine or the the benefit of switching treatment from fluoxetine to mianserin The primary goal of this study was to determine whether the amphetamine challenge test ( ACT ) response , as measured by a subjective rating scale , the How I Feel Scale ( HIF ) , could predict antidepressant treatment outcome . Following a 1-day non-blind ACT with dextroamphetamine ( d-AMPH ) , patients were treated double-blind for 6 weeks with either desipramine , alprazolam , or a desipramine-alprazolam combination . Regression ( true score ) analyses were carried out on pre- and post-ACT HIF scores and on baseline and end of study Hamilton Depression Rating Scale ( HDRS ) scores to determine the magnitudes of improvement measured in response to the ACT and antidepressant treatment , respectively . Regression analyses were performed on the residuals ( true scores of improvement ) to determine the best fitting ( linear ) prediction equation . Improvement in the HIF total score predicted HDRS improvement for the whole sample . Possible sources of error contributing to the outcome are identified and the results are discussed in relation to previous clinical investigations of the potential usefulness of the ACT as a predictor of antidepressant response BACKGROUND Clonazepam cotherapy of fluoxetine was previously demonstrated to accelerate efficacy over the first 3 weeks of treatment . A new 18-week double-blind study attempted to replicate these findings to determine whether superiority would extend to 3 months and assess risks of extension . METHOD Fifty outpatient volunteers aged 18 - 65 from Seattle and Portl and with moderate-marked depression received fluoxetine ( 20 mg ) doubled at 6 weeks if needed ; half took clonazepam ( 0.5 mg ) and half took an identical placebo , 1 or 2 tablets adjusted during the first 2 weeks , until a 3-week taper at 3 months . RESULTS No serious adverse events and no special problems with sedation or discontinuation were noted . Cotherapy was superior to fluoxetine monotherapy at Day 7 for HAM-D ( t=2.03 , df=48 , P<0.05 ) and CGI-I ( 32 vs. 4 % responders , P<0.03 , Fisher Exact Test ) but not otherwise . Cotherapy was effective in reducing insomnia but not anxiety or core symptoms ( low mood , suicidality , reduced interest ) . The only significant benefit of extending treatment was a more rapid response to increased fluoxetine at 6 weeks manifested in a mean HAM-D of 9.0 and CGI-I responder rate of 76 % after 8 weeks compared to 16 weeks for monotherapy . LIMITATIONS Small sample size ( N=50 ) limited power and rendered conclusions tentative . CONCLUSIONS Extended clonazepam cotherapy of fluoxetine appeared safe and effective for depressed out patients : it was superior to fluoxetine alone early in treatment and again following fluoxetine dose increase . Cotherapy might be considered at the start of fluoxetine treatment , especially for those with insomnia , and when a dose increase of fluoxetine is anticipated In a multicenter , placebo-controlled , clinical trial , the efficacy of Limbitrol was compared with that of its components , amitriptyline and chlordiazepoxide .  All patients had a diagnosis of primary depression . Data from 279 patients were evaluated using the Hamilton depression scale , the Beck depression inventory , and physician and patient global change measures .Statistically significant differences favoring Limbitrol occurred after 1 week of treatment , and a trend in favor of Limbitrol continued throughout the remaining 3 weeks . In most efficacy comparisons , the combination was as good as , or better than , amitriptyline alone . It was superior to chlordiazepoxide alone after 2 and 4 weeks of treatment . Each component produced an independent contribution to the total therapeutic effect : the chlordiazepoxide effect was more prominent in the first 2 weeks and the amitriptyline effect in the latter 2 weeks . A trend favoring amitriptyline over chlordiazepoxide was evident by week 4.The overall incidence of side effects was comparable in both Limbitrol- and amitriptyline-treated groups . Limbitrol-treated patients exhibited more sedation , but significantly fewer Limbitrol patients discontinued treatment prematurely because of side effects 1 . Ninety healthy adult men participated in a study of the effects on performance of 60 mg fluoxetine , 50 mg amitriptyline or placebo , alone and in combination with 5 mg diazepam or placebo . 2 . In a 2X3 factorial design study , groups of 15 Ss received one of six possible treatment combinations . 3 . Ss were tested with a battery of laboratory tests at two post-dosing times . 4 .  Amitriptyline impaired the performance of all tasks . When diazepam was added to the  amitriptyline treatment , the impairment of three tasks increased . Diazepam alone produced impairment on two measures . 5 .  Fluoxetine alone impaired no task ; some impairment occurred with the fluoxetine-diazepam combination Chlordiazepoxide-amitriptyline ( Limbitrol ) has been shown to be more rapidly effective than amitriptyline alone for treating depression . A double-blind , r and omized study was design ed to compare the effects of Limbitrol and amitriptyline on  insomnia , anxiety , and depression .  The rate of improvement of symptoms was faster with Limbitrol . No differences were noted between groups in the degree or rate of improvement of the sleep laboratory parameters nor in sleep Stages 1 to 4 . Percentages of rapid eye movement ( REM ) sleep and REM latency were similarly affected by the drugs , but REM density showed a significantly greater decrease with Limbitrol . Phasic REM factors may be crucial in the role of REM sleep and depression BACKGROUND Undertreatment of depression appears widespread but the available literature is limited to North American and European countries . We aim ed to examine the treatment received by patients with major depression in Japan and to eluci date any predictor of their treatment level . METHODS A naturalistic , prospect i ve follow-up study of an inception cohort of subjects with mood disorders was undertaken in psychiatric departments of 13 university hospitals , those of six general hospitals , three mental hospitals and one community mental health center from all over Japan . A total of 95 patients without any prior antidepressant treatment were diagnosed with major depression according to DSM-IV and were followed up every month until treatment termination and every 6 months thereafter . RESULTS The follow-up information was available in 98 to  
    Output:
    
Combined antidepressant plus benzodiazepine therapy was more effective than antidepressants alone in improving depression severity , response in depression and remission in depression in the early phase .
However , these effects were not maintained in the acute or the continuous phase .
Combined therapy result ed in fewer dropouts due to adverse events than antidepressants alone , but combined therapy was associated with a greater proportion of participants reporting at least one adverse effect .