human
***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: OBJECTIVE We examined whether a shortened form of dialectical behavior therapy , dialectical behavior therapy for adolescents ( DBT-A ) is more effective than enhanced usual care ( EUC ) to reduce self-harm in adolescents . METHOD This was a r and omized study of 77 adolescents with recent and repetitive self-harm treated at community child and adolescent psychiatric outpatient clinics who were r and omly allocated to either DBT-A or EUC .  Assessment s of self-harm , suicidal ideation , depression , hopelessness , and symptoms of borderline personality disorder were made at baseline and after 9 , 15 , and 19 weeks ( end of trial period ) , and frequency of hospitalizations and emergency department visits over the trial period were recorded . RESULTS Treatment retention was generally good in both treatment conditions , and the use of emergency services was low . DBT-A was superior to EUC in reducing self-harm , suicidal ideation , and depressive symptoms . Effect sizes were large for treatment outcomes in patients who received DBT-A , whereas effect sizes were small for outcomes in patients receiving EUC . Total number of treatment contacts was found to be a partial mediator of the association between treatment and changes in the severity of suicidal ideation , whereas no mediation effects were found on the other outcomes or for total treatment time . CONCLUSION DBT-A may be an effective intervention to reduce self-harm , suicidal ideation , and depression in adolescents with repetitive self-harming behavior . Clinical trial registration information-Treatment for Adolescents With Deliberate Self Harm ; http:// Clinical Trials.gov/ ; NCT00675129 OBJECTIVE We previously reported that a history of abuse was associated with a poorer response to combination treatment  in the Treatment of Resistant Depression in Adolescents study ( TORDIA ) . We now report on the nature and correlates of abuse that might explain these findings . METHOD Youth who did not benefit from an adequate selective serotonin re-uptake inhibitor ( SSRI ) trial ( N = 334 ) were r and omized to one of the following : an alternative SSRI ; an alternative SSRI plus cognitive behavior therapy ( CBT ) ; venlafaxine ; or venlafaxine plus CBT . Analyses examined the effect of history of abuse on response to the pharmacotherapy and combination therapy . RESULTS Those without a history of physical abuse ( PA ) or sexual abuse ( SA ) had a higher 12-week response rate to  combination therapy  compared with medication mono-therapy ( 62.8 % versus 37.6 % ; odds ratio [ OR ] = 2.8 , 95 % confidence interval [ CI ] = 1.6 - 4.7 , p < .001 ) . Those with a history of SA had similar response rates to combination versus medication monotherapy ( 48.3 % versus 42.3 % ; OR = 1.3 , 95 % CI = 0.4 - 3.7 ; p = .66 ) , whereas those with history of PA had a much lower rate of response to  combination therapy  ( 18.4 % versus 52.4 % , OR = 0.1 ; 95 % CI = 0.02 - 0.43 ) . Even after adjusting for other clinical predictors , a history of PA moderated treatment outcome . CONCLUSION These results should be considered within the limitations of a post hoc analysis , lack of detailed assessment of abuse and other forms of trauma , and neuropsychological status . Depressed patients with history of abuse , especially PA may require specialized clinical approaches . Further work is needed to underst and by what mechanisms a history of abuse affects treatment response OBJECTIVE In the Treatment of Resistant Depression in Adolescents , study participants who received medication for sleep  had a lower response rate . This report sought to clarify this finding . METHOD Depressed adolescents who had not responded to a previous adequate serotonin-selective reuptake inhibitor ( SSRI ) trial were r and omly assigned to another SSRI , venlafaxine , another SSRI+cognitive behavior therapy ( CBT ) , or venlafaxine+CBT . Augmentation with sleep medication was permitted as clinical ly indicated . RESULTS Youth who received trazodone  were six times less likely to respond than those with no sleep medication ( adjusted odds ratio [OR]=0.16 , 95 % confidence interval [ CI ] : 0.05 - 0.50 , p=0.001 ) and were three times more likely to experience self-harm ( OR=3.0 , 95 % CI : 1.1 - 7.9 , p=0.03 ) , even after adjusting for baseline differences associated with trazodone use . None ( 0/13 ) of those cotreated with trazodone and either paroxetine or fluoxetine responded . In contrast , those treated with other sleep medications had similar rates of response ( 60.0 % vs. 50.4 % , χ(2)=0.85 , p=0.36 ) and of self-harm events ( OR=0.5 , 95 % CI : 0.1 - 2.6 , p=0.53 ) as those who received no sleep medication . CONCLUSIONS These findings should be interpreted cautiously because these sleep agents were not assigned r and omly , but at clinician discretion . Nevertheless , they suggest that the use of trazodone for the management of sleep difficulties in adolescent depression should be re-evaluated and that future research on the management of sleep disturbance in adolescent depression is needed . The very low response rate of participants cotreated with trazodone and either fluoxetine or paroxetine could be due to inhibition of CYP 2D6 by these antidepressants OBJECTIVE To advance knowledge regarding strategies for treating selective serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents , we conducted a r and omized controlled trial evaluating alternative treatment strategies . In primary analyses , cognitive-behavioral therapy ( CBT ) combined with medication change was associated with higher rates of positive response to short-term ( 12-week ) treatment than medication alone . This study examines predictors and moderators of treatment response , with the goal of informing efforts to match youths to optimal treatment strategies . METHOD Youths who had not improved during an adequate SSRI trial ( N = 334 ) were r and omized to an alternative SSRI , an alternative SSRI plus CBT , venlafaxine , or venlafaxine plus CBT . Analyses examined predictors and moderators of treatment response . RESULTS Less severe depression , less family conflict , and absence of nonsuicidal self-injurious behavior predicted better treatment response status . Significant moderators of response to CBT + medication ( combined ) treatment were number of comorbid disorders and abuse history ; hopelessness was marginally significant . The CBT/combined treatment superiority over medication alone was more evident among youths who had more comorbid disorders ( particularly attention-deficit/hyperactivity disorder and anxiety disorders ) , no abuse history , and lower hopelessness . Further analyses revealed a stronger effect of combined CBT + medication treatment among youths who were older and white and had no nonsuicidal self-injurious behavior and longer pre study pharmacotherapy . CONCLUSIONS Combined treatment with CBT and antidepressant medication may be more advantageous for adolescents whose depression is comorbid with other disorders . Given the additional costs of adding CBT to medication , consideration of moderators in clinical decision making can contribute to a more personalized and effective approach to treatment Background Many young people with major depression fail first-line treatments . Treatment-resistant depression has various definitions in the literature but typically assumes nonresponse to medication . In young people , cognitive behavioral therapy ( CBT ) is the recommended first-line intervention , thus the definition of treatment resistance should be exp and ed . Therefore , our aim was to synthesize the existing evidence of any interventions for treatment-resistant depression , broadly defined , in children and adolescents and to investigate the effectiveness of CBT in this context . Methods We used Cochrane Collaboration methodology , with electronic search es of Medline , PsycINFO , Embase , and the Cochrane Depression Anxiety and Neurosis Group trials registers . Only r and omized controlled trials were included , and were assessed for risk of bias . Meta- analysis was undertaken where possible and appropriate . Results Of 953 articles retrieved , four trials were eligible for inclusion . For one study , only the trial registration document was available , because the study was never completed . All other studies were well conducted with a low risk of bias , although one study had a high dropout rate . Two studies assessed the effect of adding CBT to medication . While an assertive trial of antidepressants does appear to lead to benefit , when compared with placebo , there was no significant advantage , in either study , or in a meta- analysis of data from these trials , that clearly demonstrated an additional benefit of CBT . The third trial showed little advantage of a tricyclic antidepressant over placebo in the context of an inpatient admission . Conclusion Few r and omized controlled trials have investigated interventions for treatment-resistant depression in young people , and results from these show modest benefit from antidepressants with no additional benefit over medication from CBT . Overall , there is a lack of evidence about effective interventions to treat young people who have failed to respond to evidence -based interventions for depression . Research in this area is urgently required OBJECTIVE The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents ( TORDIA ) trial after 24 weeks of treatment , including remission and relapse rates and predictors of treatment outcome . METHOD Adolescents ( ages 12 - 18 years ) with selective serotonin reuptake inhibitor (SSRI)-resistant depression were r and omly assigned to either a medication switch alone ( alternate SSRI or venlafaxine ) or a medication switch plus cognitive-behavioral therapy ( CBT ) . At week 12 , responders could continue in their assigned treatment arm and nonresponders received open treatment ( medication and /or CBT ) for 12 more weeks ( 24 weeks total ) . The primary outcomes were remission and relapse , defined by the Adolescent Longitudinal Interval Follow-Up Evaluation as rated by an independent evaluator . RESULTS Of 334 adolescents enrolled in the study , 38.9 % achieved remission by 24 weeks , and initial treatment assignment did not affect rates of remission . Likelihood of remission was much higher ( 61.6 % versus 18.3 % ) and time to remission was much faster among those who had already demonstrated clinical response by week 12 . Remission was also higher among those with lower baseline depression , hopelessness , and self-reported anxiety . At week 12 , lower depression , hopelessness , anxiety , suicidal ideation , family conflict , and absence of comorbid dysthymia , anxiety , and drug/alcohol use and impairment also predicted remission . Of those who responded by week 12 , 19.6 % had a relapse of depression by week 24 . CONCLUSIONS Continued treatment for depression among treatment-resistant adolescents results in remission in approximately one-third of patients , similar to adults . Eventual remission is evident within the first 6 weeks in many , suggesting that earlier intervention among nonresponders could be important Acceptance and commitment therapy ( ACT ) has a small but growing data base of support . One hundred and one heterogeneous out patients reporting moderate to severe levels of anxiety or depression were r and omly assigned to traditional cognitive therapy ( CT ) or to ACT . To maximize external validity , the authors utilized very minimal exclusion criteria . Participants receiving CT and ACT  evidence d large , equivalent improvements in depression , anxiety , functioning difficulties , quality of life , life satisfaction , and clinician-rated functioning . Whereas improvements were equivalent across the two groups , the mechanisms of action appeared to differ . Changes in “ observing ” and “ describing ” one 's experiences appeared to mediate outcomes for the CT group relative to the ACT group , whereas “ experiential avoidance , ” “ acting with awareness , ” and “ acceptance ” mediated outcomes for the ACT group . Overall , the results suggest that ACT is a viable and disseminable treatment , the effectiveness of which appears equivalent to that of CT , even as its mechanisms appear to be distinct OBJECTIVE The authors sought to assess the relationship between c and i date genes and two clinical outcomes , namely , symptomatic improvement and the occurrence of suicidal events , in a sample of treatment-resistant depressed adolescents . METHOD A sub sample of depressed adolescents participating in the Treatment of SSRI-Resistant Depression in Adolescents ( TORDIA ) trial , 155 of whom were of European origin , were genotyped with respect to 21 polymorphisms on 12 genes that have a reported association with depression , treatment response , or suicidal events . Participants had not responded to a previous adequate trial with an antidepressant and were r and omized to receive either another selective serotonin reuptake inhibitor or venlafaxine , with or without cognitive-behavioral therapy ( CBT ) . Single-nucleotide polymorphism ( SNP ) analyses were conducted using PLINK with permutation procedures . RESULTS No relationship was observed between any polymorphism and response to treatment . The FKBP5 ( which codes for a protein causing subsensitivity of the glucocorticoid receptor ) rs1360780TT and rs3800373GG genotypes were associated with suicidal events ( N=18 ) , even after controlling for treatment effects and relevant covariates . These two SNPs were in significant linkage disequilibrium ( r=0.91 ) . CONCLUSIONS The FKBP5 genotypes associated with suicidal events in this study have been reported by others to cause the greatest degree of glucoc 
    Output:
    
agent
Multiple secondary data analyses of TORDIA have identified important predictors of treatment response and relapse .
***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: OBJECTIVE We examined whether a shortened form of dialectical behavior therapy , dialectical behavior therapy for adolescents ( DBT-A ) is more effective than enhanced usual care ( EUC ) to reduce self-harm in adolescents . METHOD This was a r and omized study of 77 adolescents with recent and repetitive self-harm treated at community child and adolescent psychiatric outpatient clinics who were r and omly allocated to either DBT-A or EUC .  Assessment s of self-harm , suicidal ideation , depression , hopelessness , and symptoms of borderline personality disorder were made at baseline and after 9 , 15 , and 19 weeks ( end of trial period ) , and frequency of hospitalizations and emergency department visits over the trial period were recorded . RESULTS Treatment retention was generally good in both treatment conditions , and the use of emergency services was low . DBT-A was superior to EUC in reducing self-harm , suicidal ideation , and depressive symptoms . Effect sizes were large for treatment outcomes in patients who received DBT-A , whereas effect sizes were small for outcomes in patients receiving EUC . Total number of treatment contacts was found to be a partial mediator of the association between treatment and changes in the severity of suicidal ideation , whereas no mediation effects were found on the other outcomes or for total treatment time . CONCLUSION DBT-A may be an effective intervention to reduce self-harm , suicidal ideation , and depression in adolescents with repetitive self-harming behavior . Clinical trial registration information-Treatment for Adolescents With Deliberate Self Harm ; http:// Clinical Trials.gov/ ; NCT00675129 OBJECTIVE We previously reported that a history of abuse was associated with a poorer response to combination treatment  in the Treatment of Resistant Depression in Adolescents study ( TORDIA ) . We now report on the nature and correlates of abuse that might explain these findings . METHOD Youth who did not benefit from an adequate selective serotonin re-uptake inhibitor ( SSRI ) trial ( N = 334 ) were r and omized to one of the following : an alternative SSRI ; an alternative SSRI plus cognitive behavior therapy ( CBT ) ; venlafaxine ; or venlafaxine plus CBT . Analyses examined the effect of history of abuse on response to the pharmacotherapy and combination therapy . RESULTS Those without a history of physical abuse ( PA ) or sexual abuse ( SA ) had a higher 12-week response rate to  combination therapy  compared with medication mono-therapy ( 62.8 % versus 37.6 % ; odds ratio [ OR ] = 2.8 , 95 % confidence interval [ CI ] = 1.6 - 4.7 , p < .001 ) . Those with a history of SA had similar response rates to combination versus medication monotherapy ( 48.3 % versus 42.3 % ; OR = 1.3 , 95 % CI = 0.4 - 3.7 ; p = .66 ) , whereas those with history of PA had a much lower rate of response to  combination therapy  ( 18.4 % versus 52.4 % , OR = 0.1 ; 95 % CI = 0.02 - 0.43 ) . Even after adjusting for other clinical predictors , a history of PA moderated treatment outcome . CONCLUSION These results should be considered within the limitations of a post hoc analysis , lack of detailed assessment of abuse and other forms of trauma , and neuropsychological status . Depressed patients with history of abuse , especially PA may require specialized clinical approaches . Further work is needed to underst and by what mechanisms a history of abuse affects treatment response OBJECTIVE In the Treatment of Resistant Depression in Adolescents , study participants who received medication for sleep  had a lower response rate . This report sought to clarify this finding . METHOD Depressed adolescents who had not responded to a previous adequate serotonin-selective reuptake inhibitor ( SSRI ) trial were r and omly assigned to another SSRI , venlafaxine , another SSRI+cognitive behavior therapy ( CBT ) , or venlafaxine+CBT . Augmentation with sleep medication was permitted as clinical ly indicated . RESULTS Youth who received trazodone  were six times less likely to respond than those with no sleep medication ( adjusted odds ratio [OR]=0.16 , 95 % confidence interval [ CI ] : 0.05 - 0.50 , p=0.001 ) and were three times more likely to experience self-harm ( OR=3.0 , 95 % CI : 1.1 - 7.9 , p=0.03 ) , even after adjusting for baseline differences associated with trazodone use . None ( 0/13 ) of those cotreated with trazodone and either paroxetine or fluoxetine responded . In contrast , those treated with other sleep medications had similar rates of response ( 60.0 % vs. 50.4 % , χ(2)=0.85 , p=0.36 ) and of self-harm events ( OR=0.5 , 95 % CI : 0.1 - 2.6 , p=0.53 ) as those who received no sleep medication . CONCLUSIONS These findings should be interpreted cautiously because these sleep agents were not assigned r and omly , but at clinician discretion . Nevertheless , they suggest that the use of trazodone for the management of sleep difficulties in adolescent depression should be re-evaluated and that future research on the management of sleep disturbance in adolescent depression is needed . The very low response rate of participants cotreated with trazodone and either fluoxetine or paroxetine could be due to inhibition of CYP 2D6 by these antidepressants OBJECTIVE To advance knowledge regarding strategies for treating selective serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents , we conducted a r and omized controlled trial evaluating alternative treatment strategies . In primary analyses , cognitive-behavioral therapy ( CBT ) combined with medication change was associated with higher rates of positive response to short-term ( 12-week ) treatment than medication alone . This study examines predictors and moderators of treatment response , with the goal of informing efforts to match youths to optimal treatment strategies . METHOD Youths who had not improved during an adequate SSRI trial ( N = 334 ) were r and omized to an alternative SSRI , an alternative SSRI plus CBT , venlafaxine , or venlafaxine plus CBT . Analyses examined predictors and moderators of treatment response . RESULTS Less severe depression , less family conflict , and absence of nonsuicidal self-injurious behavior predicted better treatment response status . Significant moderators of response to CBT + medication ( combined ) treatment were number of comorbid disorders and abuse history ; hopelessness was marginally significant . The CBT/combined treatment superiority over medication alone was more evident among youths who had more comorbid disorders ( particularly attention-deficit/hyperactivity disorder and anxiety disorders ) , no abuse history , and lower hopelessness . Further analyses revealed a stronger effect of combined CBT + medication treatment among youths who were older and white and had no nonsuicidal self-injurious behavior and longer pre study pharmacotherapy . CONCLUSIONS Combined treatment with CBT and antidepressant medication may be more advantageous for adolescents whose depression is comorbid with other disorders . Given the additional costs of adding CBT to medication , consideration of moderators in clinical decision making can contribute to a more personalized and effective approach to treatment Background Many young people with major depression fail first-line treatments . Treatment-resistant depression has various definitions in the literature but typically assumes nonresponse to medication . In young people , cognitive behavioral therapy ( CBT ) is the recommended first-line intervention , thus the definition of treatment resistance should be exp and ed . Therefore , our aim was to synthesize the existing evidence of any interventions for treatment-resistant depression , broadly defined , in children and adolescents and to investigate the effectiveness of CBT in this context . Methods We used Cochrane Collaboration methodology , with electronic search es of Medline , PsycINFO , Embase , and the Cochrane Depression Anxiety and Neurosis Group trials registers . Only r and omized controlled trials were included , and were assessed for risk of bias . Meta- analysis was undertaken where possible and appropriate . Results Of 953 articles retrieved , four trials were eligible for inclusion . For one study , only the trial registration document was available , because the study was never completed . All other studies were well conducted with a low risk of bias , although one study had a high dropout rate . Two studies assessed the effect of adding CBT to medication . While an assertive trial of antidepressants does appear to lead to benefit , when compared with placebo , there was no significant advantage , in either study , or in a meta- analysis of data from these trials , that clearly demonstrated an additional benefit of CBT . The third trial showed little advantage of a tricyclic antidepressant over placebo in the context of an inpatient admission . Conclusion Few r and omized controlled trials have investigated interventions for treatment-resistant depression in young people , and results from these show modest benefit from antidepressants with no additional benefit over medication from CBT . Overall , there is a lack of evidence about effective interventions to treat young people who have failed to respond to evidence -based interventions for depression . Research in this area is urgently required OBJECTIVE The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents ( TORDIA ) trial after 24 weeks of treatment , including remission and relapse rates and predictors of treatment outcome . METHOD Adolescents ( ages 12 - 18 years ) with selective serotonin reuptake inhibitor (SSRI)-resistant depression were r and omly assigned to either a medication switch alone ( alternate SSRI or venlafaxine ) or a medication switch plus cognitive-behavioral therapy ( CBT ) . At week 12 , responders could continue in their assigned treatment arm and nonresponders received open treatment ( medication and /or CBT ) for 12 more weeks ( 24 weeks total ) . The primary outcomes were remission and relapse , defined by the Adolescent Longitudinal Interval Follow-Up Evaluation as rated by an independent evaluator . RESULTS Of 334 adolescents enrolled in the study , 38.9 % achieved remission by 24 weeks , and initial treatment assignment did not affect rates of remission . Likelihood of remission was much higher ( 61.6 % versus 18.3 % ) and time to remission was much faster among those who had already demonstrated clinical response by week 12 . Remission was also higher among those with lower baseline depression , hopelessness , and self-reported anxiety . At week 12 , lower depression , hopelessness , anxiety , suicidal ideation , family conflict , and absence of comorbid dysthymia , anxiety , and drug/alcohol use and impairment also predicted remission . Of those who responded by week 12 , 19.6 % had a relapse of depression by week 24 . CONCLUSIONS Continued treatment for depression among treatment-resistant adolescents results in remission in approximately one-third of patients , similar to adults . Eventual remission is evident within the first 6 weeks in many , suggesting that earlier intervention among nonresponders could be important Acceptance and commitment therapy ( ACT ) has a small but growing data base of support . One hundred and one heterogeneous out patients reporting moderate to severe levels of anxiety or depression were r and omly assigned to traditional cognitive therapy ( CT ) or to ACT . To maximize external validity , the authors utilized very minimal exclusion criteria . Participants receiving CT and ACT  evidence d large , equivalent improvements in depression , anxiety , functioning difficulties , quality of life , life satisfaction , and clinician-rated functioning . Whereas improvements were equivalent across the two groups , the mechanisms of action appeared to differ . Changes in “ observing ” and “ describing ” one 's experiences appeared to mediate outcomes for the CT group relative to the ACT group , whereas “ experiential avoidance , ” “ acting with awareness , ” and “ acceptance ” mediated outcomes for the ACT group . Overall , the results suggest that ACT is a viable and disseminable treatment , the effectiveness of which appears equivalent to that of CT , even as its mechanisms appear to be distinct OBJECTIVE The authors sought to assess the relationship between c and i date genes and two clinical outcomes , namely , symptomatic improvement and the occurrence of suicidal events , in a sample of treatment-resistant depressed adolescents . METHOD A sub sample of depressed adolescents participating in the Treatment of SSRI-Resistant Depression in Adolescents ( TORDIA ) trial , 155 of whom were of European origin , were genotyped with respect to 21 polymorphisms on 12 genes that have a reported association with depression , treatment response , or suicidal events . Participants had not responded to a previous adequate trial with an antidepressant and were r and omized to receive either another selective serotonin reuptake inhibitor or venlafaxine , with or without cognitive-behavioral therapy ( CBT ) . Single-nucleotide polymorphism ( SNP ) analyses were conducted using PLINK with permutation procedures . RESULTS No relationship was observed between any polymorphism and response to treatment . The FKBP5 ( which codes for a protein causing subsensitivity of the glucocorticoid receptor ) rs1360780TT and rs3800373GG genotypes were associated with suicidal events ( N=18 ) , even after controlling for treatment effects and relevant covariates . These two SNPs were in significant linkage disequilibrium ( r=0.91 ) . CONCLUSIONS The FKBP5 genotypes associated with suicidal events in this study have been reported by others to cause the greatest degree of glucoc 
    Output:
    