***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 
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    ***EXAMPLES*** 
    Input: CONTEXT Existing therapies for major depression have a lag of onset of action of several weeks , result ing in considerable morbidity . Exploring pharmacological strategies that have rapid onset of antidepressant effects within a few days and that are sustained would have an enormous impact on patient care . Converging lines of evidence suggest the role of the glutamatergic system in the pathophysiology and treatment of mood disorders . OBJECTIVE To determine whether a rapid antidepressant effect can be achieved with an antagonist at the N-methyl-D-aspartate receptor in subjects with major depression . DESIGN A r and omized , placebo-controlled , double-blind crossover study from November 2004 to September 2005 . SETTING Mood Disorders Research Unit at the National Institute of Mental Health . Patients Eighteen subjects with DSM-IV major depression ( treatment resistant ) . INTERVENTIONS After a 2-week drug-free period , subjects were given an intravenous infusion of either ketamine hydrochloride ( 0.5 mg/kg ) or placebo on 2 test days , a week apart . Subjects were rated at baseline and at 40 , 80 , 110 , and 230 minutes and 1 , 2 , 3 , and 7 days postinfusion . Main Outcome Measure Changes in scores on the primary efficacy measure , the 21-item Hamilton Depression Rating Scale . RESULTS Subjects receiving ketamine showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection , which remained significant throughout the following week . The effect size for the drug difference was very large ( d = 1.46 [ 95 % confidence interval , 0.91 - 2.01 ] ) after 24 hours and moderate to large ( d = 0.68 [ 95 % confidence interval , 0.13 - 1.23 ] ) after 1 week . Of the 17 subjects treated with  ketamine  , 71 % met response and 29 % met remission criteria the day following ketamine infusion . Thirty-five percent of subjects maintained response for at least 1 week . CONCLUSIONS Robust and rapid antidepressant effects result ed from a single intravenous dose of an N-methyl-D-aspartate antagonist ; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week BACKGROUND The high-affinity N-methyl-D-aspartate ( NMDA ) antagonist ketamine exerts rapid antidepressant effects but has psychotomimetic properties . AZD6765 is a low-trapping NMDA channel blocker with low rates of associated psychotomimetic effects . This study investigated whether AZD6765 could produce rapid antidepressant effects in subjects with treatment-resistant major depressive disorder ( MDD ) . METHODS In this double-blind , r and omized , crossover , placebo-controlled study , 22 subjects with DSM-IV treatment-resistant MDD received a single infusion of either AZD6765 ( 150 mg ) or placebo on 2 test days 1 week apart . The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale , which was used to rate overall depressive symptoms at baseline and 60 , 80 , 110 , and 230 min postinfusion and on Days 1 , 2 , 3 , and 7 postinfusion . Several secondary outcome measures were also used , including the Hamilton Depression Rating Scale . RESULTS Within 80 min , Montgomery-Åsberg Depression Rating Scale scores significantly improved in subjects receiving AZD6765 compared with placebo ; this improvement remained significant only through 110 min ( d = .40 ) . On the Hamilton Depression Rating Scale , a drug difference was found at 80 and 110 min and at Day 2 ( d = .49 ) . Overall , 32 % of subjects responded to AZD6765 , and 15 % responded to placebo at some point during the trial . No difference was observed between the groups with regard to psychotomimetic or dissociative adverse effects . CONCLUSIONS In patients with treatment-resistant MDD , a single intravenous dose of the low-trapping NMDA channel blocker AZD6765 was associated with rapid but short-lived antidepressant effects ; no psychotomimetic effects were observed Antagonism of N-methyl-D-aspartate glutamatergic receptors ( NMDAR ) may represent an effective antidepressant mechanism . D-cycloserine ( DCS ) is a partial agonist at the NMDAR-associated glycine modulatory site that at high doses acts as a functional NMDAR antagonist . Twenty-six treatment-resistant major depressive disorder patients participated in a double blind , placebo-controlled , 6-wk parallel group trial with a gradually titrated high dose ( 1000 mg/d ) of DCS added to their antidepressant medication . DCS treatment was well tolerated , had no psychotomimetic effects and led to improvement in depression symptoms as measured by Hamilton Depression Rating Scale ( HAMD ; p = 0.005 ) and Beck Depression Inventory ( p = 0.046 ) . Of the 13 subjects treated with DCS , 54 % had a ≥ 50 % HAMD score reduction vs. 15 % of the 13 patients r and omized to placebo ( p = 0.039 ) . A significant ( p = 0.043 ) treatment × pre-treatment glycine serum levels interaction was registered . These findings indicate that NMDAR glycine site antagonism may be a cost-effective target for development of mechanistically novel antidepressants . Larger-sized DCS trials are warranted Accumulating evidence suggests that N-methyl-d-aspartate receptor ( NMDAR ) antagonists ( e.g. ketamine ) may exert rapid antidepressant effects in MDD patients . In the present study , we evaluated the rapid antidepressant effects of ketamine compared with the electroconvulsive therapy ( ECT ) in hospitalized patients with MDD . In this blind , r and omized study , 18 patients with DSM-IV MDD were divided into two groups which received either three intravenous infusions of ketamine hydrochloride ( 0.5 mg/kg over 45 min ) or ECT on 3 test days ( every 48 h ) . The primary outcome measure was the Beck Depression Inventory ( BDI ) and Hamilton Depression Rating Scale ( HDRS ) , which was used to rate overall depressive symptoms at baseline , 24 h after each treatment , 72 h and one week after the last ( third ) ketamine or ECT . Within 24 h , depressive symptoms significantly improved in subjects receiving the first dose of ketamine compared with ECT group . Compared to baseline level , this improvement remained significant throughout the study . Depressive symptoms after the second dose ketamine was also lower than the second ECT . This study showed that ketamine is as effective as ECT in improving depressive symptoms in MDD patients and have more rapid antidepressant effects compared with the ECT Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more We investigated whether ketamine is suitable for depressed patients who had undergone orthopedic surgery . We studied 70 patients with major depression and 25 patients as the control ( Group C ) . The depressed patients were divided r and omly into two groups ; patients in Group A ( n = 35 ) were induced with propofol , fentanyl , and ketamine and patients in Group B ( n = 35 ) were induced with propofol and fentanyl , and all patients were maintained with 1.5%–2.0 % isoflurane plus nitrous oxide .  The mean Hamilton Depression Rating ( HDR ) score was 12.7 ± 5.4 for Group A and 12.3 ± 6.0 for Group B 2 days before surgery and 9.9 ± 4.1 for Group A and 14.4 ± 3.8 for Group B 1 day after surgery . The HDR score in Group A 1 day after surgery was significantly ( P < 0.05 ) lower than that in Group B. The HDR score in Group C was 4.2 ± 1.7 2 days before surgery and 4.8 ± 1.6 1 day after surgery . Depressed mood , suicidal tendencies , somatic anxiety , and hypochondriasis significantly decreased in Group A as compared with Group B. Postoperative pain scores in Group A at 8 and 16 h after the end of anesthesia were 26.6 ± 8.7 and 24.9 ± 8.2 , respectively , which were significantly ( P < 0.05 ) lower than 34.3 ± 12.0 and 31.1 ± 8.8 in Group B. In conclusion , small-dose ketamine  improved the postoperative depressive state and relieved postoperative pain in depressed patients OBJECTIVE Ketamine , a glutamate N-methyl-d-aspartate ( NMDA ) receptor antagonist , has shown rapid antidepressant effects , but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion . The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression . METHOD This was a two-site , parallel-arm , r and omized controlled trial of a single infusion of ketamine compared to an active placebo control condition , the anesthetic midazolam .  Patients with treatment-resistant major depression experiencing a major depressive episode were r and omly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio ( N=73 ) . The primary outcome was change in depression severity 24 hours after drug administration , as assessed by the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . RESULTS The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment . After adjustment for baseline scores and site , the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points ( 95 % confidence interval [ CI ] , 3.20 to 12.71 ) . The likelihood of response at 24 hours was greater with ketamine than with midazolam ( odds ratio , 2.18 ; 95 % CI , 1.21 to 4.14 ) , with response rates of 64 % and 28 % , respectively . CONCLUSIONS Ketamine demonstrated rapid antidepressant effects in an optimized study design , further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression . More information on response durability and safety is required before implementation in clinical practice BACKGROUND Currently , no pharmacological treatments for bipolar depression exist that exert rapid ( within hours ) antidepressant or antisuicidal effects . We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression . The present study sought to replicate this finding in an independent sample . METHODS In this double-blind , r and omized , crossover , placebo-controlled study , 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate  received a single intravenous infusion of either ketamine hydrochloride ( .5 mg/kg ) or placebo on 2 test days 2 weeks apart . The primary outcome measure was the Montgomery-Asberg Depression Rating Scale , which was used to rate overall depressive symptoms at baseline ; at 40 , 80 , 110 , and 230 minutes postinfusion ; and on days 1 , 2 , 3 , 7 , 10 , and 14 postinfusion . RESULTS Within 40 minutes , depressive symptoms , as well as suicidal ideation , significantly improved in subjects receiving ketamine compared with placebo ( d = .89 , 95 % confidence interval = .61 - 1.16 , and .98 , 95 % confidence interval = .64 - 1.33 , respectively ) ; this improvement remained significant through day 3 . Seventy-nine percent of subjects responded to ketamine and 0 % responded to placebo at some point during the trial . The most common side effect was dissociative symptoms , which occurred only at the 40-minute time point . CONCLUSIONS This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response . In addition , we found that ketamine rapidly improved suicidal ideation in these patients The purpose of this study was to develop an instrument for the measurement of present-state dissociative symptoms , the  Clinician Administered Dissociative States Scale ( CADSS ) .  Reported here are interrater reliability and internal consistency of the CADSS , validity as assessed by comparisons with other instruments for the assessment of dissociation , and sensitivity of the CADSS to discriminate patients with dissociative disorders from patients with other psychiatric disorders and healthy subjects . Initial analyses indicated good interrater reliability and construct validity for the CADSS . Scores on the  CADSS  discriminated patients with dissociative disorders from the other groups Ketamine produces 
    Output:
    
Ketamine was associated with transient psychotomimetic effects , but no persistent psychosis or affective switches .
CONCLUSION Our meta- analysis suggests that single administrations ketamine are efficacious in the rapid treatment of unipolar and bipolar depression .