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: BACKGROUND Depression is one of the most disabling diseases , and causes a significant burden both to the individual and to society . WHO data suggests that depression causes 6 % of the burden of all diseases in Europe in terms of disability adjusted life years ( DALYs ) . Yet , the knowledge of the economic impact of depression has been relatively little research ed in Europe . AIMS OF THE STUDY The present study aims at estimating the total cost of depression  in Europe based on published epidemiologic and economic evidence . METHODS A model was developed to combine epidemiological and economic data on depression in Europe to estimate the cost . The model was populated with data collected from extensive literature review s of the epidemiology and economic burden of depression in Europe . The cost data was calculated as annual cost per patient , and epidemiologic data was reported as 12-month prevalence estimates . National and international statistics for the model were retrieved from the OECD and Eurostat data bases . The aggregated annual cost estimates were presented in Euro for 2004 . RESULTS In 28 countries with a population of 466 million , at least 21 million were affected by depression . The total annual cost of depression in Europe was estimated at Euro 118 billion in 2004 , which corresponds to a cost of Euro 253 per inhabitant . Direct costs alone totalled dollar 42 billion , comprised of outpatient care ( Euro 22 billion ) , drug cost ( Euro 9 billion ) and hospitalization ( Euro 10 billion ) . Indirect costs due to morbidity and mortality were estimated at Euro 76 billion . This makes depression the most costly brain disorder in Europe , accounting for 33 % of the total cost . The cost of depression corresponds to 1 % of the total economy of Europe ( GDP ) . DISCUSSION Our cost results are in good agreement with previous research findings . The cost estimates in the present study are based on model simulations for countries where no data was available . The predictability of our model is limited to the accuracy of the input data employed . As there is no earlier cost-of-illness study conducted on depression in Europe , it is , however , difficult to evaluate the validity of our results for individual countries and thus further research is needed . CONCLUSION The cost of depression poses a significant economic burden to European society . The simulation model employed shows good predictability of the cost of depression in Europe and is a novel approach to estimate the cost-of-illness in Europe . IMPLICATION S FOR HEALTH CARE PROVISION AND POLICIES : Health and social care policy and commissioning must be evidence -based . The empirical results from this study confirm previous findings , that depression is a major concern to the economic welfare in Europe which has consequences to both healthcare providers and policy makers . One important way to stop this explosion in cost is through increased research efforts in the field . Moreover , better detection , prevention , treatment and patient management are imperatives to reduce the burden of depression and its costs . Mental healthcare policies and better access to healthcare for mentally ill are other challenges to improve for Europe . IMPLICATION S FOR FURTHER RESEARCH This study has identified several research gaps which are of interest for future research . In order to better underst and the impact of depression to European society long-term prospect i ve epidemiology and cost-of-illness studies are needed . In particular data is lacking for Central European countries . On the basis of our findings , further economic evaluations of treatments for depression are necessary in order to ensure a cost-effective use of European healthcare budgets Two dimensions of compliance ( drop-outs and adherence ) were investigated in patients treated with antidepressant drugs .  Efficacy , compliance and its determinants were investigated in 66 patients suffering from major depressive disorder and treated in a double-blind manner with fluoxetine 20 mg/day or amitriptyline 150 mg/day for 9 weeks . Overall effectiveness [ 50 % decrease in the initial Hamilton Rating Scale for Depression ( HAM-D ) ] was similar in both groups ( 62.8 % for fluoxetine , 58.1 % for amitriptyline ) . The dropout rate due to side effects was 35.5 % for amitriptyline and 5.7 % for fluoxetine . A logistic regression analysis revealed that the initial HAM-D score was not predictive for dropping out , but this outcome was instead determined by sex ( increased risk for males ) , age ( increased risk for being younger ) and occurrence of severe side effects . Adherence was estimated using electronic Medication Event Monitoring System and defined as the percentage of days when the correct dose was taken out of the medication container . Of the patients studied 37 % had an adherence of less than 70 % . There was no relationship between adherence and efficacy and adherence was similar in patients on fluoxetine or amitriptyline .  Side effects were not predictive of being adherent or not , but a higher initial HAM-D score predicted a higher adherence to the medication regimen . The demographic variables bad no significant effect . The present study suggests that the link between efficacy , side effects and compliance or adherence is more complex than is generally believed and that early termination and non-adherence seem to be determined by different factors BACKGROUND This study augments a r and omized controlled trial to analyze the cost-effectiveness of 2 st and ardized treatments for major depression relative to each other and to the " usual care " provided by primary care physicians . METHODS A r and omized controlled trial was conducted in which primary care patients meeting DSM-III-R criteria for current major depression were assigned to pharmacotherapy ( where nortriptyline hydrochloride was given ) or interpersonal psychotherapy provided in a st and ardized framework or a primary physician 's usual care . Two outcome measures , depression-free days and quality -adjusted days , were developed using information on depressive symptoms over time . The costs of care were calculated . Cost-effectiveness ratios comparing the incremental outcomes with the incremental costs for the different treatments were estimated . Sensitivity analyses were performed . RESULTS In terms of both economic costs and quality -of-life outcomes , patients assigned to the pharmacotherapy group did slightly better than those assigned to interpersonal psychotherapy . Both st and ardized therapies provided better outcomes than primary physician 's usual care , but each consumed more re sources . No meaningful cost-offsets were found . The incremental direct cost per additional depression-free day for pharmacotherapy relative to usual care ranges from $ 12.66 to $ 16.87 which translates to direct cost per quality -adjusted year gained from $ 11270 to $ 19510 . CONCLUSIONS St and ardized treatments for depression lead to better outcomes than usual care but also lead to higher costs . However , the estimates of the cost per quality -of-life year gained for st and ardized pharmacotherapy are comparable with those found for other treatments provided in routine practice BACKGROUND Exp and ing access to high- quality depression treatment will depend on the balance of incremental benefits and costs . We examine the incremental cost-effectiveness of an organized depression management program for high utilizers of medical care . METHODS Computerized records at 3 health maintenance organizations were used to identify adult patients with outpatient medical visit rates above the 85th percentile for 2 consecutive years . A 2-step screening process identified patients with current depressive disorders , who were not in active treatment . Eligible patients were r and omly assigned to continued usual care ( n = 189 ) or to an organized depression management program ( n = 218 ) . The program included patient education , antidepressant pharmacotherapy initiated in primary care ( when appropriate ) , systematic telephone monitoring of adherence and outcomes , and psychiatric consultation as needed . Clinical outcomes ( assessed using the Hamilton Depression Rating Scale on 4 occasions throughout 12 months ) were converted to measures of " depression-free days . " Health services utilization and costs were estimated using health plan-st and ardized cl aims . RESULTS The intervention program led to an adjusted increase of 47.7 depression-free days throughout 12 months ( 95 % confidence interval [ CI ] , 28.2 - 67.8 days ) . Estimated cost increases were $ 1008 per year ( 95 % CI , $ 534-$1383 ) for outpatient health services , $ 1974 per year for total health services costs ( 95 % CI , $ 848-$3171 ) , and $ 2475 for health services plus time-in-treatment costs ( 95 % CI , $ 880-$4138 ) . Including total health services and time-in-treatment costs , estimated incremental cost per depression-free day was $ 51.84 ( 95 % CI , $ 17.37-$108.47 ) . CONCLUSIONS Among high utilizers of medical care , systematic identification and treatment of depression produce significant and sustained improvements in clinical outcomes as well as significant increases in health services costs Non-adherence to antidepressant drug treatment is common . In a recent study in depressed primary care patients , we reported a strong relationship between adherence and response after 6 months . With the use of a naturalistic design , the patients in that study were prospect ively followed for 2 years . The purpose of the present study was to investigate the patients ' long-term outcome and , in particular , to examine the impact of patients ' treatment adherence on response , remission and relapse .  Of the 1031 patients in the intent-to-treat ( ITT ) sample , 835 completed the study . After 2 years , the overall remission rate defined as a Montgomery – Åsberg Depression Rating Scale score of nine or less was 68 % in the ITT sample analysed with the last observation carried forward ( LOCF ) technique , and 75 % in observed cases . In total , 34 % of the responders experienced at least one relapse . Response rates ( LOCF ) were significantly higher in adherent compared to non-adherent patients at week 24 [ 95 % confidence interval (CI)=21.4–32.1 ] , year 1 ( 95 % CI=12.3–22.2 ) and year 2 ( 95 % CI=9.2–19.0 ) . Remission rates ( LOCF ) were also significantly higher in the group of adherent patients at week 24 ( 95 % CI=9.6–21.5 ) , year 1 ( 95 % CI=10.0–21.5 ) and year 2 ( 95 % CI=11.0–22.0 ) . No relationship between adherence and relapse rate was observed , although the mean time from response to first sign of relapse was significantly longer in the adherent patients ( 95 % CI=9–97 days ) . In conclusion , this 2-year follow-up study showed superior long-term recovery in patients who were adherent to antidepressant medication compared to non-adherent patients 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 CONTEXT Depression is a leading cause of disability worldwide , but treatment rates in primary care are low . OBJECTIVE To determine the cost-effectiveness from a societal perspective of 2 quality improvement ( QI ) interventions to improve treatment of depression in primary care and their effects on patient employment . DESIGN Group-level r and omized controlled trial conducted June 1996 to July 1999 . SETTING Forty-six primary care clinics in 6 community-based managed care organizations . PARTICIPANTS One hundred eighty-one primary care clinicians and 1356 patients with positive screening results for current depression . INTERVENTIONS Matched practice s were r and omly assigned to 
    Output:
    
agent
Depression frequently causes unemployment , absenteeism , and presenteeism , which results in significantly reduced productivity .
Improving patients ' compliance with their antidepressant medication results in improved outcomes and prolongs remission from depression , increasing work productivity , and thus reducing overall costs .
The implementation of remote enhanced-care programs may improve compliance and reduce overall costs .
In conclusion , depression is a common disorder with a high economic impact .
Enhanced-care programs may lower costs associated with depression and improve patients ' lives
***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 Depression is one of the most disabling diseases , and causes a significant burden both to the individual and to society . WHO data suggests that depression causes 6 % of the burden of all diseases in Europe in terms of disability adjusted life years ( DALYs ) . Yet , the knowledge of the economic impact of depression has been relatively little research ed in Europe . AIMS OF THE STUDY The present study aims at estimating the total cost of depression  in Europe based on published epidemiologic and economic evidence . METHODS A model was developed to combine epidemiological and economic data on depression in Europe to estimate the cost . The model was populated with data collected from extensive literature review s of the epidemiology and economic burden of depression in Europe . The cost data was calculated as annual cost per patient , and epidemiologic data was reported as 12-month prevalence estimates . National and international statistics for the model were retrieved from the OECD and Eurostat data bases . The aggregated annual cost estimates were presented in Euro for 2004 . RESULTS In 28 countries with a population of 466 million , at least 21 million were affected by depression . The total annual cost of depression in Europe was estimated at Euro 118 billion in 2004 , which corresponds to a cost of Euro 253 per inhabitant . Direct costs alone totalled dollar 42 billion , comprised of outpatient care ( Euro 22 billion ) , drug cost ( Euro 9 billion ) and hospitalization ( Euro 10 billion ) . Indirect costs due to morbidity and mortality were estimated at Euro 76 billion . This makes depression the most costly brain disorder in Europe , accounting for 33 % of the total cost . The cost of depression corresponds to 1 % of the total economy of Europe ( GDP ) . DISCUSSION Our cost results are in good agreement with previous research findings . The cost estimates in the present study are based on model simulations for countries where no data was available . The predictability of our model is limited to the accuracy of the input data employed . As there is no earlier cost-of-illness study conducted on depression in Europe , it is , however , difficult to evaluate the validity of our results for individual countries and thus further research is needed . CONCLUSION The cost of depression poses a significant economic burden to European society . The simulation model employed shows good predictability of the cost of depression in Europe and is a novel approach to estimate the cost-of-illness in Europe . IMPLICATION S FOR HEALTH CARE PROVISION AND POLICIES : Health and social care policy and commissioning must be evidence -based . The empirical results from this study confirm previous findings , that depression is a major concern to the economic welfare in Europe which has consequences to both healthcare providers and policy makers . One important way to stop this explosion in cost is through increased research efforts in the field . Moreover , better detection , prevention , treatment and patient management are imperatives to reduce the burden of depression and its costs . Mental healthcare policies and better access to healthcare for mentally ill are other challenges to improve for Europe . IMPLICATION S FOR FURTHER RESEARCH This study has identified several research gaps which are of interest for future research . In order to better underst and the impact of depression to European society long-term prospect i ve epidemiology and cost-of-illness studies are needed . In particular data is lacking for Central European countries . On the basis of our findings , further economic evaluations of treatments for depression are necessary in order to ensure a cost-effective use of European healthcare budgets Two dimensions of compliance ( drop-outs and adherence ) were investigated in patients treated with antidepressant drugs .  Efficacy , compliance and its determinants were investigated in 66 patients suffering from major depressive disorder and treated in a double-blind manner with fluoxetine 20 mg/day or amitriptyline 150 mg/day for 9 weeks . Overall effectiveness [ 50 % decrease in the initial Hamilton Rating Scale for Depression ( HAM-D ) ] was similar in both groups ( 62.8 % for fluoxetine , 58.1 % for amitriptyline ) . The dropout rate due to side effects was 35.5 % for amitriptyline and 5.7 % for fluoxetine . A logistic regression analysis revealed that the initial HAM-D score was not predictive for dropping out , but this outcome was instead determined by sex ( increased risk for males ) , age ( increased risk for being younger ) and occurrence of severe side effects . Adherence was estimated using electronic Medication Event Monitoring System and defined as the percentage of days when the correct dose was taken out of the medication container . Of the patients studied 37 % had an adherence of less than 70 % . There was no relationship between adherence and efficacy and adherence was similar in patients on fluoxetine or amitriptyline .  Side effects were not predictive of being adherent or not , but a higher initial HAM-D score predicted a higher adherence to the medication regimen . The demographic variables bad no significant effect . The present study suggests that the link between efficacy , side effects and compliance or adherence is more complex than is generally believed and that early termination and non-adherence seem to be determined by different factors BACKGROUND This study augments a r and omized controlled trial to analyze the cost-effectiveness of 2 st and ardized treatments for major depression relative to each other and to the " usual care " provided by primary care physicians . METHODS A r and omized controlled trial was conducted in which primary care patients meeting DSM-III-R criteria for current major depression were assigned to pharmacotherapy ( where nortriptyline hydrochloride was given ) or interpersonal psychotherapy provided in a st and ardized framework or a primary physician 's usual care . Two outcome measures , depression-free days and quality -adjusted days , were developed using information on depressive symptoms over time . The costs of care were calculated . Cost-effectiveness ratios comparing the incremental outcomes with the incremental costs for the different treatments were estimated . Sensitivity analyses were performed . RESULTS In terms of both economic costs and quality -of-life outcomes , patients assigned to the pharmacotherapy group did slightly better than those assigned to interpersonal psychotherapy . Both st and ardized therapies provided better outcomes than primary physician 's usual care , but each consumed more re sources . No meaningful cost-offsets were found . The incremental direct cost per additional depression-free day for pharmacotherapy relative to usual care ranges from $ 12.66 to $ 16.87 which translates to direct cost per quality -adjusted year gained from $ 11270 to $ 19510 . CONCLUSIONS St and ardized treatments for depression lead to better outcomes than usual care but also lead to higher costs . However , the estimates of the cost per quality -of-life year gained for st and ardized pharmacotherapy are comparable with those found for other treatments provided in routine practice BACKGROUND Exp and ing access to high- quality depression treatment will depend on the balance of incremental benefits and costs . We examine the incremental cost-effectiveness of an organized depression management program for high utilizers of medical care . METHODS Computerized records at 3 health maintenance organizations were used to identify adult patients with outpatient medical visit rates above the 85th percentile for 2 consecutive years . A 2-step screening process identified patients with current depressive disorders , who were not in active treatment . Eligible patients were r and omly assigned to continued usual care ( n = 189 ) or to an organized depression management program ( n = 218 ) . The program included patient education , antidepressant pharmacotherapy initiated in primary care ( when appropriate ) , systematic telephone monitoring of adherence and outcomes , and psychiatric consultation as needed . Clinical outcomes ( assessed using the Hamilton Depression Rating Scale on 4 occasions throughout 12 months ) were converted to measures of " depression-free days . " Health services utilization and costs were estimated using health plan-st and ardized cl aims . RESULTS The intervention program led to an adjusted increase of 47.7 depression-free days throughout 12 months ( 95 % confidence interval [ CI ] , 28.2 - 67.8 days ) . Estimated cost increases were $ 1008 per year ( 95 % CI , $ 534-$1383 ) for outpatient health services , $ 1974 per year for total health services costs ( 95 % CI , $ 848-$3171 ) , and $ 2475 for health services plus time-in-treatment costs ( 95 % CI , $ 880-$4138 ) . Including total health services and time-in-treatment costs , estimated incremental cost per depression-free day was $ 51.84 ( 95 % CI , $ 17.37-$108.47 ) . CONCLUSIONS Among high utilizers of medical care , systematic identification and treatment of depression produce significant and sustained improvements in clinical outcomes as well as significant increases in health services costs Non-adherence to antidepressant drug treatment is common . In a recent study in depressed primary care patients , we reported a strong relationship between adherence and response after 6 months . With the use of a naturalistic design , the patients in that study were prospect ively followed for 2 years . The purpose of the present study was to investigate the patients ' long-term outcome and , in particular , to examine the impact of patients ' treatment adherence on response , remission and relapse .  Of the 1031 patients in the intent-to-treat ( ITT ) sample , 835 completed the study . After 2 years , the overall remission rate defined as a Montgomery – Åsberg Depression Rating Scale score of nine or less was 68 % in the ITT sample analysed with the last observation carried forward ( LOCF ) technique , and 75 % in observed cases . In total , 34 % of the responders experienced at least one relapse . Response rates ( LOCF ) were significantly higher in adherent compared to non-adherent patients at week 24 [ 95 % confidence interval (CI)=21.4–32.1 ] , year 1 ( 95 % CI=12.3–22.2 ) and year 2 ( 95 % CI=9.2–19.0 ) . Remission rates ( LOCF ) were also significantly higher in the group of adherent patients at week 24 ( 95 % CI=9.6–21.5 ) , year 1 ( 95 % CI=10.0–21.5 ) and year 2 ( 95 % CI=11.0–22.0 ) . No relationship between adherence and relapse rate was observed , although the mean time from response to first sign of relapse was significantly longer in the adherent patients ( 95 % CI=9–97 days ) . In conclusion , this 2-year follow-up study showed superior long-term recovery in patients who were adherent to antidepressant medication compared to non-adherent patients 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 CONTEXT Depression is a leading cause of disability worldwide , but treatment rates in primary care are low . OBJECTIVE To determine the cost-effectiveness from a societal perspective of 2 quality improvement ( QI ) interventions to improve treatment of depression in primary care and their effects on patient employment . DESIGN Group-level r and omized controlled trial conducted June 1996 to July 1999 . SETTING Forty-six primary care clinics in 6 community-based managed care organizations . PARTICIPANTS One hundred eighty-one primary care clinicians and 1356 patients with positive screening results for current depression . INTERVENTIONS Matched practice s were r and omly assigned to 
    Output:
    