LITERATURE SURVEY
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Treatment
of winter depression with bright light
Treatment
of nonseasonal depression with bright light, wake therapy or both
Treatment
of winter depression with dawn simulation
Treatment
of depression with high-density negative air ions
Treatment of sleep disorders (including jet lag
and shift work distress) with light
Treatment of sleep disorders with melatonin
Safety of bright light therapy
Light treatment methodology
Parkinson's disease and light
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Treatment
of winter depression with bright light
Click on an article’s title to download a PDF, where available.
| Rosenthal
NE, Sack DA, Gillin JC, et al. Seasonal affective disorder: A description of the syndrome and preliminary findings with light therapy. Archives of General Psychiatry 1984;41:72-80. Seasonal affective disorder (SAD) is a syndrome characterized by recurrent depressions that occur annually at the same time each year. We describe 29 patients with SAD; most of them had a bipolar affective disorder, especially bipolar II, and their depressions were generally characterized by hypersomnia, overeating, and carbohydrate craving and seemed to respond to changes in climate and latitude. Sleep recordings in nine depressed patients confirmed the presence of hypersomnia and showed increased sleep latency and reduced slow-wave (delta) sleep. Preliminary studies in 11 patients suggest that extending the photoperiod with bright artificial light has an antidepressant effect. |
| Rosenthal
NE, Sack DA, Carpenter CJ, et al. Antidepressant effects of light in seasonal affective disorder. American Journal of Psychiatry 1985;142:163-170. The authors treated winter depression in 13 patients with typical seasonal affective disorder by extending the length of winter days with bright and dim light in the morning and evening in a balanced-order crossover study. Bright light had a marked antidepressant effect, whereas the dim light did not. This response could not be attributed to sleep deprivation. Subsequent pilot studies indicated that bright evening light alone is probably also effective. Several patients were able to maintain the antidepressant response throughout the winter months by continuing daily light treatments. |
| Wehr
TA, Jacobsen FM, Sack DA, et al. Phototherapy of seasonal affective disorder: Time of day and suppression of melatonin are not critical for antidepressant effects. Archives of General Psychiatry 1986;43:870-875. Seasonal affective disorder is characterized by recurring cycles of fall-winter depression and spring-summer hypomania (or euthymia). In winter, depressed patients with seasonal affective disorder respond to daily treatments with five to six hours of bright artificial light in two to three days. They relapse two to three days after light is withdrawn. In this study carefully controlled experimental conditions were used to determine whether phototherapy acts via a photoperiodic mechanism in which the timing of light is critical for its therapeutic effect. Photoperiodism is a common regulatory mechanism in animal seasonal rhythms and depends for its effect on light-induced changes in the pattern of nocturnal melatonin secretion. The results reported herein of "skeleton photoperiod" experiments indicate that the efficacy of phototherapy may not depend on its timing or its effect on melatonin secretion. |
| Lewy
AJ, Sack RL, Miller LS, et al. Antidepressant and circadian phase-shifting effects of light. Science 1987;235:352-353. Bright light can suppress nighttime melatonin production in humans, but ordinary indoor light does not have this effect. This finding suggested that bright light may have other chronobiologic effects in humans as well. Eight patients who regularly became depressed in the winter (as day length shortens) significantly improved after 1 week of exposure to bright light in the morning (but not after 1 week of bright light in the evening). The antidepressant response to morning light was accompanied by an advance (shift to an earlier time) in the onset of nighttime melatonin production. These results suggest that timing may be critical for the antidepressant effects of bright light. |
| Terman
M, Terman JS, Quitkin FM, et al. Light therapy for seasonal affective disorder: a review of efficacy. Neuropsychopharmacology 1989;2:1-22. Bright artificial light has been found effective in reducing winter depressive symptoms of Seasonal Affective Disorder, although conclusions about the true magnitude of treatment effect and importance of time of day of light exposure have been limited by methodologic problems. Individual subjects' data from 14 research centers studying 332 patients over 5 years were analyzed with a pooled clustering technique. Overall, 2500-lux intensity light exposure for at least 2 hours daily for 1 week resulted in significantly more remissions &- Hamilton Depression Rating Scale (HAM-D) score reduction of 50% or more to a level under 8 &- when administered in the early morning (53%) than in the evening (38%) or at midday (32%). All three times were significantly more effective than dim light controls (11%). Dual daily exposures (morning-plus-evening light) provided no benefit over morning light alone. In the morning-evening crossovers, remission rates were 62% under morning light alone, compared with 28% under evening light alone, with a differential morning-evening response present in 59% of morning responders compared with 10% of evening responders (p < 0.001). Remission rates with morning light were highest given low severity at baseline (HAM-D score of 10-16: 67% remission), as compared with moderate-to-severe cases (HAM-D score above 16: approximately 40% remission) where no morning-evening differences were found. Firmer conclusions await treatment studies with larger sample sizes and full assessment of atypical vegetative symptoms seen in winter depression but underrepresented in the Hamilton scale. Longer treatment course and greater light intensity may help clarify clinical response despite the impossibility of achieving a conventional blind placebo control. |
| Sack
RL, Lewy AJ, White DM, et al. Morning vs. evening light treatment for winter depression: Evidence that the therapeutic effects of light are mediated by circadian phase shifts. Archives of General Psychiatry 1990;47:342-351. Bright light exposure has been found to alleviate the symptoms of recurrent winter depression in many patients. The mechanism of light therapy may involve shifts in the timing (phase) of circadian rhythms. In this study, morning light exposure (which shifts rhythms earlier) was compared with evening light exposure (which shifts rhythms later) in a double-blind, crossover design. The onset of melatonin secretion in the evening was measured under dim light conditions as a marker for circadian timing (phase) before and after each treatment. Eight patients with winter depression and five control subjects were studied. Morning light was found to be significantly better than evening light in reducing depressive symptoms. At baseline, there was a trend for the onset of melatonin production to be later in the patients than in the controls. Morning light shifted the melatonin onset significantly earlier in the patients but not in the controls. Our findings suggest that patients with winter depression have circadian rhythms that are abnormally delayed and that bright light therapy benefits winter depression by providing a corrective advance. |
| Terman
JS, Terman M, Schlager D, et al. Efficacy of brief, intense light exposure for treatment of winter depression. Psychopharmacology Bulletin 1990;26:3-11. A high-intensity fluorescent lighting system, tilted downward toward the head, and emitting negligible levels of ultraviolet radiation, was tested under two random crossover protocols in winter-depressed patients: 30-minute sessions at a) 3,000 lux vs. 10,000 lux in early morning, and (b) morning vs. evening sessions at 10,000 lux. Judgment of clinical remission was based jointly on relative and absolute score improvements on a Structured Interview Guide for the Hamilton Depression Scale &- Seasonal Affective Disorder Version (SIGH-SAD) which includes a set of supplementary atypical-vegetative items. Data are presented for 24 subjects who showed relapse upon withdrawal. An overall remission rate of 75 percent was found for morning light at 10,000 lux. The rates for evening light (25%) and 3,000 lux morning light (19%) were significantly lower. The remission rate for morning light treatment of 10,000 lux for 30 minutes approximately equaled 2,500 lux treatment for 2 hours (data from our earlier studies), suggesting a reciprocity between dosing dimensions of intensity and duration. No pathological changes were revealed by ophthalmological examinations given after 2 to 6 weeks of daily treatment. |
| Terman
M, Amira L, Terman JS, et al. Predictors of response and nonresponse to light treatment for winter depression. American Journal of Psychiatry 1996;153(11):1423-1429. OBJECTIVE: The authors' goal was to determine whether the pattern and severity of depressive symptoms predict response to light treatment for seasonal affective disorder. METHOD: Subjects with winter depression (N = 103) were given bright light treatment. Seventy-one were classified as responders, 15 as nonresponders, and 17 as partial responders. Using depression rating scale data and correlational and multivariate analysis, the authors sought predictors of response in baseline symptom and scale scores. RESULTS: Responders were characterized by atypical symptoms, especially hypersomnia,afternoon or evening slump, reverse diurnal variation (evenings worse), and carbohydrate craving. By contrast, nonresponders were characterized mainly by melancholic symptoms, retardation, suicidality, depersonalization, typical diurnal variation (mornings worse), anxiety, early and late insomnia, appetite loss, and guilt. The ratio of atypical to classical symptoms of depression, rather than severity per se, best predicted treatment outcome for the group as a whole. Pretreatment expectations were positively correlated with improvement on the Hamilton Depression Rating Scale but not on a supplementary scale of atypical symptoms. CONCLUSIONS: Light responsive seasonal affective disorder is distinguished by a dominant atypical symptom profile closely associated with depressed mood. Nonresponders from a clinically distinct group with melancholic features. The patient's symptom profile, therefore, should be considered when diagnosing seasonal affective disorder and selecting treatment. |
| Eastman
CI, Young MA, Fogg LF, et al. Bright light treatment of winter depression, a placebo-controlled trial. Archives of General Psychiatry 1998;55,883-889. Background: Bright light therapy is the recommended treatment for winter seasonal affective disorder (SAD). However, the studies with the best placebo controls have not been able to demonstrate that light treatment has a benefit beyond its placebo effect. Methods: Ninety-six patients with SAD completed the study. Patients were randomly assigned to 1 of 3 treatments for 4 weeks, each 1.5 hours per day: morning light (average start time around 6 AM), evening light (average start about 9 PM), or morning placebo (average start about 6 AM). The bright light (~6000 lux) was produced by light boxes, and the placebos were sham negative-ion generators. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale, SAD version (SIGH-SAD) were performed weekly. Results: There were no differences among the 3 groups in expectation ratings or mean depression scores after 4 weeks of treatment. However, strict response criteria revealed statistically significant differences; after 3 weeks of treatment morning light produced more of the complete or almost complete remissions than placebo. By 1 criterion (24-item SIGH-SAD score <50% of baseline and =8), 61% of the patients responded to morning light, 50% to evening light, and 32% to placebo after 4 weeks of treatment. Conclusions: Bright light therapy had a specific antidepressant effect beyond its placebo effect, but it took at least 3 weeks for a significant effect to develop. The benefit of light over placebo was in producing more of the full remissions. |
| Lewy
AJ, Bauer VK, Cutler NL, et al. Morning vs. evening Light treatment of patients with winter depression. Archives of General Psychiatry 1998;55:890-896. Background: According to the phase-shift hypothesis for winter depression, morning light (which causes a circadian phase advance) should be more antidepressant than evening light (which causes a delay). Although no studies have shown evening light to be more antidepressant than morning light, investigations have shown either no difference or morning light to be superior. The present study assesses these light-exposure schedules in both crossover and parallel-group comparisons. Methods: Fifty-one patients and 49 matched controls were studied for 6 weeks. After a prebaseline assessment and a light/dark and sleep/wake adaptation baseline week, subjects were exposed to bright light at either 6 to 8 AM or 7 to 9 AM for 2 weeks. After a week of withdrawal from light treatment, they were crossed over to the other light schedule. Dim-light melatonin onsets were obtained 7 times during the study to assess circadian phase position. Results: Morning light phase-advanced the dim-light melatonin onset and was more antidepressant than evening light, which phase-delayed it. These finding were statistically significant for both crossover and parallel-group comparisons. Dim-light melatonin onsets were generally delayed in the patients compared with the controls. Conclusions: These results should help establish the importance of circadian (morning or evening) time of light exposure in the treatment of winter depression. We recommend that bright-light exposure be scheduled immediately on awakening in the treatment of most patients with seasonal affective disorder. |
| Terman
M, Terman JS, Ross DC. A controlled trial of timed bright light and negative air ionization for treatment of winter depression. Archives of General Psychiatry. 1998;55:875-882. BACKGROUND: Artificial bright light presents a promising nonpharmacological treatment for seasonal affective disorder. Past studies, however, have lacked adequate placebo controls or sufficient power to detect group differences. The importance of time of day of treatment--specifically, morning light superiority--has remained controversial. METHODS: This study used a morning x evening light crossover design balanced by parallel-group controls, in addition to a nonphotic control, negative air ionization. Subjects with seasonal affective disorder (N = 158) were randomly assigned to 6 groups for 2 consecutive treatment periods, each 10 to 14 days. Light treatment sequences were morning-evening, evening-morning, morning-morning, and evening-evening (10,000 lux, 30 min/d). Ion density was 2.7 x 10^6 (high) or 1.0 x 10^4 (low) ions per cubic centimeter (high-high and low-low sequences, 30 min/d in the morning). RESULTS: Analysis of depression scale percentage change scores showed low-density ion response to be inferior to all other groups, with no other group differences. Response to evening light was reduced when preceded by treatment with morning light, the sole sequence effect. Stringent remission criteria, however, showed significantly higher response to morning than evening light, regardless of treatment sequence. CONCLUSIONS: Bright light and high-density negative air ionization both appear to act as specific antidepressants in patients with seasonal affective disorder. Whether clinical improvement would be further enhanced by their use in combination, or as adjuvants to medication, awaits investigation. |
| Wirz-Justice
A. Beginning to see the light. Archives of General Psychiatry. 1998;55:861-862. |
| Golden
RN, Gaynes BN, Ekstrom RD, et al. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. American Journal of Psychiatry. 2005;162:656-662. OBJECTIVE: The purpose of this study was to assess the evidence base for the efficacy of light therapy in treating mood disorders. METHOD: The authors systematically searched PubMed (January 1975 to July 2003) to identify randomized, controlled trials of light therapy for mood disorders that fulfilled predefined criteria. These articles were abstracted, and data were synthesized by disease and intervention category. RESULTS: Only 13% of the studies met the inclusion criteria. Meta-analyses revealed that a significant reduction in depression symptom severity was associated with bright light treatment (eight studies, having an effect size of 0.84 and 95% confidence interval [CI] of 0.60 to 1.08) and dawn simulation in seasonal affective disorder (five studies; effect size=0.73, 95% CI=0.37 to 1.08) and with bright light treatment in nonseasonal depression (three studies; effect size=0.53, 95% CI=0.18 to 0.89). Bright light as an adjunct to antidepressant pharmacotherapy for nonseasonal depression was not effective (five studies; effect size=-0.01, 95% CI=-0.36 to 0.34). CONCLUSIONS: Many reports of the efficacy of light therapy are not based on rigorous study designs. This analysis of randomized, controlled trials suggests that bright light treatment and dawn simulation for seasonal affective disorder and bright light for nonseasonal depression are efficacious, with effect sizes equivalent to those in most antidepressant pharmacotherapy trials. Adopting standard approaches to light therapy's specific issues (e.g., defining parameters of active versus placebo conditions) and incorporating rigorous designs (e.g., adequate group sizes, randomized assignment) are necessary to evaluate light therapy for mood disorders. |
Treatment of nonseasonal
depression with bright light, wake therapy, or both
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on an article’s title to download a PDF, where available.
| Wirz-Justice
A, Van den Hoofdakker RH. Sleep deprivation in depression: what do we know, where do we go? Biolological Psychiatry. 1999;46:445-453. Manipulations of the sleep-wake cycle, whether of duration (total or partial sleep deprivation [SD]) or timing (partial SD, phase advance), have profound and rapid effects on depressed mood in 60% of all diagnostic subgroups of affective disorders. Relapse after recovery sleep is less when patients are receiving medication; it may be prevented by co-administration of lithium, pindolol, serotonergic antidepressants, bright light, or a subsequent phase advance procedure. Diurnal and day-to-day mood variability predict both short-term response to SD and long-term response to antidepressant drug treatment. These mood patterns can be understood in terms of a "two-process model of mood regulation" based on the model well established for sleep regulation: the interaction of circadian and homeostatic processes. The therapeutic effect of SD is postulated to be linked to changes in disturbed circadian- and sleep-wake-dependent phase relationships and concomitant increase of slow-wave-sleep pressure; additionally, SD-induced sleepiness may counteract the hyperarousal state in depression. This model has the advantage of providing a comprehensive theoretical framework and stringent protocols ("constant routine," "forced desynchrony") to dissect out specific disturbances. Many aspects tie in with current serotonergic receptor hypotheses of SD action. A treatment inducing euthymia in severely depressed patients within hours is an important therapeutic option that has come of age for clinical use. |
| Wirz-Justice
A, Terman M, Oren DA, et al. Brightening depression. Science 2004;303:467-469. |
| Wirz-Justice
A, Benedetti F, Berger M, et al. Chronotherapeutics (light and wake therapy) in affective disorders. Psychological Medicine. 2005;35:939-944. The Committee on Chronotherapeutics, delegated by the International Society for Affective Disorders (ISAD), makes the following recommendations after reviewing the evidence as of November 2004. (1) Wake therapy is the most rapid antidepressant available today: approximately 60% of patients, independent of diagnostic subtype, respond with marked improvement within hours. Treatment can be a single or repeated sleep deprivation, total (all night) or partial (second half of the night). Relapse can be prevented by daily light therapy, concomitant administration of SSRIs, lithium (for bipolar patients), or a short phase advance of sleep over 3 days following a single night of wake therapy. Combinations of these interventions show great promise. (2) Light therapy is effective for major depression--not only for the seasonal subtype. As an adjuvant to conventional antidepressants in unipolar patients, or lithium in bipolar patients, morning light hastens and potentiates the antidepressant response. Light therapy shows benefit even for patients with chronic depression of 2 years or more, outperforming their weak response to drugs. This method provides a viable alternative for patients who refuse, resist or cannot tolerate medication, or for whom drugs may be contraindicated, as in antepartum depression. (3) Given the urgent need for new strategies to treat patients with residual depressive symptoms, clinical trials of wake therapy and/or adjuvant light therapy, coupled with follow-up studies of long-term recurrence, are a high priority. |
| Tuunainen
A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Systematic Reviews. 2004;(2):CD004050. BACKGROUND: Efficacy of light therapy for non-seasonal depression has been studied without any consensus on its efficacy. OBJECTIVES: To evaluate clinical effects of bright light therapy in comparison to the inactive placebo treatment for non-seasonal depression. SEARCH STRATEGY: We searched the Depression Anxiety & Neurosis Controlled Trials register (CCDANCTR January 2003), comprising the results of searches of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 -), EMBASE (1980 -), CINAHL (1982 -), LILACS (1982 -), National Research Register, PsycINFO/PsycLIT (1974 -), PSYNDEX (1977 -), and SIGLE (1982 - ) using the group search strategy and the following terms: #30 = phototherapy or ("light therapy" or light-therapy). We also sought trials from conference proceedings and references of included papers, and contacted the first author of each study as well as leading researchers in the field. SELECTION CRITERIA: Randomized controlled trials comparing bright light with inactive placebo treatments for non-seasonal depression. DATA COLLECTION AND ANALYSIS: Data were extracted and quality assessment was made independently by two reviewers. The authors were contacted to obtain additional information. MAIN RESULTS: Twenty studies (49 reports) were included in the review. Most of the studies applied bright light as adjunctive treatment to drug therapy, sleep deprivation, or both. In general, the quality of reporting was poor, and many reviews did not report adverse effects systematically. The treatment response in the bright light group was better than in the control treatment group, but did not reach statistical significance. The result was mainly based on studies of less than 8 days of treatment. The response to bright light was significantly better than to control treatment in high-quality studies (standardized mean difference (SMD) -0.90, 95% confidence interval (CI) -1.50 to -0.31), in studies applying morning light treatment (SMD -0.38, CI -0.62 to -0.14), and in sleep deprivation responders (SMD -1.02, CI -1.60 to -0.45). Hypomania was more common in the bright light group compared to the control treatment group (risk ratio 4.91, CI 1.66 to 14.46, number needed to harm 8, CI 5 to 20).Twenty studies (49 reports) were included in the review. Most of the studies applied bright light as adjunctive treatment to drug therapy, sleep deprivation, or both. Treatment REVIEWERS' CONCLUSIONS: For patients suffering from non-seasonal depression, bright light therapy offers modest though promising antidepressive efficacy, especially when administered during the first week of treatment, in the morning, and as an adjunctive treatment to sleep deprivation responders. Hypomania as a potential adverse effect needs to be considered. Due to limited data and heterogeneity of studies these results need to be interpreted with caution. |
| Benedetti
F, Colombo C, Pontiggia A, et al. Morning light treatment hastens the antidepressant effect of citalopram: a placebo-controlled trial. Journal of Clinical Psychiatry. 2003;64:648-653. BACKGROUND: Selective serotonin reuptake inhibitors are effective in approximately 70% of patients with a major depressive episode, but therapeutic changes usually require 2 weeks of administration to become clinically relevant. Adjunct light therapy has been proposed to hasten the effects of drug treatment. The purpose of the present study was to evaluate the effect of morning light therapy or placebo combined with citalopram in the treatment of patients affected by a major depressive episode without psychotic features. METHOD: Thirty inpatients (DSM-IV major depressive disorder [N = 21] and bipolar disorder [N = 9]) were treated with citalopram, 40 mg, and randomized in a 3:2 manner to receive 30 minutes of 400 lux green light treatment in the morning or placebo (exposure to a deactivated negative ion generator) during the first 2 weeks of drug treatment. Timing of light therapy was individually defined to obtain a 2-hour phase advance to morning light. Outcome was measured with the Hamilton Rating Scale for Depression and the Zung Self-Rating Depression Scale every week, and with a Visual Analogue Scale 3 times a day during the first week. RESULTS: All outcome measures showed significantly (p <.05) better mood improvement in light-treated patients, resulting in faster responses to antidepressant treatment. CONCLUSION: The combination of citalopram and light treatment was more effective than citalopram and placebo in the treatment of major depression. With an optimized timing of administration, low-intensity light treatment significantly hastened and potentiated the effect of citalopram, thus providing the clinical psychiatrists with an augmenting strategy that was found effective and devoid of side effects. |
| Martiny
K. Adjunctive bright light in non-seasonal major depression. Acta Psychiatrica Scandinavica Suppl. 2004;(425):7-28. OBJECTIVE: Bright light treatment is an established treatment for Seasonal Affective Disorder, but in non-seasonal depression research results have been contrasting. METHOD: This study was designed as a 5-week controlled, double-blind, parallel trial in out-patients with a diagnosis (DSM-IV) of non-seasonal major depression, randomized to either active treatment (white light, 10 000 lux, 1 h daily) or placebo treatment (red light, 50 lux, 30 min daily) and concomitant treatment with sertraline in both groups. RESULTS: One hundred and two patients were included in the study. Analyses showed that on all used scales the reduction in depression scores was larger in the bright light group than in the dim light group, and this reached statistical significance on all observer rating scales and on the SCL-90R self-assessment scale. The HAM-D6 was the most sensitive scale to measure improvement at endpoint. CONCLUSION: The study results support the use of bright light as an adjunct treatment to antidepressants in non-seasonal depression. |
| Goel
N, Terman M, Terman JS, et al. Controlled trial of bright light and negative air ions for chronic depression. Psychological Medicine. 2005;35:945-955. BACKGROUND: This randomized controlled trial investigates the efficacy of two non-pharmacologic treatments, bright light and high-density negative air ions for non-seasonal chronic depression. Both methods have shown clinical success for seasonal affective disorder (SAD). METHOD: Patients were 24 (75%) women and 8 (25%) men, ages 22-65 years (mean age ± S.D., 43.7 ± 12.4 years), with Major Depressive Disorder, Single Episode (DSM-IV code, 296.2), Chronic (episode duration > or = 2 years). Patients were entered throughout the year and randomly assigned to exposure to bright light (10 000 lux, n = 10), or high-density (4.5 x 1014 ions/s flow rate, n = 12) or low-density (1.7 x 1011 ions/s, n = 10, placebo control) negative air ions. Home treatment sessions occurred for 1 h upon awakening for 5 weeks. Blinded raters assessed symptom severity weekly with the Structured Interview Guide for the Hamilton Depression Rating Scale--Seasonal Affective Disorder (SIGH-SAD) version. Evening saliva samples were obtained before and after treatment for ascertainment of circadian melatonin rhythm phase. RESULTS: SIGH-SAD score improvement was 53.7% for bright light and 51.1% for high-density ions v. 170% for low-density ions. Remission rates were 50%, 50% and 0% respectively. The presence or severity of atypical symptoms did not predict response to either treatment modality, nor were phase advances to light associated with positive response. CONCLUSIONS: Both bright light and negative air ions are effective for treatment of chronic depression. Remission rates are similar to those for SAD, but without a seasonal dependency or apparent mediation by circadian rhythm phase shifts. Combination treatment with antidepressant drugs may further enhance clinical response. |
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Treatment of winter depression
with dawn simulation
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| Terman
M, Schlager D, Fairhurst S, et al. Dawn and dusk simulation as a therapeutic intervention. Biological Psychiatry. 1989;25:966-970. |
| Terman
M and Schlager D. Twilight therapeutics, winter depression, melatonin, and sleep. Sleep and Biological Rhythms, J. Montplaisir and R. Godbout, Eds. New York: Oxford University Press, pp. 113-128. This chapter explores effects of simulated dawn twilight exposures on a group of winter depressives. We ask whether high daylight intensities are necessary to achieve the antidepressant effect if a more naturalistic exposure pattern is provided in the bedroom. Eight subjects in the New York City area were selected with a diagnosis of major affective disorder, depressed, seasonal type, winter pattern by DSM-III-R criteria.While in their depressed state during December through March the subjects were exposed, in 7- to 14-day home trials, to simulated twilight profiles delivered at the bedside. The lighting system included an encased bright fluorescent light source, light attenuation mechanism, microprocessor controller, and photosensor feedback loop. A comprehensive reference-generating algorithm was used to specify the expected momentary level of horizontal illumination of the earth's surface &- from skylight, sunlight, and starlight sources (and, optionally, from moonlight) &- across the 24-hr day at any specified day of year and geographic latitude. The morning light signals consisted of dawn profiles whose latitude, calendar date, and timing varied among the subjects. In all cases, the timing of the twilight signal corresponded to a calendar date well past the onset of natural remission for the subject. The light profiles, determined by the algorithm, progressed to a maximum illuminance approximately 1 min after sunrise, a level maintained until the subject left bed. After 2 weeks of daily dawn twilight exposure, six of the eight subjects showed full remissions of SAD symptoms. Naturalistic dawn exposures, timed to correspond to calendar dates during natural remission, appeared to be effective in alleviating symptoms of winter depression. |
| Avery
DH, Bolte MA, Dager SR, et al. Dawn simulation treatment of winter depression: a controlled study. American Journal of Psychiatry 1993;150:113-117. OBJECTIVE: This study sought to determine whether dawn simulation was superior to a shorter dimmer "placebo" dawn signal in treating winter depression. METHOD: In a randomized, parallel design, 22 patients with winter depression were treated with either 1 week of a 2-hour dawn simulation peaking at 250 lux or 1 week of a 30-minute dawn simulation peaking at 0.2 lux. The subjects were told that they would receive either a "gradual" dawn or a "rapid" dawn reaching an intensity that would be dimmer than standard bright light treatment. At the end of both the baseline week and the treatment week, subjects were assessed in a blind manner with the Hamilton Rating Scale for Depression. Analysis of covariance was used to compare the two dawn treatments. RESULTS: The 2-hour, 250-lux dawn simulation resulted in Hamilton depression scale scores that were significantly lower than scores after the 30-minute, 0.2-lux dawn simulation. CONCLUSIONS: This study indicates that dawn simulation is an effective treatment for winter depression. |
| Terman,
M. Light on sleep. Sleep Science: Integrating Basic Research and Clinical Practice, WJ Schwartz, Ed. Basel:Karger;1997,230-251. In this chapter, "the novel therapeutic applications of naturalistic light, soporific at dusk and alerting at dawn, [are evaluated]. Such an approach would have been unimaginable before it was discovered that human rhythms, like those in experimental animals, can be shifted and synchronized by photic stimuli. A good night's sleep may be one unforeseen casualty of our artificially-lit urban lifestyle." -W.J. Schwartz |
| Avery
DH, Eder DN, Bolte MA, Hellekson CJ, Dunner DL, Vitiello MV, Prinz PN. Dawn simulation and bright light in the treatment of SAD: a controlled study. Biolological Psychiatry. 2001;50:205-216. BACKGROUND: Some small controlled studies have found that dawn simulation is effective in treating seasonal affective disorder (SAD). With a larger sample size and a longer duration of treatment, we compared dawn simulation with bright light therapy and a placebo condition in patients with SAD. METHOD: Medication-free patients with SAD were randomly assigned to one of three conditions: bright light therapy (10,000 lux for 30 min, from 6:00 AM to 6:30 AM), dawn simulation (1.5 hour dawn signal from 4:30 AM to 6:00 AM peaking at 250 lux), and a placebo condition, a dim red light (1.5 hour dawn signal from 4:30 am to 6:00 AM peaking at 0.5 lux.) Over the subsequent 6 weeks, the subjects were blindly rated by a psychiatrist using the Structured Interview Guide for the Hamilton Depression Rating-Seasonal Affective Disorder Version (SIGH-SAD). We modeled the profiles of the remissions (SIGH-SAD < or = 8) and response (> or =50% decrease in SIGH-SAD) to treatment over time using Cox proportional hazards models. RESULTS: The sample consisted of 95 subjects who were randomized to the three conditions: bright light (n = 33), dawn simulation (n = 31) and placebo (n = 31). Dawn simulation was associated with greater remission (p <.05) and response (p <.001) rates compared to the placebo. Bright light did not differ significantly from the placebo. Dawn simulation was associated with greater remission (p <.01) and response (p <.001) rates compared to the bright light therapy. The mean daily hours of sunshine during the week before each visit were associated with a significant increase in likelihood of both remission (p <.001) and response (p <.001). CONCLUSIONS: Dawn simulation was associated with greater remission and response rates compared to the placebo and compared to bright light therapy. The hours of sunshine during the week before each assessment were associated with a positive clinical response. |
| Terman
M, Terman JS. Controlled trial of naturalistic dawn simulation and negative air ionization for seasonal affective disorder. American Journal of Psychiatry. 2006; in press. Background. This clinical 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. Methods. Patients were 99 adults (77 women, 22 men) with winter seasonal pattern of Major Depressive Disorder (94 cases) and Bipolar II Disorder (5 cases). Five parallel groups received: (a) dawn simulation (0.0003-250 lux in the pattern of 5 May at 45 ºN latitude); (b) a dawn light pulse (13 min, 250 lux, with illuminant dose of 3.25 x 103 lux•min matched to the simulated dawn); (c) post-awakening bright light (30 min, 10,000 lux); (d) negative air ionization at high flow rate (93 min, 4.5 x 1014 ions/sec); or (e) ionization at low flow rate (93 min, 1.7 x 1011 ions/sec). Symptoms were assessed over 3 weeks using the Structured Interview Guide for the Hamilton Depression Rating Scale – Seasonal Affective Disorder Version. Results. Posttreatment improvement was: 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 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 that seen in low-density ion nonresponders. Conclusions. Naturalistic dawn simulation and high-density ionization are active antidepressants that do not require effort of post-awakening bright light therapy. They can be considered candidate alternatives to bright light or medication. |
Treatment of depression
with high-density negative air ions
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| Terman
M and Terman JS. Treatment of seasonal affective disorder with a high-output negative ionizer. Journal of Alternative and Complementary Medicine 1995;1:87-92. This study was designed to evaluate the antidepressant effect of negative ions in the ambient air as a potential treatment modality for seasonal affective disorder. Twenty-five subjects with winter depression underwent a double-blind controlled trial of negative ions at two exposure densities, 1 x 10(4) ions/cm3 or 2.7 x 10(6) ions/cm3, using an electronic negative ion generator with wire corona emitters. Home treatments were taken in the early morning for 30 min over 20 days, followed by withdrawals. The severity of depressive symptoms (prominently including the reverse neurovegetative symptoms of hypersomnia, hyperphagia, and fatigability) decreased selectively for the group receiving high-density treatment. Standard depression rating scale assessments were corroborated by clinical impressions. When a remission criterion of 50% or greater reduction in symptom frequency/severity was used, 58% of subjects responded to high-density treatment while 15% responded to low-density treatment (chi 2 = 5.00, df = 1, p = 0.025). There were no side effects attributable to the treatment, and all subjects who responded showed subsequent relapse during withdrawal. Treatment with a high-density negative ionizer appears to act as a specific antidepressant for patients with seasonal affective disorder. The method may be useful as an alternative or supplement to light therapy and medications. |
| Terman
M, Terman JS, Ross DC. A controlled trial of timed bright light and negative air ionization for treatment of winter depression. Archives of General Psychiatry. 1998;55:875-882. BACKGROUND: Artificial bright light presents a promising nonpharmacological treatment for seasonal affective disorder. Past studies, however, have lacked adequate placebo controls or sufficient power to detect group differences. The importance of time of day of treatment--specifically, morning light superiority--has remained controversial. METHODS: This study used a morning x evening light crossover design balanced by parallel-group controls, in addition to a nonphotic control, negative air ionization. Subjects with seasonal affective disorder (N = 158) were randomly assigned to 6 groups for 2 consecutive treatment periods, each 10 to 14 days. Light treatment sequences were morning-evening, evening-morning, morning-morning, and evening-evening (10,000 lux, 30 min/d). Ion density was 2.7 x 10^6 (high) or 1.0 x 10^4 (low) ions per cubic centimeter (high-high and low-low sequences, 30 min/d in the morning). RESULTS: Analysis of depression scale percentage change scores showed low-density ion response to be inferior to all other groups, with no other group differences. Response to evening light was reduced when preceded by treatment with morning light, the sole sequence effect. Stringent remission criteria, however, showed significantly higher response to morning than evening light, regardless of treatment sequence. CONCLUSIONS: Bright light and high-density negative air ionization both appear to act as specific antidepressants in patients with seasonal affective disorder. Whether clinical improvement would be further enhanced by their use in combination, or as adjuvants to medication, awaits investigation. |
| Terman
M, Terman JS. Controlled trial of naturalistic dawn simulation and negative air ionization for seasonal affective disorder. American Journal of Psychiatry. 2006; in press. Background. This clinical 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. Methods. Patients were 99 adults (77 women, 22 men) with winter seasonal pattern of Major Depressive Disorder (94 cases) and Bipolar II Disorder (5 cases). Five parallel groups received: (a) dawn simulation (0.0003-250 lux in the pattern of 5 May at 45 ºN latitude); (b) a dawn light pulse (13 min, 250 lux, with illuminant dose of 3.25 x 103 lux•min matched to the simulated dawn); (c) post-awakening bright light (30 min, 10,000 lux); (d) negative air ionization at high flow rate (93 min, 4.5 x 1014 ions/sec); or (e) ionization at low flow rate (93 min, 1.7 x 1011 ions/sec). Symptoms were assessed over 3 weeks using the Structured Interview Guide for the Hamilton Depression Rating Scale – Seasonal Affective Disorder Version. Results. Posttreatment improvement was: 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 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 that seen in low-density ion nonresponders. Conclusions. Naturalistic dawn simulation and high-density ionization are active antidepressants that do not require effort of post-awakening bright light therapy. They can be considered candidate alternatives to bright light or medication. |
| Goel
N, Terman M, Terman JS, et al. Controlled trial of bright light and negative air ions for chronic depression. Psychological Medicine. 2005;35:945-955. BACKGROUND: This randomized controlled trial investigates the efficacy of two non-pharmacologic treatments, bright light and high-density negative air ions for non-seasonal chronic depression. Both methods have shown clinical success for seasonal affective disorder (SAD). METHOD: Patients were 24 (75%) women and 8 (25%) men, ages 22-65 years (mean age ± S.D., 43.7 ± 12.4 years), with Major Depressive Disorder, Single Episode (DSM-IV code, 296.2), Chronic (episode duration > or = 2 years). Patients were entered throughout the year and randomly assigned to exposure to bright light (10 000 lux, n = 10), or high-density (4.5 x 10^14 ions/s flow rate, n = 12) or low-density (1.7 x 10^11 ions/s, n = 10, placebo control) negative air ions. Home treatment sessions occurred for 1 h upon awakening for 5 weeks. Blinded raters assessed symptom severity weekly with the Structured Interview Guide for the Hamilton Depression Rating Scale--Seasonal Affective Disorder (SIGH-SAD) version. Evening saliva samples were obtained before and after treatment for ascertainment of circadian melatonin rhythm phase. RESULTS: SIGH-SAD score improvement was 53.7% for bright light and 51.1% for high-density ions v. 17% for low-density ions. Remission rates were 50%, 50% and 0% respectively. The presence or severity of atypical symptoms did not predict response to either treatment modality, nor were phase advances to light associated with positive response. CONCLUSIONS: Both bright light and negative air ions are effective for treatment of chronic depression. Remission rates are similar to those for SAD, but without a seasonal dependency or apparent mediation by circadian rhythm phase shifts. Combination treatment with antidepressant drugs may further enhance clinical response. |
Treatment
of sleep disorders (including jet lag and shift work distress) with light
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article’s title to download a PDF, where available.
| Eastman
CI, Gazda CJ, Burgess HJ, Crowley SJ, Fogg LF. Advancing circadian rhythms
before eastward flight: a strategy to prevent or reduce jet lag. Sleep.
2005;28(1):33-44. STUDY OBJECTIVES: To develop a practical pre-eastward flight treatment to advance circadian rhythms as much as possible but not misalign them with sleep. DESIGN: One group had their sleep schedule advanced by 1 hour per day and another by 2 hours per day. SETTING: Baseline at home, treatment in lab. PARTICIPANTS: Young healthy adults (11 men, 15 women) between the ages of 22 and 36 years. INTERVENTIONS: Three days of a gradually advancing sleep schedule (1 or 2 hours per day) plus intermittent morning bright light (one-half hour approximately 5000 lux, one-half hour of <60 lux) for 3.5 hours. MEASUREMENTS AND RESULTS: The dim light melatonin onset was assessed before and after the 3-day treatment. Subjects completed daily sleep logs and symptom questionnaires and wore wrist activity monitors. The dim light melatonin onset advanced more in the 2-hours-per-day group than in the 1-hour-per-day group (median phase advances of 1.9 and 1.4 hours), but the difference between the means (1.8 and 1.5 hours) was not statistically significant. By the third treatment day, circadian rhythms were misaligned relative to the sleep schedule, and subjects had difficulty falling asleep in the 2-hours-per-day group, but this was not the case in the 1-hour-per-day group. Nevertheless, the 2-hours-per-day group did slightly better on the symptom questionnaires. In general, sleep disturbance and other side effects were small. CONCLUSIONS: A gradually advancing sleep schedule with intermittent morning bright light can be used to advance circadian rhythms before eastward flight and, thus, theoretically, prevent or reduce subsequent jet lag. Given the morning light treatment used here, advancing the sleep schedule 2 hours per day is not better than advancing it 1 hour per day because it was too fast for the advance in circadian rhythms. A diagram is provided to help the traveler plan a preflight schedule. |
| Boulos,
Z. Bright light treatment for jet lag and shift work. In: Seasonal Affective Disorder and Beyond: Light Treatment of SAD and Non-SAD Conditions, R.W. Lam, Ed. Washington, D.C.:American Psychiatric Press; 1998, 253-288. The phase response curve (PRC) can be used to predict the degree and direction of a circadian phase shift one will have based on the timing of exposure to bright light. Once the initial circadian rhythm phase for an individual is estimated, bright light can then be used to shift the rhythm. This chapter focuses on phase shifts in sufferers of jet lag or in shift workers. Results from laboratory studies and from field tests are presented. |
| Campbell
SS, Dawson D, and Anderson MW. Alleviation of sleep maintenance insomnia with timed exposure to bright light. Journal of the American Geriatric Society 1993;41:829-836. OBJECTIVE: Half of the population over 65 suffers from chronic sleep disturbance. As a consequence, almost 40% of hypnotic medications are prescribed to people over age 60. Yet, hypnotics are often of little benefit in this population. As such, an effective non-drug alternative could prove important in the management of age-related sleep maintenance insomnia. The current study sought to evaluate the efficacy of bright light exposure in the treatment of sleep maintenance insomnia. DESIGN: Following baseline sleep and circadian rhythms assessment, subjects with sleep-maintenance insomnia were treated with timed exposure to either bright white light or dim red light for 12 consecutive days. Sleep and circadian rhythms recordings were subsequently obtained and measures of sleep quality were compared to assess efficacy of the treatments. SETTING: Baseline and post-treatment sleep and circadian rhythms assessments took place in the Laboratory of Human Chronobiology, Department of Psychiatry, Cornell University Medical College. The treatment phase of the study was conducted in participants' homes. PARTICIPANTS: Sixteen men and women between the ages of 62 and 81 years were studied. All subjects were free of hypnotic medication, and all had experienced sleep disturbance for at least 1 year prior to entering the study. RESULTS: Exposure to bright light resulted in substantial changes in sleep quality. Waking time within sleep was reduced by an hour, and sleep efficiency improved from 77.5% to 90%, without altering time spent in bed. Increased sleep time was in the form of Stage 2 sleep, REM sleep, and slow wave sleep. The effects were remarkably consistent across subjects. CONCLUSIONS: The findings demonstrate the effectiveness of timed exposure to bright light in the treatment of age-related sleep maintenance insomnia. With further refinement of treatment regimens, this non-drug intervention may prove useful in a large proportion of sleep disturbed elderly. |
| Campbell
SS, Terman M, Lewy, AJ, et al. Light treatment for sleep disorders: consensus report. V. Age-related disturbances. Journal of Biological Rhythms 1995;10:151-154. Sleep maintenance insomnia is a major complaint among the elderly. As a result, an inordinate proportion of sleeping pill prescriptions go to individuals over 65 y of age. Because of the substantial problems associated with use of hypnotics in older populations, efforts have been made to develop nondrug treatments for age-related sleep disturbance, including timed exposure to bright light. Such bright light treatments are based on the assumption that age-related sleep disturbance is the consequence of alterations in the usual temporal relationship between body temperature and sleep. Although studies are limited, results strongly suggest that evening bright light exposure is beneficial in alleviating sleep maintenance insomnia in healthy elderly subjects. Less consistent, but generally positive, findings have been reported with regard to bright light treatment of sleep and behavioral disturbance in demented patients. For both groups, it is likely that homeostatic factors also contribute to sleep disturbance, and these may be less influenced by bright light interventions. |
| Terman
M, Lewy AJ, Dijk DJ, et al. Light treatment for sleep disorders: consensus report. IV. Sleep phase and duration disturbances. Journal of Biological Rhythms 1995;10:135-147. Advanced and delayed sleep phase disorders, and the hypersomnia that can accompany winter depression, have been treated successfully by appropriately timed artificial bright light exposure. Under entrainment to the 24-h day-night cycle, the sleep-wake pattern may assume various phase relationships to the circadian pacemaker, as indexed, for example, by abnormally long or short intervals between the onset of melatonin production or the core body temperature minimum and wake-up time. Advanced and delayed sleep phase syndromes and non-24-h sleep-wake syndrome have been variously ascribed to abnormal intrinsic circadian periodicity, deficiency of the entrainment mechanism, or--most simply--patterns of daily light exposure insufficient for adequate phase resetting. The timing of sleep is influenced by underlying circadian phase, but psychosocial constraints also play a major role. Exposure to light early or late in the subjective night has been used therapeutically to produce corrective phase delays or advances, respectively, in both the sleep pattern and circadian rhythms. Supplemental light exposure in fall and winter can reduce the hypersomnia of winter depression, although the therapeutic effect may be less dependent on timing. |
| Boulos
Z, Macchi MM, Sturchler MP, et al. Light visor treatment for jet lag after westward travel across six time zones. Aviation, Space and Environmental Medicine. 2002;73:953-963. INTRODUCTION: The aim of this field study was to evaluate the efficacy of a light treatment for jet lag, using a head-mounted light visor, following a westward flight across six time zones. METHODS: There were 20 subjects who were exposed to bright white light (3000 lux) or dim red light (10 lux) for 3 h on the first two evenings after a flight from Zurich to New York. Salivary dim light melatonin onset (DLMO), assessed 2 d before and 2 d after the flight, provided a measure of circadian phase. Sleep was recorded by actigraphy, while post-flight performance testing and subjective scales provided additional indices of jet lag severity. RESULTS: The DLMO measurements showed a larger phase delay in the bright light than in the dim light group (2.59 h vs. 1.58 h, p < 0.02). There was no overall difference in sleep efficiency (SE) between the two groups, but a significant Group x Night interaction reflected a small increase across the first two post-flight nights in the bright light group, and a small decrease in the dim light group. Reaction time on one of two performance tests was consistently faster in the dim light group, but was unrelated to circadian phase or to prior sleep. There were no major group differences in subjective sleep quality, daytime sleepiness, jet lag severity, or mood. DISCUSSION: This is the first full-scale study to show that bright light treatment can accelerate circadian reentrainment following transmeridian travel. However, the effect on reentrainment rate was modest, and was not accompanied by any improvement in sleep, performance, or subjective assessments of jet lag symptoms. |
| Revell
VL, Eastman CI. How to trick mother nature into letting you fly around or stay up all night. Journal of Biological Rhythms. 2005;20:353-365. Night shift work and rapid transmeridian travel result in a misalignment between circadian rhythms and the new times for sleep, wake, and work, which has health and safety implications for both the individual involved and the general public. Entrainment to the new sleep/wake schedule requires circadian rhythms to be phase-shifted, but this is often slow or impeded. The authors show superimposed light and melatonin PRCs to explain how to appropriately time these zeitgebers to promote circadian adaptation. They review studies in which bright light and melatonin were administered to try to counteract jet lag or to produce circadian adaptation to night work. They demonstrate how jet lag could be prevented entirely if rhythms are shifted before the flight using their preflight plan and discuss the combination of interventions that they now recommend for night shift workers. |
Treatment of sleep disorders with melatonin
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| Hughes
RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement. Sleep 1998;21(1):52-68. The present investigation used a placebo-controlled, double-blind, crossover design to assess the sleep-promoting effect of three melatonin replacement delivery strategies in a group of patients with age-related sleep-maintenance insomnia. Subjects alternated between treatment and "washout" conditions in 2-week trials. The specific treatment strategies for a high physiological dose (0.5 mg) of melatonin were: (1) EARLY: An immediate-release dose taken 30 minutes before bedtime; (2) CONTINUOUS: A controlled-release dose taken 30 minutes before bedtime; (3) LATE: An immediate-release dose taken 4 hours after bedtime. The EARLY and LATE treatments yielded significant and unambiguous reductions in core body temperature. All three melatonin treatments shortened latencies to persistent sleep, demonstrating that high physiological doses of melatonin can promote sleep in this population. Despite this effect on sleep latency, however, melatonin was not effective in sustaining sleep. No treatment improved total sleep time, sleep efficiency, or wake after sleep onset. Likewise, melatonin did not improve subjective self-reports of nighttime sleep and daytime alertness. Correlational analyses comparing sleep in the placebo condition with melatonin production revealed that melatonin levels were not correlated with sleep. Furthermore, low melatonin producers were not preferentially responsive to melatonin replacement. Total sleep time and sleep efficiency were correlated with the timing of the endogenous melatonin rhythm, and particularly with the phase-relationship between habitual bedtime and the phase of the circadian timing system. |
| Hughes
RJ and Lewy AJ. Light and melatonin treatment of circadian sleep disorders. In: Seasonal Affective Disorder and Beyond: Light Treatment of SAD and Non-SAD Conditions, RW Lam, Ed. Washington, D.C.:American Psychiatric Press;1998,221-252. Three subtypes of circadian phase sleep disorders are identified and discussed, based on the melatonin phase and habitual sleeping pattern relative to normal sleep. Light treatment can be used to treat these disturbances. It appears that exogenous melatonin also affects the circadian phase. Optimal treatments using light, melatonin, or both are discussed. |
| Zhdanova
IV, Wurtman RJ, Morabito C, et al. Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans. Sleep 1996;19:423-431. Low oral doses of melatonin raise serum melatonin concentrations to those normally occurring nocturnally and facilitate polysomnographically assessed sleep onset when given at different time points throughout the day, without altering mood or performance on the morning following treatment. In the present study, 12 young healthy volunteers, free of sleep disturbances, received 0.3 or 1.0 mg of melatonin or placebo at 2100 hours, 2-4 hours prior to their habitual bedtime. Polysomnographic recording of overnight sleep began at 2200 hours and continued until 0700 hours the following morning, when subjects were awakened. Sleep onset latency and latency to stage 2 sleep were significantly decreased as a result of melatonin treatment. Neither dose of melatonin significantly altered sleep architecture. Administration of the lower dose of melatonin (0.3 mg) at 2100 hours elevated serum melatonin to levels within the normal nocturnal range (113 +/- 13.5 pg./ml) at the time the sleep test was initiated. Neither melatonin dose caused "hangover effects", as assessed by self-reports or by mood and performance tests administered on the morning following treatment. These observations provide additional evidence that nocturnal melatonin secretion has a sleep-promoting function. They also indicate that an increase in serum melatonin concentrations, within the normal physiologic range, does not significantly alter sleep architecture in subjects with normal sleep who receive the treatment several hours prior to their habitual bedtime. |
| Haimov
I, Lavie P, Laudon M, et al. Melatonin replacement therapy of elderly insomniacs. Sleep. 1995;18:598-603. Changes in sleep-wake patterns are among the hallmarks of biological aging. Previously, we reported that impaired melatonin secretion is associated with sleep disorders in old age. In this study we investigated the effects of melatonin replacement therapy on melatonin-deficient elderly insomniacs. The study comprised a running-in, no-treatment period and four experimental periods. During the second, third and fourth periods, subjects were administered tablets for 7 consecutive days, 2 hours before desired bedtime. The tablets were either 2 mg melatonin administered as sustained-release or fast-release formulations, or an identical-looking placebo. The fifth period, which concluded the study, was a 2-month period of daily administration of 1 mg sustained-release melatonin 2 hours before desired bedtime. During each of these five experimental periods, sleep-wake patterns were monitored by wrist-worn actigraphs. Analysis of the first three 1-week periods revealed that a 1-week treatment with 2 mg sustained-release melatonin was effective for sleep maintenance (i.e. sleep efficiency and activity level) of elderly insomniacs, while sleep initiation was improved by the fast-release melatonin treatment. Sleep maintenance and initiation were further improved following the 2-month 1-mg sustained-release melatonin treatment, indicating that tolerance had not developed. After cessation of treatment, sleep quality deteriorated. Our findings suggest that for melatonin-deficient elderly insomniacs, melatonin replacement therapy may be beneficial in the initiation and maintenance of sleep. |
Safety of bright light therapy
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| Gallin
PF, Terman M, Remé CE, et al. Ophthalmologic examination of patients with seasonal affective disorder, before and after bright light therapy. American Journal of Ophthalmology 1995;119:202-210. PURPOSE: We assessed the potential ocular hazards of bright light therapy for patients with seasonal affective disorder, after both short- and long-term treatment, and identified prospective patients with pre-existing ocular abnormalities. METHODS: Fifty patients with seasonal affective disorder received daily exposure to artificial light in the morning or evening for 30 minutes at an illuminance level of 10,000 lux (irradiant dose, 0.016 J/cm2). Ophthalmologic examinations were performed before and after short-term treatment (two to eight weeks) and after three to six years of use during the fall and winter months. Over the four years of patient intake, the eye examination included subsets of the following tests: visual acuity, intraocular pressure, slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, color vision, visual field, fundus photography, Amsler grid, ocular motility, pupillary reactions, contrast sensitivity, stereopsis, and the macular stress test. RESULTS: No ocular changes were detected after short-term treatment. Long-term treatment (three to six years) of 17 patients, with cumulative exposure durations of 60 to 1,250 hours, also resulted in no ocular abnormalities. CONCLUSIONS: Light therapy yields about 75% clinical remissions. It is effective as an antidepressant and appears safe for the eyes. Current knowledge is insufficient to specify any definite ocular contraindications for bright light therapy, although we recommend that patients with preexisting ocular abnormalities and those using photosensitizing drugs undergo treatment only with periodic ophthalmologic examination. |
| Remé
CE, Rol P, Grothmann K, et al. Bright light therapy in focus: lamp emission spectra and ocular safety. Technology and Health Care 1996;4:403-413. In recent years, bright light treatment of seasonal affective disorder (SAD), recurrent depressions in fall and winter, has been discovered. Newer applications include circadian sleep phase disorder, shift work and jet lag. Apart from creating the visual signal, light can modify retinal structure and physiology. UV and visible light lead to distinct lesions of ocular tissues under certain experimental and naturalistic conditions. In light therapy, a large variety of fixtures is used but the spectral emission of lamps is mostly unknown to the user and clinician leading to the potential hazard of ocular lesions. Therefore, we have analyzed a wide selection of light sources commonly used for treatment. We measured the spectral emission and calculated irradiant doses for several light therapy regimens. Based on these measurements, potential hazards are analyzed, physiological mechanisms of light action are discussed and safety measures for bright light therapy are proposed. They include recommendations for lamps devoid of damaging spectral emissions and standardized therapy fixtures, ophthalmological monitoring of patients with eye diseases and control by optometrists for patients with healthy eyes who are likely to undergo light treatment for extended periods. |
Light treatment methodology
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| Terman
M. Evolving applications of light therapy. Sleep Med Rev. 2007;11-497-507. 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. |
| Kennedy
SH, Lam RW, Cohen NL, et al. Clinical guidelines for the treatment of depressive disorders. IV. Medications and other biological treatments. Canadian Journal of Psychiatry. 2001;46 (Suppl 1):38S-58S. BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments partnered to produce clinical guidelines for psychiatrists for the treatment of depressive disorders. METHODS: A standard guidelines development process was followed. Relevant literature was identified using a computerized Medline search supplemented by review of bibliographies. Operational criteria were used to rate the quality of scientific evidence, and the line of treatment recommendations included consensus clinical opinion. This section, "Medications and Other Biological Treatments," is 1 of 7 articles that were drafted and reviewed by clinicians. Revised drafts underwent national and international expert peer review. RESULTS: Evidence-based recommendations are presented for 1) choosing an antidepressant, based on efficacy, tolerability, and safety; 2) the optimal use of antidepressants, including augmentation, combination, and switching strategies; 3) maintenance treatment; and 4) electroconvulsive therapy (ECT), light therapy, and additional somatic treatments. Evidence from metaanalyses is presented first, followed by conclusions from randomized controlled trials (RCTs) and, if appropriate, open-label data. CONCLUSIONS: There is significant evidence to support the role of selective serotonin reuptake inhibitors (SSRIs), novel agents, and classic agents in the treatment of major depressive disorder (MDD). There is also evidence to support the use of somatic treatments, including ECT and light therapy, for some patients with MDD. There is limited evidence for the use of specific medications to treat subtypes of MDD. There is emerging evidence to support augmentation and combination strategies for patients previously nonresponsive to medication. |
| Terman
M, Terman JS. Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and side effects. CNS Spectrums. 2005;10:647-63. 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. |
| Terman
M, Terman JS. Light therapy. In: Principles and Practice of Sleep Medicine, 4th edition. Edited by Kryger MH, Roth T, Dement WC. Philadelphia, Elsevier, 2005, pp 1424-1442. The susceptibility of the circadian system to selective phase shifting by timed light exposure has broad implications for the treatment of sleep-phase and depressive disorders. Light therapies have been devised that can normalize the patterns of delayed sleep phase syndrome (through circadian phase advances) and advanced sleep phase syndrome (through circadian phase delays). Doctors and patients need to become cognizant of the daily intervals when light exposure—and darkness—can facilitate or hamper adjustment. The primary intervals lie at the edges of the “subjective night,” which coincide with the tails of the nocturnal melatonin cycle, but they can be inferred clinically through a chronotype questionnaire. The lighting schedule may have to be continually adjusted as the subjective night shifts gradually in the desired direction. The treatment strategy for seasonal and nonseasonal depressive disorders is similar. In winter depression, the magnitude of phase advances correlates with the degree of mood improvement, and the optimum timing of light therapy must be specified relative to circadian rather than solar time. Apart from its use as a monotherapy, light therapy in both outpatient and inpatient trials indicates that light therapy accelerates remission of nonseasonal depression in conjunction with medication. Exploratory applications for treatment of antepartum and premenstrual depression, bulimia nervosa, sleep disruption of senile dementia, and shift work and jet lag disturbance are considered. The chapter provides the clinician with guidelines for selecting lighting apparatus based on safety, efficacy, and comfort factors; summarizes adverse effects of light overdose; and offers a straightforward protocol for selecting treatment time of day. |
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Willis GL, Kelly AM, Kennedy GA. |
Willis GL. Circadian involvement in Parkinson's disease (PD) and more specifically in nigro-striatal dopamine (NSD) function is of increasing interest to the neurosciences. Given that bright light therapy is of therapeutic value in PD, possible mechanisms underlying retinal involvement in this phenomenon was explored further by administering anti-Parkinsonian chemotherapies into the vitreus humour directly adjacent to the retina. 2 microl of a 100 mM solution of L-Dopa significantly improved motor function in the later stages of degeneration and during the day while the injection of 2 microl of a 10 mM solution of the melatonin receptor antagonist ML-23 improved motor function in the early stages of PD and during the dark phase of the light/dark cycle. The results suggest that the function of nigral cells is regulated by a more global system embracing circadian physiology that extends from the retina to the pineal. Furthermore, the induction of PD is characterised by an imbalance between melatonin and dopamine (DA) whereby this ratio is elevated at least 6 to 1 in favour of melatonin. The commonly observed treatment failures and side effects of DA replacement therapy probably result from increasing endogenous DA without taking parallel melatonin dysfunction into account. The proposed integrated function of the NSD and circadian systems may permit therapeutic targeting at a level which is safer, more effective and without the side effects of systemically administered regimens of DA replacement. |
Willis GL, Turner EJ The antagonism of melatonin in models of Parkinson's disease (PD) can reduce the severity of motor impairment associated with dopamine (DA) degeneration. In consideration of the potent antidepressant effects of bright light therapy (LT), that LT suppresses melatonin secretion, that depression is commonly observed in PD, and that exposure to constant light facilitates recovery from experimental PD, the object of the present study was to strategically administer LT to PD patients and observe the effects on depression, insomnia, and motor performance. Twelve patients diagnosed with PD were exposed to white fluorescent light for 1-1.5 h at an intensity of 1000 to 1500 lux once daily commencing 1 h prior to the usual time of sleep onset, approximately 22:00 h in most patients. All patients were assessed before LT commenced and at two weeks, five weeks, and regular intervals thereafter. Within two weeks after commencing LT, marked improvement in bradykinaesia and rigidity was observed in most patients. Tremor was not affected by LT treatment; however, agitation, dyskinaesia, and psychiatric side effects were reduced, as verified by decreased requirement for DA replacement therapy. Elevated mood, improved sleep, decreased seborrhea, reduced impotence, and increased appetite were observed after LT. LT permitted the reduction of the dose of L-dopa, bromocriptine, or deprenyl in some patients by up to 50% without loss of symptom control. Factors limiting the efficacy of LT included multiple disease states, treatment compliance, polypharmacy, emotional stress, advanced age, and predominance of positive symptoms. The results of this case series study confirms previous work describing light as efficacious in the treatment of PD and suggest that controlled trials may help to elucidate how LT might be used strategically as an adjunct therapy to improve the morbidity of PD patients. |