***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: CONTEXT Cognitive decline , mood , behavioral and sleep disturbances , and limitations of activities of daily living commonly burden elderly patients with dementia and their caregivers . Circadian rhythm disturbances have been associated with these symptoms . OBJECTIVE To determine whether the progression of cognitive and noncognitive symptoms may be ameliorated by individual or combined long-term application of the 2 major synchronizers of the circadian timing system : bright light and melatonin . DESIGN , SETTING , AND PARTICIPANTS A long-term , double-blind , placebo-controlled , 2 x 2 factorial r and omized trial performed from 1999 to 2004 with 189 residents of 12 group care facilities in the Netherl and s ; mean ( SD ) age , 85.8 ( 5.5 ) years ; 90 % were female and 87 % had dementia . INTERVENTIONS R and om assignment by facility to long-term daily treatment with whole-day bright ( + /- 1000 lux ) or dim ( + /- 300 lux ) light and by participant to evening melatonin ( 2.5 mg ) or placebo for a mean ( SD ) of 15 ( 12 ) months ( maximum period of 3.5 years ) . MAIN OUTCOME MEASURES St and ardized scales for cognitive and noncognitive symptoms , limitations of activities of daily living , and adverse effects assessed every 6 months . RESULTS Light attenuated cognitive deterioration by a mean of 0.9 points ( 95 % confidence interval [ CI ] , 0.04 - 1.71 ) on the Mini-Mental State Examination or a relative 5 % . Light also ameliorated depressive symptoms by 1.5 points ( 95 % CI , 0.24 - 2.70 ) on the Cornell Scale for Depression in Dementia or a relative 19 % , and attenuated the increase in functional limitations over time by 1.8 points per year ( 95 % CI , 0.61 - 2.92 ) on the nurse-informant activities of daily living scale or a relative 53 % difference . Melatonin  shortened sleep onset latency by 8.2 minutes ( 95 % CI , 1.08 - 15.38 ) or 19 % and increased sleep duration by 27 minutes ( 95 % CI , 9 - 46 ) or 6 % . However , melatonin adversely affected scores on the Philadelphia Geriatric Centre Affect Rating Scale , both for positive affect ( -0.5 points ; 95 % CI , -0.10 to -1.00 ) and negative affect ( 0.8 points ; 95 % CI , 0.20 - 1.44 ) . Melatonin also increased withdrawn behavior by 1.02 points ( 95 % CI , 0.18 - 1.86 ) on the Multi Observational Scale for Elderly Subjects scale , although this effect was not seen if given in combination with light . Combined treatment also attenuated aggressive behavior by 3.9 points ( 95 % CI , 0.88 - 6.92 ) on the Cohen-Mansfield Agitation Index or 9 % , increased sleep efficiency by 3.5 % ( 95 % CI , 0.8%-6.1 % ) , and improved nocturnal restlessness by 1.00 minute per hour each year ( 95 % CI , 0.26 - 1.78 ) or 9 % ( treatment x time effect ) . CONCLUSIONS Light has a modest benefit in improving some cognitive and noncognitive symptoms of dementia . To counteract the adverse effect of melatonin on mood , it is recommended only in combination with light . TRIAL REGISTRATION controlled-trials.com/is rct n Identifier : IS RCT N93133646 The effects of immediate-release melatonin on circadian rest-activity profiles , cognition , and mood were investigated in ten elderly individuals with self-reported sleep-wake disturbances .  Melatonin ( 6 mg ) , administered 2 hr before habitual bedtime , enhanced the rest-activity rhythm and improved sleep quality as observed in a reduction in sleep onset latency and in the number of transitions from sleep to wakefulness . However , total sleep time was not significantly increased nor was wake within sleep significantly reduced . The ability to remember previously learned items improved along with a significant reduction in depressed moods . No side effects or contraindications were reported by any of our participants during the 10 day trials . These data suggest that melatonin can safely improve some aspects of sleep , memory , and mood in the elderly in short-term use 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 used in vitro neurogenesis-based human neural stem cell ( hNSCs ) assays and rodent in vivo behavioral assays to identify potential novel antidepressants . A combination of buspirone and melatonin displayed antidepressant activity in these assays whereas neither buspirone nor melatonin alone showed any antidepressant-like profile . After evaluating numerous combination ratios , we determined that low dose buspirone 15 mg combined with melatonin-SR 3 mg yielded optimal antidepressant efficacy in our pre- clinical platform . The low dose of buspirone suggested that antidepressant efficacy might be achieved with only minimal adverse event liability . Based on these data , we conducted an exploratory 6-week , multi-center , double-blind , r and omized , placebo- and comparator-controlled study of the combination of buspirone and melatonin in subjects with acute Major Depressive Disorder ( MDD ) . The combination treatment revealed a significant antidepressant response in subjects with MDD on several measures ( Clinical Global Impression of Severity and Improvement , Inventory of Depressive Symptomatology ) compared to either placebo or buspirone 15 mg monotherapy . These preliminary findings have clinical implication s and suggest that a platform of pre- clinical neurogenesis matched with confirmatory behavioral assays may be useful as a drug discovery strategy Patients with winter depression ( seasonal affective disorder ( SAD ) ) commonly complain of sleepiness . Sleepiness can be objective ly measured by spectral analysis of the waking  electroencephalogram  ( EEG ) in the 1–10 Hz b and . The waking EEG was measured every 3 h in 16 female SAD patients and 13 age-matched control women throughout a  total sleep deprivation of 30 h.  Melatonin ( or placebo ) under double-blind conditions was administered subsequently ( 0.5 mg at 1700 h for 6 days ) , appropriately timed to phase advance circadian rhythms , followed by re assessment in the laboratory for 12 h. The increase in EEG power density in a narrow theta b and ( 5–5.99 Hz , derivation Fz – Cz ) during the 30 h protocol was significantly attenuated in patients compared with controls ( difference between linear trends p=0.037 ) . Sleepiness ( p=0.092 ) and energy ( p=0.045 ) self-ratings followed a similar pattern . Six patients improved after sleep deprivation ( ⩾50 % reduction on SIGH-SAD22 score ) . EEG power density dynamics was correlated with clinical response to sleep deprivation : the steeper the build-up ( as in controls ) , the better the improvement ( p<0.05 ) . There was no differential effect  of melatonin or placebo on any measure ; both treatments stabilized the improvement . Overall , patients with winter depression manifest similar wake EEG characteristics as long sleepers or late chronotype with respect to an insufficient build-up of homeostatic sleep pressure . Sleep deprivation was an effective antidepressant treatment for some patients , but evening melatonin was not more efficacious than placebo in sustaining this antidepressant effect Background In many mammals , the duration of the nocturnal melatonin elevation regulates seasonal changes in reproductive hormones such as luteinizing hormone ( LH ) . Melatonin 's effects on human reproductive endocrinology are uncertain . It is thought that the same hypothalamic pulse generator may both trigger the pulsatile release of GnRH and LH and also cause hot flashes . Thus , if melatonin suppressed this pulse generator in postmenopausal women , it might moderate hot flashes . This clinical trial tested the hypothesis that melatonin could suppress LH and relieve hot flashes . Methods Twenty postmenopausal women troubled by hot flashes underwent one week of baseline observation followed by 4 weeks of a r and omized controlled trial of melatonin or matched placebo . The three r and omized treatments were melatonin 0.5 mg 2.5–3 hours before bedtime , melatonin 0.5 mg upon morning awakening , or placebo capsules .  Twelve of the women were admitted to the GCRC at baseline and at the end of r and omized treatment for 24-hour sampling of blood for LH . Morning urine sample s were collected twice weekly to measure LH excretion . Subjective responses measured throughout baseline and treatment included sleep and hot flash logs , the CESD and QIDS depression self-ratings , and the SAFTEE physical symptom inventory . Results Urinary LH tended to increase from baseline to the end of treatment . Contrasts among the 3 r and omized groups were statistically marginal , but there was relative suppression combining the groups given melatonin as contrasted to the placebo group ( p < 0.01 one-tailed , Mann-Whitney U = 14 . ) Similar but not significant results were seen in blood LH . There were no significant contrasts among groups in hot flashes , sleep , depression , or side-effect measures and no significant adverse effects of any sort . Conclusion The data are consistent with the hypothesis that melatonin suppresses LH in postmenopausal women . An effect related to the duration of nocturnal melatonin elevation is suggested . Effects of melatonin on reproductive endocrinology should be studied further in younger women and in men . Larger studies of melatonin effects on postmenopausal symptoms would be worthwhile Five patients with winter depression received low doses of melatonin in the afternoon , and five patients received placebo capsules . Melatonin treatment significantly decreased depression ratings compared to placebo . If these findings are replicated in a larger sample with documentation of expected phase shifts , the phase shift hypothesis will be substantially supported Objectives : We sought to report the efficacy of oral melatonin as treatment for  chronic tinnitus  and to determine whether particular subsets of tinnitus patients have greater benefit from melatonin therapy than others . Methods : This was a prospect i ve , r and omized , double-blind , crossover clinical trial in an ambulatory tertiary referral otology and neurotology practice . Adults with chronic tinnitus were r and omized to 3 mg melatonin or placebo nightly for 30 days followed by a 1-month washout period . Each group then crossed into the opposite treatment arm for 30 days . The tests audiometric tinnitus matching ( TM ) , Tinnitus Severity Index ( TSI ) , Self Rated Tinnitus ( SRT ) , Pittsburgh Sleep Quality Index ( PSQI ) , and Beck Depression Inventory ( BDI ) were administered at the outset and every 30 days thereafter to assess the effects of each intervention . Results : A total of 61 subjects completed the study . A significantly greater decrease in TM and SRT scores ( p < 0.05 ) from baseline was observed after treatment with melatonin relative to the effect observed with placebo . Male gender , bilateral tinnitus , noise exposure , no prior tinnitus treatment , absence of depression and /or anxiety at baseline , and greater pretreatment TSI scores were associated with a positive response to melatonin .  Absence of depression and /or anxiety at baseline , greater pretreatment TSI scores , and greater pretreatment SRT scores were found to be positively associated with greater likelihood of improvement in both tinnitus and sleep with use of melatonin ( p < 0.05 ) . Conclusions : Melatonin is associated with a statistically significant decrease in tinnitus intensity and improved sleep quality in patients with chronic tinnitus .  Melatonin is most effective in men , those without a history of depression , those who have not undergone prior tinnitus treatments , those with more severe and bilateral tinnitus , and those with a history of noise exposure BACKGROUND Low nighttime levels of melatonin have been demonstrated in patients with insomnia , and melatonin has been shown to have hypnotic properties in some groups of such subjects . Low melatonin levels have also been observed in patients with schizophrenia ; however , there is little literature on the efficacy of exogenous melatonin in treating insomnia associated with schizophrenia . METHOD Stable DSM-IV schizophrenic out patients ( N = 40 ) with initial insomnia of at least 2 weeks ' duration were r and omly assigned to augment their current medications with either flexibly dosed melatonin ( 3 - 12 mg/night ; N = 20 ) or placebo ( N = 20 ) . By use of a question naire , double-blind assessment s of aspects of sleep functioning were obtained daily across the next 15 days . The study was conducted between March and December 2002 . RESULTS The modal stable dose of melatonin was 3 mg . Relative to placebo , melatonin significantly improved the quality and depth of nighttime sleep , reduced the number of nighttime awakenings , and increased the duration of sleep without producing a morning hangover ( p < .05 ) . Subjectively , melatonin also significantly reduced sleep-onset latency , heightened freshness on awakening , improved mood , 
    Output:
    
The two meta-analyses did not show any significant effect of melatonin .
Although some studies were positive , there was no clear evidence of a therapeutic- or prophylactic effect of melatonin against depression or depressive symptoms