Treatment measures for seasonal affective disorder: A network meta-analysis.

OBJECTIVE: The purpose of this study was to assess the potential effectiveness of several mainstream therapies, including phototherapy, antidepressants, cognitive-behavioral therapy, and negative ion generators, in the treatment of Seasonal Affective Disorder (SAD). METHODS: A systematic search of PubMed, Embase, Cochrane, and WOS databases was conducted from January 1975 to December 3, 2022. Randomized controlled trials meeting predefined selection criteria for the treatment of SAD using mainstream therapeutic approaches were identified. After reviewing abstracts, data were synthesized and categorized based on the type of intervention and the targeted disorder. RESULTS: A total of 21 randomized controlled trials, involving 1037 participants, were included. The standardized mean difference of depression scores and corresponding 95 % confidence intervals were calculated to assess the efficacy of phototherapy for Seasonal Affective Disorder. The meta-analysis revealed that phototherapy was significantly more effective than other intervention groups or control therapies, with an effect size of 4.64(2.38,7.03). Subgroup analysis demonstrated that no factors could explain the significant heterogeneity observed. Phototherapy exhibited statistically significant mild to moderate therapeutic effects in alleviating depressive symptoms and can be considered as a clinical therapy for treating Seasonal Affective Disorder. However, the quality of evidence remains low, and further well-designed, larger sample size, and high-quality studies are needed to confirm the efficacy of phototherapy in treating Seasonal Affective Disorder. CONCLUSION: In conclusion, our systematic review and meta-analysis indicate that bright light therapy is a promising first-line non-pharmacological treatment for Seasonal Affective Disorder (SAD), showing significant improvement in mood symptoms compared to placebo. The findings support the use of bright light therapy as an effective and well-tolerated intervention for SAD. However, further large-scale, multicenter randomized controlled trials with long-term follow-up are needed to assess the long-term efficacy and safety of different treatment approaches for SAD.

Delivery of bright light therapy within the Veterans Health Administration.

BACKGROUND: Bright light therapy (BLT) is efficacious for seasonal and non-seasonal depression. However, the current state of BLT use in practice is unknown, impeding efforts to identify and address utilization gaps. This study's objective was to investigate BLT delivery in a nationwide U.S. healthcare system. METHODS: This was a retrospective observational study of electronic medical records from all veterans who received outpatient mood disorder-related care in the Veterans Health Administration (VHA) from October 2008 through September 2020. BLT delivery was measured through the placement of light box consults. RESULTS: Of the 3,442,826 veterans who received outpatient mood disorder care, only 57,908 (1.68 %) received a light box consult. Consults increased by 548.44 % (99.9 % credible interval: 467.36 %, 638.74 %) over the timeframe and displayed a robust yearly cycle that peaked on either December 21st or December 22nd. Past mental health treatment for a mood disorder was associated with a higher probability of a consult (relative risk = 4.79, 99.9 % CI: 4.21, 5.60). There was low representation related to veteran age, gender, race, and ethnicity. LIMITATIONS: No information on patients who declined light boxes or actual light box use following consult placement. CONCLUSIONS: Outpatient BLT delivery for mood disorders in the VHA remains low, despite significant growth over the past decade. It also displays a strong seasonal rhythm that peaks on the winter solstice, suggesting a limited focus on seasonal depression and a suboptimal reactive approach to changing sunlight. Overall, there exists ample opportunity for novel implementation efforts aimed at increasing utilization of BLT.

Prospectively assessed summer mood status in major depression, recurrent with seasonal pattern: Evidence for SAD's construct validity.

OBJECTIVE: Seasonal patterns are often undetectable in population-based depression studies, calling into question the existence of winter seasonal affective disorder (SAD). If SAD has construct validity, individuals with SAD should show spontaneous depression remission in the summer. Data are sparse on prospectively assessed summer mood status in confirmed SAD patients. METHOD: We conducted prospective summer followup of community adults who, the winter before, were diagnosed with Major Depression, Recurrent with Seasonal Pattern on the Structured Clinical Interview for DSM-IV Axis I Disorders, developed a current SAD episode on the Structured Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective Disorder Version (SIGH-SAD), and enrolled in a clinical trial comparing group cognitive-behavioral therapy for SAD and light therapy. In July/August after treatment, 143/153 (93.5 %) participants provided data on the SIGH-SAD, the Beck Depression Inventory-Second Edition, and the Longitudinal Interval Followup Evaluation (LIFE). RESULTS: Summer mean depression scores were in the normal range, with the substantial majority in remission across different measures. On the LIFE, 113/143 (79.0 %) experienced complete summer remission, 19/143 (13.3 %) experienced partial summer remission, and 11/143 (7.7 %) had major depression in the summer. Depression scores were significantly lower at summer than post-treatment in both treatments, indicating incomplete treatment response. LIMITATIONS: This was a single-site study with a relatively homogeneous sample. CONCLUSIONS: Supporting construct validity for SAD, the substantial majority experienced complete summer remission, with a minority in partial remission and a very small minority in episode. Both treatments left residual symptoms at treatment endpoint compared to summer.

35 years of light treatment for mental disorders in the Netherlands.

BACKGROUND: Light therapy (LT) for Seasonal Affective Disorders (SAD) has been a well-known and effective treatment for 40 years. The psychiatric university clinic of Groningen, the Netherlands was an early adopter and started research and treatment of SAD in 1987. Research projects on mechanisms, the role of the circadian system, treatment optimization, and investigating new areas for the effects of light treatment have been carried out ever since, leading to a widespread interest across the country. OBJECTIVE: To provide an overview and description of the historical development of LT for mental disorders in the Netherlands. METHODS: A non-systematic, review of research on light treatment for mental problems in the Netherlands, published since 1987 was conducted. RESULTS: The fields of LT and chronotherapy are strongly based in the scientific interests of both chrono-biologists and therapists in the Netherlands. LT has shown effectiveness in treating mood disorders. Likewise, results for other mental disorders have shown some promise, but so far, the outcomes are not always unequivocal and have not always been based on robust data. Ongoing research is discussed. CONCLUSIONS: LT, and in addition exposure to the right light at the right time is an important issue in mental health. Over the past 3 decades research on light and LT in the Netherlands has become well established and is still growing.

Effects of bright light therapy on neuroinflammatory and neuroplasticity markers in a diurnal rodent model of Seasonal Affective Disorder.

BACKGROUND: Bright light therapy (BLT) is widely used for treating Seasonal Affective Disorder (SAD). However, the neural mechanisms underlying the therapeutic effects of BLT remain largely unexplored. The present study used a diurnal rodent (Nile grass rats; Arvicanthis niloticus) to test the hypothesis that the therapeutic effects of BLT could be, in part, due to reduced neuroinflammation and/or enhanced neuroplasticity. Our previous research has demonstrated that compared to grass rats housed in a summer-like daytime bright light condition (1000 lux), those housed in a winter-like daytime dim light condition (50 lux) showed increased depression- and anxiety-like behaviours, as well as impaired sociosexual behaviours and spatial memory, similar to what is observed in patients suffering from SAD. MATERIALS AND METHODS: In the present study, male and female grass rats were housed under the winter-like dim daytime light condition (lights on 600-1800 hr, 50 lux). The experimental groups received daily 1-h early morning BLT from 0600-0700 using full-spectrum light (10,000 lux), while the control groups received narrowband red light (λmax, 780 nm). Following 4 weeks of treatment, the expression of several neuroinflammatory or plasticity markers was examined in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and the CA1 of the dorsal hippocampus. RESULTS: For the neuroinflammatory markers, BLT reduced TNF-α in the BLA of females, and upregulated CD11b in the mPFC and IL6 in the BLA in males. For the neuroplasticity markers, BLT downregulated BDNF in the CA1 and TrkB in all three brain regions in females but upregulated BDNF in the BLA and CA1 in males. CONCLUSIONS: These results indicate that the therapeutic effects of BLT on sleep, mood, and cognition may be attributed in part to mechanisms involving neuroinflammation and neuroplasticity in corticolimbic brain regions. Moreover, these effects appear to vary between sexes.

Change in Seasonal Beliefs Mediates the Durability Advantage of Cognitive-Behavioral Therapy Over Light Therapy for Winter Depression.

In treating an acute episode of winter depression, cognitive-behavioral therapy for seasonal affective disorder (CBT-SAD) and light therapy are comparably efficacious, with improvement in depression symptoms during CBT-SAD mediated by reduced seasonal beliefs (i.e., maladaptive thoughts about the seasons, light availability, and weather). Here, we tested whether the enduring benefit of CBT-SAD over light therapy following treatment is associated with offsetting seasonal beliefs during CBT-SAD. Currently depressed adults with Major Depression, Recurrent with Seasonal Pattern (N = 177) were randomized to 6 weeks of light therapy or group CBT-SAD and followedup one and two winters after treatment. Outcomes measured during treatment and at each follow-up included depression symptoms on the Structured Clinical Interview for the Hamilton Rating Scale for Depression-SAD Version and Beck Depression Inventory-Second Edition. Candidate mediators measured at pre-, mid-, and posttreatment were SAD-specific negative cognitions (Seasonal Beliefs Questionnaire; SBQ); general depressogenic cognitions (Dysfunctional Attitudes Scale; DAS); brooding rumination (Ruminative Response Scale-Brooding subscale; RRS-B); and chronotype (Morningness-Eveningness Questionnaire; MEQ). Latent growth curve mediation models found a significant positive path from treatment group to the slope of SBQ during treatment, with CBT-SAD showing larger improvements in seasonal beliefs with overall change in seasonal beliefs in the medium-effect range, and significant positive paths from SBQ slope to depression scores at the first and second winter follow-ups, indicating greater change towards more flexible seasonal beliefs during active treatment was associated with less severe depression symptoms following treatment. Estimated indirect effects (treatment group → SBQ change * SBQ change → outcome) were also significant at each follow-up for each outcome with ßindirect ranging from .091 to .162. Models also found significant positive paths from treatment group to the slope of MEQ and RRS-B during treatment, with light therapy showing a greater increase in "morningness" and CBT-SAD showing a greater decrease in brooding during active treatment; however, neither construct emerged as a mediator of follow-up depression scores. Change in seasonal beliefs during treatment mediates both the acute antidepressant and long-term effects of CBT-SAD and explains lower depression severity following CBT-SAD relative to light therapy.

The underexplored presence of seasonal affective disorder in the southern hemisphere: A narrative review of the Australian literature.

BACKGROUND: Seasonal Affective Disorder (SAD) is well documented in the medical literature, particularly in more northern latitudes in agreement with proposed hypotheses for SAD's pathophysiology. However, in the southern latitudes SAD's presence remains underexplored. The second largest country in the southern hemisphere is Australia. Australia has wide ranging geographical and climatic differences that are expected to support SAD's presence. The aim of this study is therefore, to establish an evidence base for SAD in Australia. METHODS: PubMed and Google Scholar were searched for published peer-review studies focussed on, or related to SAD, winter depression or seasonal variation in mood in Australia. There were no time-period restrictions. RESULTS: Thirteen studies were identified. Studies explored the presence/nature of SAD, contributing factors, autonomic activity, treatment, and the validity of the Seasonal Pattern Assessment Questionnaire in the Australian population. An association between changes in mood and behaviour and seasonal occurrence was clearly identified, with SAD's presence varying by location. The highest percentage of study participants with SAD in a single location was observed in Tasmania, Australia's most southern state. The findings and interpretations of the studies included in this review are subject to the number of locations assessed, the number of studies undertaken at each location and individual study limitations. CONCLUSIONS: Ascertaining information on the prevalence and correlates of SAD in the southern hemisphere, particularly in high-risk locations could contribute to clinical literacy into the syndrome, support management practices, and promote the early identification and treatment of the disorder.

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

BACKGROUND: Bright 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). METHODS: Male 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. RESULTS: The 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. LIMITATIONS: The 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. CONCLUSIONS: The 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.

100,000 lumens to treat seasonal affective disorder: A proof of concept RCT of Bright, whole-ROom, All-Day (BROAD) light therapy.

BACKGROUND: Seasonal affective disorder (SAD) is common and debilitating. The standard of care includes light therapy provided by a light box; however, this treatment is restrictive and only moderately effective. Advances in LED technology enable lighting solutions that emit vastly more light than traditional light boxes. Here, we assess the feasibility of BROAD (Bright, whole-ROom, All-Day) light therapy and get a first estimate for its potential effectiveness. METHODS: Patients were randomly assigned to a treatment for 4 weeks; either a very brightly illuminated room in their home for at least 6 h per day (BROAD light therapy) or 30 min in front of a standard 10,000 lux SAD light box. Feasibility was assessed by monitoring recruitment, adherence, and side effects. SAD symptoms were measured at baseline and after 2 and 4 weeks, with the Hamilton Depression Rating Scale-Seasonal Affective Disorders 29-items, self-report version. RESULTS: All 62 patients who started treatment were available at 4-week follow-up and no significant adverse effects were reported. SAD symptoms of both groups improved similarly and considerably, in line with previous results. Exploratory analyses indicate that a higher illuminance (lux) is associated with a larger symptom improvement in the BROAD light therapy group. CONCLUSIONS: BROAD light therapy is feasible and seems similarly effective as the standard of care while not confining the participants to 30 min in front of a light box. In follow-up trials, BROAD light therapy could be modified for increased illuminance, which would likely improve its effectiveness.

Blue-Light Therapy for Seasonal and Non-Seasonal Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To determine the efficacy and safety of blue-light therapy in seasonal and non-seasonal major depressive disorder (MDD), by comparison to active and inactive control conditions. METHODS: We searched Web of Science, EMBASE, Medline, PsycInfo, and Clinicaltrials.gov through January 17, 2022, for randomized controlled trials (RCTs) using search terms for blue/blue-enhanced, light therapy, and depression/seasonal affective disorder. Two independent reviewers extracted data. The primary outcome was the difference in endpoint scores on the Structured Interview Guide for the Hamilton Depression Rating Scale - Seasonal Affective Disorder (SIGH-SAD) or the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) between blue light and comparison conditions. Secondary outcomes were response (≥ 50% improvement from baseline to endpoint on a depression scale) and remission rates (endpoint score in the remission range). RESULTS: Of 582 articles retrieved, we included nine RCTs (n = 347 participants) assessing blue-light therapy. Seven studies had participants with seasonal MDD and two studies included participants with non-seasonal MDD. Four studies compared blue light to an inactive light condition (efficacy studies), and five studies compared it to an active condition (comparison studies). For the primary outcome, a meta-analysis with random-effects models found no evidence for the efficacy of blue-light conditions compared to inactive conditions (mean difference [MD] = 2.43; 95% confidence interval [CI], -1.28 to 6.14, P = 0.20); however, blue-light also showed no differences compared to active conditions (MD = -0.11; 95% CI, -2.38 to 2.16, P = 0.93). There were no significant differences in response and remission rates between blue-light conditions and inactive or active light conditions. Blue-light therapy was overall well-tolerated. CONCLUSIONS: The efficacy of blue-light therapy in the treatment of seasonal and non-seasonal MDD remains unproven. Future trials should be of longer duration, include larger sample sizes, and attempt to better standardize the parameters of light therapy.

Elucidating treatment targets and mediators within a confirmatory efficacy trial: study protocol for a randomized controlled trial of cognitive-behavioral therapy vs. light therapy for winter depression.

BACKGROUND: This study is a confirmatory efficacy trial of two treatments for winter seasonal affective disorder (SAD): SAD-tailored group cognitive-behavioral therapy (CBT-SAD) and light therapy (LT). In our previous efficacy trial, post-treatment outcomes for CBT-SAD and LT were very similar, but CBT-SAD was associated with fewer depression recurrences two winters later than LT (27.3% in CBT-SAD vs. 45.6% in LT). CBT-SAD engaged and altered a specific mechanism of action, seasonal beliefs, which mediated CBT-SAD's acute antidepressant effects and CBT-SAD's enduring benefit over LT. Seasonal beliefs are theoretically distinct from LT's assumed target and mechanism: correction of circadian phase. This study applies the experimental therapeutics approach to determine how each treatment works when it is effective and to identify the best candidates for each. Biomarkers of LT's target and effect include circadian phase angle difference and the post-illumination pupil response. Biomarkers of CBT-SAD's target and effect include decreased pupillary and sustained frontal gamma-band EEG responses to seasonal words, which are hypothesized as biomarkers of seasonal beliefs, reflecting less engagement with seasonal stimuli following CBT-SAD. In addition to determining change mechanisms, this study tests the efficacy of a "switch" decision rule upon recurrence to inform clinical decision-making in practice. METHODS: Adults with SAD (target N = 160) will be randomzied to 6-weeks of CBT-SAD or LT in winter 1; followed in winter 2; and, if a depression recurrence occurs, offered cross-over into the alternate treatment (i.e., switch from LT➔CBT-SAD or CBT-SAD➔LT). All subjects will be followed in winter 3. Biomarker assessments occur at pre-, mid-, and post-treatment in winter 1, at winter 2 follow-up (and again at mid-/post-treatment for those crossed-over), and at winter 3 follow-up. Primary efficacy analyses will test superiority of CBT-SAD over LT on depression recurrence status (the primary outcome). Mediation analyses will use parallel process latent growth curve modeling. DISCUSSION: Consistent with the National Institute of Mental Health's priorities for demonstrating target engagement at the level of Research Domain Criteria-relevant biomarkers, this work aims to confirm the targets and mechanisms of LT and CBT-SAD to maximize the impact of future dissemination efforts. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03691792 . Registered on October 2, 2018.

Body mass index and atypical balance as predictors of winter depression remission in cognitive-behavioral therapy and light therapy.

BACKGROUND: Efficacious treatments for winter seasonal affective disorder (SAD) include light therapy (LT) and cognitive-behavioral therapy (CBT-SAD); however, baseline characteristics may differentially predict treatment outcomes. This study investigated body mass index (BMI) and atypical balance (the proportion of atypical depression symptoms), as predictors of depression remission. METHODS: The parent study randomized 177 adults diagnosed with Major Depression, Recurrent with Seasonal Pattern to 6-weeks of CBT-SAD (n = 88) or LT (n = 89) and followed participants one and two winters later. At baseline, BMI was measured and atypical balance was derived using the Structured Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective Disorder Version (SIGH-SAD) as 8-item atypical subscale score/total SIGH-SAD score × 100. Depression remission was defined using standard SIGH-SAD cutpoints. Hierarchical logistic regressions tested the main effects of treatment modality, BMI, and atypical balance and their interactive effects on depression remission at post-treatment and follow-ups. RESULTS: The BMI × treatment and atypical balance × treatment interactions significantly predicted depression remission at second winter follow-up. The probability of remission was higher in CBT-SAD than LT at BMI ≤ 26.1 and atypical balance ≤ 40.3%. This predictive relationship survived when adjusting atypical balance for BMI, but not vice-versa. LIMITATIONS: Participants were predominantly White and older. BMI does not account for muscle mass or fat distribution. CONCLUSIONS: BMI and atypical balance prescriptively predicted higher likelihood of depression remission two winters following CBT-SAD but not LT. This work informs clinical decision-making and precision medicine efforts.

[Chronobiology of Depression].

Seasonal fluctuations in mood, drive, energy, sleeping- and eating behavior, weight, as well as further important mental and physical functions, and the utilization of light as an effective treatment option were already described by Hippocrates of Kos and Araeteus, the Cappadocian. The concept of the so-called seasonal affective disorder (SAD) as a disruption of the circadian rhythm precipitated by a deficiency of environmental light during darker seasons was first described in the 1980s. Furthermore, chronobiological and hormonal dysregulation in SAD patients was repeatedly shown to be accompanied by alterations on a neuroreceptor and neurotransmitter level and to normalize after remission. Hence, SAD represents one of the most important models of a chronobiological disorder with over 1000 international publications on its aetiology and treatment options, whereby their underpinnings could be elucidated on a clinical as well as molecular level. The present article summarizes the current understanding of etiological mechanisms of SAD and provides an overview of diagnostic and therapeutic strategies, which are based on available international evidence including clinical trials, systematic reviews, and meta-analyses. According to current recommendations of international guidelines, promising treatment options as bright light therapy, psychopharmacotherapy, therapeutic sleep deprivation, and their underlying mechanisms of action are presented.

Light therapy for seasonal affective disorder in visual impairment and blindness - a pilot study.

OBJECTIVE: Seasonal and non-seasonal depression are prevalent conditions in visual impairment (VI). We assessed the effects and side effects of light therapy in persons with severe VI/blindness who experienced recurrent depressive symptoms in winter corresponding to seasonal affective disorder (SAD) or subsyndromal SAD (sSAD). RESULTS: We included 18 persons (11 with severe VI, 3 with light perception and 4 with no light perception) who met screening criteria for sSAD/SAD in a single-arm, assessor-blinded trial of 6 weeks light therapy. In the 12 persons who completed the 6 weeks of treatment, the post-treatment depression score was reduced (p < 0.001), and subjective wellbeing (p = 0.01) and sleep quality were improved (p = 0.03). In 6/12 participants (50%), the post-treatment depression score was below the cut-off set for remission. In four participants with VI, side effects (glare or transiently altered visual function) led to dropout or exclusion. CONCLUSION: Light therapy was associated with a reduction in depressive symptoms in persons with severe VI/blindness. Eye safety remains a concern in persons with residual sight.

Second-generation antidepressants for treatment of seasonal affective disorder.

BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: This is an update of an earlier 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). We hand searched the reference lists of all included studies and other systematic reviews. We searched ClinicalTrials.gov for unpublished/ongoing trials. We ran a separate update search 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Ethics analysis of light and vitamin D therapies for seasonal affective disorder.

OBJECTIVE: The aim of this ethics analysis was to highlight the overt and covert value issues with regard to two health technologies (light therapy and vitamin D therapy), the health technology assessment (HTA) and the disease of seasonal affective disorder (SAD). The present ethics analysis served as a chapter of a full HTA report that aimed to assist decision makers concerning the two technologies. METHOD: First, we used the revised Socratic approach of Hofmann et al. to build overarching topics of ethical issues, and then, we conducted a hand search and a comprehensive systematic literature search on between 12 and 14 February 2019 in seven databases. RESULTS: The concrete ethical issues found concerned vulnerability of the target population and the imperative to treat depressive symptoms for the sake of preventing future harm. Further disease-related ethical issues concerned the questionable nature of SAD as a disease, autonomy, authenticity, and capacity for decision making of SAD patients, and the potential stigma related to the underdiagnosis of SAD, which is contrasted with the concern over unnecessary medicalization. Regarding the interventions and comparators, the ethical issues found concerned their benefit-harm ratios and the question of social inequality. The ethical issues related to the assessment process relate to the choice of comparators and the input data for the selected health economic studies. CONCLUSIONS: The concrete ethical issues related to the interventions, the disease, and the assessment process itself were made overt in this ethics analysis. The ethics analysis provided an (additional) value context for making future decisions regarding light and vitamin D therapies.

Seasonal Affective Disorder: Common Questions and Answers.

Seasonal affective disorder is a mood disorder that is a subtype or qualifier of major depressive disorder or bipolar disorder in the Diagnostic and Statistical Manual of Mental Disorders. It is characterized by depressive symptoms that occur at a specific time of year (typically fall or winter) with full remission at other times of year (typically spring or summer). Possible risk factors include family history, female sex, living at a more northern latitude, and young adulthood (18 to 30 years of age). With the temporal nature of the mood episodes, diagnosis requires full remission when the specified season ends and two consecutive years of episodes in the same season. First-line therapy for seasonal affective disorder includes light therapy, antidepressants, and cognitive behavior therapy, alone or in combination. Commercial devices are available for administering light therapy or dawn simulation. The light intensity and duration of treatment depend on the device and the patient's initial response, but 2,500 to 10,000 lux for 30 to 60 minutes at the same time every day is typically effective. Lifestyle interventions, such as increasing exercise and exposure to natural light, are also recommended. If seasonal affective disorder recurs, long-term treatment or preventive intervention is typically indicated, and bupropion appears to have the strongest evidence supporting long-term use. Continuing light therapy or other antidepressants is likely beneficial, although evidence is inconclusive. Evidence is also inconclusive for psychotherapy and vitamin D supplementation.

Light therapy in non-seasonal depression: An update meta-analysis.

The effect of light therapy in treating seasonal affective disorder has been demonstrated amongst previous studies. However, the effect of light therapy in treating non-seasonal depression remains unclear. This meta-analysis aimed to determine the efficacy of light therapy in non-seasonal depression. We searched for randomized controlled trials (RCTs) in the PubMed, Web of Science, Chinese National Knowledge Infrastructure, and Chinese Biomedical Database up to February 2020. The pooled post-trial standardized mean difference in depression scores with corresponding 95% confidence intervals was calculated to evaluate the efficacy of light therapy in non-seasonal depression. A total of 23 RCTs with 1120 participants were included. The meta-analysis demonstrated the light therapy was significantly more effective than comparative treatments. Subgroup analyses revealed that none of the factors explained the significantly heterogeneity. Light therapy has a statistically significant mild to moderate treatment effect in reducing depressive symptoms, can be used as a clinical therapy in treating non-seasonal depression. But the quality of evidence is still low, more well-designed studies with larger sample size and high quality are needed to confirm the efficiency of light therapy in treating non-seasonal depression.