***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 Although clinicians frequently add a second medication to an initial , ineffective antidepressant drug , no r and omized controlled trial has compared the efficacy of this approach . METHODS We r and omly assigned 565 adult out patients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy  ( mean final dose , 55 mg per day ) to receive sustained-release bupropion ( at a dose of up to 400 mg per day ) as augmentation and 286 to receive buspirone ( at a dose of up to 60 mg per day ) as augmentation . The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) at the end of this study ; scores were obtained over the telephone by raters blinded to treatment assignment . The 16-item Quick Inventory of Depressive Symptomatology -- Self-Report ( QIDS-SR-16 ) was used to determine the secondary outcomes of remission ( defined as a score of less than 6 at the end of this study ) and response ( a reduction in baseline scores of 50 percent or more ) . RESULTS The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission ( 29.7 percent and 30.1 percent , respectively ) , QIDS-SR-16 remission ( 39.0 percent and 32.9 percent ) , and QIDS-SR-16 response ( 31.8 percent and 26.9 percent ) . Sustained-release bupropion , however , was associated with a greater reduction ( from baseline to the end of this study ) in QIDS-SR-16 scores than was buspirone ( 25.3 percent vs. 17.1 percent , P<0.04 ) , a lower QIDS-SR-16 score at the end of this study ( 8.0 vs. 9.1 , P<0.02 ) , and a lower dropout rate due to intolerance ( 12.5 percent vs. 20.6 percent , P<0.009 ) . CONCLUSIONS Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical setting s. Augmentation with sustained-release bupropion does have certain advantages , including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events . ( Clinical Trials.gov number , NCT00021528 . ) Depression with psychotic features has been shown to respond to selective serotonin reuptake inhibitors ( SSRIs ) . The serotonin transporter ( 5-HTT ) is a prime target for SSRIs . A functional polymorphism within the promoter region of the 5-HTT gene , leading to different transcriptional efficiency , was recently reported . We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antidepressant response to fluvoxamine and /or augmentation with pindolol ( a serotonin autoreceptors antagonist ) which has been suggested as an augmentation therapy for nonresponders . One hundred and two in patients with major depression with psychotic features were r and omly assigned to treatment with a fixed dose of fluvoxamine and either placebo or pindolol for 6 weeks . Depression severity was assessed once a week using the Hamilton Depression Rating Scale . Allelic variation in each subject was determined using a PCR-based method . Data were analyzed with a three-way repeated measures analysis of variance . Both homozygotes for the long variant ( l/l ) of the 5-HTT promoter and heterozygotes ( l/s ) showed a better response to fluvoxamine than homozygotes for the short variant ( s/s ) . In the group treated with fluvoxamine plus pindolol all the genotypes acted like l/l treated with fluvoxamine alone .  Fluvoxamine efficacy in delusional depression seems to be related to allelic variation within the promoter of the 5-HTT gene . Even though other factors may be implicated , genotyping at 5-HTT promoter may represent a promising tool to individualize the pharmacological treatment of depression In the context of a long term follow-up study , we analysed the possible implication of the 5-HTTLPR polymorphism at the serotonin transporter gene in clinical response and remission of major depressive patients treated with citalopram .  The sample consisted of 131 patients , all of Spanish origin , diagnosed according to DSM-IV criteria .  A 21-item Hamilton Depression Rating Scale ( HDRS ) was used to evaluate severity of the symptoms during the follow-up and to determine clinical response and remission condition of the patients at 4th and 12th week , respectively . Our results showed that S/S genotype of the 5-HTTLPR polymorphism was associated with the non-Remission condition at 12th week ( χ2 = 8.7 , P = 0.013 ) . Moreover , homozygous for the allele S presented three times more risk for non reaching remission of depressive episode  after citalopram treatment than patients with any other 5-HTTLPR genotype combination ( χ2 : 7.29 , P = 0.006 ; OR = 3.23 [ 95%CI : 1.24–8.5 ] ) . In conclusion , our results show that genetic variation of serotonin transporter is involved in clinical remission of major depressive episodes after twelve weeks of citalopram treatment We examined allelic polymorphisms of the serotonin transporter ( 5-HTT ) gene and antidepressant response to 6 weeks ' treatment with the selective serotonin reuptake inhibitor ( SSRI ) drugs fluoxetine or paroxetine . We genotyped 120 patients and 252 normal controls , using polymerase chain reaction of genomic DNA with primers flanking the second intron and promoter regions of the 5-HTT gene . Diagnosis of depression was not associated with 5-HTT polymorphisms . Patients homozygous I/I in intron2 or homozygous s/s in the promoter region showed better responses than all others ( p < 0.0001 , p = 0.0074 , respectively ) . Lack of the I/I allele form in intron 2 most powerfully predicted non-response ( 83.3 % ) . Response to SSRI drugs  is related to allelic variation in the 5-HTT gene in depressed Korean patients BACKGROUND Episodes of depression are the most frequent cause of disability among patients with bipolar disorder . The effectiveness and safety of st and ard antidepressant agents for depressive episodes associated with bipolar disorder ( bipolar depression ) have not been well studied . Our study was design ed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania . METHODS In this double-blind , placebo-controlled study , we r and omly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo , under conditions generalizable to routine clinical care . A st and ardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders , fourth edition , was used at all follow-up visits . The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery ( 8 consecutive weeks of euthymia ) . Secondary effectiveness outcomes and rates of treatment-emergent affective switch ( a switch to mania or hypomania early in the course of treatment ) were also examined . RESULTS Forty-two of the 179 subjects ( 23.5 % ) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery , as did 51 of the 187 subjects ( 27.3 % ) receiving a mood stabilizer plus a matching placebo ( P=0.40 ) . Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes . Rates of treatment-emergent affective switch were similar in the two groups . CONCLUSIONS The use of adjunctive , st and ard antidepressant medication , as compared with the use of mood stabilizers , was not associated with increased efficacy or with increased risk of treatment-emergent affective switch . Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder . ( Clinical Trials.gov number , NCT00012558 [ Clinical Trials.gov ] . ) Serotonin systems appear to play a key role in the pathogenesis of major depression and the therapeutic mechanisms of antidepressants . The firing rate of dorsal raphe serotonergic neurons is controlled by somatodendritic 5-hydroxytryptamine 1A ( HTR1A ) autoreceptors , and desensitization of these receptors is implicated in the antidepressant mechanism of selective serotonin reuptake inhibitors . We tested whether a functional polymorphism ( C-1019 G ) in the promoter region of the HTR1A gene and serotonin-related genetic variants are related to fluoxetine antidepressant effect . We genotyped the HTR1A C-1019 G polymorphism as well as polymorphisms in the serotonin transporter gene-linked polymorphic region ( SERTPR ) , variable-number t and em-repeat polymorphisms in intron 2 ( STin2 ) of the serotonin transporter gene , serotonin 2A receptor ( T102C ) , tryptophan hydroxylase ( A218C ) , and G-protein beta3 subunit ( C825 T ) in 224 Chinese patients from southern Taiwan with major depression , who accepted 4-week  fluoxetine treatment and therapeutic evaluation . Our results demonstrated that the HTR1A −1019C/C carriers ( P=0.009 ) and SERTPR l/l carriers ( P<0.001 ) showed a better response to fluoxetine  , while other polymorphisms were not associated with fluoxetine therapeutic response . The major limitation of this study is the lack of a placebo control . Future prospect i ve study with placebo control may help to predict and individualize antidepressant treatment BACKGROUND It has been recently reported that the short variant of the serotonin transporter ( 5-HTT ) gene-linked functional polymorphic region ( 5-HTTLPR ) influences the antidepressant response to certain selective serotonin reuptake inhibitors . The aim of the present study was to test this finding in a sample of major and bipolar depressives , with or without psychotic features . METHODS One hundred fifty-five in patients were treated with fluvoxamine 300 mg and either placebo or pindolol in a double-blind design for 6 weeks . The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression . Allelic variation of 5-HTTLPR in each subject was determined using a polymerase chain reaction-based technique . RESULTS 5-HTTLPR short variant was associated with a poor response to fluvoxamine treatment , independently from the recorded clinical variables . More specifically , the diagnosis , the presence of psychotic features , and the severity of depressive symptomatology did not influence this association . Conversely ,  pindolol augmentation may ameliorate the rate of response in 5-HTTLPR short variant subjects , thus reducing the difference in the response rate among the genotype variants . CONCLUSIONS If confirmed , these results may improve patient care by helping the clinician to individualize treatment according to the patient 's genetic 5-HTTLPR pattern Several studies and meta-analyses have implicated a polymorphism in the promoter region of the serotonin transporter ( 5-HTT ) gene , 5-HTTLPR in treatment outcomes of selective serotonin re-uptake inhibitors in patients with major depression . In this study we investigated the impact of 5-HTTLPR and a functional SNP rs25531 on the treatment outcomes to escitalopram in depressive patients . The study sample consisted of 135 out patients with major depressive disorder ( mean age 31.1+/-11.6 years , 68 % females ) treated with escitalopram 10 - 20 mg/day for 12 weeks . There were no significant associations between 5-HTT promoter region polymorphisms and response rate or mean change of depressive symptoms during escitalopram treatment . However we showed that patients carrying S allele of 5-HTTLPR may have increased risk for some side effects , including headache , induced by escitalopram medication The relationship of the serotonin transporter gene promoter region polymorphism ( 5-HTTLPR ) to antidepressant response was examined in 95 elderly patients receiving a protocol ized treatment for depression with paroxetine or nortriptyline .  Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations . Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele . There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression ( HRSD ) scores or anxiety symptoms . During acute treatment with paroxetine , mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele , despite equivalent paroxetine concentrations . Onset of response to  nortriptyline  was not affected . Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serot 
    Output:
    
RESULTS There was no statistically significant effect on antidepressant response .
No significant effect on remission rate was seen for SS versus LL and SS/SL versus LL .
The 5-HTTLPR biallelic short/long polymorphism by itself does not seem to usefully predict antidepressant response