Controlled trial of safety and efficacy of bright light therapy vs. negative air ions in patients with bipolar depression.

Treatment of bipolar disorder often results in patients taking several drugs in an attempt to alleviate residual depressive symptoms, which can lead to an accumulation of side effects. New treatments for bipolar depression that do not increase the side effect burden are needed. One nonpharmacological treatment with few side effects, bright light therapy, has been shown to be an effective therapy for seasonal affective disorder, yet has not been extensively studied for other forms of depression. Forty-four adults with bipolar disorder, depressed phase were randomized to treatment with bright light therapy, low-density or high-density negative ion generator for 8 weeks. The primary measure of efficacy was the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS). Adverse events were assessed using the Young Mania Rating Scale (YMRS) and Systematic Assessment for Treatment Emergent effects (SAFTEE). All outcome variables were statistically analyzed using a mixed model repeated measure analysis of variance (ANOVA). The results showed no statistically significant differences between groups in any outcome measures at study end point; adverse events, including switches into hypomania, were rare. Further research is needed to determine the efficacy of bright light therapy in this population.

Effects of a dawn-dusk simulation on circadian rest-activity cycles, sleep, mood and well-being in dementia patients.

Light is the most powerful "zeitgeber" signal to synchronize circadian sleep-wake cycles. In dementia, these rhythms are often fragmented - probably due to loss of neuronal function of the suprachiasmatic nuclei (the biological "master clock" in the brain) and/or weakness of external zeitgebers. We investigated the effects of a prototype dawn-dusk simulator (DDS) on circadian rest-activity cycles, sleep, mood and well-being in a balanced crossover design during fall and winter in 20 institutionalized patients with dementia (86 ±â€¯6 y, 17 f). All participants had one baseline week followed by exposure to individually timed DDS over their beds for 7-8 weeks. They spent 8 weeks without DDS as a control. Mood, self-reliant daily activity, social behavior, agitation, and quality of life were assessed by standardized questionnaires and visual analogue scales, regularly rated by trained caregivers. Circadian and sleep characteristics of their rest-activity cycles were analyzed by actimetry over 17 weeks. DDS exposure led to significantly better mood in the morning hours after waking. The effects were most pronounced in the second 4 weeks with DDS, indicating that positive effects emerged gradually. Differences in circadian rest-activity cycles and sleep were mainly age-dependent. We found statistically significant correlations between measures of higher quality of life and better mood, greater alertness and circadian rhythm stability. We conclude that continuous, long-term application of dawn-dusk simulation at the sleep-wake transitions appears to increase external zeitgeber strength in institutionalized patients with dementia. The DDS may provide an effective, non-invasive tool to improve mood and ameliorate patients' quality of life.

New perspectives on techniques for the clinical psychiatrist: Brain stimulation, chronobiology and psychiatric brain imaging.

This review summarizes a scientific dialogue between representatives in non-pharmacological treatment options of affective disorders. Among the recently introduced somatic treatments for depression those with most evidenced efficacy will be discussed. The first part of this article presents current opinions about the clinical applications of transcranial magnetic stimulation in the treatment of depression. The second part explains the most relevant uses of chronobiology in mood disorders, while the last part deals with the main perspectives on brain imaging techniques in psychiatry. The aim was to bridge gaps between the research evidence and clinical decisions, and reach an agreement on several key points of chronobiological and brain stimulation techniques, as well as on relevant objectives for future research.

Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial.

OBJECTIVE: Patients with bipolar disorder have recurrent major depression, residual mood symptoms, and limited treatment options. Building on promising pilot data, the authors conducted a 6-week randomized double-blind placebo-controlled trial to investigate the efficacy of adjunctive bright light therapy at midday for bipolar depression. The aims were to determine remission rate, depression symptom level, and rate of mood polarity switch, as well as to explore sleep quality. METHOD: The study enrolled depressed adults with bipolar I or II disorder who were receiving stable dosages of antimanic medication (excluding patients with hypomania or mania, mixed symptoms, or rapid cycling). Patients were randomly assigned to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light (N=23 for each group). Symptoms were assessed weekly with the Structured Interview Guide for the Hamilton Depression Scale With Atypical Depression Supplement (SIGH-ADS), the Mania Rating Scale, and the Pittsburgh Sleep Quality Index. Remission was defined as having a SIGH-ADS score of 8 or less. RESULTS: At baseline, both groups had moderate depression and no hypomanic or manic symptoms. Compared with the placebo light group, the group treated with bright white light experienced a significantly higher remission rate (68.2% compared with 22.2%; adjusted odds ratio=12.6) at weeks 4-6 and significantly lower depression scores (9.2 [SD=6.6] compared with 14.9 [SD=9.2]; adjusted ß=-5.91) at the endpoint visit. No mood polarity switches were observed. Sleep quality improved in both groups and did not differ significantly between them. CONCLUSIONS: The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.

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.

Controlled trial of naturalistic dawn simulation and negative air ionization for seasonal affective disorder.

OBJECTIVE: This trial assessed two novel nonpharmaceutical treatments for winter depression-naturalistic dawn simulation and high-density negative air ionization-delivered during the final hours of sleep. METHOD: The patients were 99 adults (77 women and 22 men) with the winter seasonal pattern of major depressive disorder (94 cases) and bipolar II disorder (five cases). Five parallel groups received 1) dawn simulation (0.0003-250 lux in the pattern of May 5 at 45 degrees north latitude); 2) a dawn light pulse (13 minutes, 250 lux, with an illuminant dose of 3.25x10(3) lux-minutes matched to the simulated dawn); 3) postawakening bright light (30 minutes, 10,000 lux); 4) negative air ionization at high flow rate (93 minutes, 4.5x10(14 )ions/second); or 5) ionization at low flow rate (93 minutes, 1.7x10(11) ions/second). The symptoms were assessed over 3 weeks with the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version. RESULTS: Posttreatment improvement results were bright light, 57.1%; dawn simulation, 49.5%; dawn pulse, 42.7%; high-density ions, 47.9%; and low-density ions, 22.7% (significantly lower than the others). Contrary to the authors' hypothesis, analysis of variance failed to find superiority of dawn simulation to the dawn pulse or bright light. However, the dawn pulse led to a pattern of residual or exacerbated depressive symptoms similar to those seen in low-density ion nonresponders. CONCLUSIONS: Naturalistic dawn simulation and high-density ionization are active antidepressants that do not require the effort of postawakening bright light therapy. They can be considered candidate alternatives to bright light or medication.

Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and side effects.

Bright light therapy for seasonal affective disorder (SAD) has been investigated and applied for over 20 years. Physicians and clinicians are increasingly confident that bright light therapy is a potent, specifically active, nonpharmaceutical treatment modality. Indeed, the domain of light treatment is moving beyond SAD, to nonseasonal depression (unipolar and bipolar), seasonal flare-ups of bulimia nervosa, circadian sleep phase disorders, and more. Light therapy is simple to deliver to outpatients and inpatients alike, although the optimum dosing of light and treatment time of day requires individual adjustment. The side-effect profile is favorable in comparison with medications, although the clinician must remain vigilant about emergent hypomania and autonomic hyperactivation, especially during the first few days of treatment. Importantly, light therapy provides a compatible adjunct to antidepressant medication, which can result in accelerated improvement and fewer residual symptoms.

Twilights widen the range of photic entrainment in hamsters.

The range of entrainment of the circadian rhythm of locomotor activity was compared in four groups of Syrian hamsters (eight animals per group) initially exposed to daily light-dark (LD) cycles with either abrupt transitions between light and darkness (LD-rectangular) or simulated twilights (LD-twilight). Lighting was provided by arrays of white light-emitting diodes; daytime illuminance (10 lux) and the total amount of light emitted per day were the same in the two conditions. The period (T) of the LD cycles was then gradually increased to 26.5 h or gradually decreased to 21.5 h, at the rate of 5 min/day. Under LD-rectangular, the upper and lower limits of entrainment were 25.0 to 25.5 h and 22.0 to 22.5 h, respectively, whereas under LD-twilight, 50% of the animals exposed to the lengthening cycles were still entrained at T = 26.5 h and 50% of those exposed to the shortening cycles were still entrained at T = 21.5 h. In a second experiment, two groups of hamsters were exposed to fixed T = 25 h LD-rectangular (n = 15) or LD-twilight cycles (n = 7). Only 33% of the animals entrained in LD-rectangular, whereas 86% of the animals entrained in LD-twilight. Free-running periods in constant darkness were longer following successful entrainment to T = 25 h but did not differ between the animals that entrained to LD-rectangular and those that entrained to LD-twilight. The widening of the range of entrainment observed in LD-twilight indicates that twilight transitions increase the strength of the LD zeitgeber. In LD-twilight, successful entrainment to T = 26.5 h was accompanied by an expansion of activity time to 16.52+/-1.22 h, with activity onsets preceding mid-dusk by 12.56+/-2.15 h. Together with earlier data showing similar phase response curves for hour-long dawn, dusk, and rectangular light pulses, these results suggest that the effect of twilights on the range of entrainment may involve parametric rather than nonparametric mechanisms.

An open trial of morning light therapy for treatment of antepartum depression.

OBJECTIVE: About 5% of pregnant women meet criteria for major depression. No pharmacotherapy is specifically approved for antepartum depression; novel treatment approaches may be welcome. The authors explored the use of morning bright light therapy for antepartum depression. METHOD: An open trial of bright light therapy in an A-B-A design was conducted for 3-5 weeks in 16 pregnant patients with major depression. The Hamilton Depression Rating Scale, Seasonal Affective Disorders Version, was administered to assess changes in mood. A follow-up questionnaire was used to assess outcome after delivery. RESULTS: After 3 weeks of treatment, mean depression ratings improved by 49%. Benefits were seen through 5 weeks of treatment. There was no evidence of adverse effects of light therapy on pregnancy. CONCLUSIONS: These data provide evidence that morning light therapy has an antidepressant effect during pregnancy. A randomized controlled trial is warranted to test this alternative to medication.

Randomized clinical trial of bright light therapy for antepartum depression: preliminary findings.

BACKGROUND: Bright light therapy was shown to be a promising treatment for depression during pregnancy in a recent open-label study. In an extension of this work, we report findings from a double-blind placebo-controlled pilot study. METHOD: Ten pregnant women with DSM-IV major depressive disorder were randomly assigned from April 2000 to January 2002 to a 5-week clinical trial with either a 7000 lux (active) or 500 lux (placebo) light box. At the end of the randomized controlled trial, subjects had the option of continuing in a 5-week extension phase. The Structured Interview Guide for the Hamilton Depression Scale-Seasonal Affective Disorder Version was administered to assess changes in clinical status. Salivary melatonin was used to index circadian rhythm phase for comparison with antidepressant results. RESULTS: Although there was a small mean group advantage of active treatment throughout the randomized controlled trial, it was not statistically significant. However, in the longer 10-week trial, the presence of active versus placebo light produced a clear treatment effect (p =.001) with an effect size (0.43) similar to that seen in antidepressant drug trials. Successful treatment with bright light was associated with phase advances of the melatonin rhythm. CONCLUSION: These findings provide additional evidence for an active effect of bright light therapy for antepartum depression and underscore the need for an expanded randomized clinical trial.

Dimensions of temperament and bright light response in seasonal affective disorder.

Scale scores on the Tridimensional Personality Questionnaire (TPQ)-novelty seeking (NS), harm avoidance (HA), and reward dependence (RD)-can predict response to antidepressants. This study examined 89 patients with Bipolar Disorder (I, II) or Major Depressive Disorder, both with recurrent winter seasonal pattern. The TPQ was administered while the patients were depressed, following 10-14 days of bright light therapy (30 min, 10,000 lux) and after spontaneous springtime remission. The Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD) assessed the severity of depression. At baseline, there were no significant differences between diagnostic subgroups or responders and non-responders on the TPQ or SIGH-SAD scales, though baseline RD scores were significantly higher in women than men. Furthermore, neither severity of depression nor magnitude of post-treatment clinical improvement was significantly correlated with baseline TPQ scores. Only HA scores decreased after treatment, with responders showing the greatest effect. HA scores also decreased from the baseline to springtime assessments for the group as a whole, with no difference between responders and non-responders. This is the first study to demonstrate that HA is state- rather than trait-dependent in seasonal affective disorder. The TPQ dimensions of temperament do not predict response to light therapy.

Outpatient triple chronotherapy for bipolar depression: case report.

There is an urgent need for rapid, effective, and safe treatments for bipolar depression. Triple chronotherapy is a combination of sleep deprivation, sleep phase advance, and bright light therapy that has been shown to induce accelerated and sustained remissions in bipolar depression. This case report describes the first outpatient program designed to administer triple chronotherapy and reviews the organizational and clinical requirements for providing such care.

A randomized, double-blind, placebo-controlled study of light therapy for antepartum depression.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01043289.