title: Agomelatine prevents relapse in patients with major depressive disorder without evidence of a discontinuation syndrome: a 24-week randomized, double-blind, placebo-controlled trial. Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Agomelatine in the treatment of seasonal affective disorder Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder: a randomized, double-blind comparison with sertraline. Effects of morning phototherapy on circadian markers in seasonal affective disorder. The Can-SAD study: a randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder. Morning or night-time melatonin is ineffective in seasonal affective disorder. Seasonal Affective Disorder and Its Prevention by Anticipatory Treatment with Bupropion XL Prophylactic treatment of seasonal affective disorder (SAD) by using light visors: bright white or infrared light? Prevalence of seasonal affective disorder at four latitudes Mindfulness-based cognitive therapy for seasonal affective disorder: a pilot study. Effect of controlled-release melatonin on sleep quality, mood, and quality of life in subjects with seasonal or weather-associated changes in mood and behaviour
abstract: OBJECTIVE This study evaluates the efficacy of agomelatine , the first antidepressant that is an agonist at MT(1)/MT(2 ) receptors and an antagonist at 5-HT(2C ) receptor , in the prevention of relapse of depression following successful response . METHOD Patients with DSM-IV-TR major depressive disorder who responded to an 8- or 10-week course of agomelatine 25- or 50-mg daily treatment were r and omly assigned to receive continuation treatment with agomelatine ( n=165 ) or placebo ( n=174 ) during a 24-week , r and omized , double-blind treatment period . The main outcome measure was time to relapse during the double-blind treatment period . The cumulative probability of relapse was calculated using the Kaplan-Meier method of survival analysis . The study was conducted from February 2005 to February 2007 . RESULTS During the 6-month evaluation period , the incidence of relapse was significantly lower in patients who continued treatment than in those switched to placebo  ( P=.0001 ) . The cumulative relapse rate at 6 months for agomelatine-treated patients was 21.7 % ; that for placebo-treated patients was 46.6 % . Agomelatine was also superior to placebo in preventing relapse in the subset of patients with baseline 17-item Hamilton Depression Rating Scale total score > or = 25 . Measures of tolerability and safety of both doses of agomelatine were similar to placebo . No pattern of early relapse or adverse events suggestive of withdrawal symptoms was obtained after abrupt cessation of agomelatine . CONCLUSIONS The findings are important in 2 respects . First , agomelatine is an effective and safe antidepressant continuation therapy , which confirms efficacy seen in short-term studies . Second , few early relapses were observed in the patient group switched to placebo : the survival curve for placebo separated gradually from that of patients taking agomelatine . We suggest this reflects solely the underlying properties of the illness , which is only possible due to the lack of discontinuation syndrome after agomelatine withdrawal . It underlines the novel clinical profile of agomelatine , which quite likely reflects its innovative pharmacology . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N53193024 Seasonal affective disorder ( SAD ) is a syndrome characterized by recurrent depressions that occur annually at the same time each year . We describe 29 patients with SAD ; most of them had a bipolar affective disorder , especially bipolar II , and their depressions were generally characterized by hypersomnia , overeating , and carbohydrate craving and seemed to respond to changes in climate and latitude . Sleep recordings in nine depressed patients confirmed the presence of hypersomnia and showed increased sleep latency and reduced slow-wave ( delta ) sleep . Preliminary studies in 11 patients suggest that extending the photoperiod with bright artificial light has an antidepressant effect Rationale The novel antidepressant agomelatine acts as a melatonergic ( MT1 and MT2 ) receptor agonist and as a serotonin-2C receptor antagonist . Previous studies showed that agomelatine is able to restore disrupted circadian rhythms , which were implicated in the pathophysiology of seasonal affective disorder ( SAD ) . Objectives The aim of this study was to investigate the efficacy and tolerability of agomelatine in the treatment of SAD . Material s and methods Thirty-seven acutely depressed SAD patients were included in an open study with agomelatine ( 25 mg/day in the evening ) over 14 weeks . Efficacy assessment s included the Structured Interview Guide for the Hamilton Depression Rating Scale ( SAD version ; SIGH-SAD ) , the Clinical Global Impression of Severity ( CGI-S ) and Improvement ( CGI-I ) , the Circscreen , a self-rating scale for the assessment of sleep and circadian rhythm disorders , and the Hypomania Scale . Results Agomelatine led to a progressive and statistically significant decrease of SIGH-SAD , CGI-S , and CGI-I scores from week 2 onward ( p < 0.001 ) . Furthermore , scores on the Circscreen improved significantly during the study ( p < 0.001 ) . Treatment with agomelatine over 14 weeks yielded a response rate of 75.7 % ( SIGH-SAD < 50 % of baseline value ) and a remission rate ( SIGH-SAD < 8) of 70.3 % in the intention to treat sample . Scores on the Hypomania Scale were consistently low during the study . Agomelatine showed good overall tolerability : throughout the study only one adverse event ( mild fatigue ) was related to the study drug . Conclusions The results of this study suggest that seasonal depression may be effectively and safely treated with agomelatine OBJECTIVE This study evaluates the efficacy of agomelatine , the first antidepressant to be an agonist at MT(1)/MT(2 ) receptors and an antagonist at 5-HT(2C ) receptors , versus sertraline with regard to the amplitude of the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder ( MDD ) . METHOD Out patients with DSM-IV-TR-defined MDD received either agomelatine 25 to 50 mg ( n = 154 ) or sertraline 50 to 100 mg ( n = 159 ) during a 6-week , r and omized , double-blind treatment period . The study was conducted from 2005 to 2006 . The main outcome measure was the relative amplitude of the individual rest-activity cycles , expressed as change from baseline to week 6 and collected from continuous records using wrist actigraphy and sleep logs . Secondary outcome measures were sleep efficiency and sleep latency , both derived from actigraphy , and efficacy on depression symptoms ( 17-Item Hamilton Depression Rating Scale total score and Clinical Global Impressions scale scores ) and anxiety symptoms ( Hamilton Anxiety Rating Scale total score and subscores ) . RESULTS A significant difference in favor of agomelatine compared to sertraline on the relative amplitude of the circadian rest-activity cycle was observed at the end of the first week ( P = .01 ) . In parallel , a significant improvement of sleep latency ( P < .001 ) and sleep efficiency ( P < .001 ) from week 1 to week 6 was observed with agomelatine as compared to sertraline . Over the 6-week treatment period , depressive symptoms improved significantly more with agomelatine than with sertraline ( P < .05 ) , as did anxiety symptoms ( P < .05 ) . CONCLUSIONS The favorable effect of agomelatine on the relative amplitude of the circadian rest-activity/sleep-wake cycle in depressed patients at week 1 reflects early improvement in sleep and daytime functioning . Higher efficacy results were observed with agomelatine as compared to sertraline on both depressive and anxiety symptoms over the 6-week treatment period , together with a good tolerability profile . These findings indicate that agomelatine offers promising benefits for MDD patients . TRIAL REGISTRATION www.is rct n.org : IS RCT N49376288 BACKGROUND The suppression of melatonin by light at 00.30 hours has been shown to be greater in winter than in summer on patients with seasonal affective disorder ( SAD ) but not in matched normal controls . METHOD In this study 12 patients with SAD and 12 matched normal controls were exposed to morning light therapy in the winter .  Melatonin profiles and sensitivity to light were measured before and after treatment . RESULTS The SAD but not the normal group showed a phase advance of melatonin rhythms in response to phototherapy . There was an association between phase position and phase shift in the SAD but not in the normal group . CONCLUSIONS There may be instability of circadian rhythms in SAD mediated by a high-amplitude phase response curve , rather than a fixed phase abnormality as had been previously suggested . This instability may be secondary to impaired serotoninergic function in the afferent pathways to the suprachiasmatic nuclei OBJECTIVE Light therapy and antidepressants have shown comparable efficacy in separate studies of seasonal affective disorder treatment , but few studies have directly compared the two treatments . This study compared the effectiveness of light therapy and an antidepressant within a single trial . METHOD This double-blind , r and omized , controlled trial was conducted in four Canadian centers over three winter seasons . Patients met DSM-IV criteria for major depressive disorder with a seasonal ( winter ) pattern and had scores > or = 23 on the 24-item Hamilton Depression Rating Scale . After a baseline observation week , eligible patients were r and omly assigned to 8 weeks of double-blind treatment with either 1 ) 10,000-lux light treatment and a placebo capsule , or 2 ) 100-lux light treatment ( placebo light ) and fluoxetine , 20 mg/day . Light treatment was applied for 30 minutes/day in the morning with a fluorescent white-light box ; placebo light boxes used neutral density filters . RESULTS A total of 96 patients were r and omly assigned to a treatment condition . Intent-to-treat analysis showed overall improvement with time , with no differences between treatments . There were also no differences between the light and fluoxetine treatment groups in clinical response rates ( 67 % for each group ) or remission rates ( 50 % and 54 % , respectively ) . Post hoc testing found that light-treated patients had greater improvement at 1 week but not at other time points . Fluoxetine was associated with greater treatment-emergent adverse events ( agitation , sleep disturbance , palpitations ) , but both treatments were generally well-tolerated with no differences in overall number of adverse effects . CONCLUSIONS Light treatment showed earlier response onset and lower rate of some adverse events relative to fluoxetine , but there were no other significant differences in outcome between light therapy and antidepressant medication . Although limited by lack of a double-placebo condition , this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and suggests that other clinical factors , including patient preference , should guide selection of first-line treatment Melatonin , at the same doses used to treat circadian-rhythm related sleep disturbances , had no effect on the depressive symptoms in seasonal affective disorder ( SAD ) patients , whether given early ( 7 a.m. ) or late ( 11 p.m. ) for a week . Slight improvements in sleep were seen with nighttime administration . The circadian rhythmicity of urinary 6-sulphatoxymelatonin was not modified in any way . Melatonin at this dosage ( 5 mg/day ) or at these two times is therefore not a potential alternative treatment for SAD ; light remains the therapy of choice BACKGROUND Seasonal affective disorder ( SAD ) can cause significant distress and impairment . No antidepressant studies have previously attempted to prevent the onset of autumn-winter depression . METHODS Three prospect i ve , r and omized , placebo-controlled prevention trials were conducted on 1042 SAD patients , enrolled in autumn and treated while still well , across the northern US and Canada . Patients received either bupropion XL 150 - 300 mg or placebo daily by mouth from enrollment until spring and were then followed off medications for 8 additional weeks . Primary efficacy variables were end-of-treatment depression-free rates and survival distributions of depressive recurrence . RESULTS Despite a reported average of 13 previous seasonal depressive episodes , almost 60 % of patients had never previously been treated for depression . Major depression recurrence rates during the three studies for bupropion XL and placebo groups were 19 % versus 30 % ( p = 0.026 ) , 13 % versus 21 % ( p = 0.049 ) , and 16 % versus 31 % ; yielding a relative risk reduction across the three studies of 44 % for patients taking bupropion XL .  Survival analyses for depression onset also favored bupropion XL over placebo ( p = .081 , .057 , and < .001 ) . CONCLUSIONS It is possible to prevent recurrence of seasonal major depressive episodes by beginning bupropion treatment early in the season while patients are still well BACKGROUND Thirty-eight patients with SAD participated in a light visor study addressing two questions . 1 . Can the development of a depressive episode be prevented by daily exposure to bright light started before symptom onset in early fall and continued throughout the winter ? 2 . Does the light have to be visible in order to have beneficial effects ? METHODS Three groups participated in the study : I ( n = 14 ) received bright white light ( 2500 lux ) ; II , ( n = 15 )  received infrared light ( 0.18 lux ) ; III ( n = 9 ,  control group ) did not receive any light treatment at all . RESULTS Infrared light is just as effective as bright white light . Both are more effective than the control condition . CONCLUSIONS Light visors can be effectively used to prevent the development of SAD . The fact that exposure to infrared light was as effective as exposure to bright white light questions the specific role of visible light in the treatment of SAD The Seasonal Pattern Assessment Question naire ( SPAQ ) was mailed to a sample population balanced for sex and r and omly selected from local telephone directories in four areas : Nashua , NH , New York , NY , Montgomery County , MD , and Sarasota , FL . On the basis of responses to this question naire , prevalence rates of winter seasonal affective disorder ( winter SAD ) , summer seasonal affective disorder ( summer SAD ) , and subsyndromal winter SAD were estimated for the four areas . Rates of winter SAD and subsyndromal SAD were found to be significantly higher at the more northern latitudes , while no correlation was found between latitude and summer SAD . The positive correlation between latitude and prevalence of winter SAD applied predominantly to the age groups over 35 BACKGROUND The best available treatment for seasonal affective disorder ( SAD ) is light therapy . Yet , this treatment does not prevent recurrence of depression in subsequent seasons . The aim of the study is to gain preliminary insight in the efficacy of Mindfulness Based Cognitive Therapy ( MBCT ) in the prevention of SAD recurrence . METHODS This is a r and omized controlled pilot study , in which SAD patients in remission were r and omly allocated to an individual format of MBCT or a control condition ( i.e. treatment as usual ) . MBCT was given between May and June 2011 , when there was no presence of depressive symptoms . The Inventory for Depressive Symptomatology Self-Report ( IDS-SR ) , which patients received on a weekly basis from September 2011 to April 2012 , was used to assess moment of recurrence ( ≥20 ) and severity at moment of recurrence . RESULTS 23 SAD patients were r and omized to MBCT and 23 to the control condition . Kaplan-Meier survival curve showed that the groups did not differ in moment of recurrence ( χ²(1).41 , p=.52 ) . T-tests showed no group difference in mean IDS-SR scores at moment of recurrence ( t(31)=-.52 , p=.61 ) . LIMITATIONS The results are limited by small sample size ( n=46 ) and missing data of weekly IDS-SR assessment s. CONCLUSION The findings of this pilot RCT suggest that individual MBCT is not effective in preventing a SAD recurrence when offered in a symptom free period ( i.e. spring ) This study aim ed to explore the effects of melatonin on sleep , waking up and well being in subjects with varying degrees of seasonal or weather-associated changes in mood and behaviour . Fifty-eight healthy adults exhibiting subsyndromal seasonal affective disorder ( s-SAD ) and /or the negative or positive type of weather-associated syndrome ( WAS ) were r and omised to either 2 mg of sustained-release melatonin or placebo tablets 1 - 2 h before a desired bedtime for 3 weeks . Outcome measures were changes from baseline in sleep quality , sleepiness after waking , atypical depressive symptoms and health-related quality of life by week three . Early morning salivary melatonin concentrations were measured at baseline and treatment cessation in all subjects . Melatonin administration significantly improved the quality of sleep ( P=0.03 ) and vitality ( P=0.02 ) in the subjects with s-SAD , but attenuated the improvement of atypical symptoms and physical parameters of quality of life compared to placebo in the subjects with WAS , positive type
target: AUTHORS ' CONCLUSIONS No available method ologically sound evidence indicates that melatonin or agomelatine is or is not an effective intervention for prevention of SAD and improvement of patient-centred outcomes among adults with a history of SAD .
  A well-conducted RCT of melatonin or agomelatine for prevention of SAD would assess the comparative benefits and risks of these interventions against others currently used to treat the disorder
background: BACKGROUND Seasonal affective disorder ( SAD ) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring .
  The prevalence of SAD in the United States ranges from 1.5 % to 9 % , depending on latitude .
  The predictable seasonal aspect of SAD provides a promising opportunity for prevention .
  This is one of four review s on the efficacy and safety of interventions to prevent SAD ; we focus on agomelatine and melatonin as preventive interventions .
  OBJECTIVES To assess the efficacy and safety of agomelatine and melatonin ( in comparison with each other , placebo , second-generation antidepressants , light therapy , psychological therapy or lifestyle interventions ) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD .