***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: CONTEXT Pregnancy has historically been described as a time of emotional well-being , providing " protection " against psychiatric disorder . However , systematic delineation of risk of relapse in women who maintain or discontinue pharmacological treatment during pregnancy is necessary . OBJECTIVE To describe risk of relapse in pregnant women who discontinued antidepressant medication proximate to conception compared with those who maintained treatment with these medications . DESIGN , SETTING , AND PATIENTS A prospect i ve naturalistic investigation using longitudinal psychiatric assessment s on a monthly basis across pregnancy ; a survival analysis was conducted to determine time to relapse of depression during pregnancy . A total of 201 pregnant women were enrolled between March 1999 and April 2003 from 3 centers with specific expertise in the treatment of psychiatric illness during pregnancy . The cohort of women was recruited from ( 1 ) within the hospital clinics  , ( 2 ) self-referral via advertisements and community outreach detailing the study , and ( 3 ) direct referrals  from the community .  Participants were considered eligible if they ( 1 ) had a history of major depression prior to pregnancy , ( 2 ) were less than 16 weeks ' gestation , ( 3 ) were euthymic for at least 3 months prior to their last menstrual period , and ( 4 ) were currently or recently ( < 12 weeks prior to last menstrual period ) receiving antidepressant treatment . Of the 201 participants , 13 miscarried , 5 electively terminated their pregnancy , 12 were lost to follow-up prior to completion of pregnancy , and 8 chose to discontinue participation in the study . MAIN OUTCOME MEASURE Relapse of major depression defined as fulfilling Structured Clinical Interview for DSM-IV [ Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ] Diagnosis ( SCID ) criteria . RESULTS Among the 201 women in the sample , 86 ( 43 % ) experienced a relapse of major depression during pregnancy . Among the 82 women who maintained their medication throughout their pregnancy , 21 ( 26 % ) relapsed compared with 44 ( 68 % ) of the 65 women who discontinued medication . Women who discontinued medication relapsed significantly more frequently over the course of their pregnancy compared with women who maintained their medication ( hazard ratio , 5.0 ; 95 % confidence interval , 2.8 - 9.1 ; P<.001 ) . CONCLUSIONS Pregnancy is not " protective " with respect to risk of relapse of major depression . Women with histories of depression who are euthymic in the context of ongoing antidepressant therapy should be aware of the association of depressive relapse during pregnancy with antidepressant discontinuation OBJECTIVE Loss of response to a previously effective antidepressant is a common clinical problem . Retrospective analyses have shown that the pattern of response during antidepressant treatment ( late onset and persistent versus other patterns ) can be used to predict relapse during continuation and maintenance treatment and possibly to identify placebo responses to treatment . This study was design ed to test the predictive value of response pattern prospect ively and to examine the data for other predictors of relapse . METHOD Five hundred seventy persons with major depressive disorder were treated with fluoxetine for 12 weeks and their pattern of response was determined . Those who responded ( N=292 ) underwent r and om assignment , under double-blind conditions , to continue taking fluoxetine or to switch to placebo for 52 weeks or until relapse . Survival analysis was used to examine the effect of covariates on relapse . RESULTS Although fluoxetine was significantly more effective than placebo during maintenance treatment , this chronically ill group had a high rate of relapse . Contrary to previous findings , a pattern of acute response was not predictive of relapse . Chronicity , symptom severity , a neurovegetative symptom pattern , and female gender were all associated with a significantly greater risk of relapse , with no difference observed between fluoxetine and placebo . CONCLUSIONS The pattern of response to acute treatment appears to be inconsistently predictive of relapse . There is a high rate of relapse with both active medication and placebo in patients with chronic depression . Illness characteristics predict loss of response both to fluoxetine and to placebo . No variable examined was predictive of differential relapse rates between fluoxetine and placebo OBJECTIVE Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder ( MDD ) . METHODS In this r and omized , double-blind trial , patients age > or = 18 meeting DSM-IV criteria for MDD were r and omized to placebo ( N=99 ) , duloxetine 80 mg/day ( N=93 ) , duloxetine 120 mg/day ( N=103 ) , or paroxetine 20 mg/day ( N=97 ) . The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression ( HAMD(17 ) ) total score after 8 weeks of treatment ; a number of secondary efficacy measures also were assessed . Safety and tolerability were assessed via collection and analysis of treatment-emergent adverse events ( TEAEs ) , vital signs , and weight . The Arizona sexual experiences scale was used to assess sexual functioning . Patients who had a > or = 30 % reduction from baseline in the HAMD(17 ) total score  at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase ; efficacy and safety/tolerability outcomes were assessed during continuation treatment . RESULTS More than 87 % of patients completed the acute phase in each treatment group . Duloxetine-treated patients ( both doses ) showed significantly greater improvement ( P<0.05 ) in the HAMD(17 ) total score at week 8 compared with placebo . Paroxetine was not significantly different from placebo ( P=0.089 ) on mean change on the HAMD(17 ) .  Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures ( six of nine ) compared with placebo while duloxetine 80 mg/day ( three of nine ) and paroxetine ( three of nine ) were significantly superior to placebo on fewer secondary measures . HAMD(17 ) mean change data from this study and an identical sister study were pooled as defined a priori for the purpose s of performing a non-inferiority test versus paroxetine . Both duloxetine doses met statistical criteria for non-inferiority to paroxetine .  TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases . CONCLUSIONS The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated . Tolerability , as measured by TEAEs , and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD BACKGROUND One of the strongest predictors of depression recurrence in those who respond to treatment is the presence of residual depressive symptoms . Our goal was to examine stressful life event exposure as a mechanism of recurrence in previously depressed patients with residual depression symptoms . That is , we predicted that higher levels of residual symptoms will significantly predict exposure to acute life events that will then heighten prospect i ve recurrence risk . METHODS Participants included 68 adult out patients with major depression ( 42 women ; age 18 - 60 ) who completed a 12-month naturalistic follow-up after achieving remission in a 20-week r and omized , open label trial of interpersonal psychotherapy , cognitive-behavioral therapy , or antidepressant medication .  Depression recurrence was defined as the reemergence of an episode of major depression as determined by structured interview . Acute life events and chronic stressors were assessed at the end of follow-up using a context ual interview . RESULTS Posttreatment depression scores significantly prospect ively predicted an increased risk for recurrence , and acute life events in the follow-up period . Cox regression survival analyses modeling life events as time-dependent covariates showed that life event exposure mediated the relation of residual symptoms to recurrence even controlling for chronic stress . CONCLUSIONS Our findings implicate residual symptoms in heightening depression recurrence risk through exposure to stressful life events . Depression recurrence adds significantly to the burden of the disorder . Therefore , rigorous follow-up of patients targeting the stressful context has the potential to prevent a lifelong pattern of illness The efficacy and safety of Hypericum extract WS 5570 in preventing relapse during 6 months ' continuation treatment and 12 months ' long-term maintenance treatment after recovery from an episode of recurrent depression were investigated in a double-blind , placebo controlled multicenter trial . Adult out- patients with a recurrent episode of moderate major depression , a 17-item Hamilton Depression Rating Scale ( HAMD ) total score > or = 20 and > or =3 previous episodes in 5 years participated . After 6 weeks of single-blind treatment with 3 x 300 mg/day WS 5570 patients with score < or = 2 on item ' Improvement ' of the Clinical Global Impressions ( CGI ) scale and a HAMD total score decrease > or = 50 % versus baseline were r and omized to 3 x 300 mg/day WS 5570 or placebo for 26 weeks . 426 patients were evaluated for efficacy . Relapse rates during continuation treatment were 51/282 ( 18.1 % ) for WS 5570 and 37/144 ( 25.7 % ) for placebo .  Average time to relapse was 177+/-2.8 and 163+/-4.4 days for WS 5570 and placebo , respectively ( time-to-event analysis ; p=0.034 ; alpha=0.025 one-sided ) . Patients treated with WS 5570 showed more favorable HAMD and Beck Depression Inventory time courses and greater over-all improvement ( CGI ) than those r and omized to placebo . In long-term maintenance treatment a pronounced prophylactic effect of WS 5570 was observed in patients with an early onset of depression as well as in those with a high degree of chronicity . Adverse event rates under WS 5570 were comparable to placebo . WS 5570 showed a beneficial effect in preventing relapse after recovery from acute depression . Tolerability in continuation and long-term maintenance treatment was on the placebo level Objective : We compared mindfulness-based cognitive therapy ( MBCT ) with both cognitive psychological education ( CPE ) and treatment as usual ( TAU ) in preventing relapse to major depressive disorder ( MDD ) in people currently in remission following at least 3 previous episodes . Method : A r and omized controlled trial in which 274 participants were allocated in the ratio 2:2:1 to MBCT plus TAU , CPE plus TAU , and TAU alone , and data were analyzed for the 255 ( 93 % ; MBCT = 99 , CPE = 103 , TAU = 53 ) retained to follow-up . MBCT was delivered in accordance with its published manual , modified to address suicidal cognitions ; CPE was modeled on MBCT , but without training in meditation . Both treatments were delivered through 8 weekly classes . Results : Allocated treatment had no significant effect on risk of relapse to MDD over 12 months follow-up , hazard ratio for MBCT vs. CPE = 0.88 , 95 % CI [ 0.58 , 1.35 ] ; for MBCT vs. TAU = 0.69 , 95 % CI [ 0.42 , 1.12 ] . However , severity of childhood trauma affected relapse , hazard ratio for increase of 1 st and ard deviation = 1.26 ( 95 % CI [ 1.05 , 1.50 ] ) , and significantly interacted with allocated treatment . Among participants above median severity , the hazard ratio was 0.61 , 95 % CI [ 0.34 , 1.09 ] , for MBCT vs. CPE , and 0.43 , 95 % CI [ 0.22 , 0.87 ] , for MBCT vs. TAU . For those below median severity , there were no such differences between treatment groups . Conclusion : MBCT provided significant protection against relapse for participants with increased vulnerability due to history of childhood trauma , but showed no significant advantage in comparison to an active control treatment and usual care over the whole group of patients with recurrent depression BACKGROUND Previous studies indicate that depressed patients with partial remission and residual symptoms following antidepressant treatment  are common and have high rates of relapse . There is evidence that cognitive therapy may reduce relapse rates in depression . METHODS One hundred fifty-eight patients with recent major depression , partially remitted with antidepressant treatment ( mean daily doses equivalent to 185 mg of amitriptyline or 33 mg of fluoxetine ) but with residual symptoms of 2 to 18 months ' duration , were included in a controlled trial . Subjects were r and omized to receive clinical management alone or clinical management plus cognitive therapy for 16 sessions during 20 weeks , with 2 subsequent booster sessions . Subjects were assessed regularly throughout the 20 weeks ' treatment and for a further year . They received continuation and maintenance antidepressants at the same dose throughout . RESULTS Cognitive therapy reduced relapse rates for acute major depression and persistent severe residual symptoms , in both intention to treat and treated per protocol sample s. The cumulative relapse rate at 68 weeks was reduced significantly , from 47 % in 
    Output:
    
Placebo substitution trial methodology represents only one approach to assess ADM maintenance .