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 common and the efficacy of antidepressants is suboptimal . High plasma homocysteine has been consistently associated with depression , and treatment with certain B vitamins demonstrably reduces its concentration . AIMS To determine whether vitamins B6 , B12 and folic acid enhance response to antidepressant treatment  over 52 weeks . METHOD R and omised , double-blind , placebo-controlled trial of citalopram ( 20 - 40 g ) together with 0.5 mg of vitamin B12 , 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks ( Australian and New Zeal and Clinical Trials Registry : 12609000256279 ) . Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression . We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . The primary outcome was remission of the depressive episode after 12 , 26 and 52 weeks . Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12 . Results In total , 153 people were r and omised ( 76 placebo , 77 vitamins ) .  Remission of symptoms was achieved by 78.1 and 79.4 % of participants treated with placebo and vitamins by week 12 ( P = 0.840 ) , by 76.5 and 85.3 % at week 26 and 75.8 and 85.5 % at week 52 ( effect of intervention over 52 weeks : odds ratio ( OR ) = 2.49 , 95 % CI 1.12 - 5.51 ) . Group differences in MADRS scores over time were not significant ( P = 0.739 ) . The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group ( OR = 0.33 , 95 % CI 0.12 - 0.94 ) . CONCLUSIONS B vitamins did not increase the 12-week efficacy of antidepressant treatment , but enhanced and sustained antidepressant response over 1 year . Replication of these findings would m and ate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults Objective Major depression is a mood disorder that causes changes in physical activity , appetite , sleep and weight . Regarding the role of zinc in the pathology of depression , the present study was aim ed to investigate the effects of zinc supplementation in the treatment of this disease . Methods This study was a double-blind r and omized clinical trial . Forty four patients with major depression were r and omly assigned to groups receiving zinc supplementation and placebo . Patients in Zinc group received daily supplementation with 25 mg zinc adjunct to antidepressant ; Selective Serotonin Reuptake Inhibitors ( SSRIs ) , while the patients in placebo group received placebo with antidepressants ( SSRIs ) for twelve weeks . Severity of depression was measured using the Beck Depression Inventory at baseline and was repeated at the sixth and twelfth weeks . ANOVA with repeated measure was used to compare and track the changes during the study . Results The mean score of Beck test decreased significantly in the zinc supplement group at the end of week 6 ( P < 0.01 ) and 12 ( P < 0.001 ) compared to the baseline . The mean score of Beck Depression Inventory reduced significantly compared to the placebo group at the end of 12th week ( P < 0.05 ) Conclusion The results of the present study indicate that zinc supplementation together with SSRIs antidepressant drug improves major depressive disorders more effectively in patients with placebo plus antidepressants ( SSRIs ) BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids ( PUFAs ) , including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents ( red blood cell membrane , plasma , etc . ) and dietary intake . However , more evidence is needed to support its relation . In this study , we conducted an 8-week , double-blind , placebo-controlled trial , comparing omega-3 PUFAs ( 6.6 g/day ) [ corrected ] with placebo , on the top of the usual treatment , in 28 patients with major depressive disorder . Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group ( P < 0.001 ) . From the preliminary findings in this study , omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder The efficacy of a deficit oriented add-on therapy with free amino acids in depressive patients treated with the antidepressant Remeron ®  was evaluated . About 40 in- patients were investigated by a r and omised double-blind  placebo-controlled study during 4 weeks . Plasma levels of 20 amino acids and measures of depression , suicidal behaviour and aggression were surveyed on admission and after a 4 weeks ’ therapy with Remeron ® plus an individualized amino acid mixture or placebo . The preparation of the amino acid mixture was based on an aminogram and consisted of essential amino acids plus vitamins and trace elements as co-factors for the amino acid metabolism . Patients of the experimental group showed a significantly better improvement of depression and a higher responder rate than those of the placebo group . The results suggest that oral application of a deficit oriented amino acid mixture can improve the therapeutic outcome of an antidepressant . Furthermore , lacking side effects of the amino acids result ing also in a better patient compliance may improve the benefit/risk ratio Controversy exists as to whether eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) or both are responsible for the efficacy of n-3 polyunsaturated fatty acids in depression . We conducted a single-center , r and omized , double-blind , placebo-controlled , multi-arm , parallel-group trial , comparing the efficacy of EPA versus DHA as adjuvants to maintenance medication treatments for mild-to-moderate depression . Eighty-one mild-to-moderately depressed out patients were r and omly assigned to receive either 1g/d of EPA or DHA or placebo ( coconut oil ) for 12 weeks . The primary outcome measure was the 17-item Hamilton Depression Rating Scale ( HDRS ) final score in the modified intention-to-treat population , which comprised of all r and omized patients with at least 1 post-r and omization observation ( n=62 ; 61.3 % female ; mean age 35.1 ± 1.2 years ) . Allocated treatments were well tolerated . Although there was no significant difference between groups at baseline , patients in the EPA group showed a significantly lower mean HDRS score at study endpoint compared with those in the DHA ( p<0.001 ) or placebo ( p=0.002 ) groups . Furthermore , response to treatment ( defined as a ≥ 50 % decrease from the baseline HDRS score ) was only observed in 6 patients receiving EPA , while no one in any of DHA or placebo groups responded to treatment . Overall , these data suggest greater efficacy of EPA compared to DHA or placebo as an adjunctive treatment in mild-to-moderate depression . However , further , r and omized controlled trials are needed to support these findings One hundred and fifteen patients from 5 general practice s participated in a 12-week , double-blind study comparing L-tryptophan , amitriptyline , L-tryptophan-amitriptyline combination and placebo in the treatment of depression . Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo . Significantly more patients were withdrawn as treatment failures in the placebo group compared with the active treatment groups . Side-effects necessitated withdrawal of more patients from the amitriptyline group than from the other active treatment groups , but this difference was not significant . Plasma amitriptyline and nortriptyline levels were similar in the amitriptyline and combined treatment groups . St and ard haematological and biochemical profiles did not alter significantly in any group , but mean heart rate was significantly increased in patients receiving amitriptyline . There was no change in free or total plasma tryptophan concentration with treatment or on remission of symptoms CONTEXT Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids . OBJECTIVE To determine whether omega-3 improves the response to sertraline  in patients with major depression and coronary heart disease ( CHD ) . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial . Between May 2005 and December 2008 , 122 patients in St Louis , Missouri , with major depression and CHD were r and omized . INTERVENTIONS After a 2-week run-in period , all patients were given 50 mg/d of sertraline and r and omized in double-blind fashion to receive 2 g/d of omega-3 acid ethyl esters ( 930 mg of eicosapentaenoic acid [ EPA ] and 750 mg of docosahexaenoic acid [ DHA ] ) ( n=62 ) or to corn oil placebo capsules ( n=60 ) for 10 weeks . MAIN OUTCOME MEASURES Scores on the Beck Depression Inventory ( BDI-II ) and the Hamilton Rating Scale for Depression ( HAM-D ) . RESULTS Adherence to the medication regimen was 97 % or more in both groups for both medications . There were no differences in weekly BDI-II scores ( treatment x time interaction = 0.02 ; 95 % confidence interval [ CI ] , -0.33 to 0.36 ; t(112 ) = 0.11 ; P = .91 ) , pre-post BDI-II scores  ( placebo , 14.8 vs omega-3 , 16.1 ; 95 % difference-in-means CI , -4.5 to 2.0 ; t(116 ) = -0.77 ; P = .44 ) , or HAM-D scores ( placebo , 9.4 vs omega-3 , 9.3 ; 95 % difference-in-means CI , -2.2 to 2.4 ; t(115 ) = 0.12 ; P = .90 ) . The groups did not differ on predefined indicators of depression remission ( BDI-II < or = 8 : placebo , 27.4 % vs omega-3 , 28.3 % ; odds ratio [ OR ] , 0.96 ; 95 % CI , 0.43 - 2.15 ; t(113 ) = -0.11 ; P = .91 ) or response ( > 50 % reduction in BDI-II from baseline : placebo , 49.0 % vs omega-3 , 47.7 % ; OR , 1.06 ; 95 % CI , 0.51 - 2.19 ; t(112 ) = 0.15 ; P = .88 ) . CONCLUSIONS Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks , compared with sertraline and placebo . Whether higher doses of omega-3 or sertraline , a different ratio of EPA to DHA , longer treatment , or omega-3 monotherapy can improve 
    Output:
    
agent
Mixed results were found for zinc , folic acid , vitamin C , and tryptophan , with nonsignificant results for inositol .
No major adverse effects were noted in the studies ( aside from minor digestive disturbance ) .
A meta- analysis of adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3 .
Conversely , a meta- analysis of folic acid revealed a nonsignificant difference from placebo .
Current evidence supports adjunctive use of SAMe , methylfolate , omega-3 , and vitamin D with antidepressants to reduce depressive symptoms
***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 common and the efficacy of antidepressants is suboptimal . High plasma homocysteine has been consistently associated with depression , and treatment with certain B vitamins demonstrably reduces its concentration . AIMS To determine whether vitamins B6 , B12 and folic acid enhance response to antidepressant treatment  over 52 weeks . METHOD R and omised , double-blind , placebo-controlled trial of citalopram ( 20 - 40 g ) together with 0.5 mg of vitamin B12 , 2 mg of folic acid and 25 mg of vitamin B6 for 52 weeks ( Australian and New Zeal and Clinical Trials Registry : 12609000256279 ) . Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression . We measured severity of symptoms with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . The primary outcome was remission of the depressive episode after 12 , 26 and 52 weeks . Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12 . Results In total , 153 people were r and omised ( 76 placebo , 77 vitamins ) .  Remission of symptoms was achieved by 78.1 and 79.4 % of participants treated with placebo and vitamins by week 12 ( P = 0.840 ) , by 76.5 and 85.3 % at week 26 and 75.8 and 85.5 % at week 52 ( effect of intervention over 52 weeks : odds ratio ( OR ) = 2.49 , 95 % CI 1.12 - 5.51 ) . Group differences in MADRS scores over time were not significant ( P = 0.739 ) . The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group ( OR = 0.33 , 95 % CI 0.12 - 0.94 ) . CONCLUSIONS B vitamins did not increase the 12-week efficacy of antidepressant treatment , but enhanced and sustained antidepressant response over 1 year . Replication of these findings would m and ate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults Objective Major depression is a mood disorder that causes changes in physical activity , appetite , sleep and weight . Regarding the role of zinc in the pathology of depression , the present study was aim ed to investigate the effects of zinc supplementation in the treatment of this disease . Methods This study was a double-blind r and omized clinical trial . Forty four patients with major depression were r and omly assigned to groups receiving zinc supplementation and placebo . Patients in Zinc group received daily supplementation with 25 mg zinc adjunct to antidepressant ; Selective Serotonin Reuptake Inhibitors ( SSRIs ) , while the patients in placebo group received placebo with antidepressants ( SSRIs ) for twelve weeks . Severity of depression was measured using the Beck Depression Inventory at baseline and was repeated at the sixth and twelfth weeks . ANOVA with repeated measure was used to compare and track the changes during the study . Results The mean score of Beck test decreased significantly in the zinc supplement group at the end of week 6 ( P < 0.01 ) and 12 ( P < 0.001 ) compared to the baseline . The mean score of Beck Depression Inventory reduced significantly compared to the placebo group at the end of 12th week ( P < 0.05 ) Conclusion The results of the present study indicate that zinc supplementation together with SSRIs antidepressant drug improves major depressive disorders more effectively in patients with placebo plus antidepressants ( SSRIs ) BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids ( PUFAs ) , including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents ( red blood cell membrane , plasma , etc . ) and dietary intake . However , more evidence is needed to support its relation . In this study , we conducted an 8-week , double-blind , placebo-controlled trial , comparing omega-3 PUFAs ( 6.6 g/day ) [ corrected ] with placebo , on the top of the usual treatment , in 28 patients with major depressive disorder . Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group ( P < 0.001 ) . From the preliminary findings in this study , omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder The efficacy of a deficit oriented add-on therapy with free amino acids in depressive patients treated with the antidepressant Remeron ®  was evaluated . About 40 in- patients were investigated by a r and omised double-blind  placebo-controlled study during 4 weeks . Plasma levels of 20 amino acids and measures of depression , suicidal behaviour and aggression were surveyed on admission and after a 4 weeks ’ therapy with Remeron ® plus an individualized amino acid mixture or placebo . The preparation of the amino acid mixture was based on an aminogram and consisted of essential amino acids plus vitamins and trace elements as co-factors for the amino acid metabolism . Patients of the experimental group showed a significantly better improvement of depression and a higher responder rate than those of the placebo group . The results suggest that oral application of a deficit oriented amino acid mixture can improve the therapeutic outcome of an antidepressant . Furthermore , lacking side effects of the amino acids result ing also in a better patient compliance may improve the benefit/risk ratio Controversy exists as to whether eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) or both are responsible for the efficacy of n-3 polyunsaturated fatty acids in depression . We conducted a single-center , r and omized , double-blind , placebo-controlled , multi-arm , parallel-group trial , comparing the efficacy of EPA versus DHA as adjuvants to maintenance medication treatments for mild-to-moderate depression . Eighty-one mild-to-moderately depressed out patients were r and omly assigned to receive either 1g/d of EPA or DHA or placebo ( coconut oil ) for 12 weeks . The primary outcome measure was the 17-item Hamilton Depression Rating Scale ( HDRS ) final score in the modified intention-to-treat population , which comprised of all r and omized patients with at least 1 post-r and omization observation ( n=62 ; 61.3 % female ; mean age 35.1 ± 1.2 years ) . Allocated treatments were well tolerated . Although there was no significant difference between groups at baseline , patients in the EPA group showed a significantly lower mean HDRS score at study endpoint compared with those in the DHA ( p<0.001 ) or placebo ( p=0.002 ) groups . Furthermore , response to treatment ( defined as a ≥ 50 % decrease from the baseline HDRS score ) was only observed in 6 patients receiving EPA , while no one in any of DHA or placebo groups responded to treatment . Overall , these data suggest greater efficacy of EPA compared to DHA or placebo as an adjunctive treatment in mild-to-moderate depression . However , further , r and omized controlled trials are needed to support these findings One hundred and fifteen patients from 5 general practice s participated in a 12-week , double-blind study comparing L-tryptophan , amitriptyline , L-tryptophan-amitriptyline combination and placebo in the treatment of depression . Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo . Significantly more patients were withdrawn as treatment failures in the placebo group compared with the active treatment groups . Side-effects necessitated withdrawal of more patients from the amitriptyline group than from the other active treatment groups , but this difference was not significant . Plasma amitriptyline and nortriptyline levels were similar in the amitriptyline and combined treatment groups . St and ard haematological and biochemical profiles did not alter significantly in any group , but mean heart rate was significantly increased in patients receiving amitriptyline . There was no change in free or total plasma tryptophan concentration with treatment or on remission of symptoms CONTEXT Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids . OBJECTIVE To determine whether omega-3 improves the response to sertraline  in patients with major depression and coronary heart disease ( CHD ) . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial . Between May 2005 and December 2008 , 122 patients in St Louis , Missouri , with major depression and CHD were r and omized . INTERVENTIONS After a 2-week run-in period , all patients were given 50 mg/d of sertraline and r and omized in double-blind fashion to receive 2 g/d of omega-3 acid ethyl esters ( 930 mg of eicosapentaenoic acid [ EPA ] and 750 mg of docosahexaenoic acid [ DHA ] ) ( n=62 ) or to corn oil placebo capsules ( n=60 ) for 10 weeks . MAIN OUTCOME MEASURES Scores on the Beck Depression Inventory ( BDI-II ) and the Hamilton Rating Scale for Depression ( HAM-D ) . RESULTS Adherence to the medication regimen was 97 % or more in both groups for both medications . There were no differences in weekly BDI-II scores ( treatment x time interaction = 0.02 ; 95 % confidence interval [ CI ] , -0.33 to 0.36 ; t(112 ) = 0.11 ; P = .91 ) , pre-post BDI-II scores  ( placebo , 14.8 vs omega-3 , 16.1 ; 95 % difference-in-means CI , -4.5 to 2.0 ; t(116 ) = -0.77 ; P = .44 ) , or HAM-D scores ( placebo , 9.4 vs omega-3 , 9.3 ; 95 % difference-in-means CI , -2.2 to 2.4 ; t(115 ) = 0.12 ; P = .90 ) . The groups did not differ on predefined indicators of depression remission ( BDI-II < or = 8 : placebo , 27.4 % vs omega-3 , 28.3 % ; odds ratio [ OR ] , 0.96 ; 95 % CI , 0.43 - 2.15 ; t(113 ) = -0.11 ; P = .91 ) or response ( > 50 % reduction in BDI-II from baseline : placebo , 49.0 % vs omega-3 , 47.7 % ; OR , 1.06 ; 95 % CI , 0.51 - 2.19 ; t(112 ) = 0.15 ; P = .88 ) . CONCLUSIONS Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks , compared with sertraline and placebo . Whether higher doses of omega-3 or sertraline , a different ratio of EPA to DHA , longer treatment , or omega-3 monotherapy can improve 
    Output:
    