Prevention of winter seasonal affective disorder by bright-light treatment. Cognitive-behavioral therapy vs. light therapy for preventing winter depression recurrence: study protocol for a randomized controlled trial Seasonal Affective Disorder and Its Prevention by Anticipatory Treatment with Bupropion XL Agomelatine in the treatment of seasonal affective disorder Hypericum in the treatment of seasonal affective disorders. Effects of rapid tryptophan depletion in patients with seasonal affective disorder in remission after light therapy. An attempt to prevent winter depression by light exposure at the end of September Seasonal depression: the dual vulnerability hypothesis revisited. Treatment of seasonal affective disorder (SAD) with hypericum extract. Follow-up study of seasonal affective disorder in Switzerland. Prevalence of seasonal affective disorder at four latitudes A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder
In patients with winter seasonal affective disorder ( SAD ) the onset of a depressive episode is probably associated with the decreasing amount of light during the autumn . A highly predictable onset of a recurrent depressive episode with seasonal pattern provides a rationale for testing the efficacy of bright-light treatment as a preventive measure . Twelve out- patients with winter SAD were assigned to start bright light treatment either when they were well , or not to start it until the first symptoms of depression had already emerged . The severity of depressive symptoms was prospect ively rated for a parallel r and omized comparison . Bright light given well in advance of the emerging symptoms prevented a depressive episode . Clinical remission was significantly more frequent in the former subgroup of the patients in January and in March . To sum up , bright light can be successfully administered as prophylactic treatment for the prevention of winter SAD Background Seasonal affective disorder ( SAD ) is a subtype of recurrent depression involving major depressive episodes during the fall and /or winter months that remit in the spring . The central public health challenge in the management of SAD is prevention of winter depression recurrence .  Light therapy ( LT ) is the established and best available acute SAD treatment . However , long-term compliance with daily LT from first symptom through spontaneous springtime remission every fall/winter season is poor . Time-limited alternative treatments with effects that endure beyond the cessation of acute treatment are needed to prevent the annual recurrence of SAD . Methods / design This is an NIMH-funded R01-level r and omized clinical trial to test the efficacy of a novel , SAD-tailored cognitive-behavioral group therapy ( CBT ) against LT in a head-to-head comparison on next winter outcomes . This project is design ed to test for a clinical ly meaningful difference between  CBT and LT on depression recurrence in the next winter ( the primary outcome ) . This is a concurrent two-arm study that will r and omize 160 currently symptomatic community adults with major depression , recurrent with seasonal pattern , to CBT or LT .  After 6 weeks of treatment in the initial winter , participants are followed in the subsequent summer , the next winter , and two winters later . Key method ological issues surround timing study procedures for a predictably recurrent and time-limited disorder with a focus on long-term outcomes . Discussion The chosen design answers the primary question of whether prior exposure to CBT is associated with a substantially lower likelihood of depression recurrence the next winter than LT . This design does not test the relative contributions of the cognitive-behavioral treatment components vs. nonspecific factors to CBT ’s outcomes and is not adequately powered to test for differences or equivalence between cells at treatment endpoint . Alternative design s addressing these limitations would have required more patients , increased costs , and reduced power to detect a difference in the primary outcome .Trial registration Clinical trials.gov identifier 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 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 Seasonal affective disorder ( SAD ) represents a subgroup of major depression with a regular occurrence of symptoms in autumn/winter and full remission in spring/summer . Light therapy ( LT ) has become the st and ard treatment of this type of depression . Apart from this , pharmacotherapy with antidepressants also seems to provide an improvement of SAD symptoms . The aim of this controlled , single-blind study was to evaluate if hypericum , a plant extract , could be beneficial in treating SAD patients and whether the combination with LT would be additionally advantageous . Patients who fulfilled DSM-III-R criteria for major depression with seasonal pattern were r and omized in a 4-week treatment study with 900 mg of hypericum per day combined with either bright ( 3000 lux , n = 10 ) or dim ( < 300 lux , n = 10 ) light condition . Light therapy was applied for 2 hours daily . We found a significant ( MANOVA , P < .001 ) reduction of the Hamilton Depression Scale score in both groups but no significant difference between the two groups . Our data suggest that pharmacologic treatment with hypericum may be an efficient therapy in patients with seasonal affective disorder BACKGROUND Previous studies show that rapid tryptophan depletion reverses the effects of therapy with serotonergic , but not noradrenergic , antidepressant drugs in patients with remitted nonseasonal depression . The objective of this study was to investigate the effects of rapid tryptophan depletion in patients with seasonal affective disorder ( SAD ) that was in clinical remission after light therapy .  METHODS Patients who met DSM-III-R criteria for recurrent major depressive episodes , seasonal ( winter ) pattern ( equivalent to SAD ) , were treated with a st and ard course of light therapy .  Ten patients with SAD in clinical remission after light therapy  underwent rapid tryptophan depletion in a placebo-controlled , double-blind crossover study . Behavioral ratings and plasma tryptophan levels were obtained before and after rapid tryptophan depletion . RESULTS Plasma total and free tryptophan levels were significantly reduced to 20 % of normal levels by the rapid tryptophan depletion . The depletion session result ed in significant increases in depression scores compared with the sham control session . Six of 10 patients had a clinical ly significant relapse of their depression following the tryptophan depletion session . CONCLUSIONS Rapid tryptophan depletion appears to reverse the antidepressant effect of bright light therapy in patients with SAD . This suggests that the therapeutic effects of bright light in SAD may involve a serotonergic mechanism Seasonal affective disorder ( SAD ) , winter type , is characterized by the occurrence of depression in autumn/winter , followed by a complete recovery in spring/summer . In SAD patients , some atyp- ical symptoms are highly characteristic , such as hypersomnia , carbohydrate craving , weight gain , fatigue , and loss of social inter- actions ( Rosenthal et ai 1984 ) . The repeated occurrence of symp- toms during successive winters is one of the diagnostic criteria , l ~ lot every SAD patient becomes depressed every year , however . In prospect i ve studies it was found that 70,4 % of the SAD diagnosed subjects who were followed from a symptom-free moment at the end of September , became depressed during the following winter ( Meesters et al 1991 ; 1993a ) , In a previous study it was found that severe winter depression can be prevented by light treatment administered at the first signs of an emerging winter depression , that is , the moment subjects reported complaints of slight depression ( Meesters et al 1991 ; 1993a ) . In the present study , the question was raised whether light exposure given at the beginning of the winter season , when sub- jeers are still free of symptoms , could be successful in preventing the development of a winter depressmn during the rest of the season . Such a ueatment , which might prevent depression alto- gether , would be highly advantageous OBJECTIVE In DSM-IV , winter seasonal affective disorder ( SAD ) is classified as a seasonal pattern of recurrent major depressive episodes in winter with full remission of symptoms in summer . However , other groups with " winter depression " have been identified , including patients with incomplete summer remission ( ISR ) and subsyndromal SAD ( sub-SAD , winter depressive symptoms that do not meet criteria for major depression ) . In this study , we compare the clinical characteristics of these three seasonal groups and their response to light therapy . METHOD 558 patients assessed at a specialized SAD Clinic were diagnosed using DSM-III-R or DSM-IV criteria . Clinical information was recorded using a checklist at index assessment . A subset of patients ( N=192 ) were treated with an open , 2 week trial of light therapy using a 10000 lux fluorescent light box for 30 min per day in the early morning . Patients were assessed before and after treatment with the 29 item modified Hamilton Depression Rating Scale and clinical response was defined as greater than 50 % improvement in scores . RESULTS The rates of some melancholic symptoms , anxiety , panic , suicidal ideation , and family history of mood disorder were lowest in the sub-SAD group . The clinical response rates to light therapy  were highest in the sub-SAD group ( N=32 , 78 % ) , intermediate in the SAD group ( N=113 , 66 % ) , and lowest in the ISR group ( N=47 , 51 % ) . LIMITATIONS This was a retrospective study of patients seen in a specialty clinic , although information was obtained in a st and ardized format . The light therapy trial had an open design so that placebo response could not be determined . CONCLUSIONS There are differences in both the patterns of clinical symptoms and the response to light therapy  in these three groups with winter depression . These results are consistent with a dual vulnerability hypothesis that considers these groups to result from interaction of separate factors for seasonality and depression Seasonal affective disorder ( SAD ) is a subgroup of major depression and characterized by a regular occurrence of symptoms in autumn/winter and full remission or hypomania in spring/summer . Light therapy ( LT ) and recently pharmacotherapy with specific antidepressants have been shown to be beneficial . Within the array of pharmacotherapy hypericum extract has also been found to be effective in a single-blind study ( Martinez et al. , 1994 ) . In this 4 weeks treatment study 900 mg of hypericum was associated with a significant reduction in the total score of the Hamilton Depression Rating Scale . There was no significant difference when bright light therapy was combined with hypericum , compared to the situation without bright light therapy . Overall , hypericum was well tolerated and therefore the data suggest that pharmacological treatment with hypericum may be an efficient therapy in patients with SAD , which needs to be substantiated in further controlled studies Of 39 diagnosed Seasonal Affective Disorder ( SAD ) patients who were interviewed 2 - 5 years after participation in a light therapy trial , 10 continued to have recurrent  major depressive episodes  in winter , and 17 manifested sub-syndromal SAD ( 2 patients also had recurrent brief depression , seasonal type ) . 8 patients had recovered , and 4 had shifted in symptomatology . Thus , over a number of years , the clinical diagnosis changed for the better in 64 % of the patients , suggesting that SAD is not a prodromal form of a more chronic major affective disorder , and that light therapy ( and perhaps also light-oriented behaviour ) reduced the incidence and depth of subsequent depressive episodes . Further evidence for this was the large reduction in use of conventional antidepressant drugs ( from 17 to 1 ) during the follow-up period . Diagnosis of SAD was stable and reliable 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 Rationale Seasonal affective disorder ( SAD ) is a relatively common cyclical depressive illness characterized by seasonal depressions during winter . The disorder is commonly responsive to light therapy , but antidepressant drug efficacy has not been definitely established . Serotonin selective re-uptake inhibitors are potentially efficacious treatments for SAD . Objectives The objective of this study was to evaluate the efficacy , tolerability and safety of sertraline treatment for SAD . Methods One hundred and eighty seven out patients with seasonal pattern recurrent winter depression ( DSM-III-R defined ) and a minimum 29-item Hamilton depression scale ( SIGH-SAD version ) score of 22 were r and omized to 8 weeks treatment with either sertraline or placebo in a double-blind , multi-country , multi-center , parallel-group , flexible dose ( 50–200 mg once daily ) study . Efficacy was investigated using physician and patient-rated scales measuring depression , anxiety and symptoms characteristic of seasonal affective disorder . Results Sertraline produced a significantly greater response than placebo at endpoint as measured by changes in the 29-item and 21-item Hamilton depression scales , the clinical global impression ( CGI ) severity scale , the Hamilton anxiety scale , and the hospital anxiety and depression scale . The proportion of sertraline-treated subjects achieving a response on the CGI improvement rating ( ratings of 1 or 2 ) at endpoint ( last observation carried forward ) was significantly greater than that of the placebo group . Overall sertraline was well tolerated with the most frequent placebo adjusted adverse events , being nausea , diarrhea , insomnia and dry mouth . Adverse events were mostly mild to moderate and transient . Conclusions Sertraline pharmacotherapy has been demonstrated to be an effective and well-tolerated therapy for out patients with SAD . As such , sertraline offers an important pharmacological option in the clinical management of this condition
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 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 .