Nonseasonal Major Depressive Disorder Research Articles

Objective and subjective sleep in patients with non-seasonal major depressive disorder and eveningness – Results from a randomized controlled trial of bright light therapy

Study objectivesThis study examines the (dis)agreement between objective and subjective sleep and their prospective changes in a randomized controlled trial of bright light therapy (BLT) in patients with major depressive disorder (MDD) and eveningness. MethodsA total of 93 adults were randomized to receive either 30-min daily of 10,000 lux BLT or 50lux placebo dim red light therapy (DRL group) for a total of 5 weeks. Actigraphic data were collected at the baseline and during the last week of treatment. (Dis)Concordance of diary and actigraphic sleep parameters were assessed by partial correlations and Bland-Altman plots, and the associations between these discrepancies to depression severity was assessed by linear regression models. Changes of sleep parameters were assessed by linear mixed models. ResultsSignificant correlations were found between subjective sleep timings and chronotype to actigraphic parameters. Discrepancies between diary- and actigraphic-measures were observed, and patients with more severe depressive symptoms were associated with a greater under-estimation of total sleep time (TST). A greater advance in the diary-based time to fall sleep and rise time were achieved in the BLT group as compared to the DRL group, while diary-based wake after sleep onset (WASO), TST and sleep efficiency (SE) comparably improved with time in both groups. There was no significant difference between the two groups in the actigraphic parameters after treatment. ConclusionsIn this study, we found that depression severity influenced subjective report of sleep. BLT led to a greater advance in subjective sleep timings when compared to the placebo group.

Subclinical alterations of resting state functional brain network for adjunctive bright light therapy in nonseasonal major depressive disorder: A double blind randomized controlled trial.

The treatment effect of bright light therapy (BLT) on major depressive disorder (MDD) has been proven, but the underlying mechanism remains unclear. Neuroimaging biomarkers regarding disease alterations in MDD and treatment response are rarely focused on BLT. This study aimed to identify the modulatory mechanism of BLT in MDD using resting-state functional magnetic resonance imaging (rfMRI). This double-blind, randomized controlled clinical trial included a dim red light (dRL) control group and a BLT experimental group. All participants received light therapy for 30 min every morning for 4 weeks. The assessment of the Hamilton Depression Rating Scale-24 (HAMD-24) and brain MRI exam were performed at the baseline and the 4-week endpoint. The four networks in interest, including the default mode network (DMN), frontoparietal network (FPN), salience network (SN), and sensorimotor network (SMN), were analyzed. Between-group differences of the change in these four networks were evaluated. There were 22 and 21 participants in the BLT and dRL groups, respectively. Age, sex, years of education, baseline severity, and improvement in depressive symptoms were not significantly different between the two groups. The baseline rfMRI data did not show any significant functional connectivity differences within the DMN, FPN, SN, and SMN between the two groups. Compared with the dRL group, the BTL group showed significantly increased functional connectivity after treatment within the DMN, FPN, SN, and SMN. Graph analysis of the BLT group demonstrated an enhancement of betweenness centrality and global efficiency. BLT can enhance intra-network functional connectivity in the DMN, FPN, SN, and SMN for MDD patients. Furthermore, BLT improves the information processing of the whole brain. The ClinicalTrials.gov identifier was NCT03941301.

Adjunctive Bright Light Therapy for Non-Seasonal Major Depressive Disorder: A Randomized Controlled Trial.

This double-blind, randomized controlled trial assessed bright light therapy (BLT) augmentation efficacy compared with placebo light in treating non-seasonal major depressive disorder. The study participants belonged to a subtropical area (24.5°–25.5°N) with extensive daylight and included outpatients who had received stable dosages and various regimens of antidepressive agents for 4 weeks before enrollment. The outcomes were the 17-item Hamilton Depression Rating Scale, Montgomery–Asberg Depression Rating Scale, and Patient Health Questionnaire-9, which were assessed at weeks 1, 2, and 4. A total of 43 participants (mean age 45 years, ranging from 22–81) were randomized into the BLT [n = 22] and placebo light groups [n = 21]. After a 4-week administration of morning light therapy (30 min/day), depressive symptoms did not reduce significantly, which might be due to the small sample size. Nonetheless, this study had some strengths because it was conducted in warmer climates, unlike other studies, and examined diverse Asians with depression. Our findings suggest that several factors, such as poor drug response, different antidepressive regimens, duration of BLT, and daylength variability (i.e., natural daylight in the environment) may influence the utility of add-on BLT. Researchers may consider these important factors for future non-seasonal depression studies in subtropical environments.

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

ObjectivesTo 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.MethodsWe 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).ResultsOf 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.ConclusionsThe 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.

Functional outcomes with bright light in monotherapy and combined with fluoxetine in patients with major depressive disorder: Results from the LIFE-D trial

BackgroundBright light therapy has been shown to improve depressive symptoms in patients with nonseasonal major depressive disorder (MDD) but there are few studies examining functional outcomes. MethodsWe examined secondary functional outcomes in the 8-week randomized, placebo-sham-controlled LIFE-D trial comparing light therapy, fluoxetine, and the combination in patients with nonseasonal MDD. Functional assessments included the Sheehan Disability Scale (SDS) and, for employed participants, the Lam Employment Absence and Productivity Scale (LEAPS). Analysis of covariance (ANCOVA) was conducted with SDS and LEAPS change scores from baseline to week 8 as dependent variables, treatment modality (light, fluoxetine) as an independent variable, and baseline SDS and LEAPS scores as covariates. ResultsOf 122 randomized participants, SDS data were available for 105 and LEAPS data for 70. For the SDS, there were no interaction effects, but there was a significant small- to medium-sized main effect of light treatment on total SDS scores with corresponding significant effects in the Social Life and Family Life domains, but not in the Work/Study domain. There were no significant interaction or main effects with LEAPS scores. ConclusionLight therapy significantly improved social and family life functioning in patients with MDD. However, work functioning was not significantly improved despite large effect sizes; these results were limited by low statistical power because of small sample sizes. Future studies should use longer treatment durations and be powered to detect clinically relevant differences in functional outcomes.

Predictive validity of the Seasonal Beliefs Questionnaire for discriminating between seasonal and nonseasonal major depressive disorder.

The Seasonal Beliefs Questionnaire (SBQ) is a 26-item self-report measure of a winter seasonal affective disorder (SAD)-specific cognitive vulnerability consisting of maladaptive thoughts about the seasons, light availability, and weather conditions. In a known groups comparison, currently depressed adults with SAD had significantly higher SBQ scores than currently depressed adults with nonseasonal major depressive disorder (MDD) and healthy controls, and the MDD group had significantly higher SBQ scores than controls. Using that database, this study explored the predictive validity of using an SBQ cutoff score to differentiate SAD from MDD. Receiver operator characteristic curve analyses used SBQ total score to predict SAD versus MDD, SAD versus control, and MDD versus control status. The SBQ subscale combined score, derived from multivariable logistic regression with SBQ subscales, was examined as an alternative predictor. SBQ total score with a cutpoint of 132 had good predictive ability for distinguishing SAD from MDD (C-statistic = .792, sensitivity = .798, specificity = .794). The SBQ subscale combination score slightly improved predictive ability for the SAD/MDD distinction (C-statistic = .813), with better sensitivity (.930) but worse specificity (.571). In contrast, the score on a generic measure of depressogenic cognitive vulnerability, the Dysfunctional Attitudes Scale, was poor for differentiating SAD from MDD. SBQ total score was excellent in discriminating SAD cases from controls with a cutpoint of 121 (C-statistic = .962, sensitivity = .939, specificity .873), but had poor sensitivity for discriminating MDD cases from controls. Results support using the SBQ to screen for probable SAD in practice settings. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Supplemental Material for Predictive Validity of the Seasonal Beliefs Questionnaire for Discriminating Between Seasonal and Nonseasonal Major Depressive Disorder

Supplemental Material for Predictive Validity of the Seasonal Beliefs Questionnaire for Discriminating Between Seasonal and Nonseasonal Major Depressive Disorder

Quality of Life Impacts of Bright Light Treatment, Fluoxetine, and the Combination in Patients with Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial.

Bright light therapy is increasingly recommended (alone or in combination with antidepressant medication) to treat symptoms of nonseasonal major depressive disorder (MDD). However, little is known about its impacts on quality of life (QoL), a holistic, patient-valued outcome. This study utilizes secondary outcome data from an 8-week randomized, controlled, double blind trial comparing light monotherapy (n = 32), fluoxetine monotherapy (n = 30), and the combination of these (n = 27) to placebo (n = 30). QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Treatment-related differences in QoL improvements were assessed using a repeated measures analysis of variance. The influence of potential predictors of QoL (demographic variables and change in depressive symptoms) were investigated via hierarchical linear regression. Q-LES-Q-SF scores significantly improved across all treatment conditions; however, no significant differences were observed between treatment arms. QoL remained poor relative to community norms by the end of the trial period: Across conditions, 70.6% of participants had significantly impaired QoL at the 8-week assessment. Reduction in depressive scores was a significant predictor of improved QoL, with the final model accounting for 54% of variance in QoL change scores. The findings of this study emphasize that improvement in QoL and reduction in depressive symptoms in MDD, while related, cannot be taken to be synonymous. Adjunctive therapies may be required to address unmet QoL needs in patients with MDD receiving antidepressant or light therapies. Further research is required to explore additional predictors of QoL in order to better refine treatments for MDD.

A measure of cognitions specific to seasonal depression: Development and validation of the Seasonal Beliefs Questionnaire.

We introduce the Seasonal Beliefs Questionnaire (SBQ), a self-report inventory of maladaptive thoughts about the seasons, light availability, and weather conditions, proposed to constitute a unique cognitive vulnerability to winter seasonal affective disorder (SAD; Rohan, Roecklein, & Haaga, 2009). Potential items were derived from a qualitative analysis of self-reported thoughts during SAD-tailored cognitive-behavioral therapy (CBT-SAD) and subsequently refined based on qualitative feedback from 48 SAD patients. In the psychometric study (N = 536 college students), exploratory and confirmatory factor analyses pruned the items to a 26-item scale with a 5-factor solution, demonstrating good internal consistency, convergent and divergent validity, and 2-week test-retest reliability. In a known groups comparison, the SBQ discriminated SAD patients (n = 86) from both nonseasonal major depressive disorder (MDD) patients (n = 30) and healthy controls (n = 110), whereas a generic measure of depressogenic cognitive vulnerability (the Dysfunctional Attitudes Scale [DAS]) discriminated MDD patients from the other groups. In a randomized clinical trial comparing CBT-SAD with light therapy (N = 177), SBQ scores improved at twice the rate in CBT-SAD than in light therapy. Greater change in SBQ scores during CBT-SAD, but not during light therapy, was associated with a lower risk of depression recurrence 2 winters later. In contrast, DAS scores improved comparably during CBT-SAD and light therapy, and DAS change was unrelated to recurrence following either treatment. These results support using the SBQ as a brief assessment tool for a SAD-specific cognitive vulnerability and as a treatment target in CBT-SAD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Melanopsin-Driven Pupil Response and Light Exposure in Non-seasonal Major Depressive Disorder.

Background: Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) signal non-imaging forming effects of environmental light for circadian phoentrainment, the pupil light reflex, and mood regulation. In seasonal affective disorder, ipRGC dysfunction is thought to cause abberant transmission of the external illumination for photoentrainment. It is not known if patients with non-seasonal depression have abnormal melanospin mediated signaling and/or irregular environmental light exposure.Methods: Twenty-one adults who live in a sub-tropical region, including eight patients with non-seasonal depression and thirteen age-matched healthy controls were recruited. The Mini International Neuropsychiatry Interview diagnosed the presence of a major depressive disorder. Light exposure was determined using actigraphy over a 2 week period. The melanopsin mediated post-illumination pupil response (PIPR) and outer retinal inputs to ipRGCs (transient pupil response and maximum pupil constriction amplitude) were measured in response to 1 s, short and long wavelength light with high and low melanopsin excitation.Results: The mean daylight exposure as a function of clock hours and total light exposure duration (mins) to illumination levels commonly recommended for depression therapy were not significantly different between groups. Out of 84 pupil measurements (42 each in the depression and control groups), the melanopsin-mediated PIPR amplitude, transient pupil response, and pupil constriction amplitude were not significantly different between groups.Conclusions: This report provides initial evidence of normal melanopsin function and environmental light exposures in patients with pre-dominately mid and moderate non-seasonal depression in a subtropical location in the southern hemisphere.

Appetitive Symptoms Differentially Predict Treatment Response to Fluoxetine, Light, and Placebo in Nonseasonal Major Depression.

We previously reported that morning bright light therapy is efficacious in adults with nonseasonal major depressive disorder (MDD), both on its own and in combination with fluoxetine. Given that appetitive symptoms predict response to bright light therapy in seasonal depression, we examined, in this secondary analysis, whether the same held true in these nonseasonal MDD patients. Data were collected from October 7, 2009, to March 11, 2014. One hundred twenty-two patients who met DSM-IV-TR criteria for MDD without a seasonal pattern were randomly assigned to light monotherapy, fluoxetine, combination light and fluoxetine, or double-placebo (inactivated negative ion generator plus placebo pill). Multiple regression assessed the percentage change in Montgomery-Asberg Depression Rating Scale (MADRS) scores based on treatment condition, appetitive symptom score at baseline (sum of 4 items on the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders version), and the condition-by-appetitive score interaction. Sex was considered as a possible moderator of these effects. The overall regression model predicting treatment response was highly significant (P < .001), and the treatment condition-by-appetitive score interaction was a strong predictor of MADRS change scores (t = 2.65, P = .009). For individuals in the placebo group, more appetitive symptoms at baseline predicted less decrease in MADRS scores at 8 weeks (r = -0.37; large effect size). In contrast, for individuals in the active treatment groups, more appetitive symptoms at baseline predicted more of a decrease in depression scores at 8 weeks (fluoxetine group r = +0.23, medium effect size; light therapy group r = +0.11, small effect size; combination group r = +0.32, medium to large effect size). No moderation effect of sex was found. More severe appetitive symptoms at baseline predicted treatment response differentially across the 4 treatment groups. Contrary to prior findings in seasonal depression, this association was not robust for MDD patients receiving light therapy alone, although it was stronger in patients receiving fluoxetine with or without light. As the group sample sizes were modest, the current findings should be considered as preliminary only. ClinicalTrials.gov identifier: NCT00958204.

The effectiveness of bright light therapy in combination with antidepressants compared to antidepressants alone in patients with nonseasonal major depressive disorder

The effectiveness of bright light therapy in combination with antidepressants compared to antidepressants alone in patients with nonseasonal major depressive disorder

Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial.

Bright light therapy is an evidence-based treatment for seasonal depression, but there is limited evidence for its efficacy in nonseasonal major depressive disorder (MDD). To determine the efficacy of light treatment, in monotherapy and in combination with fluoxetine hydrochloride, compared with a sham-placebo condition in adults with nonseasonal MDD. Randomized, double-blind, placebo- and sham-controlled, 8-week trial in adults (aged 19-60 years) with MDD of at least moderate severity in outpatient psychiatry clinics in academic medical centers. Data were collected from October 7, 2009, to March 11, 2014. Analysis was based on modified intent to treat (randomized patients with ≥1 follow-up rating). Patients were randomly assigned to (1) light monotherapy (active 10,000-lux fluorescent white light box for 30 min/d in the early morning plus placebo pill); (2) antidepressant monotherapy (inactive negative ion generator for 30 min/d plus fluoxetine hydrochloride, 20 mg/d); (3) combination light and antidepressant; or (4) placebo (inactive negative ion generator plus placebo pill). Change score on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the 8-week end point. Secondary outcomes included response (≥50% reduction in MADRS score) and remission (MADRS score ≤10 at end point). A total of 122 patients were randomized (light monotherapy, 32; fluoxetine monotherapy, 31; combination therapy, 29; placebo, 30). The mean (SD) changes in MADRS score for the light, fluoxetine, combination, and placebo groups were 13.4 (7.5), 8.8 (9.9), 16.9 (9.2), and 6.5 (9.6), respectively. The combination (effect size [d] = 1.11; 95% CI, 0.54 to 1.64) and light monotherapy (d = 0.80; 95% CI, 0.28 to 1.31) were significantly superior to placebo in the MADRS change score, but fluoxetine monotherapy (d = 0.24; 95% CI, -0.27 to 0.74) was not superior to placebo. For the respective placebo, fluoxetine, light, and combination groups at the end point, response was achieved by 10 (33.3%), 9 (29.0%), 16 (50.0%), and 22 (75.9%) and remission was achieved by 9 (30.0%), 6 (19.4%), 14 (43.8%), and 17 (58.6%). Combination therapy was superior to placebo in MADRS response (β = 1.70; df = 1; P = .005) and remission (β = 1.33; df = 1; P = .02), with numbers needed to treat of 2.4 (95% CI, 1.6 to 5.8) and 3.5 (95% CI, 2.0 to 29.9), respectively. All treatments were generally well tolerated, with few significant differences in treatment-emergent adverse events. Bright light treatment, both as monotherapy and in combination with fluoxetine, was efficacious and well tolerated in the treatment of adults with nonseasonal MDD. The combination treatment had the most consistent effects. clinicaltrials.gov Identifier: NCT00958204.

Optimized light therapy for non-seasonal major depressive disorder: Effects of timing and season

Light Therapy (LT) when combined with standard antidepressant treatment for unipolar depression hastens recovery. We studied the influence of LT timing on the antidepressant efficacy of LT and the influence of the season of treatment and recurrence on the response to treatment. We studied 70 inpatients affected by Unipolar Depression, treated for three weeks with combined LT and venlafaxine. Two-third of the patients received LT following a predictive algorithm based on MEQ scores; the others received LT at 11:00 a.m. Severity of depression was rated on the Hamilton Depression Rating Scale (HDRS). A subgroup of patients wore activity monitors. HDRS scores significantly decreased during treatment (Friedman's ANOVA: χ2=186.82, p<0.00001). LT administered in the early morning showed a better relative efficacy than late morning (F=4.576; p=0.012) with the clinical improvement correlating with an advance in rest-activity rhythm acrophase (r=-0.336; p=0.017). Season of hospitalization interacted with LT timing and time in influencing response to treatment (F=3.101; p=0.049) and season of episode recurrence significantly interacted with LT timing, season of hospitalization and time (F=5.925; p=0.0035). The major limitation of the study is the small sample size when considering simultaneously LT schedules, season of treatment and recurrence. Moreover, even if none of the patients fulfilled DSM-IV criteria for seasonal pattern of recurrence, they were not administered any questionnaire about seasonality. We confirmed the usefulness of LT as a non-pharmacological antidepressant therapy for non-seasonal depression. Season and timing of administration and timing of the rest-activity cycle affected response to treatment.

A Randomized, Double-Blind, Placebo-Controlled Study of Light Therapy for Antepartum Depression

Affective disorder during pregnancy is a common condition requiring careful judgment to treat the depression while minimizing risk to the fetus. Following up on promising pilot trials, we studied the efficacy of light therapy. Twenty-seven pregnant women with nonseasonal major depressive disorder according to DSM-IV (outpatients, university polyclinic) were randomly assigned to 7,000 lux fluorescent bright white or 70 lux dim red (placebo) light administered at home in the morning upon awakening for 1 h/d in a 5-week double-blind trial carried out between October 2004 and October 2008. Clinical state was monitored weekly with the 29-item Structured Interview Guide for the Hamilton Depression Rating Scale (HDRS) with Atypical Depression Supplement (SIGH-ADS). Changes of rating scale scores over time were analyzed with the general linear model. Differences from baseline of SIGH-ADS and 17-item HDRS scores at every time point were the dependent variables, time was the within-subjects factor, and treatment was the between-subjects factor. The model also included baseline score of depression and gestational age at intervention start. The superiority of bright light over dim light placebo was shown for both SIGH-ADS (R² = 0.251; F(3,23) = 3.91; P < .05) and HDRS (R² = 0.338; F(3,23) = 5.42; P < .01) when analyzing the week-by-week change from baseline, and HDRS scores showed a significant interaction of treatment with time (F(4,92) = 2.91; P < .05). Categorical analysis revealed that the response rate (HDRS ≥ 50% improvement) at week 5 was significantly greater for bright light (81.3%, n = 16) than for placebo light (45.5%, n = 11) (P < .05). Remission (final score ≤ 8) was attained by 68.6% versus 36.4%, respectively (P < .05). Expectation ratings did not differ significantly between groups. Bright white light treatment for 5 weeks improved depression during pregnancy significantly more than placebo dim red light. The study provides evidence that light therapy, a simple, cost-effective antidepressant modality with minimal side effects for the mother and no known risk for the unborn child, may be a useful nonpharmacologic approach in this difficult situation. clinicaltrials.gov Identifier: NCT01043289.

Bright Light Treatment in Elderly Patients With Nonseasonal Major Depressive Disorder

Major depressive disorder (MDD) in elderly individuals is prevalent and debilitating. It is accompanied by circadian rhythm disturbances associated with impaired functioning of the suprachiasmatic nucleus, the biological clock of the brain. Circadian rhythm disturbances are common in the elderly. Suprachiasmatic nucleus stimulation using bright light treatment (BLT) may, therefore, improve mood, sleep, and hormonal rhythms in elderly patients with MDD. To determine the efficacy of BLT in elderly patients with MDD. Double-blind, placebo-controlled randomized clinical trial. Home-based treatment in patients recruited from outpatient clinics and from case-finding using general practitioners' offices in the Amsterdam region. Eighty-nine outpatients 60 years or older who had MDD underwent assessment at baseline (T0), after 3 weeks of treatment (T1), and 3 weeks after the end of treatment (T2). Intervention Three weeks of 1-hour early-morning BLT (pale blue, approximately 7500 lux) vs placebo (dim red light, approximately 50 lux). Mean improvement in Hamilton Scale for Depression scores at T1 and T2 using parameters of sleep and cortisol and melatonin levels. Intention-to-treat analysis showed Hamilton Scale for Depression scores to improve with BLT more than placebo from T0 to T1 (7%; 95% confidence interval, 4%-23%; P = .03) and from T0 to T2 (21%; 7%-31%; P = .001). At T1 relative to T0, get-up time after final awakening in the BLT group advanced by 7% (P < .001), sleep efficiency increased by 2% (P = .01), and the steepness of the rise in evening melatonin levels increased by 81% (P = .03) compared with the placebo group. At T2 relative to T0, get-up time was still advanced by 3% (P = .001) and the 24-hour urinary free cortisol level was 37% lower (P = .003) compared with the placebo group. The evening salivary cortisol level had decreased by 34% in the BLT group compared with an increase of 7% in the placebo group (P = .02). In elderly patients with MDD, BLT improved mood, enhanced sleep efficiency, and increased the upslope melatonin level gradient. In addition, BLT produced continuing improvement in mood and an attenuation of cortisol hyperexcretion after discontinuation of treatment. clinicaltrials.gov Identifier NCT00332670.

Bright light in elderly subjects with nonseasonal major depressive disorder: a double blind randomised clinical trial using early morning bright blue light comparing dim red light treatment

BackgroundDepression frequently occurs in the elderly. Its cause is largely unknown, but several studies point to disturbances of biological rhythmicity. In both normal aging, and depression, the functioning of the suprachiasmatic nucleus (SCN) is impaired, as evidenced by an increased prevalence of day-night rhythm perturbations, such as sleeping disorders. Moreover, the inhibitory SCN neurons on the hypothalamus-pituitary adrenocortical axis (HPA-axis) have decreased activity and HPA-activity is enhanced, when compared to non-depressed elderly. Using bright light therapy (BLT) the SCN can be stimulated. In addition, the beneficial effects of BLT on seasonal depression are well accepted. BLT is a potentially safe, nonexpensive and well accepted treatment option. But the current literature on BLT for depression is inconclusive.Methods/DesignThis study aims to show whether BLT can reduce non-seasonal major depression in elderly patients. Randomized double blind placebo controlled trial in 126 subjects of 60 years and older with a diagnosis of major depressive disorder (MDD, DSM-IV/SCID-I). Subjects are recruited through referrals of psychiatric outpatient clinics and from case finding from databases of general practitioners and old-people homes in the Amsterdam region. After inclusion subjects are randomly allocated to the active (bright blue light) vs. placebo (dim red light) condition using two Philips Bright Light Energy boxes type HF 3304 per subject, from which the light bulbs have been covered with bright blue- or dim red light- permitting filters. Patients will be stratified by use of antidepressants. Prior to treatment a one-week period without light treatment will be used. At three time points several endocrinological, psychophysiological, psychometrically, neuropsychological measures are performed: just before the start of light therapy, after completion of three weeks therapy period, and three weeks thereafter.DiscussionIf BLT reduces nonseasonal depression in elderly patients, then additional lightning may easily be implemented in the homes of patients to serve as add-on treatment to antidepressants or as a stand-alone treatment in elderly depressed patients. In addition, if our data support the role of a dysfunctional biological clock in depressed elderly subjects, such a finding may guide further development of novel chronobiological oriented treatment strategies.Trial registrationClinicalTrials.gov identifier: NCT00332670

Evolving applications of light therapy

The psychiatric intervention, light therapy, grew from an intensive 25-year research focus on seasonal affective disorder (SAD). Dosing and timing strategies have been honed to optimize the antidepressant effect, and efficacy relative to placebo has provided the evidence base for widespread implementation. A persistent question has been whether the model system for SAD has wider utility for psychiatric disturbance, even beyond depression. The circadian phase-shifting capacity of timed light exposure is universal, and chronobiological factors are at play across the disease spectrum. Recent promising initiatives extend to light treatment for nonseasonal major depressive disorder and bipolar depression, including drug- and electroconvulsive therapy-resistant cases. With light therapy, patients with antepartum depression may find an alternative to medication during pregnancy. Cognitive improvement under light therapy has been noted in adult attention deficit hyperactivity disorder. Motor function in Parkinson's disease has improved in parallel with the antidepressant effect of light therapy. The rest-activity disturbance of elderly dementia has been partially allayed under light therapy. In a new initiative, three major chronotherapeutic inventions-light therapy, sleep deprivation (wake therapy) and sleep time displacement (sleep phase advance therapy) are being combined to snap hospitalized patients out of deep depression and maintain long-term improvement.

Generic and health-related quality of life in patients with seasonal and nonseasonal depression

Although a relatively large body of research has now accumulated concerning the relationship between quality of life (QoL) and nonseasonal depression, there is a dearth of information about QoL in seasonal affective disorder (SAD). The aim of this study was to compare perceived levels of broad (‘generic’) and health-related QoL in patients with seasonal and nonseasonal depression. Participants were 72 patients with SAD enrolled in an on-going multicentre study in Canada, and 72 patients with nonseasonal major depressive disorder (MDD) matched for severity of depression attending an outpatient psychiatric clinic in Vancouver, British Columbia. All participants completed two measures of QoL (the 20-item Medical Outcomes Study [MOS] Short-Form General Health Survey [SF-20] and the Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q]) at baseline prior to treatment. The results of the study indicated that both generic and health-related QoL were compromised in patients with SAD compared with general population norms. For example, mean Q-LES-Q scores (range 0–100, where higher scores indicate better QoL) were 44%, compared with scores of 83% reported for the general population. Patients with nonseasonal depression showed significantly poorer functioning in several domains on the SF-20, but no significant differences in Q-LES-Q scores emerged. Perceived QoL is impaired in patients with SAD. Degree of impairment between seasonal and nonseasonal depressives is equivalent when assessed using the Q-LES-Q, but significant inter-group differences are apparent in SF-20 domain scores. Future research is required to determine whether perceived QoL is improved by treatment interventions for seasonal depression such as light therapy or antidepressant medication.

Morning and Evening Plasma Melatonin and Dexamethasone Suppression Test in Patients with Nonseasonal Major Depressive Disorder from Northern Greece (Latitude 40–41.5°)

Introduction: The present study aimed to search for correlations between melatonin (MT) levels and the dexamethasone suppression test (DST) and clinical variables. Methods: Fifty depressed patients aged 21–60 years took part in the study. The Schedules for Clinical Assessment in Neuropsychiatry, version 2.0, and the International Personality Disorders Examination were used for diagnosis. Psychometric assessment included the Hamilton Depression Rating Scale, the Hamilton Anxiety Scale, the General Assessment of Funtioning Scale, the Newcastle scales and the Diagnostic Melancholia Scale. The DST and 9.00 and 23.00 h MT values were assessed. Statistical analysis included Student’s t test, Pearson product moment correlation coefficient and forward stepwise multiple linear regression analysis. Results: Melancholic patients had lower 23.00 h MT values in comparison to the rest of the patients and the atypical and ‘undifferentiated’ patients. Conclusion: The current study shows that low MT values were closely related to melancholic depression. Distinct quality of mood, psychomotor agitation or retardation and anorexia or weight loss seemed to be responsible for this relationship.