***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 As compared with the long variant ( L ) , the short variant ( S ) of the functional polymorphic region of the serotonin transporter gene ( 5-HTTLPR ) has been associated with a lower antidepressant efficacy in major depression , but some replication studies have evidence d contradictory results . Sex differences may explain these contradictory results . Methods One hundred and three in patients ( 74 women and 29 men ) with a major depressive episode were assessed prospect ively for antidepressant efficacy after 4 weeks of treatment with selective serotonin reuptake inhibitors ( SSRI ) and non-SSRI drugs . Results As compared with LL/LS , the SS genotype of the 5-HTTLPR was associated with a lower antidepressant efficacy in depressed women ( 79 vs. 50 % responders , P = 0.035 ) . This result was shown with both SSRI and non-SSRI antidepressants . The logistic regression performed in women showed that response to treatment was related to genotype ( odds ratio=0.15 ; 95 % confidence interval=0.03–0.85 ; P = 0.03 ) and not to other variables . No effect of 5-HTTLPR was found in depressed men . Conclusion Despite a low power , this study suggests a significant effect of 5-HTTLPR genotype on antidepressant efficacy in depressed women but not in men , with both SSRI and non-SSRI drugs . Further research is needed to confirm this result and investigate its underlying mechanisms BACKGROUND Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters . We wished to investigate whether genetic variation could be used to target or personalise treatment , in a comparison of selective serotonin reuptake inhibitors ( SSRIs ) with noradrenaline reuptake inhibitors ( NARIs ) . AIMS To test the hypothesis that patients homozygous for the long ( insertion ) polymorphism of the serotonin transporter ( 5-HTTLPR ) have an increased response to SSRI antidepressants but not to NARI antidepressants . METHOD In an individually r and omised , parallel-group controlled trial , people meeting criteria for a depressive episode who were referred by their general practitioner were r and omised to receive either citalopram ( an SSRI ) or reboxetine ( an NARI ) . R and omisation was by means of a remote automated system accessed by telephone . The main outcome was depressive symptoms , measured by Beck Depression Inventory ( BDI ) total score 6 weeks after r and omisation . The trial was registered with the International St and ard R and omised Controlled Trials Number registry ( IS RCT N31345163 ) . RESULTS Altogether 298 participants were r and omised to receive citalopram and 303 were r and omised to reboxetine . At 6 weeks follow-up , complete data were available for 258 participants taking citalopram and 262 taking reboxetine . We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment . The interaction term for BDI score at 6 weeks was 0.50 ( 95 % CI -2.04 to 3.03 , P = 0.70 ) , which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype . CONCLUSIONS It is unlikely that the 5-HTTLPR polymorphism alone will be clinical ly useful in predicting response to antidepressants in people with depression BACKGROUND The " long/short"polymorphism ( 5HTTLPR ) in the promoter of the serotonin transporter gene ( SLC6A4 ) has been proposed as a pharmacogenetic marker for antidepressant efficacy . Some but not all studies have found that the short form of 5HTTLPR ( S allele ) results in decreased efficacy of selective serotonin reuptake inhibitors . OBJECTIVE To determine if the 5HTTLPR polymorphism influences the efficacy and tolerability of mirtazapine and paroxetine hydrochloride , 2 frequently prescribed antidepressants with differing pharmacologic profiles , in geriatric depression . DESIGN Double-blind , r and omized 8-week study . SETTING Eighteen academic and private outpatient clinics . PATIENTS We evaluated 246 cognitively intact patients 65 years or older with major depression . INTERVENTIONS Antidepressant therapy with 15 to 45 mg/d of mirtazapine ( n = 124 ) or 20 to 40 mg/d of paroxetine ( n = 122 ) . MAIN OUTCOME MEASURES The Hamilton Depression Rating Scale-17 and Geriatric Depression Scale , severity of adverse events and dosing compliance indexes , and discontinuations due to adverse events . Outcome measures were stratified according to 5HTTLPR genotypes . RESULTS Geriatric Depression Scale scores indicated that S allele carriers treated with paroxetine showed a small impairment in antidepressant response . Among mirtazapine-treated patients , there was little indication that the 5HTTLPR genotype affected antidepressant efficacy . However , the 5HTTLPR polymorphism had a dramatic effect on adverse events . Among paroxetine-treated subjects , S allele carriers experienced more severe adverse events during the course of the study , achieved significantly lower final daily doses , and had more discontinuations at days 14 , 21 , 28 , 42 , and 49 . Surprisingly , among mirtazapine-treated subjects , S allele carriers had fewer discontinuations due to adverse events , experienced less severe adverse events , and achieved higher final daily doses . CONCLUSIONS These results support the hypothesis that the S allele of 5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment with selective serotonin reuptake inhibitors . However , the major effect was on the tolerability of these drugs rather than efficacy . Results from mirtazapine-treated patients indicate that the effect of this polymorphism on outcome may depend on the mechanism of antidepressant action BACKGROUND Treatment guidelines recommend antidepressant treatment be continued for at least 6 months to ensure maximal improvement and to prevent relapse . Naturalistic studies show that the average length of treatment is shorter than 6 months and that dropout rates are high . Factors leading patients to discontinuation of therapy are not well understood . This study investigates when and why patients stop treatment and whether they inform their doctors . METHOD Patients ( N = 272 ) receiving antidepressant therapy due to an episode of major depressive disorder ( DSM-IV ) were asked to complete an antidepressant compliance question naire . Patients were then telephoned monthly while they continued on antidepressant therapy , up to 6 months . During each call , patients were asked st and ard questions . RESULTS By endpoint , 53 % of patients had discontinued antidepressant treatment . The most common reason given was " feeling better . " However , different dropout reasons were prevalent at different times after initiation of therapy . Overall , 24 % of the patients did not inform their physician about stopping the antidepressant medication . The likelihood of patients ' informing their physicians differed according to the patients ' reasons for discontinuation and according to the patients ' perceptions of their relationship with their physicians . CONCLUSION These results provide new guidelines for improving compliance . Strategy should be adapted to the stage of treatment , as patients ' reasons for discontinuation vary as treatment progresses . The attitude of the physician and the information provided by the physician significantly influence whether patients inform the physician when they discontinue antidepressant therapy The present study aim ed to compare the effects of two currently used selective serotonin reuptake inhibitors ( SSRIs ) in Japan taking the individual background in 5-HTT gene-linked polymorphic region ( 5HTTLPR ) genotype into account . Clinical responses to paroxetine and fluvoxamine were evaluated by total and cluster depressive symptoms for 81 Japanese patients who were diagnosed with major depression . Patients with the l allele had a greater percentage reduction on the total score ( P=0.059 ) and somatic anxiety items ( P=0.026 ) of the 21-item Hamilton Depression Rating Scale ( HAM-D ) score compared to s/s genotype carriers . Paroxetine was significantly more effective than fluvoxamine in the s/s carriers , as evaluated on the percentage reduction in total score ( P=0.012 ) and core ( P=0.049 ) HAM-D after 4 weeks of medication , but not in the l/s carriers . These findings suggest that the genetic test may be useful in investigating the efficacy of the two SSRIs , and that normalization by the 5HTTLPR genotypes may lead to improvement of the precision of comparative analysis 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 Rationale A common polymorphism ( 5HTTLPR ) within the promoter region of the serotonin transporter gene ( LSC6A4 ) has been shown to influence response time as well as overall response to selective serotonin reuptake inhibitors ( SSRIs ) in subjects with major depressive disorder . We hypothesized that a similar effect in response time to sertraline would be observed and that no effect on response time would be seen in a placebo arm . Objectives We tested the hypothesis that subjects homozygous for the long allele at the 5HTTLPR polymorphism would respond more rapidly to sertraline than subjects carrying one or two copies of the short allele . Methods HAM-D and CGI-I responses to sertraline and placebo were measured weekly in the context of an 8-week , placebo-controlled study in elderly depressed subjects . Genotyping of the 5HTTLPR polymorphism was performed to test for correlations with response at each week in the  sertraline  and  placebo groups ( n=206 ) . Results Subjects homozygous for the long allele of 5HTTLPR showed a significant increase in response at week 1 and week 2 , as assessed by the CGI-I scale compared with subjects carrying one or two copies of the short allele ( P=0.01 at both weeks ) . No significant difference was observed in the placebo group . Conclusions These results suggest that genetic variation in the serotonin transporter gene effects the response time to sertraline and provides complementing evidence to previous reports that this polymorphism affects response time to other SSRIs In this study , we tested the influence of the serotonin type 2A , 3A and 3B receptor genes ( HTR2A , HTR3A , HTR3B ) in addition to a polymorphism in the promoter region of the serotonin transporter ( SERTPR ) , and investigated the different characteristics of clinical responses to paroxetine and fluvoxamine . A total of 100 Japanese patients affected by major recurrent depression were enrolled in a r and omized 6-week study . The clinical response was evaluated using the Hamilton Rating Scale for Depression ( HAM-D ) , and adverse drug reactions were assessed at each visit . Patients with the l allele of SERTPR showed a better response to SSRIs than s/s genotype carriers ( p = 0.015–0.042 ) , more significantly to fluvoxamine . The –1438G/G genotype of HTR2A was associated with a good response to SSRIs ( p = 0.010–0.039 ) , especially to fluvoxamine , and significantly with severe nausea in paroxetine-treated patients ( p = 0.013 ) . The 178C/C genotype of the HTR3A was associated with an antidepressant response ( p = 0.022–0.042 ) , and more significantly in paroxetine-treated patients ( p = 0.002–0.042 ) . These effects were independent of one another . We replicated the finding that the SERPTR polymorphism was associated with a response to SSRIs . We additionally found that HTR2A and HTR3A polymorphisms are associated with the efficacy , and the HTR2A polymorphism is also associated with adverse drug reactions . Furthermore , the effects of these polymorphisms varied from one SSRI to another and thus may depend on the characteristics of each SSRI In the present study , we investigated the relationship between the serotonin transporter gene linked polymorphic regions ( 5-HTTLPR ) or plasma paroxetine levels and clinical response to paroxetine in depressed patients . Sixty patients who met the DSM-IV criteria for major depressive disorder were enrolled in the study . Twenty-two were male and 38 were female , with ages ranging from 25 to 71 ( mean + /- SD = 42 + /- 16 ) years . The clinical improvement of patients was assessed using the Hamilton rating scale for depression ( Ham-D ) before and every week after paroxetine administration . According to the data reported previously , patients with an at least 50 % decrease in their Ham-D score were classified as responders 
    Output:
    
This meta- analysis provides no evidence of an association between 5-HTTLPR and discontinuation from antidepressant treatment in Europeans .
The low number of studies in East Asian sample s using SSRIs reduces confidence in our evidence that the S allele decreases the odds of discontinuation in this population .