title: A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder Seasonal depression: the dual vulnerability hypothesis revisited. Prevention of winter seasonal affective disorder by bright-light treatment. Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Moclobemide and fluoxetine in treatment of seasonal affective disorder. The Impact of Latitude on the Prevalence of Seasonal Depression Side effects of short-term 10,000-lux light therapy. Mood and energy regulation in seasonal and non-seasonal depression before and after midday treatment with physical exercise or bright light The Can-SAD study: a randomized controlled trial of the effectiveness of light therapy and fluoxetine in patients with winter seasonal affective disorder. Ophthalmologic examination of patients with seasonal affective disorder, before and after bright light therapy. Cognitive-behavioral therapy, light therapy, and their combination in treating seasonal affective disorder. A controlled trial of timed bright light and negative air ionization for treatment of winter depression. Controlled trial of bright light and negative air ions for chronic depression. Epidemiological findings of seasonal changes in mood and behavior. A telephone survey of Montgomery County, Maryland. Effects of fluoxetine versus bright light in the treatment of seasonal affective disorder. Bright light therapy: side effects and benefits across the symptom spectrum. Modafinil treatment in patients with seasonal affective disorder/winter depression: an open-label pilot study. Hypericum in the treatment of seasonal affective disorders. Seasonal Affective Disorder and Its Prevention by Anticipatory Treatment with Bupropion XL Effects of Alpha-Methyl-Para-Tyrosine-Induced Catecholamine Depletion in Patients with Seasonal Affective Disorder in Summer Remission Multicenter, placebo-controlled study of fluoxetine in seasonal affective disorder. Estimated Prevalence of the Seasonal Subtype of Major Depression in a Canadian Community Sample Effects of tryptophan depletion on drug-free patients with seasonal affective disorder during a stable response to bright light therapy. Relapse prevention by citalopram in SAD patients responding to 1 week of light therapy. A placebo‐controlled study Effects of rapid tryptophan depletion in patients with seasonal affective disorder in remission after light therapy. Is winter depression a bipolar disorder? Reboxetine in seasonal affective disorder: an open trial Treatment of winter depression in Norway The circadian basis of winter depression.
abstract: 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 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 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 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 Of a total of 581 consecutive depressed subjects attending psychiatric services of 6 centres in Finl and , 183 patients were eligible and completed a 6-week r and omised double-blind trial with either moclobemide or fluoxetine . Of these , 32 ( 17.5 % ) patients met the DSM-III-R criteria for mood disorder with a seasonal ( winter ) pattern and 19 patients ( 10.5 % ) met the original criteria for seasonal affective disorder ( SAD ) . There were no significant difference in the antidepressive response to the treatment between the patients with SAD and other depressive disorder . The treatment of 6 weeks with either moclobemide ( 300 - 450 mg daily ) or fluoxetine ( 20 - 40 mg daily ) result ed in a full remission in 15 ( 52 % ) patients with SAD and in 44 ( 37 % ) patients with other depressive disorder . Altogether , 23 ( 79 % ) and 83 ( 70 % ) patients , respectively , got significant benefit from the treatment . The improvement in the health-related quality of life in terms of ability to work was significantly more extensive in the patients with SAD assigned to receive moclobemide compared with the other depressive patients allocated to the same medication . Subjects who in addition met the operational criteria for atypical depression were equally distributed into the SAD and other depressive patient groups Background : This study sought to determine whether the prevalence of the seasonal subtype of major depression ( SAD ) in the community varied as a function of latitude . Methods : R and om telephone numbers were generated across 8 degrees of latitude ( 41.5 ° N to 49.5 ° N ) for the province of Ontario . Eight strata of 1 degree each were sample d equally throughout a 12-month period . Using a vali date d and structured diagnostic interview , we interviewed by telephone  respondents over 20 years of age who had lived in the region for 3 years or more . We evaluated patterns of symptom change across seasons to establish a diagnosis of SAD according to DSM-IV criteria . Results : Of the 2078 households that were assessed for eligibility , 1605 ( 77 % ) completed the interview . The crude prevalence of lifetime SAD was 2.6 % ( 95 % CI , 1.9 to 3.5 ) . There was no impact of latitude on prevalence of either major depression or the seasonal subtype across the 8 strata , although the global measure of the severity of seasonal change in mood was significantly negatively correlated with latitude . Conclusions : SAD is a common subtype of major depression in Ontario , but there is no evidence to support an increase in prevalence with increasing latitude . Context e : Cette étude visait à déterminer si la prévalence du caractère saisonnier de la dépression majeure ( DMS ) dans la communauté variait selon la latitude . Méthodes : Des numéros de téléphone aléatoires ont été fournis sur 8 degrés de latitude ( de 41,5 ° N. à 49,5 ° N. ) dans la province de l'Ontario . Huit b and es de 1 degré chacune ont été échantillonnées également sur une période de 12 mois . À l'aide d'une entrevue diagnostique validée et structurée , nous avons interviewé par téléphone des répondants âgés de plus de 20 ans qui habitaient la région depuis 3 ans ou plus . Nous avons évalué les changements des modèles de symptômes selon les saisons pour établir un diagnostic de DMS selon les critères du DSM-IV . Résultats : Sur les 2 078 ménages admissibles , 1 605 ( 77 % ) ont terminé l'entrevue . La prévalence brute de la DMS à vie était de 2,6 % ( 95 % IC , 1,9 à 3,5 ) . La latitude n'influait pas sur la prévalence de la dépression majeure ou du caractère saisonnier dans les 8 b and es , bien que la mesure globale de la sévérité du changement saisonnier de l'humeur ait indiqué une corrélation négative significative à la latitude . Conclusions : La dépression majeure saisonnière est un sous-type rép and u de la dépression majeure en Ontario , mais aucune preuve ne soutient une augmentation de la prévalence parallèle à l'accroissement de la latitude OBJECTIVE Previous reports of side effects from light therapy were mostly based on administration of 2,500-lux treatments . It has become common practice to use brighter , 10,000-lux exposure when treating seasonal affective disorder . The authors studied side effects produced by short-term 10,000-lux light therapy . METHOD Seventy subjects with seasonal affective disorder who underwent brief 10,000-lux light therapy  were asked to report side effects . RESULTS Of the 70 subjects , 32 ( 45.7 % ) experienced side effects , and nine ( 12.9 % ) reported two or more apiece . Headaches and eye or vision problems were the most common . Almost all were mild , were transient , and did not interfere with treatment . CONCLUSIONS Short-term 10,000-lux light therapy often produces side effects early in treatment . These are not serious or prolonged , however , confirming findings from earlier studies that used dimmer light The effects of two non-drug treatments ( physical exercise and bright light ) on mood , body weight and oxygen consumption were compared in age-matched groups of female subjects with winter depression , non-seasonal depression or without depression . It was found that oxygen consumption in the pre-treatment condition was similar in non-depressed subjects ( n=18 ) and depressed non-seasonals ( n=18 ) , while comparatively lower values were obtained in winter depression ( n=27 ) . Neither mood nor metabolic parameters changed significantly in the group of nine untreated winter depressives . One week of physical exercise ( 1-h pedaling on a bicycle ergometer between 13.00 and 14.00 h ) increased oxygen consumption in the group of nine winter depressives and lowered oxygen consumption in nine-subject groups of depressed and non-depressed non-seasonals . One week of bright light treatment ( 2-h exposure to 2500 lux between 14.00 and 16.00 h ) increased oxygen consumption in nine winter depressives and nine non-depressed subjects , while no significant change in oxygen consumption was found in nine subjects with non-seasonal depression . Weight loss was observed in the groups treated with physical exercise and in the group of light-treated winter depressives . Winter depression responded equally well to exercising and light , while a significant therapeutic difference in favor of exercising was found in non-seasonal depression . Overall , the results of the study suggest that energy-regulating systems are implicated in the antidepressant action of the non-drug treatments 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 PURPOSE We assessed the potential ocular hazards of bright light therapy for patients with seasonal affective disorder , after both short- and long-term treatment , and identified prospect i ve patients with pre-existing ocular abnormalities .  METHODS Fifty patients with seasonal affective disorder received daily exposure to artificial light in the morning or evening for 30 minutes at an illuminance level of 10,000 lux ( irradiant dose , 0.016 J/cm2 ) . Ophthalmologic examinations  were performed before and after short-term treatment ( two to eight weeks ) and after three to six years of use during the fall and winter months . Over the four years of patient intake , the eye examination included subsets of the following tests : visual acuity , intraocular pressure , slit-lamp biomicroscopy , direct and indirect ophthalmoscopy , color vision , visual field , fundus photography , Amsler grid , ocular motility , pupillary reactions , contrast sensitivity , stereopsis , and the macular stress test . RESULTS No ocular changes were detected after short-term treatment . Long-term treatment ( three to six years ) of 17 patients , with cumulative exposure duration s of 60 to 1,250 hours , also result ed in no ocular abnormalities . CONCLUSIONS Light therapy yields about 75 % clinical remissions . It is effective as an antidepressant and appears safe for the eyes . Current knowledge is insufficient to specify any definite ocular contraindications for bright light therapy , although we recommend that patients with preexisting ocular abnormalities and those using photosensitizing drugs undergo treatment only with periodic ophthalmologic examination BACKGROUND The need to develop supplementary or alternative treatments for seasonal affective disorder ( SAD ) is underscored by the significant minority ( 47 % ) of SAD patients that is refractory to light therapy , the persistence of residual symptoms despite light treatment , and poor long-term compliance with light use . Because preliminary studies suggest that cognitive and behavioral factors are involved in SAD , cognitive-behavioral therapy ( CBT ) warrants investigation as a possible treatment option . METHODS We piloted a 6-week r and omized clinical trial to compare a st and ard light therapy protocol ; a novel , SAD-tailored , group CBT intervention ; and their combination in ameliorating and remitting a current SAD episode and as prophylaxis against episode recurrence . Depressive symptom severity and remission rates were assessed at post-treatment and at a 1-year follow-up visit to examine long-term treatment durability . RESULTS CBT , light therapy , and their combination all demonstrated significant reductions in depressive symptoms on two different outcome measures . Remission rates varied by measure , but did not reach statistical significance . During the subsequent winter , CBT , particularly in combination with light therapy , appeared to improve long-term outcome regarding symptom severity , remission rates , and relapse rates . No CBT-treated participant , with or without light , experienced a full SAD relapse compared to over 60 % of those treated with light alone . LIMITATIONS These results should be viewed as preliminary and are limited by the small sample size ( n=23 ) and lack of a control group . CONCLUSIONS The nearly half of SAD patients who do not remit with light alone may benefit from CBT as an adjunct or alternative treatment , especially as a prophylaxis against episode recurrence BACKGROUND Artificial bright light presents a promising nonpharmacological treatment for seasonal affective disorder . Past studies , however , have lacked adequate placebo controls or sufficient power to detect group differences . The importance of time of day of treatment -- specifically , morning light superiority -- has remained controversial . METHODS This study used a morning x evening light crossover design balanced by parallel-group controls , in addition to a nonphotic control , negative air ionization .  Subjects with seasonal affective disorder ( N = 158 ) were r and omly assigned to 6 groups for 2 consecutive treatment periods , each 10 to 14 days . Light treatment sequences were morning-evening , evening-morning , morning-morning , and evening-evening ( 10,000 lux , 30 min/d ) . Ion density was 2.7 x 10(6 ) ( high ) or 1.0 x 10(4 ) ( low ) ions per cubic centimeter ( high-high and low-low sequences , 30 min/d in the morning ) . RESULTS Analysis of depression scale percentage change scores showed low-density ion response to be inferior to all other groups , with no other group differences . Response to evening light  was reduced when preceded by treatment with morning light , the sole sequence effect . Stringent remission criteria , however , showed significantly higher response to morning than evening light , regardless of treatment sequence . CONCLUSIONS Bright light and high-density negative air ionization both appear to act as specific antidepressants in patients with seasonal affective disorder . Whether clinical improvement would be further enhanced by their use in combination , or as adjuvants to medication , awaits investigation BACKGROUND This r and omized controlled trial investigates the efficacy of two non-pharmacologic treatments , bright light and high-density negative air ions for non-seasonal chronic depression .  Both methods have shown clinical success for seasonal affective disorder ( SAD ) . METHOD Patients were 24 ( 75 % ) women and 8 ( 25 % ) men , ages 22 - 65 years ( mean age + /- S.D. , 43.7 + /- 12.4 years ) , with Major Depressive Disorder , Single Episode ( DSM-IV code , 296.2 ) , Chronic ( episode duration > or = 2 years ) . Patients were entered throughout the year and r and omly assigned to exposure to bright light ( 10 000 lux , n = 10 ) , or high-density ( 4.5 x 10(14 ) ions/s flow rate , n = 12 ) or low-density ( 1.7 x 10(11 ) ions/s , n = 10 , placebo control ) negative air ions . Home treatment sessions occurred for 1 h upon awakening for 5 weeks . Blinded raters assessed symptom severity weekly with the Structured Interview Guide for the Hamilton Depression Rating Scale -- Seasonal Affective Disorder ( SIGH-SAD ) version . Evening saliva sample s were obtained before and after treatment for ascertainment of circadian melatonin rhythm phase . RESULTS SIGH-SAD score improvement was 53.7 % for bright light and 51.1 % for high-density ions v. 17.0 % for low-density ions . Remission rates were 50 % , 50 % and 0 % respectively . The presence or severity of atypical symptoms did not predict response to either treatment modality , nor were phase advances to light associated with positive response . CONCLUSIONS Both bright light and negative air ions are effective for treatment of chronic depression . Remission rates are similar to those for SAD , but without a seasonal dependency or apparent mediation by circadian rhythm phase shifts . Combination treatment with antidepressant drugs may further enhance clinical response Patterns of seasonal changes in  mood and behavior in Montgomery County , Maryl and , were evaluated in r and omly selected household sample s by lay interviewers using a telephone version of the Seasonal Pattern Assessment Question naire . The method for selecting the sample unit was r and om-digit dialing . We found that 92 % of the survey subjects noticed seasonal changes of mood and behavior to varying degrees . For 27 % of the sample seasonal changes were a problem and 4.3 % to 10 % of subjects , depending on the case-finding definition , rated a degree of seasonal impairment equivalent to that of patients with seasonal affective disorder . The seasonal pattern of " feeling worst " exhibited a bimodal distribution with a greater winter and a substantially lower summer peak ( ratio , 4.5:1 ) . Younger women who have a problem with seasonal changes and who feel worse on short days tended to exhibit the highest seasonality scores . It is apparent from our study that seasonal affective disorder represents the extreme end of the spectrum of seasonality that affects a large percentage of the general population . The influence of environmental factors on mood disorders and mood changes in the general population might provide valuable insight into pathogenesis , treatment , and prevention of affective illness BACKGROUND Disturbances of serotonergic neurotransmission appear to be particularly important for the pathophysiology of winter depression . This study investigated whether fluoxetine has antidepressant effects comparable to bright light in the treatment of seasonal affective disorder ( winter type ) . METHOD A r and omized , parallel design was used with rater and patients blind to treatment conditions . One week of placebo ( phase I ) was followed by 5 weeks of treatment ( phase II ) with fluoxetine ( 20 mg per day ) and a placebo light condition versus bright light ( 3000 lux , 2 h per day ) and a placebo drug . There were 40 patients ( 20 in each treatment condition ) suffering from seasonal affective disorder ( SAD ) according to DSM-III-R who had a total score on the Hamilton Depression Scale of at least 16 . RESULTS Forty patients entered phase II and 35 completed it ( one drop-out in the fluoxetine group and four in the bright light group ) . Fourteen ( 70 % ) of the patients treated with bright light and 13 ( 65 % ) of those treated with fluoxetine were responders ( NS ) . The remission rate in the bright light group tended to be superior ( bright light 50 % , fluoxetine 25 % ; P = 0.10 ) . Light therapy  improved HDRS scores significantly faster , while fluoxetine had a faster effect on atypical symptoms . Light treatment in the morning produced a significantly faster onset of improvement , but at the end of treatment the time of light application seemed not to be crucial . CONCLUSION Both treatments produced a good antidepressant effect and were well tolerated . An apparently better response to bright light requires confirmation in a larger sample BACKGROUND Bright light therapy has been established for treatment of winter depression , or seasonal affective disorder ( SAD ) . Analysis of side effects most often have focused on a narrow set of suspected symptoms , based on clinical observation ( e.g. , headache , eyestrain , nausea , insomnia , and hyperactivity ) . This study broadens the purview to a set of 88 physical and subjective symptoms that might emerge , remit , or remain unchanged relative to baseline , thus reducing bias toward assessment of presumed side effects . METHOD Eighty-three patients with SAD ( DSM-III-R criteria for mood disorders with seasonal pattern [ winter type ] and National Institute of Mental Health criteria for SAD ) received bright light therapy at 10,000 lux for 30 minutes daily in the morning or evening for 10 to 14 days . They completed a question naire ( Systematic Assessment for Treatment Emergent Effects ) , rating symptom severity before and after treatment . Results were compared for morning or evening treatment and for responders and nonresponders . RESULTS Several side effects emerged -- mostly mildly -- including jumpiness/jitteriness ( 8.8 % ) , headache ( 8.4 % ) , and nausea ( 15.9 % ) , mirroring findings of past studies with a less inclusive scope . In most cases , remission rate equalled or exceeded emergence rate . Several nondepressive symptoms also showed large improvement , including poor vision and skin rash/itch/irritation . Being overactive/excited/elated showed greater emergence under morning light and greater remission under evening light . Emergence of nausea was greater than remission in responders . CONCLUSION The dominant effect of light treatment was improvement in bothersome symptoms . Although patients should be advised of side effects and guided in dose manipulations to reduce them , attention also should be drawn to the substantial benefit-to-risk ratio . Improvement of symptoms outside the depressive cluster , seen in both responders and nonresponders , may point to new therapeutic uses of light therapy BACKGROUND Hypersomnia is a cardinal symptom of seasonal affective disorder/winter depression . This open-label pilot study assessed modafinil , a novel wake-promoting agent , as treatment for seasonal affective disorder/winter depression . METHODS Total daily modafinil dose was 100 mg ( all patients week 1 ) , and 100 mg or 200 mg split dose ( weeks 2 - 8 ) . Efficacy assessment s ( weeks 1 , 2 , 5 , and 8) included the Structured Interview Guide for the Hamilton Depression ( HAM-D ) Rating Scale , Seasonal Affective Disorder Version ( SIGH-SAD ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impression of Change ( CGI-C ) , Fatigue Severity Scale ( FSS ) , and Epworth Sleepiness Scale ( ESS ) . RESULTS Thirteen patients ( 11 women ; mean age , 41 years ) were enrolled , 12 were evaluable for efficacy ( 100 mg dose , five patients ; 200 mg dose , seven patients ) , and nine completed treatment . Modafinil significantly improved winter depression as shown by reductions from baseline in mean SIGH-SAD at week 1 ( P<0.01 ) through week 8 ( P<0.001 weeks 2 - 8 ) and MADRS total scores from week 2 through week 8 ( P<0.01 for all ) . At week 8 , mean SIGH-SAD total score was 17.1 ( versus 37.2 at baseline , P<0.001 ) , and mean MADRS total score was 13.3 ( versus 26.9 at baseline , P<0.01 ) . Modafinil significantly improved overall clinical condition at all time points ( P<0.001 ) . The response rate was 67 % on the SIGH-SAD ( 29 item ) , HAM-D ( 21 item ) , and MADRS , and 100 % on eight atypical SIGH-SAD items . Modafinil significantly reduced fatigue ( FSS ) and improved wakefulness ( ESS ) from weeks 2 through 8 ( P<0.01 ) . Modafinil was well tolerated . LIMITATIONS This was an open-label , single site study . CONCLUSIONS Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression 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 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 Noradrenergic and dopaminergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder ( SAD ) . We investigated the effects of catecholamine depletion using α-methyl-para-tyrosine ( AMPT ) , an inhibitor of tyrosine hydroxylase , in patients with SAD in natural summer remission . Nine drug-free patients with SAD by DSM-IV criteria , in summer remission for at least eight weeks , completed a double-blind , crossover study . Behavioral ratings and serum HVA and MHPG levels were obtained for 3-day sessions during which patients took AMPT or an active control drug , diphenhydramine . The active AMPT session significantly reduced serum levels of HVA and MHPG compared with the control diphenhydramine session . The AMPT session result ed in higher depression ratings with all nine patients having significant clinical relapse , compared with two patients during the diphenhydramine session . All patients returned to baseline scores after drug discontinuation . Catecholamine depletion results in significant clinical relapse in patients with SAD in the untreated , summer-remitted state . AMPT-induced  depressive relapse may be a trait marker for SAD , and /or brain catecholamines may play a direct role in the pathogenesis of SAD OBJECTIVE The authors investigated the efficacy and safety of fluoxetine in the treatment of winter seasonal affective disorder . METHOD Sixty-eight out patients who met the DSM-III-R criteria for recurrent major depressive episodes , seasonal ( winter ) pattern , were r and omly assigned to 5 weeks of treatment with fluoxetine , 20 mg/day ( N = 36 ) , or placebo ( N = 32 ) . The outcome measures included the 29-item modified Hamilton Depression Rating Scale , administered by experienced clinicians , and the self-rated Beck Depression Inventory ; adverse events and safety data were also recorded . Clinical response was defined as a greater than 50 % reduction in depression score between baseline and study termination . RESULTS Both groups showed significant improvement . The fluoxetine group had lower depression scores at termination than the placebo group , but these differences did not achieve statistical significance . However , the rate of clinical response in the fluoxetine group ( 59 % ) was superior to that in the placebo group ( 34 % ) . Post hoc analyses showed that the greatest fluoxetine responses were in the most markedly depressed patients and that overall response was greater for patients studied later in the season . Fluoxetine was well tolerated , and few subjects dropped out because of adverse events . CONCLUSIONS On the basis of clinical response rate , fluoxetine appears to be an effective , well-tolerated treatment for seasonal affective disorder . Because the differences between fluoxetine and placebo in the continuous outcome measures did not reach statistical significance , further studies with larger study groups and longer treatment periods are required to conclusively demonstrate efficacy of fluoxetine for seasonal affective disorder Objective : To examine estimates of lifetime prevalence of  seasonal affective disorder ( SAD ) in Toronto , Ontario . Method R and om telephone numbers were generated for the city of Toronto , and 781 respondents completed a telephone interview .  Trained nonphysician interviewers conducted all interviews , which involved structured questions for diagnosing major depression . Patterns of symptom change across seasons were evaluated to establish a diagnosis of SAD according to DSM-III-R criteria . Results Correcting for sex and age , the prevalence of SAD defined by DSM-III-R criteria was 2.9 % ( 95%CI , 1.7 % to 4.0 % ) , and the overall lifetime prevalence of major depression in the sample was 26.4 % ( 95%CI , 23.3 % to 29.4 % ) . Some subjects were contacted for a follow-up interview conducted in person ; the positive predictive value for the diagnosis of major depression for the telephone interview was 100 % , and the negative predictive value was 93 % . Conclusions The seasonal subtype of depression represents 11 % of all subjects with major depression , suggesting that SAD is a significant public health concern . The telephone interview demonstrated adequate reliability , indicating that it is appropriate for epidemiological surveys of this nature BACKGROUND A dysfunction of the serotonin system may play a major role in the pathogenesis of seasonal affective disorder .  Bright light therapy has been shown to be effective in the treatment of winter depression in patients with seasonal affective disorder .  Light therapy-induced remission from depression may be associated with changes in brain serotonin function . METHODS After at least 2 weeks of clinical remission , 12 drug-free patients who had had depression with seasonal affective disorder underwent tryptophan depletion in a double-blind , placebo-controlled , balanced cross-over design study . RESULTS Short-term tryptophan depletion induced a significant decrease in plasma free and total tryptophan levels ( P < .001 for both , repeated measures analysis of variance ) , with peak effects occurring 5 hours after ingestion of a tryptophan-free amino acid drink . It emerged that tryptophan depletion leads to a transient depressive relapse , which was most pronounced on the day after the tryptophan-depletion testing . No clinical ly relevant mood changes were observed in the control testing . CONCLUSIONS The maintenance of light therapy-induced remission from depression in patients with seasonal mood cycles seems to depend on the functional integrity of the brain serotonin system . Our results suggest that the serotonin system might be involved in the mechanism of action of light therapy Objective : We have tested the relapse‐preventive effect of citalopram when compared with placebo in 282 patients with Seasonal Affective Disorder ( SAD ) responding to 1 week of light therapy 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 Sixty-one winter depressive patients were evaluated for evidence of bipolar illness .  Using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version and the General Behavior Inventory , only nine ( 15 % ) could be considered bipolar . On prospect i ve evaluation of patients during the summer following winter depression , few showed signs of manic or hypomanic symptoms . Also , few patients had a family history of bipolar illness . When patients were asked to evaluate symptoms of winter depression , lack of energy was found to be the most prominent feature of the syndrome Seasonal affective disorder ( SAD ) , winter type , is a condition characterized by the annual recurrence of depressive episodes during fall/winter , alternating with spring/summer euthymia or hypomania . Various neurotransmitters have been implicated in the etiology of SAD , the strongest evidence involving serotonin . Recently , increasing attention has been paid to the potential role of catecholaminergic pathways in the pathophysiology of SAD . We investigated the efficacy and tolerability of  reboxetine  , a selective noradrenaline inhibitor , in patients with SAD . Eleven out of sixteen patients who were included in a 6-week drug surveillance during winter season experienced full remission of depressive symptoms . Nine patients reported a rapid relief of preexistent severe atypical depressive symptoms within the first treatment week . Reboxetine might therefore be an effective and well-tolerated treatment option for SAD patients . In conclusion , our preliminary results are in line with evidence from recent studies suggesting that catecholaminergic systems might also be involved in the pathophysiology of SAD Thirty‐four patients with seasonal affective disorder , winter depression type ( WD ) were r and omly distributed to receive the selective monoamine oxidase‐A inhibitor moclobemide ( 400 mg daily ) or placebo in a double‐blind , parallel group study lasting for up to 14 weeks . Severity measures were the Montgomery‐Åsberg Depression Rating Scale ( MADRS ) extended with characteristic symptoms of WD ; summed score of the “ atypical ” symptoms hypersomnia , hyperphagia and carbohydrate craving ; and Clinical Global Impressions ( CGI ) . After 3 weeks , patients with unsatisfactory response were switched to open moclobemide . Three patients on placebo dropped out before 3 weeks . Extended MADRS and CGI showed no significant difference between the groups at 3 weeks , whereas the atypical score was reduced significantly more on moclobemide than on placebo already after one week . Nonresponders after 3 weeks ( 9 of 16 on moclobemide and 7 of 15 on placebo ) improved rapidly after being given open moclobemide . Predictor analysis showed a remarkably high negative correlation between improvement at 3 weeks ( extended MADRS ) and age in the placebo group and a strong , nonsignificant trend in the same direction in the moclobemide group . Dichotomizing the patients according to the median age ( 45 years ) result ed in a somewhat better effect  of moclobemide than placebo in the older age group . There were no significant differences in side effects between moclobemide and placebo The following test of the circadian phase-shift hypothesis for patients with winter depression ( seasonal affective disorder , or SAD ) uses low-dose melatonin administration in the morning or afternoon/evening to induce phase delays or phase advances , respectively , without causing sleepiness . Correlations between depression ratings and circadian phase revealed a therapeutic window for optimal alignment of circadian rhythms that also appears to be useful for phase-typing SAD patients for the purpose of administering treatment at the correct time . These analyses also provide estimates of the circadian component of SAD that may apply to the antidepressant mechanism of action of appropriately timed bright light exposure , the treatment of choice . SAD may be the first psychiatric disorder in which a physiological marker correlates with symptom severity before , and in the course of , treatment in the same patients . The findings support the phase-shift hypothesis for SAD , as well as suggest a way to assess the circadian component of other psychiatric , sleep , and chronobiologic disorders
target: Recent systematic review s have shown that  light therapy  is an efficacious and well-tolerated treatment for SAD .
  There is also evidence for efficacy of pharmacotherapy to treat and prevent SAD .
  SAD is a common condition with significant psychosocial impairment .
background: BACKGROUND Seasonal affective disorder ( SAD ) consists of recurrent major depressive episodes in the fall/winter with remissions in spring/summer .
  RESULTS A careful history is important to make the diagnosis and differentiate SAD from other similar conditions such as subsyndromal SAD and atypical depression .
  Seasonal patterns with winter worsening are also recognized in " nonseasonal " depression as well as many other psychiatric conditions , and comorbidity with SAD is common .
  The pathophysiology of SAD seems to be heterogeneous as research on circadian , neurotransmitter function and genetic hypotheses have shown discrepant results .
  A dual vulnerability model with differential loading on separate seasonal and depression factors has been proposed to explain these findings .