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2126 Am J Psychiatry 163:12, December 2006ajp.psychiatryonline.org
Controlled Trial of Naturalistic Dawn Simulation and
Negative Air Ionization for Seasonal Affective Disorder
Michael Terman, Ph.D.
Jiuan Su Terman, Ph.D.
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 sea-
sonal pattern of major depressive disor-
der (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° north latitude); 2)
a dawn light pulse (13 minutes, 250 lux,
with an illuminant dose of 3.25×10
3
lux-
minutes matched to the simulated
dawn); 3) postawakening bright light (30
minutes, 10,000 lux); 4) negative air ion-
ization at high flow rate (93 minutes,
4.5×10
14
ions/second); or 5) ionization at
low flow rate (93 minutes, 1.7×10
11
ions/
second). The symptoms were assessed
over 3 weeks with the Structured Inter-
view Guide for the Hamilton Depression
Rating Scale—Seasonal Affective Disorder
Version.
Results: Posttreatment improvement re-
sults were bright light, 57.1%; dawn simu-
lation, 49.5%; dawn pulse, 42.7%; high-
density ions, 47.9%; and low-density ions,
22.7% (significantly lower than the oth-
ers). Contrary to the authors’ hypothesis,
analysis of variance failed to find superi-
ority of dawn simulation to the dawn
pulse or bright light. However, the dawn
pulse led to a pattern of residual or exac-
erbated depressive symptoms similar to
those seen in low-density ion nonre-
sponders.
Conclusions: Naturalistic dawn simula-
tion and high-density ionization are active
antidepressants that do not require the
effort of postawakening bright light ther-
apy. They can be considered candidate al-
ternatives to bright light or medication.
(Am J Psychiatry 2006; 163:2126–2133)
Findings over the last decade have demonstrated that
morning bright light exposure ameliorates symptoms of
seasonal affective disorder when gauged against non-
photic placebos (1, 2). Concurrently, basic biological
rhythm research has pointed to dimmer gradual naturalis-
tic dawn and dusk simulation as a potent alternative to
bright light exposure. For example, hamsters show stron-
ger circadian entrainment to non-24-hour light-dark cy-
cles under naturalistic twilights than under conventional
rectangular transitions (3). Rats self-select the dimmer
twilight signal to maintain circadian entrainment when
given the opportunity to escape daylight exposure (4). The
rat retina responds to naturalistic dawn simulation with
accelerated shedding of rod outer disk segments com-
pared with sudden light onset (5). In the human labora-
tory, naturalistic dawn simulation prevents the delay drift
of rhythms under dim light conditions (6). Bedside admin-
istration of a naturalistic dusk-to-dawn signal advances
the sleep episode in demented elderly, with a tendency to-
ward reduced sleep latency, longer duration, and de-
creased nocturnal activity (7).
In identifying early morning bright light exposure as
more effective than later morning or evening light for pa-
tients with seasonal affective disorder (8), our attention
was drawn to the early dawn interval, when melatonin
wanes, core body temperature begins to rise, and the cir-
cadian timing system has the greatest propensity for light-
elicited phase advances (9). In the wintertime at northerly
latitudes, this is also the period when it remains dark out-
doors, a putative trigger of the depression. Therefore, we
set out to explore the antidepressant effects of simulated
dawn illumination during the final hours of sleep (10).
Although we previously demonstrated effective treat-
ment for winter depression by using naturalistic dawn
simulation in a case series (11, 12), until now it has not
been tested against control subjects given placebo or
compared directly with postawakening bright light expo-
sure. However, Avery and associates (13–15) have investi-
gated a variant of dawn simulation in hypersomnic pa-
tients with seasonal affective disorder with a 90-minute
sigmoidal illumination ramp with accelerated brief expo-
sures and dim red exposures as controls. They found the
sigmoidal simulation superior to postawakening bright
light therapy (15). However, some patients experienced
side effects that we had not observed with naturalistic
dawns: premature awakening during the initial exposure
to the rising signal, occasionally accompanied by hypo-
mania. The sigmoidal signal contrasts with naturalistic
Am J Psychiatry 163:12, December 2006 2127
M. TERMAN AND J. TERMAN
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dawns, which begin several hours earlier in astronomical
twilight and rise more gradually (Figure 1).
Negative air ionization is another environmental vari-
able with antidepressant properties for patients with sea-
sonal affective disorder (2, 16). Our tests of this nonphotic
modality followed the use of Eastman and associates (17)
of a deactivated ionizer as an inert placebo control for
light therapy (1). With the activated device, we found im-
provement with 30-minute postawakening exposures to
high-density negative air ions, whereas low-density ion-
ization was ineffective. This comparison provided a true
double blind—impossible with light—because ambient
ion concentration is not perceptible.
In the present study, we examined the efficacy of high-
density ion exposure and naturalistic dawn simulation,
both presented toward the end of sleep. We compared
both methods with low-density negative air ionization (as
a placebo) and postawakening bright light (as an estab-
lished effective treatment). Additionally, as a control for
the gradual naturalistic dawn signal, we presented a brief
sunrise pulse, matched in total illuminant dose, just be-
fore wake-up time.
Method
Subjects
Research volunteers (ages 18–65) were screened for symptoms
of winter depression. Diagnoses were based on the Structured
Clinical Interview for DSM-III-R (18) or DSM-IV (19), including
major depressive disorder, recurrent, or bipolar disorder not oth-
erwise specified (bipolar II disorder) with a seasonal pattern. The
subjects also met the criteria of Rosenthal et al. for seasonal affec-
tive disorder (20), including at least 2 preceding years of depres-
sion during the winter and summer remission. The subjects
scored at least 20 points on the 29-item Structured Interview
Guide for the Hamilton Depression Rating Scale—Seasonal Affec-
tive Disorder Version (SIGH-SAD) (21), with a 21-item Hamilton
Depression Rating Scale (HAM-D) score of 10 or more and an
eight-item atypical symptom score of 5 or more. The subjects
were medically healthy, as determined by a physical examination,
standard blood work with a thyroid panel, and urinalysis. They
were required to abstain from alcohol, psychotropic medication,
and recreational drugs (verified by urine toxicology). Exclusion
criteria included comorbid axis I disorders, a suicide attempt
within 3 years, pregnancy, habitual sleep onset later than 0100
hours or a wake-up time later than 0900 hours, and past treat-
ment with light or negative air ions. Written informed consent
was obtained from the subjects after they had been given a full
description of the study. The institutional review board of the
New York State Psychiatric Institute approved the study protocol.
Protocol
Subjects were randomly assigned to one of five treatment con-
ditions: dawn simulation, dawn pulse, bright light, or high- or
low-density ionization. During the baseline phase (7–14 days),
the subjects established consistent habitual sleep schedules
(within a 30-minute range around the target times for sleep onset
and offset) that they would maintain throughout the study. Daily
treatment was taken at home for 3 weeks (dawn and ion condi-
tions preceding habitual wake-up time, bright light within 10
minutes of awakening). Compliance was monitored by daily call-
ins upon completion of the treatment session.
The subjects rated expectations on a 5-point scale from “no im-
provement” (1) to “full recovery” (5) based on written descrip-
tions of the rationale for the assigned treatment modality. Ratings
were made in three sets, for 1) the dawn signal (with no distinc-
tion between dawn simulation and dawn pulse), 2) ionization
(without reference to dose), and 3) bright light therapy.
Trained raters who were blind to the treatment assignments
evaluated depression severity at baseline and the treatment re-
sponse after 10 days (midpoint) and 21 days (endpoint). The sub-
jects who showed remission with a SIGH-SAD score reduction to
8 points or lower were monitored for up to 3 weeks of withdrawal
for ascertainment of relapse to the minimum entry score of 20.
Nonresponders and partial responders did not receive a with-
drawal phase. The subjects also rated potential side effects at
baseline and endpoint using the Systematic Assessment for Treat-
ment Emergent Effects (22).
Treatment Apparatus and Procedure
Naturalistic Dawn Simulation. The signal was generated by a
microprocessor-based control box (SphereOne, Inc., Silver
Plume, Colo.) simulating sunrise on May 5 at 45° north latitude
based on our MacLite algorithm (23). Figure 1 displays the 3.5-
hour curvilinear transition from a protracted starlight glow at
0.0003 lux to an attenuated sunrise level of 250 lux (428 µw/cm
2
;
Model J17 photometer/radiometer, Tektronix, Inc., Beaverton,
Ore.), as would be experienced outdoors under tree cover.
Calibrated output of the control box powered a glass-shielded
250-watt halogen bulb (#66490 Osram GmbH., Munich) in an
overhanging wedge-shaped (1.59×10
3
cm
2
) indirect light diffuser
(SphereOne, Inc.) mounted on a tripod beside the bed. The light
projected toward the pillow from a distance of 91 cm. After the
simulated sunrise, which was set for wake-up time, the signal ter-
minated with a 90-second logarithmic-linear ramp, and the pa-
FIGURE 1. Duration, Intensity, and Timing of Three Light-
ing Conditions in a Study of Seasonal Affective Disorder:
Naturalistic Dawn Simulation, Dawn Pulse, and Bright
Light Therapy
a
a
For illustration, sunrise and wake-up time were anchored at 0700
hours, although they varied according to the individual’s habitual
sleep schedule. The gradual dawn signal and dawn pulse were
equated for total illuminant dose in lux-minutes. The curved shape
of dawn varies with latitude and day of the year (35), as determined
by the solar angle, the tilt of the earth and its orbital speed, atmo-
spheric refraction, air mass penetrated, and a set of empirical con-
stants (36). Variations in cloud cover had negligible influence be-
fore sunrise. The fastest transitions occur at the equinoxes, and the
slowest transitions at the solstices. Accuracy of the simulation has
been verified against outdoor measurements (37).
100,000
10,000
1,000
100
10
1
0.1
0.01
0.001
0.0001
4:00 5:00 6:00 7:00 8:00
Illuminance (lux)
Time of Day (a.m.)
Dawn,
May 5,
45º north
latitude
250 lux,
13 minutes
10,000 lux,
30 minutes
2128 Am J Psychiatry 163:12, December 2006
TREATMENTS FOR SEASONAL AFFECTIVE DISORDER
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tient was exposed to uncontrolled bedroom illumination. For late
risers, the light of outdoor dawn could precede the scheduled
dawn signal and penetrate the bedroom if the shades were open;
however, we verified that such spontaneous light exposure did
not allay the depression.
The power spectrum of the halogen signal (measured with a fi-
ber optic spectrometer; Model USB2000, Ocean Optics, Inc.,
Dunedin, Fla.) varied smoothly across the visible range. Increas-
ing irradiance from 0.25 to 250 lux reduced the relative power of
short wavelengths (380–500 nm, 39% to 16%), with increases in
the midrange (500–625 nm, 19% to 29%) and at long wavelengths
(625–740 nm, 41% to 55%). At 250 lux, there was negligible ultravi-
olet radiation in the ultraviolet A (280–315 nm, 6.8 µw/cm
2
) and
ultraviolet B (315–380 nm, 7.6 µw/cm
2
) ranges.
Dawn Pulse. As a control for naturalistic dawn simulation, we
presented a trapezoidal light pulse of 250 lux (13 minutes) before
wake-up time, with 90-sec logarithmic-linear onset and offset
ramps, for a total duration of 16 minutes (Figure 1). The illumi-
nant dose, 3.25×10
3
lux-minutes, equaled that of the dawn signal.
Bright Light. The light box (UpLift Technologies, Dartmouth,
N.S., Canada) presented 10,000 lux (2600 µw/cm
2
) white light
from three Osram Dulux 40-watt, 3,000-Kelvin fluorescent bulbs
mounted behind an ultraviolet-filtered acrylic smooth diffusing
screen (58.5×27.9 cm Acrylite OP-3, Piedmont Plastics, Inc., Char-
lotte, NC; modified with sandblasted diffusion surface by Uplift,
Inc.). It was positioned with a downward angle toward the head of
the bed at a 31-cm distance on a table stand. The subjects sat at
the light box for 30 minutes within 10 minutes of rising, without
looking directly at the screen.
The fluorescent power spectrum was composed of seven dis-
tinct peaks, with negligible ultraviolet radiation (ultraviolet A, 6.6
µw/cm
2
; ultraviolet B, 6.8 µw/ cm
2
). The relative power at short
visible wavelengths was 17% (similar to that of the halogen lamp
at 250 lux) but was weighted strongly toward the midrange (54%),
with a reduction at long wavelengths (29%).
Negative Air Ionization. The negative air ion generator
(SphereOne, Inc.) produced ion flow rates of 4.5 ×10
14
ions/sec-
ond (high-density exposure) or 1.7×10
11
ions/second (low-den-
sity exposure). The ionizer was mounted on a tripod at the sub-
ject’s bedside, with the ion emitter directed toward the pillow at a
distance of 61 cm. Ion flow toward the body was maximized by
use of a grounded conductive bed sheet (Charleswater, Inc., Can-
ton, Mass.) and activated by a timer for 93 minutes before wake-
up time, corresponding to the dawn simulation interval above
0.001 lux.
Data Analysis
Repeated measures analysis of covariance (ANCOVA) of SIGH-
SAD scores tested group differences, with age, gender, and base-
line score covariates, by using Fisher’s method of least significant
differences for post hoc comparisons. Post hoc ANCOVAs evalu-
ated HDRS and Atypical Symptom Scale scores and percentage
improvement. Categorical measures of endpoint response and
the relative frequency of residual or exacerbated symptoms were
evaluated with the chi-square test or Fisher’s exact test in cases of
low expected frequency. Students’ paired and unpaired t tests
were used for various between-group comparisons. The correla-
tion between continuous variables was expressed by Pearson’s r.
An alpha level of 0.05 was used throughout.
Results
During the 6 years of the study (conducted November to
March), 126 subjects entered the study and 118 (93.7%)
completed it. The noncompleters all withdrew before the
10-day midpoint evaluation, two for noncompliance (low-
density ions, one; bright light, one), with six dropouts
(low-density ions, one; high-density ions, three; bright
light, one; and dawn simulation, one). Of the completers,
19 who experienced remission (16.1%) did not show re-
lapse during the withdrawal phase; they were distributed
across all five groups with no significant differences
(Fisher’s exact test). Because such sustained improvement
cannot be distinguished from spontaneous seasonal re-
mission, they were excluded according to protocol (2, 24)
from the final data set. The results were analyzed for 99
subjects who either remained depressed at treatment end-
point or showed relapse during the withdrawal phase. The
group included 77 (77.8%) women and 22 (22.2%) men,
TABLE 1. Depression Scale Measures in a Study of Naturalistic Dawn Simulation and Negative Air Ionization in Individuals
With Seasonal Affective Disorder
a
Measure Bright Light (N=19) Dawn Simulation (N=21)
Mean SD Mean SD
Structured Interview Guide for the Hamilton Depression
Rating Scale—Seasonal Affective Disorder Version
(SIGH-SAD) score
Baseline 26.4 5.0 26.7 3.5
Midpoint (8 to 12 days) 12.8 8.7 16.8 9.0
Endpoint (19 to 23 days) 11.3 7.9 13.7 9.7
Hamilton Depression Rating Scale score
Baseline 15.3 3.2 15.1 3.0
Midpoint 6.9 5.4 8.5 4.8
Endpoint 5.9 4.6 7.0 6.2
Atypical Symptom Scale score
Baseline 11.2 4.0 11.6 2.7
Midpoint 5.9 4.0 8.3 5.3
Endpoint 5.4 4.3 6.7 4.5
% SD % SD
SIGH-SAD improvement 57.1 29.3 49.5 33.7
Proportion 95% CI Proportion 95% CI
≥50% 0.63 0.44–0.82 0.62 0.44–0.80
Score ≤8 0.42 0.23–0.61 0.33 0.16–0.50
Score <20 0.84 0.65–1.00 0.70 0.52–0.88
a
Based on the SIGH-SAD (22).
Am J Psychiatry 163:12, December 2006 2129
M. TERMAN AND J. TERMAN
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ages 19–63 years (mean=40.4 years, SD=10.4). The distri-
butions of age and gender were closely balanced, with no
significant differences by univariate analysis of variance
and Fisher’s exact test, respectively. The diagnoses were
major depressive disorder in 94 (94.9%) of the cases and
bipolar disorder not otherwise specified or bipolar II dis-
order in five (5.1%) of the cases.
Rating Scale Means and Percentage
Improvement
The overall mean SIGH-SAD score at baseline was 26.5
(SD=8.0), with an HAM-D mean score of 15.8 (SD=4.9) and
an Atypical Symptom Scale mean score of 10.6 (SD=3.3).
Univariate ANOVAs showed no significant baseline differ-
ences among the five groups (Table 1). A repeated mea-
sures ANCOVA of SIGH-SAD scores across the three as-
sessment points, with baseline score, age, and gender as
covariates, revealed the following significant effects: group
(F=2.48, df=4, 91, p=0.05), time (F=3.60, df=2, 90, p=0.03),
and group-by-time interaction (F=2.51, df=4, 91, p=0.05).
There were no significant effects of age (F=0.38, df=1, 91,
p=0.94) or gender (F=1.02, df=1, 91, p=0.32). Improvement
was greatest between baseline and the 10-day midpoint,
with little change between midpoint and endpoint (Table
1). Least significant difference comparisons between
groups showed that the percentage improvement for the
low-density ion group was significantly lower than for the
four alternate groups (p=0.001 to p=0.02), and there were
no significant differences among the latter groups. Post-
treatment improvement was far lower for the low-density
ion group (22.7%) than for the alternate groups (42.7% to
57.1%). The ANCOVA for raw scores also revealed signifi-
cant effects of the baseline score covariate (F=14.29, df=1,
91, p<0.001) and the baseline score-by-time interaction
(F=13.98, df=2, 90, p<0.001), which reflected greater op-
portunity for score reduction in more severe cases (r=0.28,
N=99, p=0.004) (25).
ANCOVAs on the scores from the HAM-D and Atypical
Symptom Scale yielded contrasting results. The HAM-D
showed the following significant effects, mirroring results
for the SIGH-SAD: group (F=2.97, df=4, 91, p<0.03), time
(F=4.19, df=2, 90, p<0.02), group-by-time interaction (F=
2.99, df=4, 91, p<0.03), baseline score covariate (F=14.23,
df=1, 91, p<0.001), and baseline score-by-time interaction
(F=21.09, df=2, 90, p<0.001). On the Atypical Symptom
Scale, however, the only significant effects were for the
baseline score covariate (F=65.15, df=1, 91, p<0.001) and
the baseline score-by-time interaction (F=15.23, df=2, 90,
p<0.001). Nonsignificant effects included group (F=1.96,
df=4, 91, p=0.11), time (F=1.36, df=2, 90, p=0.26), and the
group-by-time interaction (F=2.02, df=4, 91, p=0.10).
When we used percentage improvement rather than raw
scores, the Atypical Symptom Scale did show a significant
group effect (F=2.76, df=4, 91, p=0.03) that isolated low-
density ions as less effective treatment, also seen on the
HAM-D (F=3.16, df=4, 91, p=0.02). The two scales showed
similar magnitudes of improvement except under low-
density ions (HAM-D: mean=29.2%, SD=39.7%; Atypical
Symptom Scale: mean=3.9%, SD=56.3%) (t=1.95, df=34, p=
0.06, two-tailed), which may indicate a blunted placebo
response for the symptoms of hypersomnia, hyperphagia,
and fatigue. Further analyses focused on the combined
SIGH-SAD scale.
Categorical Measures of Treatment Response
The proportion of patients achieving 50% or greater im-
provement (Table 1) differed significantly between groups
(χ
2
=10.55, df=4, p=0.03) and was far lower under low-den-
sity ions than under the other conditions (which did not
differ significantly from each other). The proportion of
Dawn Pulse (N=20) High-Density Ions (N=21) Low-Density Ions (N=18)
Mean SD Mean SD Mean SD
26.8 4.9 27.2 5.4 25.0 3.8
14.7 11.0 17.3 7.3 19.9 6.9
14.3 10.4 13.6 8.1 18.9 7.5
16.8 3.7 15.9 4.1 16.1 3.1
8.6 6.4 9.6 4.1 12.1 4.9
8.2 7.1 7.3 4.3 11.9 4.9
10.1 2.7 11.3 4.1 8.9 2.6
6.1 5.1 7.8 4.6 7.8 3.8
6.1 4.6 6.3 4.5 7.8 3.9
% SD % SD % SD
42.7 46.3 47.9 33.3 22.7 30.7
Proportion 95% CI Proportion 95% CI Proportion 95% CI
0.50 0.31–0.69 0.52 0.34–0.70 0.17 0.02–0.32
0.35 0.16–0.54 0.28 0.10–0.46 0.17 0.02–0.32
0.60 0.41–0.79 0.67 0.49–0.85 0.33 0.18–0.48
2130 Am J Psychiatry 163:12, December 2006
TREATMENTS FOR SEASONAL AFFECTIVE DISORDER
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patients meeting the remission criterion of a SIGH-SAD
score of 8 or lower followed a similar pattern, although
the groups did not differ significantly (χ
2
=3.15, df=4, p=
0.53), which may reflect the higher remission rate for low-
density ions (mean=0.17, SD=0.15) than in our previous
parallel group study (mean=0.05, SD=0.09) (2). The pro-
portion with posttreatment scores below the 20-point
baseline entry level, however, varied significantly (χ
2
=
11.37, df=4, p=0.02), with the low-density ion group fall-
ing lower than the others.
Residual Symptoms, Emergence, and
Exacerbation
Of 88 potential somatic and psychological side effects
tabulated by the Systematic Assessment for Treatment
Emergent Effects, the only ones to show posttreatment
emergence or exacerbation to moderate or high severity
fell into the depression cluster (Table 2). The patients re-
porting these symptoms were all nonresponders who
showed the same symptoms at baseline; thus, none of
these symptoms was emergent, and all reflected exacerba-
tion under ineffective treatment. Accordingly, they oc-
curred most often under low-density ions. The dawn pulse
produced a profile very similar to that for low-density
ions, although poor concentration was reported only by
patients under the dawn pulse, and sleep disturbance was
reported only under low-density ions. When residual and
exacerbated symptoms were combined, a significantly
higher proportion of the patients reported disturbance
under the dawn pulse than under dawn simulation
(mean=0.50, SD=0.19, versus mean=0.19, SD=0.14) (χ
2
=
4.36, df=1, p=0.04).
Because the Systematic Assessment for Treatment
Emergent Effects does not assess suicidality, we analyzed
baseline and endpoint ratings for the HAM-D item. There
were only two cases of emergence or exacerbation, both
under the dawn pulse. One patient who scored 0 points at
baseline scored 2 points (“wishes he were dead or any pos-
sible thoughts of death to self”) at the end of treatment,
whereas the second patient moved from a score of 2 to 3
points (“suicidal ideas or gesture”).
Expectations
Mean expectation ratings differed across groups by less
than 1 point on the 5-point scale: bright light, 3.5 (SD=
0.9); dawn signals, 3.3 (SD=0.7); and ions, 2.7 (SD=0.9) (F=
8.27, df=2, 96, p<0.001). Comparisons of the least signifi-
cant difference showed that both the bright light and the
dawn groups had higher expectations than the ion group.
Of importance, expectations were not significantly differ-
ent between the dawn simulation and dawn pulse sub-
groups (mean=3.4, SD=0.7, versus mean=3.1, SD=0.8) or
the low- and high-density ion subgroups (mean=2.8, SD=
1.0, versus mean=2.5, SD=0.9). Overall, expectation rat-
ings were significantly correlated with endpoint SIGH-
SAD percentage improvement (r=0.36, N=99, p<0.001),
which was also observed separately in the three light
groups (r=0.28, N=60, p=0.03) and the two ion groups (r=
0.37, N=39, p=0.02).
Discussion
The trial design provided for several tests of efficacy, fol-
lowing the hypotheses that both dawn simulation and
high-density ions would produce greater antidepressant
response than low-density ions and that dawn simulation
would be superior to both the dawn pulse and bright light
treatment. Analysis of raw depression scale scores showed
that dawn simulation and high-density ions were superior
to low-density ions. However, the responses to bright light
therapy and dawn pulse did not differ significantly from
the response to dawn simulation. Percentage improve-
ment and categorical measures of response and remission
showed similar patterns. On this basis, we concluded that
1) naturalistic dawn simulation provided no advantage
(other than convenience of use) over postawakening
bright light therapy and 2) the dawn pulse is an effective
treatment when we consider its superiority to low-density
TABLE 2. Emergence or Exacerbation of Symptoms in Score on the Systematic Assessment of Treatment Emergent Effects
(≥3) in a Study of Naturalistic Dawn Simulation and Negative Air Ionization in Individuals With Seasonal Affective Disorder
a
Symptom
Bright Light
(N=19)
Dawn Simulation
(N=21)
Dawn Pulse
(N=20)
High-Density Ions
(N=21)
Low-Density Ions
(N=18)
N%N%N%N%N%
Depression
Depressed mood 4
b
20.0 5 27.8
Irritability 3 15.0 5 27.8
Fatigue 4 20.0 5 27.8
Drowsiness 420.0314.3316.7
Poor concentration 4 20.0
Sleep
Middle insomnia 316.7
Late insomnia 316.7
Appetite/weight
Appetite increase 314.3
Weight gain 419.0
Somatic: headache 4 20.0 3 16.7
a
Moderate to severe on the Systematic Assessment for Treatment Emergent Effects (22).
b
Minimum of three individuals per group.
Am J Psychiatry 163:12, December 2006 2131
M. TERMAN AND J. TERMAN
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ions. Thus, it appears that gradual twilight is not necessary
for therapeutic action during sleep. There is a partial pre-
cedent for such a dawn pulse effect in an uncontrolled
trial of remitted depressed patients with residual hyper-
somnia (26). When the patients were briefly exposed to
500 lux incandescent light switched on by a timer 10 min-
utes before the desired wake-up time, they reported easier
awakening and a shortened sleep duration.
Despite the superiority of the dawn pulse over low-den-
sity ions and lack of difference from the other active treat-
ments, overall response to the pulse was undermined by a
distinct group of nonresponders. The Systematic Assess-
ment for Treatment Emergent Effects ratings showed a
pattern of exacerbation of depressive symptoms under the
dawn pulse similar to that under low-density ions. Fur-
thermore, HAM-D ratings showed two cases of emergent
or exacerbated suicidality (both without active intent). By
contrast, dawn simulation showed no such problems. We
conclude that although the dawn pulse is therapeutically
active in some patients, the risk of symptom persistence
and emergence and exacerbation in other patients makes
it an unfavorable option.
Several potential dosing parameters of naturalistic
dawn simulation—dawn pulse, bright light, and negative
air ions—might change their relative efficacy. For dawn
simulation, there are the choices of day of year (solstices
slowest, equinoxes fastest), illuminance anchor at sunrise
(unshielded sunrise provides approximately 800 lux), sun-
rise time anchor relative to habitual wake-up time, spec-
tral composition of the signal, and duration of the signal
after sunrise. An additional factor for the dawn pulse is its
duration preceding wake-up. Apart from spectral charac-
teristics (27), the duration and intensity of bright light
therapy (24) and its timing relative to the individual’s cir-
cadian rhythm phase (28) are known to affect remission
rate. As for negative air ions, the effects of flow rate (result-
ing in proximal ion density) and timing and duration of ex-
posure have yet to be explored.
Expectation ratings for ions in our study were slightly
but significantly lower than the ratings for light, which
raises the question of the adequacy of low-density ions as
a placebo control. Several results mitigate this potential
confound. First, the low-density ion group showed no sig-
nificant correlation of expectation ratings with SIGH-SAD
percentage improvement (r=0.16, N=18, p=0.53). Second,
the ratings did not differ significantly between the low-
and high-density ion groups, yet the response was far
greater to the high-density ions. Third, the response to
high-density ions did not differ significantly from that for
the light groups.
As in our previous trials of light therapy (24) and negative
air ionization (2), we used a strict criterion for data entry
into the primary analysis, observation of relapse to the
minimum baseline SIGH-SAD score of 20 within 3 weeks of
discontinuation for the patients who showed remission
during the treatment phase. Two factors support the exclu-
sion of nonrelapsers. First, maintained improvement after
treatment discontinuation during the expected period of a
major depressive episode is prima facie evidence of a pla-
cebo response (29). Especially in studies with a relatively
small group size, higher placebo rates can seriously reduce
the power to detect significant differences. This is less of a
problem in larger drug trials with hundreds of patients
with seasonal affective disorder (30), which have been eco-
nomically infeasible for nondrug alternatives (31). Second,
within a time-limited winter episode, it is impossible to
know whether maintained remission after discontinuation
reflects spontaneous seasonal improvement or a response
to active treatment. We have reported universal relapse af-
ter treatment early in the winter season (32). It is possible
that prior light therapy trials that failed to find superiority
over placebos would have concluded differently if relapse
during a withdrawal phase had been ascertained and non-
relapsers excluded. To test this supposition, we conducted
a post hoc analysis of SIGH-SAD improvement of 50% or
greater, including all patients, regardless of relapse. Per-
force, response rates increased, especially for low-density
ions. Although the pattern of group contrasts was retained,
it fell short of statistical significance: bright light, mean=
0.67, SD=0.17; dawn simulation, mean=0.67, SD=0.17;
dawn pulse, mean=0.63, SD=0.17; high-density ions,
mean=0.57, SD=0.17; low-density ions, mean=0.35, SD=
0.17) (χ
2
=6.75, df=4, p=0.15). Similarly, ANCOVAs on raw
scores fell short of statistical significance.
The hypothesis that dawn simulation is superior to
bright light therapy has been attractive because of the
springtime pattern of illumination, which is lacking in
winter (10). However, the hypothesis becomes less attrac-
tive given the similarity of response to dawn and post-
awakening bright light in our study. Like Avery and associ-
ates (13–15), we showed that a dawn signal presented
toward the end of sleep was superior to that of placebo in
comparison subjects (in their case, dim or brief light
ramps with lower illuminant dose; in our case, low-density
negative air ionization), also presented during sleep. Un-
like Avery and associates (15), however, we did not find
dawn simulation superior to postawakening bright light
exposure. Furthermore, they found similar responses to
bright light and the dim red control. Without the exclusion
of nonrelapsers, as determined in a withdrawal phase,
their high placebo response rate (approximately 65%) may
have impeded detection of a group difference. Alterna-
tively, the reduced efficacy of bright light relative to dawn
simulation in their study may have resulted from confine-
ment to hypersomnic patients with standardized wake-up
and treatment at 0600 hours, which is likely not individu-
ally optimal (28). In our study, bright light was used shortly
after habitual wake-up time, which ranged from 0530
hours to 0900 hours (mean=0705, SD=1.16).
Given the approximate equivalence of naturalistic dawn
simulation, high-density ionization, and bright light, the
choice between them may depend on convenience and
2132 Am J Psychiatry 163:12, December 2006
TREATMENTS FOR SEASONAL AFFECTIVE DISORDER
ajp.psychiatryonline.org
ease of compliance. In this respect, automated exposure
to the dawn signal or ions during sleep has an advantage
over postawakening bright light therapy. On the other
hand, dawn presentation in the bedroom can disturb a
sleep partner with a later wake-up time, whereas bright
light therapy can be administered privately in a separate
room. Negative air ionization during sleep appears to be
the most innocuous alternative; thus far, we have received
no reports of disturbance in bed partners. Although the
antidepressant effect of negative air ionization in seasonal
affective disorder recently has been independently repli-
cated using postawakening administration (personal
communication, R.K. Flory, May 23, 2006), the result for
administration during sleep remains a novel observation.
For open treatment, we recommend starting patients
with postawakening bright light therapy, which has seen
the most extensive investigation and replication (31). If it
is unsuccessful or proves impractical, given nonresponse,
intractable side effects (33), scheduling inconvenience, or
noncompliance, dawn simulation (whether naturalistic or
sigmoidal), high-density negative air ionization, and anti-
depressant drugs (34) provide an armamentarium of alter-
nate treatments.
Received Feb. 25, 2005; revisions received April 24 and May 23,
2005; accepted June 20, 2005. From the Department of Biopsychol-
ogy, New York State Psychiatric Institute, and the Department of Psy-
chiatry, Columbia University. The authors report no competing inter-
ests. Address correspondence and reprint requests to Dr. Terman,
Department of Psychiatry, Columbia University, and New York State
Psychiatric Institute, 1051 Riverside Dr., Unit 50, New York, NY
10032; mt12@columbia.edu (e-mail).
Supported by NIH grant RO1-MH-42931.
The authors thank Namni Goel, Ph.D., Joy Jacobs, J.D., Mariana M.
Macchi, Ph.D., Jamie B. Rifkin, A.B., and Sarah Trosper, B.A., for serv-
ing as screeners and raters; Gary Regester for design of the dawn sim-
ulation light diffuser; Paul Schwartz and Steven Tricamo for design of
the grounded ionizer; and UpLift Technologies, Inc., for donation of
the light boxes.
References
1. Eastman CI, Young MA, Fogg LF, Liu L, Meaden PM: Bright light
treatment for winter depression: a placebo-controlled trial.
Arch Gen Psychiatry 1998; 55:883–889
2. Terman M, Terman JS, Ross DC: A controlled trial of timed
bright light and negative air ionization for treatment of winter
depression. Arch Gen Psychiatry 1998; 55:875–882
3. Boulos Z, Macchi MM, Terman M: Twilights widen the range of
circadian entrainment in hamsters. J Biol Rhythms 2000; 17:
353–363
4. Terman M, Remé CE, Wirz-Justice A: The visual input stage of
the mammalian circadian pacemaking system, II: the effect of
light and drugs on retinal function. J Biol Rhythms 1991; 6:31–
48
5. Remé CE, Bush R, Hafezi F, Wenzel A, Grimm C: Photostasis and
beyond: where adaptation ends, in Photostasis and Related
Topics. Edited by Williams TP, Thistle A. New York, Plenum
Press, 1998, pp 199–206
6. Danilenko KV, Wirz-Justice A, Kräuchi K, Weber JM, Terman M:
The human circadian pacemaker can see by the dawn’s early
light. J Biol Rhythms 2000; 15:437–446
7. Gasio PF, Kräuchi K, Cajochen C, van Someren E, Amrhein I,
Pache M, Savaskan E, Wirz-Justice A: Dawn-dusk simulation
light therapy of disturbed circadian rest-activity cycles in de-
mented elderly. Exp Gerontol 2003; 38:207–216
8. Terman JS, Terman M, Lo ES, Cooper TB: Circadian time of
morning light administration and therapeutic response in win-
ter depression. Arch Gen Psychiatry 2001; 58:69–75
9. Dijk DJ, Lockley SW: Integration of human sleep-wake regula-
tion and circadian rhythmicity. J Appl Physiol 2002; 92:852–
862
10. Terman M: Light on sleep, in Sleep Science: Integrating Basic
Research and Clinical Practice. Edited by Schwartz WJ. Basel,
Switzerland, Karger, 1997, pp 229–249
11. Terman M, Schlager D, Fairhurst S, Perlman B: Dawn and dusk
simulation as a therapeutic intervention. Biol Psychiatry 1989;
25:966–970
12. Terman M, Schlager DS: Twilight therapeutics, winter depres-
sion, melatonin, and sleep, in Sleep and Biological Rhythms.
Edited by Montplaisir J, Godbout R. New York, Oxford Univer-
sity Press, 1990, pp 113–128
13. Avery DH, Bolte MA, Dager SR, Wilson LG, Weyer M, Cox GB,
Dunner DL: Dawn simulation treatment of winter depression:
a controlled study. Am J Psychiatry 1993; 150:113–117
14. Avery DH, Bolte MA, Wolfson JK, Kazaras AL: Dawn simulation
compared with a dim red signal in the treatment of winter de-
pression. Biol Psychiatry 1994; 36:181–188
15. Avery DH, Eder DN, Bolte MA, Hellekson CJ, Dunner DL, Vitiello
MV, Prinz PN: Dawn simulation and bright light in the treat-
ment of SAD: a controlled study. Biol Psychiatry 2001; 50:205–
216
16. Terman M, Terman JS: Treatment of seasonal affective disorder
with a high-output negative air ionizer. J Altern Complement
Med 1995; 1:87–92
17. Eastman CI, Lahmeyer HW, Watell LG, Good GD, Young MA: A
placebo-controlled trial of light treatment for winter depres-
sion. J Affect Disord 1992; 26:211–222
18. Spitzer RL, Williams JB, Gibbon M, First MB: The Structured Clin-
ical Interview for DSM-III-R (SCID), I: History, rationale, and de-
scription. Arch Gen Psychiatry 1992; 49:624–629
19. First MB, Spitzer RL, Gibbon M, Williams JBW: Structured Clini-
cal Interview for DSM-IV Axis I Disorders, Patient Edition (With
Psychotic Screen). New York, New York State Psychiatric Insti-
tute, 1995
20. Rosenthal NE, Sack DA, Gillin JC, Lewy AJ, Goodwin FK, Daven-
port Y, Mueller PS, Newsome DA, Wehr TA: Seasonal affective
disorder: a description of the syndrome and preliminary find-
ings with light therapy. Arch Gen Psychiatry 1984; 41:72–80
21. Williams JBW, Link MJ, Rosenthal NE, Terman M: Structured In-
terview Guide for the Hamilton Depression Rating Scale—Sea-
sonal Affective Disorder Version (SIGH-SAD). New York, New
York State Psychiatric Institute, 2002
22. National Institute of Mental Health: Systematic Assessment for
Treatment Emergent Effects (SAFTEE). Rockville, Md, NIMH,
1986
23. Fairhurst S, Levitt J, Terman M: MacLite Operations Manual.
New York, Research Foundation for Mental Hygiene, 2000
24. Terman JS, Terman M, Schlager D, Rafferty B, Rosofsky M, Link
MJ, Gallin PF, Quitkin FM: Efficacy of brief, intense light expo-
sure for treatment of winter depression. Psychopharmacol Bull
1990; 26:3–11
25. Lord MF: Elementary models for measuring change, in Prob-
lems in Measuring Change. Edited by Harris CW. Madison, Wis,
University of Wisconsin Press, 1962, pp 21–38
26. Jacobsen FM: Waking in a lighted room (letter). Biol Psychiatry
1990; 27:372–374
27. Oren DA, Brainard GC, Johnston SH, Joseph-Vanderpool JR,
Sorek E, Rosenthal NE: Treatment of seasonal affective disor-
Am J Psychiatry 163:12, December 2006 2133
M. TERMAN AND J. TERMAN
ajp.psychiatryonline.org
der with green light and red light. Am J Psychiatry 1991; 148:
509–511
28. Terman M, Terman JS: Light therapy, in Principles and Practice
of Sleep Medicine, 4th ed. Edited by Kryger MH, Roth T, De-
ment WC. Philadelphia, Elsevier, 2005, pp 1424–1442
29. Stewart JW: On placebo effects, SAD assessment, and with-
drawal to relapse (letter). Light Treatment Biol Rhythms 1991;
3:19–20
30. Modell JG, Rosenthal NE, Harriett AE, Krishen A, Asgharian A,
Foster VJ, Metz A, Rockett CB, Wightman DS: Seasonal affective
disorder and its prevention by anticipatory treatment with bu-
propion XL. Biol Psychiatry 2005, 58:658–667
31. Golden RN, Gaynes BN, Ekstrom RD, Hamer RM, Jacobsen FM,
Suppes T, Wisner KL, Nemeroff CB: The efficacy of photother-
apy in the treatment of mood disorders: a review and meta-
analysis of the evidence. Am J Psychiatry 2005; 162:656–662
32. Terman JS, Terman M, Amira L: One-week light treatment of
winter depression at its onset: the time course of relapse. De-
pression 1994; 2:20–31
33. Terman M, Terman JS: Bright light therapy: side effects and
benefits across the symptom spectrum. J Clin Psychiatry 1999;
60:799–808
34. Lam RW, Levitt AJ, Levitan RD, Enns MW, Morehouse R, Micha-
lak EE, Tam EM: The CAN-SAD study: randomized controlled
trial of the effectiveness of light therapy and fluoxetine in pa-
tients with winter seasonal affective disorder. Am J Psychiatry
2006; 163:805–812
35. Danilenko KV, Wirz-Justice A, Kräuchi K, Cajochen C, Wever JM,
Fairhurst S, Terman M: Phase advance after one or three simu-
lated dawns in humans. Chronobiol Int 2000; 17:659–668
36. Rozenberg GV: Twilight Study in Atmospheric Optics. New York,
Plenum Press, 1966
37. Terman M, Fairhurst S, Perlman B, Levitt J, McCluney R: Day-
light deprivation and replenishment: a psychobiological prob-
lem with a naturalistic solution, in Architecture and Natural
Light. Atlanta, American Society of Heating, Refrigerating and
Air-Conditioning Engineers, 1989, pp 438–445