Treatment Of Seasonal Affective Disorder Research Articles

Effects of light therapy on sleep/wakefulness, daily rhythms, and the central orexin system in a diurnal rodent model of seasonal affective disorder

BackgroundBright light therapy (BLT) is the first-line treatment for seasonal affective disorder. However, the neural mechanisms underlying BLT are unclear. To begin filling this gap, the present study examined the impact of BLT on sleep/wakefulness, daily rhythms, and the wakefulness-promoting orexin/hypocretin system in a diurnal rodent, Nile grass rats (Arvicanthis niloticus). MethodsMale and female grass rats were housed under a 12:12 h light/dark cycle with dim light (50 lx) during the day. The experimental group received daily 1-h early morning BLT (full-spectrum white light, 10,000 lx), while the control group received narrowband red light for 4 weeks. Sleep/wakefulness and in-cage locomotor activity were monitored, followed by examination of hypothalamic prepro-orexin and orexin receptors OX1R and OX2R expression in corticolimbic brain regions. ResultsThe BLT group had higher wakefulness during light treatment, better nighttime sleep quality, and improved daily rhythm entrainment compared to controls. The impact of BLT on the orexin system was sex- and brain region-specific, with males showing higher OX1R and OX2R in the CA1, while females showed higher prepro-orexin but lower OX1R and OX2R in the BLA, compared to same-sex controls. LimitationsThe present study focused on the orexin system in a limited number of brain regions at a single time point. Sex wasn't a statistical factor, as male and female cohorts were run independently. ConclusionsThe diurnal grass rats show similar behavioral responses to BLT as humans, thus could be a good model for further elucidating the neural mechanisms underlying the therapeutic effects of BLT.

CME: Light Therapy: Why, What, for Whom, How, and When (And a Postscript about Darkness).

Light therapy has become established as an evidence-based treatment for Seasonal Affective Disorder. Light impacts the timing and stability of circadian rhythms as expressed in sleep, mood, alertness, and cognition. Forty years of clinical trials and open treatment have led to guidelines for patient selection, using light alone or in combination with antidepressants (or lithium for bipolar depression). Mood and sleep disturbances can also respond to adjunct light therapy in a broader set of psychiatric, neurologic and medical illnesses. We specify criteria for choice of treatment devices: optimum dose (10,000 lux), spectrum (white light), exposure duration (30-60 minutes) and timing (early morning). Protocol adjustment requires continual monitoring with attention to rate of improvement and management of potential side effects.

Melatonin/Cyclodextrin Inclusion Complexes: A Review.

Melatonin (MLT) is involved in many functions of the human body, mainly in sleeping-related disorders. It also has anti-oxidant potential and has been proven very effective in the treatment of seasonal affective disorders (SAD), which afflict some people during short winter days. Melatonin has been implicated in a range of other conditions, including Parkinson’s disease, Alzheimer’s and other neurological conditions, and in certain cancers. Its poor solubility in water leads to an insufficient absorption that led scientists to investigate MLT inclusion in cyclodextrins (CDs), as inclusion of drugs in CDs is a way of increasing the solubility of many lipophilic moieties with poor water solubility. The aim of this review is to gather all the key findings on MLT/CD complexes. The literature appraisal concluded that MLT inclusion leads to a 1:1 complex with the majority of CDs and increases the solubility of the hormone. The interactions of MLT with CDs can be studied by a variety of techniques, such as NMR, FT-IR, XRD and DCS. More importantly, the in vivo experiments showed an increase in the uptake of MLT when included in a CD.

Second-generation antidepressants for treatment of seasonal affective disorder.

Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second-generation antidepressants (SGAs), light therapy, or psychotherapy. To assess the efficacy and safety of second-generation antidepressants (SGAs) for the treatment of seasonal affective disorder (SAD) in adults in comparison with placebo, light therapy, other SGAs, or psychotherapy. This is an update of anearlier review first published in 2011. We searched the Cochrane Central Register of Controlled Trials(CENTRAL; 2020, Issue 1) in the Cochrane Library (all years), Ovid MEDLINE, Embase, and PsycINFO (2011 to January 2020), together with the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all available years), for reports of randomised controlled trials (RCTs). Wehand searchedthereference listsof all included studiesand other systematic reviews. We searched ClinicalTrials.gov for unpublished/ongoing trials.We ran a separate updatesearch for reports of adverse events in the Ovid databases. SELECTION CRITERIA: For efficacy we included RCTs of SGAs compared with other SGAs, placebo, light therapy, or psychotherapy in adult participants with SAD. For adverse events we also included non-randomised studies. Two review authors independently screened abstracts and full-text publications against the inclusion criteria. Data extraction and 'Risk of bias' assessment were conducted individually. We pooled data for meta-analysis where the participant groups were similar, and the studies assessed the same treatments with the same comparator and had similar definitions of outcome measures over a similar duration of treatment. In this update we identified no new RCT on the effectiveness of SGAs in SAD patients. We included 2 additional single-arm observational studies that reported on adverse events of SGAs. For efficacy we included three RCTs of between five and eight weeks' duration with a total of 204 participants. For adverse events we included two RCTs and five observational (non-randomised) studies of five to eight weeks' duration with a total of 249 participants. All participants met the DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for SAD. The average age ranged from 34 to 42 years, and the majority of participants were female (66% to 100%). Results from one trial with 68 participants showed that fluoxetine (20/36)was numerically superior to placebo (11/32)in achieving clinical response; however, the confidence interval (CI) included both a potential benefit as well as no benefit of fluoxetine (risk ratio (RR) 1.62, 95% CI 0.92 to 2.83, very low-certainty evidence). The number of adverse events was similar in both groups (very low-certainty evidence). Two trials involving a total of 136 participants compared fluoxetine versus light therapy. Meta-analysis showed fluoxetine and light therapy to be approximately equal in treating seasonal depression: RR of response 0.98 (95% CI 0.77 to 1.24, low-certainty evidence), RR of remission 0.81 (95% CI 0.39 to 1.71, very low-certainty evidence). The number of adverse events was similar in both groups (low-certainty evidence). We did not identify any eligible study comparing SGA with another SGA or with psychotherapy. Two RCTs and five non-randomised studies reported adverse event data on a total of 249 participants who received bupropion, fluoxetine, escitalopram, duloxetine, nefazodone, reboxetine, light therapy, or placebo. We were only able to obtain crude rates of adverse events, therefore caution is advised regarding interpretation of this information. Between 0% and 100% of participants who received an SGA suffered an adverse event, and between 0% and 25% of participants withdrew from the study due to adverse events. Evidence for the effectiveness of SGAs is limited to one small trial of fluoxetine compared with placebo showing a non-significant effect in favour of fluoxetine, and two small trials comparing fluoxetine against light therapy suggesting equivalence between the two interventions. The lack of available evidence precluded us from drawing any overall conclusions on the use of SGAs for SAD. Further, larger RCTs are required to expand and strengthen the evidence base on this topic, and should also include comparisons with psychotherapy and other SGAs. Data on adverse events were sparse, and a comparative analysis was not possible. The data we obtained on adverse events is therefore not robust, and our confidence in the data is limited. Overall, up to 25% of participants treated with SGAs for SAD withdrew from the study early due to adverse events.

This Winter, Pandemic May Intensify Seasonal Depression

This Winter, Pandemic May Intensify Seasonal Depression

The Symptom Structure of Seasonal Affective Disorder: Integrating Results from Factor and Network Analyses in the Context of the Dual Vulnerability Model

Research on seasonal affective disorder (SAD) has produced several etiological models of SAD symptomatology, including a common cause model that conceptualizes symptoms as the result of a single underlying disease process and the Dual Vulnerability Model (Young et al., Journal of Affective Disorders, 22, 191–197 1991) which posits that cognitive/affective symptoms of depression are responses to vegetative symptoms (fatigue, hypersomnia, increased appetite) in individuals with a cognitive vulnerability to these seasonal changes. This study used exploratory factor analysis and network analyses to examine 22 symptoms of winter SAD in 177 adults at the start of a randomized SAD treatment trial (Rohan et al., American Journal of Psychiatry, 172, 862–9 2015). The factor analysis supported a novel four-factor model that included Negative Cognition, Loss of Vitality, Increased Appetite/Weight and Dysregulation across symptom domains. The results of the network model of interacting symptoms paralleled those of the factor analysis in producing four clusters of inter-correlated symptoms. A directed acyclic graph was constructed to model possible causal relations between symptom factors/clusters. Results suggest that vegetative symptoms (Loss of Vitality and Appetite/Weight) contribute to Dysregulation and that Loss of Vitality and Dysregulation contribute to Negative Cognition, supporting the overall structure of the Dual Vulnerability Model but with greater symptom differentiation. Findings have implications for how SAD should be researched (e.g., clusters vs. diagnosis or individual symptoms), opportunities for intervention, and the expected course of onset and remission.

Antidepressant Effect of Blue Light on Depressive Phenotype in Light-Deprived Male Rats.

Blue light has been previously reported to play a salient role in the treatment of seasonal affective disorder. The present study aimed to investigate whether blue light had antidepressant effect on light-deprivation-induced depression model, and the underlying visual neural mechanism. Blue light mitigated depression-like behaviors induced by light deprivation as measured by elevated sucrose preference and reduced immobility time. Blue light enhanced melanopsin expression and light responses in the retina. We also found the upregulation of serotonin and brain derived neurotrophic factor expression in the c-fos-positive areas of rats treated with blue light compared with those maintained in darkness. The species gap between nocturnal albino (Sprague-Dawley rat) and diurnal pigmented animals (human) might have influenced extrapolating data to humans. Blue light has antidepressant effect on light-deprived Sprague-Dawley rats, which might be related to activating the serotonergic system and neurotrophic activity via the retinoraphe and retinoamygdala pathways. Blue light is the effective component of light therapy for treatment of depression.

Cognitive Vulnerabilities as Prognostic Predictors of Acute and Follow-up Outcomes in Seasonal Affective Disorder Treatment with Light Therapy or Cognitive-Behavioral Therapy.

First-line treatments for winter seasonal affective disorder include light therapy and cognitive-behavioral therapy; however, it is unclear whether particular patient profiles respond differentially to each treatment type. This study examined baseline patient cognitive and chronobiological vulnerabilities as prognostic and prescriptive predictors of acute and follow-up treatment outcomes. 177 adults with seasonal affective disorder were randomized to 6-weeks of either light therapy or cognitive-behavioral therapy. Participants completed baseline measures of cognitive vulnerabilities (Dysfunctional Attitudes Scale; Ruminative Response Scale; Seasonal Belief Questionnaire) and chronobiological vulnerability (Morningness-Eveningness Questionnaire). Depression was assessed at pre- and post-treatment and at follow-ups one and two winters later. Pre-treatment depression severity correlated significantly with each cognitive vulnerability measure, and significantly predicted future depression. After controlling for pre-treatment depression, higher scores on the Morningness-Eveningness Questionnaire were prognostic of lower depression at treatment endpoint, but no cognitive vulnerability emerged as a prognostic or prescriptive predictor of outcome. Greater morningness was associated with less severe post-treatment depression in both cognitive-behavior therapy and light therapy. No cognitive vulnerability emerged as a prognostic or prescriptive predictor, perhaps because they correlated with pre-treatment depression severity, a robust predictor of outcome. Future research should test alternative cognitive constructs.

The Efficacy of Light Therapy in the Treatment of Seasonal Affective Disorder: A Meta-Analysis of Randomized Controlled Trials

Background: Bright light therapy (BLT) has been used as a treatment for seasonal affective disorder (SAD) for over 30 years. This meta-analysis was aimed to assess the efficacy of BLT in the treatment of SAD in adults. Method: We performed a systematic literature search including randomized, single- or double-blind clinical trials investigating BLT (≥1,000 lx, light box or light visor) against dim light (≤400 lx) or sham/low-density negative ion generators as placebo. Only first-period data were used from crossover trials. The primary outcome was the post-treatment depression score measured by validated scales, and the secondary outcome was the rate of response to treatment. Results: A total of 19 studies finally met our predefined inclusion criteria. BLT was superior over placebo with a standardized mean difference of –0.37 (95% CI: –0.63 to –0.12) for depression ratings (18 studies, 610 patients) and a risk ratio of 1.42 (95% CI: 1.08–1.85) for response to active treatment (16 studies, 559 patients). We found no evidence for a publication bias, but moderate heterogeneity of the studies and a moderate-to-high risk of bias. Conclusions: BLT can be regarded as an effective treatment for SAD, but the available evidence stems from methodologically heterogeneous studies with small-to-medium sample sizes, necessitating larger high-quality clinical trials.

Melatonin and agomelatine for preventing seasonal affective disorder.

Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly starts in autumn or winter and remits in spring. The prevalence of SAD depends on latitude and ranges from 1.5% to 9%. The predictable seasonal aspect of SAD provides a promising opportunity for prevention in people who have a history of SAD. This is one of four reviews on the efficacy and safety of interventions to prevent SAD; we focus on agomelatine and melatonin as preventive interventions. 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 person-centred outcomes among adults with a history of SAD. We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. To examine efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we intended also to include non-randomised studies. We planned to include studies that compared agomelatine versus melatonin, or agomelatine or melatonin versus placebo, any second-generation antidepressant, light therapy, psychological therapies or lifestyle changes. We also intended to compare melatonin or agomelatine in combination with any of the comparator interventions mentioned above versus the same comparator intervention as monotherapy. Two review authors screened abstracts and full-text publications, abstracted data and assessed risk of bias of included studies independently. We intended to pool data in a meta-analysis using a random-effects model, but included only one study. We identified 3745 citations through electronic searches and reviews of reference lists after deduplication of search results. We excluded 3619 records during title and abstract review and assessed 126 full-text papers for inclusion in the review. Only one study, providing data of 225 participants, met our eligibility criteria and compared agomelatine (25 mg/day) with placebo. We rated it as having high risk of attrition bias because nearly half of the participants left the study before completion. We rated the certainty of the evidence as very low for all outcomes, because of high risk of bias, indirectness, and imprecision.The main analysis based on data of 199 participants rendered an indeterminate result with wide confidence intervals (CIs) that may encompass both a relevant reduction as well as a relevant increase of SAD incidence by agomelatine (risk ratio (RR) 0.83, 95% CI 0.51 to 1.34; 199 participants; very low-certainty evidence). Also the severity of SAD may be similar in both groups at the end of the study with a mean SIGH-SAD (Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders) score of 8.3 (standard deviation (SD) 9.4) in the agomelatine group and 10.1 (SD 10.6) in the placebo group (mean difference (MD) -1.80, 95% CI -4.58 to 0.98; 199 participants; very low-certainty evidence). The incidence of adverse events and serious adverse events may be similar in both groups. In the agomelatine group, 64 out of 112 participants experienced at least one adverse event, while 61 out of 113 did in the placebo group (RR 1.06, 95% CI 0.84 to 1.34; 225 participants; very low-certainty evidence). Three out of 112 patients experienced serious adverse events in the agomelatine group, compared to 4 out of 113 in the placebo group (RR 0.76, 95% CI 0.17 to 3.30; 225 participants; very low-certainty evidence).No data on quality of life or interpersonal functioning were reported. We did not identify any studies on melatonin. Given the uncertain evidence on agomelatine and the absence of studies on melatonin, no conclusion about efficacy and safety of agomelatine and melatonin for prevention of SAD can currently be drawn. The decision for or against initiating preventive treatment of SAD and the treatment selected should consider patient preferences and reflect on the evidence base of all available treatment options.

Psychological therapies for preventing seasonal affective disorder.

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 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 reviews on the efficacy and safety of interventions to prevent SAD; we focus on psychological therapies as preventive interventions. To assess the efficacy and safety of psychological therapies (in comparison with no treatment, other types of psychological therapy, second-generation antidepressants, light therapy, melatonin or agomelatine or lifestyle interventions) in preventing SAD and improving person-centred outcomes among adults with a history of SAD. We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. To examine efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. To examine adverse events, we intended to include non-randomised studies. We planned to include studies that compared psychological therapy versus no treatment, or any other type of psychological therapy, light therapy, second-generation antidepressants, melatonin, agomelatine or lifestyle changes. We also planned to compare psychological therapy in combination with any of the comparator interventions listed above versus no treatment or the same comparator intervention as monotherapy. Two review authors screened abstracts and full-text publications against the inclusion criteria, independently extracted data, assessed risk of bias, and graded the certainty of evidence. We identified 3745 citations through electronic searches and reviews of reference lists after deduplication of search results. We excluded 3619 records during title and abstract review and assessed 126 articles at full-text review for eligibility. We included one controlled study enrolling 46 participants. We rated this RCT at high risk for performance and detection bias due to a lack of blinding.The included RCT compared preventive use of mindfulness-based cognitive therapy (MBCT) with treatment as usual (TAU) in participants with a history of SAD. MBCT was administered in spring in eight weekly individual 45- to 60-minute sessions. In the TAU group participants did not receive any preventive treatment but were invited to start light therapy as first depressive symptoms occurred. Both groups were assessed weekly for occurrence of a new depressive episode measured with the Inventory of Depressive Syptomatology-Self-Report (IDS-SR, range 0-90) from September 2011 to mid-April 2012. The incidence of a new depressive episode in the upcoming winter was similar in both groups. In the MBCT group 65% of 23 participants developed depression (IDS-SR ≥ 20), compared to 74% of 23 people in the TAU group (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.60 to 1.30; 46 participants; very low quality-evidence).For participants with depressive episodes, severity of depression was comparable between groups. Participants in the MBCT group had a mean score of 26.5 (SD 7.0) on the IDS-SR, and TAU participants a mean score of 25.3 (SD 6.3) (mean difference (MD) 1.20, 95% CI -3.44 to 5.84; 32 participants; very low quality-evidence).The overall discontinuation rate was similar too, with 17% discontinuing in the MBCT group and 13% in the TAU group (RR 1.33, 95% CI 0.34 to 5.30; 46 participants; very low quality-evidence).Reasons for downgrading the quality of evidence included high risk of bias of the included study and imprecision.Investigators provided no information on adverse events. We could not find any studies that compared psychological therapy with other interventions of interest such as second-generation antidepressants, light therapy, melatonin or agomelatine. The evidence on psychological therapies to prevent the onset of a new depressive episode in people with a history of SAD is inconclusive. We identified only one study including 46 participants focusing on one type of psychological therapy. Methodological limitations and the small sample size preclude us from drawing a conclusion on benefits and harms of MBCT as a preventive intervention for SAD. Given that there is no comparative evidence for psychological therapy versus other preventive options, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences and other preventive interventions that are supported by evidence.

Second-generation antidepressants for preventing seasonal affective disorder in adults.

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 ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Two review authors independently screened abstracts and full-text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi2 statistic and the Cochran Q. We used the I2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de-duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall, moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.

Light therapy for preventing seasonal affective disorder.

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 ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on light therapy as a preventive intervention. Light therapy is a non-pharmacological treatment that exposes people to artificial light. Mode of delivery and form of light vary. To assess the efficacy and safety of light therapy (in comparison with no treatment, other types of light therapy, second-generation antidepressants, melatonin, agomelatine, psychological therapies, lifestyle interventions and negative ion generators) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we also intended to include non-randomised studies. We intended to include studies that compared any type of light therapy (e.g. bright white light, administered by visors or light boxes, infrared light, dawn stimulation) versus no treatment/placebo, second-generation antidepressants, psychological therapies, melatonin, agomelatine, lifestyle changes, negative ion generators or another of the aforementioned light therapies. We also planned to include studies that looked at light therapy in combination with any comparator intervention. Two review authors screened abstracts and full-text publications, independently abstracted data and assessed risk of bias of included studies. We identified 3745 citations after de-duplication of search results. We excluded 3619 records during title and abstract review. We assessed 126 full-text papers for inclusion in the review, but only one study providing data from 46 people met our eligibility criteria. The included RCT had methodological limitations. We rated it as having high risk of performance and detection bias because of lack of blinding, and as having high risk of attrition bias because study authors did not report reasons for dropouts and did not integrate data from dropouts into the analysis.The included RCT compared preventive use of bright white light (2500 lux via visors), infrared light (0.18 lux via visors) and no light treatment. Overall, white light and infrared light therapy reduced the incidence of SAD numerically compared with no light therapy. In all, 43% (6/14) of participants in the bright light group developed SAD, as well as 33% (5/15) in the infrared light group and 67% (6/9) in the non-treatment group. Bright light therapy reduced the risk of SAD incidence by 36%; however, the 95% confidence interval (CI) was very broad and included both possible effect sizes in favour of bright light therapy and those in favour of no light therapy (risk ratio (RR) 0.64, 95% CI 0.30 to 1.38; 23 participants, very low-quality evidence). Infrared light reduced the risk of SAD by 50% compared with no light therapy, but the CI was also too broad to allow precise estimations of effect size (RR 0.50, 95% CI 0.21 to 1.17; 24 participants, very low-quality evidence). Comparison of both forms of preventive light therapy versus each other yielded similar rates of incidence of depressive episodes in both groups (RR 1.29, 95% CI 0.50 to 3.28; 29 participants, very low-quality evidence). Reasons for downgrading evidence quality included high risk of bias of the included study, imprecision and other limitations, such as self-rating of outcomes, lack of checking of compliance throughout the study duration and insufficient reporting of participant characteristics.Investigators provided no information on adverse events. We could find no studies that compared light therapy versus other interventions of interest such as second-generation antidepressants, psychological therapies, melatonin or agomelatine. Evidence on light therapy as preventive treatment for people with a history of SAD is limited. Methodological limitations and the small sample size of the only available study have precluded review author conclusions on effects of light therapy for SAD. Given that comparative evidence for light therapy versus other preventive options is limited, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.

Brain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy

Increased cerebral monoamine oxidase A (MAO-A) levels have been shown in non-seasonal depression using positron emission tomography (PET). Seasonal affective disorder (SAD) is a sub-form of major depressive disorder and is typically treated with bright light therapy (BLT). The serotonergic system is affected by season and light. Hence, this study aims to assess the relevance of brain MAO-A levels to the pathophysiology and treatment of SAD. Changes to cerebral MAO-A distribution (1) in SAD in comparison to healthy controls (HC), (2) after treatment with BLT and (3) between the seasons, were investigated in 24 patients with SAD and 27 HC using [11C]harmine PET. PET scans were performed in fall/winter before and after 3 weeks of placebo-controlled BLT, as well as in spring/summer. Cerebral MAO-A distribution volume (VT, an index of MAO-A density) did not differ between patients and HC at any of the three time-points. However, MAO-A VT decreased from fall/winter to spring/summer in the HC group (F1, 187.84 = 4.79, p < 0.050), while SAD showed no change. In addition, BLT, but not placebo, resulted in a significant reduction in MAO-A VT (F1, 208.92 = 25.96, p < 0.001). This is the first study to demonstrate an influence of BLT on human cerebral MAO-A levels in vivo. Furthermore, we show that SAD may lack seasonal dynamics in brain MAO-A levels. The lack of a cross-sectional difference between patients and HC, in contrast to studies in non-seasonal depression, may be due to the milder symptoms typically shown by patients with SAD.

The effects of low-intensity narrow-band blue-light treatment compared to bright white-light treatment in seasonal affective disorder

BackgroundEver since a new photoreceptor was discovered with a highest sensitivity to 470–490 nm blue light, it has been speculated that blue light has some advantages in the treatment of Seasonal Affective Disorder (SAD) over more traditional treatments. In this study we compared the effects of exposure to narrow-band blue light (BLUE) to those of broad-wavelength white light (BLT) in the treatment of SAD. MethodsIn a 15-day design, 45 patients suffering from SAD completed 30-min sessions of light treatment on 5 consecutive days.21 subjects received white-light treatment (BLT, broad-wavelength without UV, 10 000 lx, irradiance 31.7 W/m2), 24 subjects received narrow-band blue light (BLUE, 100 lx, irradiance 1.0 W/m2). All participants completed weekly questionnaires concerning mood and energy levels, and were also assessed by means of the SIGH-SAD, which is the primary outcome measure. ResultsOn day 15, SIGH-SAD ratings were significantly lower than on day 1 (BLT 73.2%, effect size 3.37; BLUE 67%, effect size 2.63), which outcomes were not statistically significant different between both conditions. LimitationsSmall sample size. ConclusionsLight treatment is an effective treatment for SAD. The use of narrow-band blue light is equally effective as a treatment using bright white-light.

Efficacy of bright light therapy in bipolar depression

For 30 years, bright light therapy (BLT) has been considered as an effective, well-tolerated treatment for seasonal affective disorder (SAD). Because of low response rates, new treatment strategies are needed for bipolar depression (BD), which resembles SAD in certain respects. Few placebo-controlled studies of BLT efficacy have been carried out for BD. Accordingly, this study evaluates the efficacy and safety of BLT as an add-on treatment for BD. Thirty-two BD outpatients were randomly assigned to BLT (10000lx) or dim light (DL, < 500lx). During a two-week period, light was administered each morning for 30min. The Hamilton Rating Scale for Depression and the Montgomery-Ǻsberg Depression Rating Scale assessed clinical outcome, and the UKU Side Effects Rating Scale evaluated side effects. No significant difference was observed in baseline depression scores in the two groups. Response rates for BLT and DL were 81% and 19%, and remission rates were 44% and 12.5%, respectively. Analyses showed statistically significant reductions in depression scores for the BLT group compared with the DL group on all scales. Side effects were similar in both groups, with headache as the most common side effect. The results suggest that BLT is an effective and safe add-on treatment for BD.

Clinical efficacy, onset time and safety of bright light therapy in acute bipolar depression as an adjunctive therapy: A randomized controlled trial

BackgroundBright light therapy (BLT) is an effective treatment for seasonal affective disorder and non- seasonal depression. The efficacy of BLT in treating patients with bipolar disorder is still unknown. AimsThe aim of this study is to examine the efficacy, onset time and clinical safety of BLT in treating patients with acute bipolar depression as an adjunctive therapy (trial registration at ClinicalTrials.gov: NCT02009371). MethodsThis was a multi-center, single blind, randomized clinical trial. Seventy-four participants were randomized in one of two treatment conditions: BLT and control (dim red light therapy, dRLT). Sixty-three participants completed the study (33 BLT, 30 dRLT). Light therapy lasted for two weeks, one hour every morning. All participants were required to complete several scales assessments at baseline, and at the end of weeks 1 and 2. The primary outcome measures were the clinical efficacy of BLT which was assessed by the reduction rate of HAMD-17 scores, and the onset time of BLT which was assessed by the reduction rate of QIDS-SR16 scores. The secondary outcome measures were rates of switch into hypomania or mania and adverse events. Results1) Clinical efficacy: BLT showed a greater ameliorative effect on bipolar depression than the control, with response rates of 78.19% vs. 43.33% respectively (p < 0.01). 2) Onset day: Median onset day was 4.33 days in BLT group. 3) BLT-emergent hypomania: No participants experienced symptoms of hypomania. 4) Side effects: No serious adverse events were reported. ConclusionBLT can be considered as an effective and safe adjunctive treatment for patients with acute bipolar depression.

Controlled trial evaluation of exposure duration to negative air ions for the treatment of seasonal affective disorder

This study evaluated the effectiveness of 30 or 60min of daily exposure to high-density or to zero-density (placebo condition) negative air ions over 18 days on the symptoms of seasonal affective disorder (SAD) in 40 participants under controlled laboratory conditions. Exposure to high-density negative air ions was superior to zero-density negative air ions in alleviating depression and the atypical symptoms of SAD. Also, more subjects in the high-density negative air ions groups met two different clinical response criteria than did those in the zero-density groups. Within the high density treatment group, both the short and long daily exposure reduced SAD symptoms. Exposure to negative air ions produced no negative side effects, and no ozone was produced by the ion generators. In both the high-density negative air ions and zero-density negative air ions groups, a significant placebo effect was found for most clinical measures. Finally, for the high-density negative air ion groups, subjects with a morningness chronotype responded better to treatment with high-density negative air ions than did those with an eveningness chronotype.

Bupropion Sustained released versus Placebo for seasonal affective Disorder

Background: The majority of seasonal affective disorder (SAD) studies have evaluated the use of light or selective serotonin reuptake inhibitors (SSRI). The purpose of the present study was to evaluate bupropion sustained-released (SR), a non-SSRI antidepressant, for the treatment of SAD.

Eye disorder differentiates seasonality outcomes in persons with severe visual impairment

BackgroundLight plays a crucial role in both the pathogenesis and treatment of seasonal affective disorder (SAD). Consequently decreased retinal sensitivity to light has been suggested to be a risk factor for SAD. In a population of persons with severe visual impairment we recently found a highly increased prevalence of SAD. We now aimed to identify eye disorders or anatomical locations with specific association to seasonality. MethodsIn 912 cases (33%) from our prior seasonal pattern assessment questionnaire (SPAQ) screening study, we retrieved eye diagnoses from the Danish National Patient Registry and analyzed for specific eye disorders or anatomical locations that significantly differentiated SPAQ outcomes (global seasonality score, (GSS) and SPAQ-SAD prevalence). ResultsPersons with early life eye disorders (congenital conditions or retinopathy of prematurity) reported less symptoms of SAD (median GSS 4.5) than persons with acquired eye disorders (median GSS 5.0, p=0.005). Persons with macular degenerative disorders (MD) had highly increased seasonality outcomes (hazard ratio 2.23, p=0.002, median GSS 5 vs. 8, p=0.01). Limitationsthe study is a cross-sectional study based on a self-report questionnaire. Register data may be incomplete. ConclusionsMD is significantly associated to high-level seasonality and SAD prevalence. Early life eye disorder is associated to slightly lower seasonality compared to acquired eye disorder. Longitudinal studies are needed to assess causality.