***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 Eighty patients admitted to hospital with major depression were r and omly allocated to six weeks of treatment with tranylcypromine , amitriptyline , or tranylcypromine and amitriptyline in combination , in a double-blind study . Scores on the HRSD improved significantly in all three groups , but there were no differences between the three groups . Patients on tranylcypromine and amitriptyline combined improved more according to their self-ratings after six weeks , and response was earlier as measured by a clinical global improvement scale . Those with endogenous depression improved more than those with neurotic depression , irrespective of treatment group . Combined treatment was less well tolerated than single treatments and gave rise to more side-effects , although there was no serious toxicity . Orthostatic hypotension was observed more frequently in patients on combined treatment . This group also experienced a significant increase in weight and prolongation of the P-R interval on ECG Abstract Objective . This r and omized , 6-week , open-label study compared efficacy of CAD and antidepressant monotherapies ( ADM ) that had been chosen according to clinical judgment of the attending psychiatrist . Methods . A total of 60 in patients ( intent-to-treat analysis ) with depressive disorder ( ≥ 1 unsuccessful antidepressant treatment ) were r and omly assigned to the interventions . The responders who completed the acute phase of study , were evaluated for relapse within 2 months of follow-up treatment . The primary outcome measure was change in the Montgomery – Åsberg Depression Rating Scale ( MADRS ) and response was defined as a ≥ 50 % reduction of MADRS score . Results . Mean changes in total MADRS score from baseline to week 6 for patients in both treatment modalities were not different ( ADM = 13.2 ± 8.6 points ; CAD = 14.5 ± 9.5 points ; P = 0.58 ) . The analysis of covariance performed for significantly higher value of imipramine equivalent dose in CAD group showed only a non-significant between-group difference for total MADRS change ( P = 0.17 ) . There were also no differences between groups in response rate ( ADM = 48 % ; CAD = 58 % ) and number of drop-outs in acute treatment as well as proportion of responders ’ relapses in the follow-up . Conclusion . Both treatment modalities produced clinical ly relevant reduction of depressive symptomatology in acute treatment of patients with resistant depression and their effect was comparable INTRODUCTION Only about a third of patients with an episode of major depressive disorder remit with a given treatment and few remissions occur within the first weeks of treatment . This study tested whether combining escitalopram and bupropion as initial treatment would result in quicker remission and a higher remission rate than monotherapy with either drug . METHOD Two hundred forty-five out patients aged 18 - 65 having non-psychotic , non-bipolar major depression were r and omly assigned to double-blind treatment with bupropion or escitalopram or the combination dosed to a maximum of bupropion 450 mg/d and /or escitalopram 40 mg/d for 12 weeks . A Montgomery-Asberg Depression Rating Scale score of 22 was required for r and omization , while a Hamilton Rating Scale for Depression score ≤ 7 defined remission . We hypothesized that bupropion plus escitalopram would outperform both monotherapies in both earlier onset of remission and higher rate of remission . RESULTS Primary analyses did not demonstrate that dual therapy outperformed both monotherapies in either timing of remission or remission rate . All three treatments were well tolerated . DISCUSSION These results do not support initial use of bupropion plus escitalopram to speed or enhance antidepressant response . CLINICAL TRIALS REGISTRATION NCT00519428 To compare the efficacy and safety of augmenting paroxetine with risperidone , buspirone , valproate , trazodone , or thyroid hormone in patients with treatment-resistant depression ( TRD ) , 225 patients with retrospectively and /or prospect ively identified stage II TRD were r and omly assigned to receive an 8-week treatment of paroxetine 20 mg/d augmented with risperidone 2 mg/d ( n = 45 ) , sodium valproate 600 mg/d ( n = 39 ) , buspirone 30 mg/d ( n = 46 ) , trazodone 100 mg/d ( n = 47 ) , or thyroid hormone 80 mg/d ( n = 48 ) . The primary outcome was the remission rate defined as the 17-item Hamilton Rating Scale for Depression score of 7 or less at the end of study . Secondary outcomes included remission rate based on the Self-rating Depression Scale score of 50 or less at the end of study , response rate based on 17-item Hamilton Rating Scale for Depression total score of 50 % improvement or greater from baseline , and the change in scores of Clinical Global Impression-Improvement scale , the Short Form 36 Health Survey , and the Life Satisfaction Rating Scale . The remission rates were 26.7 % for risperidone , 48.7 % for valproate , 32.6 % for buspirone , 42.6 % for trazodone , and 37.5 % for thyroid hormone . There was no statistical significance among treatment arms in remission rates , secondary outcome measures , and adverse events .  Risperidone , valproate , buspirone , trazodone , or thyroid hormone augmentation to paroxetine 20 mg/d was effective and well tolerated in Chinese patients with TRD . Large- sample studies are warranted to support or refute these findings INTRODUCTION Non-response to an antidepressant monotherapy in unipolar depression is quite common . Therefore strategies for subsequent treatment steps are necessary . However , there is a lack of direct comparisons of these different strategies . In this naturalistic study we compared the outcome to different strategies after failure of the primary antidepressant treatment . METHODS Failure of primary antidepressant monotherapy occurred in 135 patients . 98 of these patients have been administered 4 treatment strategies of the physicians ' choice : lithium augmentation ( Li-Augm ) , switching to another antidepressant ( AD-Switch ) , combination of 2 antidepressants ( AD-Comb ) or augmentation with second generation antipsychotic ( SGA-Augm ) . Primary outcome measure was the 17-item Hamilton rating scale for depression ( HRSD ) . RESULTS Patients who received Li-Augm or augmentation with SGAs showed significantly greater improvement in HRSD and BDI compared to patients with antidepressant switch or antidepressant combination . Remission rates for Li-Augm and SGA-Augm were 89.3 % and 86.2 % compared to 40.7 % for AD-Switch and 42.9 % for AD-Comb . DISCUSSION Changing to another pharmacological class ( Li-Augm or augmentation with SGAs ) showed better treatment results than sticking to the class of antidepressants ( AD-Switch and AD-Comb ) after primary failure in response to antidepressant monotherapy in unipolar depression . The lack of r and omization and absence of a non-response definition are design flaws . Controlled studies are required to confirm the findings of this trial 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 OBJECTIVE Various classes of antidepressant medications generally induce remission of major depressive disorder  in only about one-third of patients . In a previous study using mirtazapine or paroxetine alone or in combination from treatment initiation , the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone . In this double-blind study , the authors sought to produce evidence for the superiority of different combinations of antidepressant drugs from treatment initiation . METHOD Patients ( N=105 ) meeting DSM-IV criteria for major depressive disorder were r and omly assigned to receive , from treatment initiation , either fluoxetine monotherapy ( 20 mg/day ) or mirtazapine ( 30 mg/day ) in combination with fluoxetine ( 20 mg/day ) , venlafaxine ( 225 mg/day titrated in 14 days ) , or bupropion ( 150 mg/day ) for 6 weeks . The primary outcome measure was the Hamilton Depression Rating Scale ( HAM-D ) score . RESULTS The overall dropout rate was 15 % , without notable differences among the four groups . Compared with fluoxetine monotherapy , all three combination groups had significantly greater improvements on the HAM-D. Remission rates ( defined as a HAM-D score of 7 or less ) were 25 % for fluoxetine , 52 % for mirtazapine plus fluoxetine , 58 % for mirtazapine plus venlafaxine , and 46 % for mirtazapine plus bupropion . Among patients who had a marked response , double-blind discontinuation of one agent produced a relapse in about 40 % of cases . CONCLUSIONS The combination treatments were as well tolerated as fluoxetine monotherapy and more clinical ly effective . The study results , which add to a growing body of evidence , suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication The aims of this study were to examine whether pindolol , a serotonin ( 5-hydroxytryptamine [5-HT])-1A receptor antagonist , and mianserin , a 5-HT2A/C and alpha2-adrenoceptor ( alpha2-AR ) antagonist , may augment the clinical efficacy of fluoxetine , a selective serotonin reuptake inhibitor , and shorten the latency of onset of antidepressive activity in the treatment of major and treatment-resistant depression ( TRD ) . Ten days after admission to the hospital , 31 major depressed patients were r and omly assigned using a double-blind , controlled design to receive fluoxetine 20 mg daily , fluoxetine 20 mg daily plus pindolol 7.5 mg daily , or fluoxetine 20 mg plus mianserin 30 mg daily for 5 weeks . The 17-item Hamilton Rating Scale for Depression ( HAM-D ) score was the primary outcome measure . Analysis of efficacy was conducted according to the intent-to-treat analysis principle considering the change from baseline to endpoint . It was found that fluoxetine plus pindolol and fluoxetine plus mianserin were significantly more effective than fluoxetine alone . Using an outcome measure of 50 % reduction in the HAM-D , a 60 % response rate was found in patients treated with either fluoxetine plus pindolol or fluoxetine plus mianserin compared with a 9 % response rate in patients treated with fluoxetine alone . The HAM-D score 1 week after starting fluoxetine plus mianserin decreased more than 4 points and was significantly greater than that obtained by fluoxetine alone . The results suggest that pindolol and mianserin augment the efficacy of fluoxetine in the treatment of TRD and that mianserin , but not pindolol , may significantly shorten the latency of onset of antidepressive action when combined with fluoxetine BACKGROUND Although several antidepressants are now available , all 
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Meta-regression revealed an association of SMD with difference in imipramine-equivalent dose .
Combining a reuptake inhibitor with an antagonist of presynaptic α2-autoreceptors was superior to other combinations .
Conclusion : Combining ADs seems to be superior to monotherapy with only slightly more patients dropping out .
Combining a reuptake inhibitor with an antagonist of presynaptic α2-autoreceptors seems to be significantly more effective than other combinations .