***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: There have been no systematic follow-up studies of depressed patients with documented refractoriness to antidepressants treated with lithium augmentation .  To assess their longitudinal course , 66 ( 88 % ) of an original cohort of 75 such patients were followed in a retrospective , naturalistic design for 29.0 + /- SD 15.3 months . At follow-up , 29 % had poor , 23 % fair , and 48 % good outcomes . An acute marked positive response to lithium augmentation predicted a good subsequent course . Acute partial and non-responders had a less benign outcome despite subsequent treatments . These findings indicate that outcomes of patients with documented refractory depression are heterogeneous . There is a suggestion that an acute marked response to  lithium augmentation  is sustained regardless of the duration of taking lithium , but this must be regarded as speculative BACKGROUND Treatment-resistant depression ( TRD ) is a long-term , disabling illness . We report on the characteristics and outcomes of a large cohort of patients with a level of treatment resistance that is very substantial and who were treated for 2 years with st and ard care . METHOD This 2-year prospect i ve , multicenter , observational study ( patients enrolled from January 2001 through July 2004 ) tracked the outcomes of 124 patients with treatment-resistant , nonpsychotic major depressive disorder ( N = 109 ) or bipolar depressed phase disorder ( N = 15 ) who received treatment as usual ( TAU ) ( i.e. ,  any therapeutic regimen agreed to by patients and psychiatrists , including medications , electroconvulsive therapy [ ECT ] , and psychotherapy ) . Treatments could be adjusted , started , and stopped as necessary . The primary outcome , treatment response , was defined a priori as > or = 50 % improvement from baseline as measured by the 30-item Inventory of Depressive Symptomatology-Self-Report ( IDS-SR-30 ) . Remission was defined as an IDS-SR-30 score of < or = 14 . The Medical Outcomes Study ( MOS ) 36-item Short Form Health Survey ( SF-36 ) was used to monitor quality -of-life changes . RESULTS The 12- and 24-month IDS-SR-30 response rates were 11.6 % ( 13/112 ) and 18.4 % ( 19/103 ) , respectively . Of the 13 responders at 12 months , only 5 were responders at 24 months . The 12- and 24-month IDS-SR-30 remission rates were 3.6 % ( 4/112 ) and 7.8 % ( 8/103 ) , respectively . Only 1 of the 4 12-month remitters was also a remitter at 24 months . The SF-36 indicated globally poor quality of life in this sample . CONCLUSIONS Despite the wide range of treatment options available for depression , the response rates , remission rates , and quality -of-life results in this study show that most patients with a substantial degree of treatment resistance continue to have significant symptomatology and functional disability when receiving TAU BACKGROUND This paper describes the Household Survey from the National Survey of Psychiatric Morbidity . This covered a sample drawn at r and om from the population of Britain , with the exception of the Highl and s and Isl and s of Scotl and . METHODS The Postcode Address file was used as the sampling frame . Nearly 13000 adults aged 16 - 65 were selected for interview , of whom 10108 ( 79.4 % ) were successfully interviewed . Eight per cent could not be contacted and 13 % refused interview .  Psychiatric assessment  was carried out by lay interviewers using the CIS-R. Subjects were also screened for psychosis , and screen-positive individuals were examined by psychiatrists using SCAN . RESULTS Sixteen per cent of subjects scored above the st and ard cut-off of 12 on the CIS-R. The overall 1-week prevalence of neurotic disorder was 12.3 % in males and 19.5 % in females . Unmarried and post-marital groups had high rates of disorder , as did single parents and people living on their own . Respondents in Social Class I had notably lower rates of neurotic disorder than the remainder of the sample . Unemployment was strongly associated with disorder . Subjects living in urban areas had a higher overall prevalence , but there was no significant variation by region . Black respondents had higher rates of disorders that were entirely explained by their age , family type and social class . Individual neurotic disorders were all significantly commoner in women , with the exception of panic disorder . The 1-year prevalence of functional psychoses was 4 per 1000 , with no sex difference . Alcohol and drug dependence was considerably more prevalent in men . CONCLUSIONS For the first time , the survey provides data on the prevalence and correlates of psychiatric disorder on a nationwide sample that can be used to inform equitable and effective national psychiatric services OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are widely used to treat depression , but the rates , timing , and baseline predictors of remission in " real world " patients are not established . The authors ' primary objectives in this study were to evaluate the effectiveness of citalopram , an SSRI , using measurement-based care in actual practice , and to identify predictors of symptom remission in out patients with major depressive disorder . METHOD This clinical study included out patients with major depressive disorder who were treated in 23 psychiatric and 18 primary care " real world " setting s. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks . The clinicians were assisted by a clinical research coordinator in the application of measurement-based care , which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures . Remission was defined as an exit score of < or=7 on the 17-item Hamilton Depression Rating Scale ( HAM-D ) ( primary outcome ) or a score of < or=5 on the 16-item Quick Inventory of Depressive Symptomatology , Self-Report ( QIDS-SR ) ( secondary outcome ) . Response was defined as a reduction of > or=50 % in baseline QIDS-SR score . RESULTS Nearly 80 % of the 2,876 out patients in the analyzed sample had chronic or recurrent major depression ; most also had a number of comorbid general medical and psychiatric conditions . The mean exit citalopram dose was 41.8 mg/day . Remission rates were 28 % ( HAM-D ) and 33 % ( QIDS-SR ) . The response rate was 47 % ( QIDS-SR ) . Patients in primary and psychiatric care setting s did not differ in remission or response rates . A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment . Participants who were Caucasian , female , employed , or had higher levels of education or income had higher HAM-D remission rates ; longer index episodes , more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse ) , more general medical disorders , and lower baseline function and quality of life were associated with lower HAM-D remission rates . CONCLUSIONS The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials . The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results OBJECTIVE This study investigated the influence of incomplete recovery from first lifetime major depressive episodes on long-term outcome . METHOD After their first lifetime major depressive episode , patients were divided into asymptomatic ( N=70 ) and residual subthreshold depressive symptom ( N=26 ) recovery groups  and compared on longitudinal course during up to 12 years of prospect i ve naturalistic follow-up . RESULTS Patients with residual subthreshold depressive symptoms during recovery had significantly more severe and chronic future courses . Those with residual symptoms relapsed to major and minor depressive episodes faster and had more recurrences , shorter well intervals , and fewer symptom-free weeks during follow-up than asymptomatic patients . CONCLUSIONS Resolution of major depressive episodes with residual subthreshold depressive symptoms , even the first lifetime episode , appears to be the first step of a more severe , relapsing , and chronic future course . When ongoing subthreshold symptoms continue after major depressive episodes , the illness is still active , and continued treatment is strongly recommended CONTEXT There are no studies of the natural history of major depressive disorder that lack prevalence and clinic biases . OBJECTIVES To estimate risk factors for first lifetime onset and parameters of chronicity following the first episode , including duration , recovery , and recurrence , and to search for predictors of each parameter . DESIGN Prospect i ve population -based cohort study with 23 years of follow-up . SETTING East Baltimore , Maryl and , an urban setting . PARTICIPANTS Probability sample of 3481 adult household residents in 1981 , including 92 with first lifetime onset of major depressive disorder during the course of the follow-up , and 1739 other participants followed up for at least 13 years . OUTCOME MEASURES Diagnostic Interview Schedule and Life Chart Interview . RESULTS Female participants showed higher risk of onset of disorder , longer duration of episodes , and a nonsignificant tendency for higher risk of recurrence . Sex was not related to recovery . The median episode length was 12 weeks . About 15 % of 92 individuals with first episodes did not have a year free of episodes , even after 23 years . About 50 % of first episode participants recovered and had no future episodes . The evolution of the course was relatively stable from first to later episodes . Individuals with 1 or 2 short alleles of the serotonin transporter gene were at higher risk for an initial episode , but experienced episodes of shorter duration . There were few strong predictors of recovery or recurrence . CONCLUSIONS Major depressive disorder is unremitting in 15 % of cases and recurrent in 35 % . About half of those with a first-onset episode recover and have no further episodes Eighty-nine consecutive admissions with primary depressive illness were prospect ively ascertained and diagnosed in 1965 - 66 by R. E. Kendell , who also allocated each a position on a neurotic-psychotic continuum on the basis of previous discriminant function analysis . In 1983 - 84 , 94 % of the survivors were personally interviewed by a psychiatrist blind to index admission data . Operational outcome criteria were employed and longitudinal data were established for 98 % of the series . Mortality risk was doubled overall , and increased sevenfold for women under 40 years at index admission . Less than one-fifth of the survivors had remained well , and over one-third of the series suffered unnatural death or severe chronic distress and h and icap . Patients whose index episode marked their first psychiatric contact had a 50 % chance of readmission within their lifetime , but those with previous admissions had a 50 % chance of readmission within three years . Readmissions occurred even after 12 years of being symptom-free , and conversely patients recovered after as long as 15 years of illness . There was a high incidence of other disorders ( schizoaffective disorder , alcoholism , schizophrenia ) , and only four patients showed pure recurrent unipolar histories . Patients at the psychotic end of the continuum were more likely to be readmitted and to have very poor outcomes BACKGROUND To investigate the mortality rates in affective disorders due to unnatural and natural causes with respect to illness subtype and social-demographic features . METHODS Mortality data were determined from a prospect i ve study of 354 out patients with affective disorders during a follow-up period of 5 years . Death from natural and unnatural causes was compared to sex- and age-specific expectations in the general population . St and ardized mortality rates ( SMR ) in diagnostic subgroups and the influence of social-demographic features were investigated . RESULTS The observed 30 deaths represented nearly three times ( SMR , 2.9 ) the number expected on the basis of age- and sex-st and ardized reference population rates . Death from natural causes occurred with the same rate as expected ( SMR , 1.0 ) , death from unnatural causes was 28.8 times higher than expected . Women with affective disorders had a considerable high risk to die from unnatural causes ( SMR , 47.1 ) . A significant excess of unnatural death was found in all subtypes of affective disorders , particularly in recurrent major depressive episodes ( SMR , 46.7 ) . LIMITATIONS The sample was restricted in size . Therefore subgroup differences and multiple relationships of risk factors could not be analyzed with high statistical power . CONCLUSIONS The results corroborate earlier findings of excess mortality in major affective disorders and strengthen the view that suffering from recurrent major depression confers per se an important biological risk for suicide . Natural causes of death in affective disorders are comparable to expectations from reference population s. Social-demographic characteristics may contribute to an additional risk of premature death by suicide , particularly in women BACKGROUND Previous reports have described the effects of vagus nerve stimulation plus treatment as usual ( VNS+TAU ) during open trials of patients with treatment-resistant depression ( TRD ) . To better underst and these effects on long-term outcome , we compared 12-month VNS+TAU outcomes with those of a comparable TRD group . METHODS Admission criteria were similar for those receiving VNS+TAU ( n = 205 ) or only TAU ( n = 124 ) . In the primary analysis , repeated- measures linear regression was used to compare the VNS+TAU group ( monthly data ) with the TAU group ( quarterly data ) according to scores of the 30-item Inventory of Depressive Symptomatology-Self-Report ( IDS- 
    Output:
    
TRD is associated with poorer clinical outcome , particularly among those who require multiple antidepressant medications .