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: The pharmacokinetics and safety of duloxetine were evaluated in a single-blind , placebo-controlled , escalating multiple-dose study in 12 healthy male subjects . In the treatment group ( n = 8) , duloxetine was administered orally at a starting dose of 20 mg twice daily ( bid ) and escalated at weekly intervals to 30 mg bid , then to 40 mg bid . The observed plasma concentration-time data at all three dose levels were adequately described by a one-compartment model with a first-order absorption rate constant . The mean oral clearance , apparent volume of distribution , and half-life values were 114 L/h ( range : 44 to 218 L/h ) , 1943 L ( range : 803 to 3531 L ) , and 12.5 h ( range : 9.2 to 19.1 h ) , respectively . Somnolence , nausea , and dry mouth were observed following the initial dose , but they resolved with continuing drug administration . Duloxetine was not associated with clinical ly significant changes in blood pressure ( BP ) or heart rate ( HR ) measured in the st and ing position . However , in recumbent position , small increases in systolic ( < or = 9 mmHg ) and diastolic ( < or = 5 mmHg ) BP and small decreases in HR ( < or = 6 beats/min ) were observed . Abrupt discontinuation of duloxetine was associated with a small increase in mean HR ( < or = 12 beats/min ) . In 3 subjects , abrupt discontinuation was also associated with transient sleep disturbance . No clinical ly important changes in electrocardiograms , cardiac intervals , clinical laboratory tests , and neurological functions were observed . These results indicate that duloxetine exhibits linear pharmacokinetics with respect to dose and duration of treatment and that a multiple oral dose regimen starting at 20 mg bid and gradually escalating up to 40 mg bid was generally well tolerated This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer OBJECTIVE To determine efficacy of continued treatment with the serotonin norepinephrine reuptake inhibitor duloxetine on symptom reduction and functional improvement in out patients with dysthymia . METHOD Fifty out patients with DSM-IV-TR diagnosed dysthymia who had participated in a 10 week double-blind , placebo-controlled study of duloxetine received open treatment for three months . Nineteen duloxetine responders continued duloxetine , 24 patients initially treated with placebo started open duloxetine treatment , and 7 duloxetine non-responders were treated with desvenlafaxine or bupropion , selected by clinician choice . RESULTS Patients continuing duloxetine maintained symptom improvement , 84 % meeting response and 63 % remission criteria at week 22 . Patients initially treated with placebo showed similarly high levels of response ( 83 % ) and remission ( 62 % ) at week 22 , and most duloxetine non-responders subsequently responded to other antidepressants . Duloxetine-continuation patients improved modestly between weeks 10 and 22 on measures of social and cognitive functioning and temperament . Despite this improvement concurrently across several functional domains , 66.7 % of patients continuing duloxetine remained in the impaired range of functioning according to the Social Adjustment Scale ( SAS ) . CONCLUSIONS Continued duloxetine treatment appears to be effective in maintaining symptom response in dysthymic disorder , and has positive effects on social functioning . However , the majority of patients do not show normalization of functioning , even when controlling for remission status . Additional treatments should be considered to target residual impairments in social functioning in mood remitted patients with persistent depressive disorder The objective of this prospect i ve study was to assess the efficacy and tolerability of duloxetine in the treatment of in military veterans with posttraumatic stress disorder (PTSD).Twenty subjects were enrolled in this 12-week , open-label trial . Diagnosis and symptom severity were assessed with the Clinician Administered PTSD Scale ( CAPS ) . Depressive symptoms were assessed the Hamilton Depression Rating Scale . All subjects had a CAPS score of at least 60 at baseline . Subjects with lifetime history of psychotic disorders or bipolar illness were excluded . Fifteen participants completed 12 weeks of treatment , five dropped-out from the trial , 3 due to side effects . For patients who discontinued , missing values were estimated using " the last observation carried forward " method . Significant improvements were seen on : CAPS total and all subscales , depression and sleep measures . Most of the improvement was observed by week 2 of treatment . Nine participants ( 45 % ) were classified as responders , defined by 20 % or greater improvement on CAPS total score . The mean daily dose of duloxetine was 81 mg . The most common side effects were constipation ( 20 % ) diarrhea ( 25 % ) and nausea ( 20 % ) . Two subjects developed tachycardia , one withdrew from the trial due to this problem . Duloxetine had a fast onset of action and was effective in about half of the subjects , it was well tolerated in most subjects . These preliminary results in a difficult to treat population warrant the conduction of a double blind , placebo-controlled study of duloxetine in PTSD Panic disorder with or without agoraphobia is a common , often chronic and refractory anxiety disorder . Although a number of pharmacotherapies are now indicated for panic disorder , many patients do not respond to available interventions . We hypothesized that duloxetine , a serotonin‐norepinephrine reuptake inhibitor ( SNRI ) that has greater initial noradrenergic effects than venlafaxine , would have broad efficacy for individuals with panic disorder . Fifteen individuals with panic disorder with or without agoraphobia received 8 weeks of open label duloxetine flexibly dosed from 60 to 120 mg per day . Duloxetine treatment result ed in significant anxiolysis as measured by the primary outcome measure , the Panic Disorder Severity Scale ( PDSS ) ( paired t(df ) = 4.02(14 ) , P= 0.0013 ) , as well as measures of generalized anxiety , depression and quality of life ( all P < 0.05 ) . Although definitive conclusions are limited due to its small open‐label nature , this first prospect i ve study provides preliminary support for the efficacy of duloxetine for panic disorder and suggests larger r and omized controlled study is warranted Objective : Premenstrual dysphoric disorder ( PMDD ) is a complex clinical syndrome that is notoriously difficult to treat . The purpose of the present study was to provide preliminary data on the effectiveness of duloxetine in PMDD . Research design and methods : Fifty-five women with PMDD were treated with a 60 mg/day dosage of duloxetine for two menstrual cycles . Responses were assessed at first and second treatment cycle . Main outcome measures : Outcome measures included a visual analogue scale , the Zung Self-rating Scale for Depression , the Hamilton Depression Rating Scale , the Hamilton Anxiety Rating Scale and the Clinical Global Impressions Scale . Results : Fifty patients completed the trial . All had significant improvement of depression and anxiety and response , defined as a 50 % decrease in daily symptom scores , occurred in 39 ( 78 % ) patients . The effects of active treatment were marked by the first active cycle of menstruation . Conclusions : Duloxetine 60 mg/day was effective in reducing PMDD symptoms and generally well tolerated . Limitations of the study were open-label design and lack of placebo control . However , the results appeared to be strong and consistent across measures . Adverse events ( nausea , insomnia , poor appetite ) were low . Further studies are needed to confirm these results Abstract Aim : Though premature ejaculation ( PE ) has been overshadowed by current attention given to erectile dysfunction , it is the most widespread form of male sexual dysfunction . Delayed or inhibited ejaculation , a known side effect of selective serotonin reuptake inhibitors ( SSRIs ) , has made SSRIs potentially useful in the treatment of this disorder . In the present study , we examined the efficacy of duloxetine , an SSRI , in the treatment of PE . Method : The study included 20 married patients diagnosed with PE . The patients were r and omly assigned to two groups , duloxetine ( group I ) and placebo ( group II ) , each consisting of 10 patients . The effects on the ejaculatory function were estimated by the intravaginal ejaculation latency time . All patients were evaluated by using clinical global impression-improvement Scale ( CGI-I ) . Results : The increase in the intravaginal ejaculation latency time in the duloxetine group was statistically significant than that of placebo group . Of group I patients , four ( 40 % ) were considered as “ very much improved ” and four ( 40 % ) “ much improved ” by CGI-I and only one of group II patients ( 10 % ) showed “ much improved ” . Conclusion : Duloxetine appears to be superior to placebo in the pharmacological treatment of PE when administered on a chronic basis OBJECTIVE The aim of this observational study was to evaluate the effects of duloxetine in the treatment of seasonal affective disorder ( SAD ) . PATIENTS AND METHODS 26 SAD patients were treated with open-label duloxetine 60 - 120 mg per day over 8 weeks . Ratings included the Structured Interview Guide for the Hamilton Depression Rating Scale ( SAD version ; SIGH-SAD ) and the Clinical Global Impression ( CGI ) . To estimate treatment effects on social functioning in SAD we employed the Social Adaptation Self Evaluation Scale ( SASS ) , the Sheehan Disability Scale ( SDS ) , and assessment s of days lost due to illness and days with reduction in productivity . RESULTS Duloxetine led to a significant improvement ( p<0.001 ) of SIGH-SAD , CGI severity , SASS , and SDS scores . Days lost due to illness and days with reduction in productivity were significantly diminished during treatment ( p<0.001 ) . Treatment with duloxetine over 8 weeks yielded a response rate ( SIGH-SAD<50 % of baseline value ) of 80.8 % and a remission rate ( SIGH-SAD<8 ) of 76.9 % in the intention to treat sample . The drop-out rate due to side effects was 15.4 % . CONCLUSIONS Our preliminary results indicate that duloxetine might be effective and able to ameliorate the negative social consequences of SAD Premenstrual dysphoric disorder ( PMDD ) affects 3 - 8 % of women of reproductive age and is characterized by severe mood symptoms that cause important functional impairment . Serotonergic antidepressants appear to be an effective treatment for this disorder . The purpose of this study was to collect evidence on the efficacy and tolerability of duloxetine , a dual reuptake inhibitor of serotonin and norepinephrine , in the treatment of PMDD . We conducted a pilot , single-blind , non-controlled , fixed-dose trial . After two cycles for diagnosis confirmation , including a single-blind placebo cycle , 20 women with PMDD were treated continuously for three menstrual cycles with 60 mg/d duloxetine . The primary measure of the efficacy of treatment with duloxetine was the significant reduction in premenstrual symptoms demonstrated by the comparison between the mean Daily Record of Severity of Problems ( DRSP ) scores at baseline to endpoint ( p=0.0002 ) . Statistically significant symptom reduction was observed in the first treatment cycle and throughout all the treatment phase . Clinical response , defined as a reduction 50 % of baseline premenstrual symptoms , occurred in 65 % of subjects ( intention-to-treat population ) . Significant improvements were demonstrated by secondary measures , including reduction in self-rated functional impairment ( p=0.01 ) and improvement in quality of life ( p=0.04 ) . The main side-effects associated with duloxetine were dry mouth , nausea , drowsiness , insomnia , decreased appetite , decreased libido , and sweating . Duloxetine was effective and generally well tolerated in the treatment of PMDD . Further large-scale , double-blind , placebo-controlled studies are needed to evaluate duloxetine as an additional treatment strategy for the management of PMDD OBJECTIVE Numerous double-blind studies have assessed the efficacy of antidepressants in treating chronic depressive disorder , including dysthymic disorder , low- grade chronic depression . However , there are no double-blind , placebo-controlled studies of serotonin-norepinephrine reuptake inhibitors in chron 
    Output:
    
agent
Results : Duloxetine may be an effective treatment for mood spectrum disorders , panic disorder , several symptom clusters of borderline personality , and as add-on drug in schizophrenia .
Modest or conflicting results have been found for the efficacy of duloxetine in obsessive-compulsive disorder , posttraumatic stress disorder , eating , and sexual disorders .
***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: The pharmacokinetics and safety of duloxetine were evaluated in a single-blind , placebo-controlled , escalating multiple-dose study in 12 healthy male subjects . In the treatment group ( n = 8) , duloxetine was administered orally at a starting dose of 20 mg twice daily ( bid ) and escalated at weekly intervals to 30 mg bid , then to 40 mg bid . The observed plasma concentration-time data at all three dose levels were adequately described by a one-compartment model with a first-order absorption rate constant . The mean oral clearance , apparent volume of distribution , and half-life values were 114 L/h ( range : 44 to 218 L/h ) , 1943 L ( range : 803 to 3531 L ) , and 12.5 h ( range : 9.2 to 19.1 h ) , respectively . Somnolence , nausea , and dry mouth were observed following the initial dose , but they resolved with continuing drug administration . Duloxetine was not associated with clinical ly significant changes in blood pressure ( BP ) or heart rate ( HR ) measured in the st and ing position . However , in recumbent position , small increases in systolic ( < or = 9 mmHg ) and diastolic ( < or = 5 mmHg ) BP and small decreases in HR ( < or = 6 beats/min ) were observed . Abrupt discontinuation of duloxetine was associated with a small increase in mean HR ( < or = 12 beats/min ) . In 3 subjects , abrupt discontinuation was also associated with transient sleep disturbance . No clinical ly important changes in electrocardiograms , cardiac intervals , clinical laboratory tests , and neurological functions were observed . These results indicate that duloxetine exhibits linear pharmacokinetics with respect to dose and duration of treatment and that a multiple oral dose regimen starting at 20 mg bid and gradually escalating up to 40 mg bid was generally well tolerated This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer OBJECTIVE To determine efficacy of continued treatment with the serotonin norepinephrine reuptake inhibitor duloxetine on symptom reduction and functional improvement in out patients with dysthymia . METHOD Fifty out patients with DSM-IV-TR diagnosed dysthymia who had participated in a 10 week double-blind , placebo-controlled study of duloxetine received open treatment for three months . Nineteen duloxetine responders continued duloxetine , 24 patients initially treated with placebo started open duloxetine treatment , and 7 duloxetine non-responders were treated with desvenlafaxine or bupropion , selected by clinician choice . RESULTS Patients continuing duloxetine maintained symptom improvement , 84 % meeting response and 63 % remission criteria at week 22 . Patients initially treated with placebo showed similarly high levels of response ( 83 % ) and remission ( 62 % ) at week 22 , and most duloxetine non-responders subsequently responded to other antidepressants . Duloxetine-continuation patients improved modestly between weeks 10 and 22 on measures of social and cognitive functioning and temperament . Despite this improvement concurrently across several functional domains , 66.7 % of patients continuing duloxetine remained in the impaired range of functioning according to the Social Adjustment Scale ( SAS ) . CONCLUSIONS Continued duloxetine treatment appears to be effective in maintaining symptom response in dysthymic disorder , and has positive effects on social functioning . However , the majority of patients do not show normalization of functioning , even when controlling for remission status . Additional treatments should be considered to target residual impairments in social functioning in mood remitted patients with persistent depressive disorder The objective of this prospect i ve study was to assess the efficacy and tolerability of duloxetine in the treatment of in military veterans with posttraumatic stress disorder (PTSD).Twenty subjects were enrolled in this 12-week , open-label trial . Diagnosis and symptom severity were assessed with the Clinician Administered PTSD Scale ( CAPS ) . Depressive symptoms were assessed the Hamilton Depression Rating Scale . All subjects had a CAPS score of at least 60 at baseline . Subjects with lifetime history of psychotic disorders or bipolar illness were excluded . Fifteen participants completed 12 weeks of treatment , five dropped-out from the trial , 3 due to side effects . For patients who discontinued , missing values were estimated using " the last observation carried forward " method . Significant improvements were seen on : CAPS total and all subscales , depression and sleep measures . Most of the improvement was observed by week 2 of treatment . Nine participants ( 45 % ) were classified as responders , defined by 20 % or greater improvement on CAPS total score . The mean daily dose of duloxetine was 81 mg . The most common side effects were constipation ( 20 % ) diarrhea ( 25 % ) and nausea ( 20 % ) . Two subjects developed tachycardia , one withdrew from the trial due to this problem . Duloxetine had a fast onset of action and was effective in about half of the subjects , it was well tolerated in most subjects . These preliminary results in a difficult to treat population warrant the conduction of a double blind , placebo-controlled study of duloxetine in PTSD Panic disorder with or without agoraphobia is a common , often chronic and refractory anxiety disorder . Although a number of pharmacotherapies are now indicated for panic disorder , many patients do not respond to available interventions . We hypothesized that duloxetine , a serotonin‐norepinephrine reuptake inhibitor ( SNRI ) that has greater initial noradrenergic effects than venlafaxine , would have broad efficacy for individuals with panic disorder . Fifteen individuals with panic disorder with or without agoraphobia received 8 weeks of open label duloxetine flexibly dosed from 60 to 120 mg per day . Duloxetine treatment result ed in significant anxiolysis as measured by the primary outcome measure , the Panic Disorder Severity Scale ( PDSS ) ( paired t(df ) = 4.02(14 ) , P= 0.0013 ) , as well as measures of generalized anxiety , depression and quality of life ( all P < 0.05 ) . Although definitive conclusions are limited due to its small open‐label nature , this first prospect i ve study provides preliminary support for the efficacy of duloxetine for panic disorder and suggests larger r and omized controlled study is warranted Objective : Premenstrual dysphoric disorder ( PMDD ) is a complex clinical syndrome that is notoriously difficult to treat . The purpose of the present study was to provide preliminary data on the effectiveness of duloxetine in PMDD . Research design and methods : Fifty-five women with PMDD were treated with a 60 mg/day dosage of duloxetine for two menstrual cycles . Responses were assessed at first and second treatment cycle . Main outcome measures : Outcome measures included a visual analogue scale , the Zung Self-rating Scale for Depression , the Hamilton Depression Rating Scale , the Hamilton Anxiety Rating Scale and the Clinical Global Impressions Scale . Results : Fifty patients completed the trial . All had significant improvement of depression and anxiety and response , defined as a 50 % decrease in daily symptom scores , occurred in 39 ( 78 % ) patients . The effects of active treatment were marked by the first active cycle of menstruation . Conclusions : Duloxetine 60 mg/day was effective in reducing PMDD symptoms and generally well tolerated . Limitations of the study were open-label design and lack of placebo control . However , the results appeared to be strong and consistent across measures . Adverse events ( nausea , insomnia , poor appetite ) were low . Further studies are needed to confirm these results Abstract Aim : Though premature ejaculation ( PE ) has been overshadowed by current attention given to erectile dysfunction , it is the most widespread form of male sexual dysfunction . Delayed or inhibited ejaculation , a known side effect of selective serotonin reuptake inhibitors ( SSRIs ) , has made SSRIs potentially useful in the treatment of this disorder . In the present study , we examined the efficacy of duloxetine , an SSRI , in the treatment of PE . Method : The study included 20 married patients diagnosed with PE . The patients were r and omly assigned to two groups , duloxetine ( group I ) and placebo ( group II ) , each consisting of 10 patients . The effects on the ejaculatory function were estimated by the intravaginal ejaculation latency time . All patients were evaluated by using clinical global impression-improvement Scale ( CGI-I ) . Results : The increase in the intravaginal ejaculation latency time in the duloxetine group was statistically significant than that of placebo group . Of group I patients , four ( 40 % ) were considered as “ very much improved ” and four ( 40 % ) “ much improved ” by CGI-I and only one of group II patients ( 10 % ) showed “ much improved ” . Conclusion : Duloxetine appears to be superior to placebo in the pharmacological treatment of PE when administered on a chronic basis OBJECTIVE The aim of this observational study was to evaluate the effects of duloxetine in the treatment of seasonal affective disorder ( SAD ) . PATIENTS AND METHODS 26 SAD patients were treated with open-label duloxetine 60 - 120 mg per day over 8 weeks . Ratings included the Structured Interview Guide for the Hamilton Depression Rating Scale ( SAD version ; SIGH-SAD ) and the Clinical Global Impression ( CGI ) . To estimate treatment effects on social functioning in SAD we employed the Social Adaptation Self Evaluation Scale ( SASS ) , the Sheehan Disability Scale ( SDS ) , and assessment s of days lost due to illness and days with reduction in productivity . RESULTS Duloxetine led to a significant improvement ( p<0.001 ) of SIGH-SAD , CGI severity , SASS , and SDS scores . Days lost due to illness and days with reduction in productivity were significantly diminished during treatment ( p<0.001 ) . Treatment with duloxetine over 8 weeks yielded a response rate ( SIGH-SAD<50 % of baseline value ) of 80.8 % and a remission rate ( SIGH-SAD<8 ) of 76.9 % in the intention to treat sample . The drop-out rate due to side effects was 15.4 % . CONCLUSIONS Our preliminary results indicate that duloxetine might be effective and able to ameliorate the negative social consequences of SAD Premenstrual dysphoric disorder ( PMDD ) affects 3 - 8 % of women of reproductive age and is characterized by severe mood symptoms that cause important functional impairment . Serotonergic antidepressants appear to be an effective treatment for this disorder . The purpose of this study was to collect evidence on the efficacy and tolerability of duloxetine , a dual reuptake inhibitor of serotonin and norepinephrine , in the treatment of PMDD . We conducted a pilot , single-blind , non-controlled , fixed-dose trial . After two cycles for diagnosis confirmation , including a single-blind placebo cycle , 20 women with PMDD were treated continuously for three menstrual cycles with 60 mg/d duloxetine . The primary measure of the efficacy of treatment with duloxetine was the significant reduction in premenstrual symptoms demonstrated by the comparison between the mean Daily Record of Severity of Problems ( DRSP ) scores at baseline to endpoint ( p=0.0002 ) . Statistically significant symptom reduction was observed in the first treatment cycle and throughout all the treatment phase . Clinical response , defined as a reduction 50 % of baseline premenstrual symptoms , occurred in 65 % of subjects ( intention-to-treat population ) . Significant improvements were demonstrated by secondary measures , including reduction in self-rated functional impairment ( p=0.01 ) and improvement in quality of life ( p=0.04 ) . The main side-effects associated with duloxetine were dry mouth , nausea , drowsiness , insomnia , decreased appetite , decreased libido , and sweating . Duloxetine was effective and generally well tolerated in the treatment of PMDD . Further large-scale , double-blind , placebo-controlled studies are needed to evaluate duloxetine as an additional treatment strategy for the management of PMDD OBJECTIVE Numerous double-blind studies have assessed the efficacy of antidepressants in treating chronic depressive disorder , including dysthymic disorder , low- grade chronic depression . However , there are no double-blind , placebo-controlled studies of serotonin-norepinephrine reuptake inhibitors in chron 
    Output:
    