Journal cf Affectire Disorders, 26 (1992) 21 l-222 211

0 1992 Elsevier Science Publishers B.V. All rights reserved 01650327/92/$05.00

J AD 00946

o-controlled trial of light treatment

r winter depression *

Charmzwe I. Eastman ‘, Hem-y W. Lahmeyer b, Lucie 6. Watell b, Glenn D. Good c

and Michael A. Young d
UBiological Rhythms Research Laboratory, Psychology Department, * Psychiatry and Psycho,logyDepartments,
Rush-Presbyterian-St. Luke’s Medical Center, Chicago, ’ Psychiatry Department, Unit-e&y of lilinois Medica/ Center, Chicago and
(‘Biostatistics Department, College of American Pathologists, Northfield, I&%ois~USA
(Received 30 March 1992)
(Revision received 23 July 1992)
(Accepted 7 August 1992)

We studied 32 patients with winter seasonal affective disorder (SAD) in a counterbalanced crossover
design comparing 1 h of morning light treatment (about 7000 lux) to 1 h of morning placebo treatment
(deactivated negative ion generator). Both treatments significantly reduced depression ratings, but there
was no difference between the antidepressant response to light and to placebo. Several possible
explanations for this result were discussed including an inadequate ‘dose’ of light (e.g., ineffective
duration or intensity), an unusual sample of patients, and a placebo mechanism.

Key words: Bright light; Seasonal affective disorder; Winter depression; Phototherapy; Placebo

Introduction tion in the northern half of the United States

Winter seasonal affective disorder {SAD) is
estimated to affect about 510% of the popula-
Correspondence to: Charmane Eastman, Biological Rhythms
Research Laboratory, Rush-Presbyterian-St. Luke’s Medical
Center, 1653 West Congress Parkway, Chicago, IL 60612-
3864, USA.
* Presented in part at the 1st Annual Meeting of the Society
for Light Treatment and Biological Rhythms, Washington,
DC., June, 1989 and the 2nd Annual Meeting of the
Society for Light Treatment and Biological Rhythms, New
York, May, 1990.
(Rosen et al., 1990). Many researchers have come
to the conclusion that high intensity light is an
effective treatment for this disorder (e.g., Rosen-
thai et al., 19881, whereas others remain skeptical
(e.g., Brown, 1990). In general, treatments are
colrsidered effective if they produce improve-
ments beyond that attributable to placebo eff-zts.
Improvements in depression ratings, regardless of
magnitude, are not sufficient to prove efficacy,
since placebos can also reduce depression (Critelli
and Neumann, 1984; Eastman, 1990b; Stewart,
1990). The problem with demonstrating efficacy
for light treatment lies in the diffi-uity of finding
an appropriate placebo control.
Early light therapy studies used low intensity
light as the placebo control. There are several
reasons why low intensity illumination is not a
satisfactory placebo for high intensity light. Sub-
jects find low intensity light to be obviously differ-
ent from high intensity light. Even in the first
light therapy study the majority of patients pre-
dicted that high intensity light would be more
helpful (Rosenthal et al., 1984). This raises the
possibility that the superiority of high intensity
light was due to its placebo effect. In addition,
several SAD studies have not shown the expected
differences between high and low intensity light
(Grota et al., 1989; Issacs et al., 1988; Lam et al.,
1991; Levitt et al., 1991; Moui et al., 1990; Tei-
cher et al., 1992; Wirz-Justice ct al., 1986), lead-
ing to the suggestion that low intensity light might
actually be an active treatment (Greta et al.,
1989; Moui et al., 1990; Wirz-Justice et al., 1986).
The hypothesis that light’s antidepressant effect
is due to a placebo mechanism is rarely presented
as a likely explanation for the results. In any case,
low intensity light is not a satisfactory placebo
control treatment (c.f., Brown, 1990).
It has been suggested that light therapy pre-
sented in the evening is not a specific antidepres-
sant, and is therefore an acceptable placebo con-
trol for morning exposure (Lcwy et al., 1987;
1989). However, others have found no differences
between morning and evening treatments (Hei-
iekson et al., 1986; Wirz-Justice et al., 1989) or
have shown that morning-evening differences are
a function of crossover design (Rafferty et al.,
le30; Terman et al., 1990b). In addition, morning
and evening treatments are not equally disruptive
of most patient’s daily occupational, family, and
personal routines. This differential personal ‘cost’
of treatment is another reason why evening light
is not the best placebo control for morning light.
The ideal placebo control for light sh.:uid share
as many procedural similarities to light treatment
as possible (Stewart, 1990). Lignt treatment usu-
ally involves a considerable investment in time
and a period of relative inactivity. It usually re-
quires an earlier wake-up time and some sleep
deprivation. A placebo should control for these
factors as well as the usual non-specific effects
such as the passage of time and attention from
the research staff. In addition the placebo should
be plausible to the patient, ideally producing the
same expectations for improvement as the active
treatment. Finally, the placebo should be inert.
We have developed a placebo control treatment
that satisfies these requirements. The purpose of
this study was to test the efficacy ot morning high
intensity light treatment for winter SAD using an
appropriate placebo control treatment.
Method
Subjects
Subjects were recruited through advertise-
ments, the media, and were referred by mental
health professionals. Incllusion criteria were: 13 a
diagnosis of current major depression by DSM-
III-R criteria (American Psychiatric Association,
19871, 2) a diagnosis of seasonal affective disor-
der by the criteria of Rosenthal et al. (19841,
except that subjects meeting full DSM-III-R cri-
teria for mania in the spring or summer were
excluded, 31 loss of energy, increased appetite or
weight, and increased sleep, and 4) a score of 21
or more on the 24-item composite scale com-
posed of the original 17-item Hamilton Depres-
sion Rating Scale (HDRSI (Hamilton, 1960) and
7 ‘atypical’ supplementary items (Rosenthal and
Heffernan, 1986). These and other items were
administered using the SIGH-SAD structured in-
terview (Williams et al., 1988). The study was
conducted during two consecutive winters, 1988-
1989 and 1989-1990. One subject entered the
treatment protocol in November, two entered in
December, and the rest entered in January or
February. None of the subjects were taking psy-
chotropic medications during the fail/winter that
they participated in the study, but a few had
taken such medications during the previous win-
ter. None of the subjects had previously received
bright light treatment.
Experirneritul promol
The study compared two treatments which
consisted of sitting in front of an electrical device,
either a light box or a ncga,rve ion generator.
Both treatments were 1 h in duration beginning
immediately upon waking in the morning. The

light isloxwas 65 cm wide and 43.5 cm tall (Apollo
Light Systems, Orem, UT). It contained six, two-
foot (61 cm) cool-white fluorescent lamps. Sub-
jects sat at a table or desk with the light box
directly in front of them. They were instructed to
prop the light box up on books if their head was
above the middle of the light box. They used a
one-foot ruler to measure exactly 12” (30.5 cm)
from their nose to the middle of the plexiglass
screen of the light box. They were given written
instructions with diagrams and a one-foot ruler to
ta!:e home. Subjects usually read or ate during
the 1 h exposure time. They were told that it was
not necessary to stare at or glance up at the
lights, but at that distance it is difficult not to
occasionally look into the light.
Illuminance was measured with an Extech In-
struments Lux Meter (R401025) which has a flat
photosensor. With the photosensor pointed di-
rectly at the light box at a distance of 12” read-
ings were initially slightly greater than 10,000 lux,
but diminished to about 9000 lux after about
lo-20 min as the lamps warmed up. With the
photosensor in the position of a subject’s eyes
pointing down at reading material on the table,
readings were between about 3000 and 9000 lux,
depending on head angle and position and time
elapsed since the light box was turned on. The
most natural position for reading resulted in an
illuminance of about 7000 lux for most of the
hour.
The negative ion generator was placed on the
same table or desk as the light box. It was placed
two feet (61 cm) away from the subject at a 45’
angle, positioned so that the negative ions were
blown across the table in front of the subject.
Some subjects were given generators that were
deactivated by changing a circuit within the gen-
erator. However, the signal light indicating ion
generation and the fan remained on. Subjects
were informed that they might receive an active
or a deactivated generator, but that they would
not be able to tell which type they had received.
This report only includes subjects who received
deactivated generators. The deactivated genera-
tors provided the placebo treatment.
Before subjects agreed to participate, one of
us (CIE) showed them a light box and negative
ion generator and explained the rationale for
213
these treatments. It was pointed out that several
environmental factors vary seasonally, and that
people are exposed to more negative ions in the
summer as well as to more fight. At this meeting
potential subjects were given a packet of informa-
tion from the scientific and lay literature about
negative ions and light treatment. They were told
that some people respond better to ions than
light, some respond better to lights than ions,
some respond to both, and some to neither. The
attitude that the research staff displayed to pa-
tients with regard to both treatments was gener-
ally neutral and cautious rather than enthusiastic.
‘Written informed consent was obtained from all
participants.
The study used a 5-week counterbalanced
crossover design with a baseline (B) week, two
consecutive weeks of light treatment (Ll and L2)
and two consecutive weeks of placebo treatment
(Pl and P2). Each subject was required to select
and then adhere to a fixed wake-up time for the
entire S-week study, including weekends. The lat-
est wake-up time permitted was 8:00 am. Subjects
chose a wake time that would permit them to
sleep as late as possible, but still allow time for
the morning treatment and their usual morning
preparations. Wake-up times for different indi-
viduals ranged from 4:20 am to 8:00 am with a
mean of 6:26 am. Compliance was assisted and
checked by periodic morning phone calls at wake-
up time. Subjects were required to go to bed at
least 7 h before their scheduled wake-up time.
They were permitted to go to bed earlier, but not
Later than this time. Naps were permitted as long
as they started at least 2 h after the scheduled
wake-up time. These rules were intended to limit
the amount of sleep deprivation caused by the
early wake-up times. Alcoholic beverages were
prohibited during the experiment, and caf-
feinated beverages were only permitted before
noon.
Subjects completed several daily and weekly
questionnaires. In addition to providing data,
these questionnaires helped monitor and encour-
age compliance to the rules of the protocol. The
Daily Sleep Log provided estimates of sleep on-
set, nocturnal awakenings greater than 5 min,
wake times, and naps. Before the experiment
began subjects kept a simpler sleep chart indicat-
‘1-l

ing sleep and nap times. Another Daily Log in- factor was order (light first, light last) and the
cluded sections for caffeine and alcohol intake. within-subjects factor was treatment (baseline,
The Daily Ion and Light Log was for recording end of light treatment (L21, end of placebo treat-
the times of treatment as well as all times the ment (P2)). Significant MA QVA effects were
subjects went outside during daylight. Some of followed up with the univariate ANOVAs for the
the data on Baylight exposure have been pub- three scales. Other analyses will be described in
lished (Eastman, 1990a). At the end of each week the appropriate places in the results section. In
subjects completed a ‘comaosite Beck scale’ corn. all statistical test we used a significance level of
posed of the 214tem Beck Depression Inventory 0.05, two-tailed, except whcrc noted.
(BDI) (Beck et al., 1961) and three ‘atypical’
items which we added to assess increased sleep, es&s
increased appetite, and weight gain.
Subjects visited the University of Illinois Medi- Thirty-nine subjects start4 the 5-week proto-
cal Center once a week where a rater ‘blind’ to col and 32 completed it (5 m ies ar?d 27 females).
treatment condition administered the SIGH-SAD. The mean 4 &SD) age of -Ike completers was
The pre-baseline (PRE-B) rating was made be- 36.1 f 8.6 years.
fore the 5-week protocol began. After the inter-
views the subjects walked a few blocks to Rush- Depression ratings
Presbyterian-St Luke’s Medical Center where Fig. 1 shows that the composite HDRS scores
their daily and weekly questionnaires were declined over the course of the study in both
checked by research assistants and where they
received or exchanged their equipment. We be.. Hamilton Depression Ratings
lieve that this division of functions between the Light First. N=18
two medical centers helped to maintain the blind.
For convenience, subjects did not use the equip-
ment on the day they visited the medical centers.
Therefore, treatments were actually six days/
week. At the end of the baseline week subjects
completed an Expectation Questionnaire contain-
ing four 100 mm visual analog scales, 1 for each
of the upcoming four treatment weeks. Thus, all
ratings were performed before treatment began.
The 100 mm lines were anchored with ‘will r’eei PRE-B B Ll i2 Pl P2
much better’ (0 mm) and ‘will feel much worse’
Light Las”; X=14
(100 mm). The phrase ‘no change’ appeared at 50 -I
mms. The treatment planned for each of the four r- 0

weeks, ‘lights’ or ‘ions,’ was written onto each I+

t 8 E 00
individual’s Expectation Questionnaire. A subset
of subjects had their core body temperature mon-
itored throughout the study. These results will be
1 20
presented elsewhere. .d
M
3 10
0
Data analysis r- 8 0
6 0
Statistical analyses were performed on the 0
PRE-B B Pl P2 Ll L2
composite HDRS, the original 17-item HDRS
and the composite Beck scale. Since these scales Fig. 1. Composite Hamilton Depression Ratings Scale scores
over the course of the study for the light first and light last
are intercorrelated measures of depression, we
order groups. 0: individual subjsc? scores. : means. The
conducted a multivariate analysis of variance horizontal lines at 16 show one of t’~~:criteria for antidepres-
(MANOVA) (Wirier, 1971). The between-subjects sant respon’:
 215

TABLE 1 Examination of the univariate ANOVAS indi-

Clinical ratings cated that these findings were consistent across
all three scales. The main effects of treatment
Hamilton depression rating scale were significant: composite HDRS (F = 21.02, df
PRE-B B Ll L2 PI P2 = X29, P < O.OfKIl), the original 17-item HDRS
Light first (N = 18) (F = 19.98, df = 2,29, P < 0.0001) the composite
17 Original items 14.8 14.4 12.4 11.2 11.3 9.7 Beck (F = 11.41, df = 2,29, P < 0.0001). For all
(4.7) (3.8) (5.9) (6.0) (6.1) (4.9) three scales, Neuman-Keuls post-hoc tests found
7 Atypical items 16.8 14.9 13.0 11.4 13.4 11.8
(3.3)
that light and placebo were not significantly dif-
(3.2) (5.6) (4.5) (4.3) (3.3)
ferent from each other.
Light last ( N = 14)
Fig. 1 suggests the possibility of an interaction
17 Original items 16.8 16.4 9.6 8.4 12.4 12.3
(4.0)
such that in the second half of the experiment
(5.6) (4.7) (5.0) (6.4) (5.9)
7 Atypical items 15.4 13.9 10.3 8.6 11.2 11.4 light produced greater improvement than placebo.
(3.7) (3.5) (4.1) (3.1) (3.2) (3.9) While the MANOVA did not find this effect
statistically significant, in order to fully under-
Beck depression inventory stand the data, we examined the first half (base-
PRE-B B Ll L2 Pl P2 line to first treatment) and second half (first
Light first (N = 18) treatment to second treatment) of the study sepa-
21 Original items 17.6 iii.4 11.5 12.3 11.8 11.2 rately (Armitage and Barry, 1987). These analyses
(8.5) (8.6) (8.0) (8.2) (7.0) (6.8)
3 Atypical items (t1, 3.1 2.8 2.9 3.3 3.1
suggested that scores declined over time, regard-
less of treatment. This is consistent with the
(2.5) (2.0) (1.8) (2.2) (1.7)
original MANOVA results that there was no dif-
Light last (IV = 14) ference between the antidepressant effects of light
21 Original items 19.8 16.2 8.6 7.9 12.7 11.9
and placebo treatment conditions.
(8.0) (6.7) (5.2) (4.8) (5.2) (5.8)
3 Atypical items $1 2.8 2.6 2.7 2.8 2.5 We also analyzed the data by categorizing sub-
(1.9) (1.9) (1.5) (1.7) (1.6) jects as responders or non-responders by criteria
similar to those used by Terman et al. (1989). A
Means with SD in parentheses.
responder was defined as a subject whose com-
posite HDRS score after treatment was at least
50% less than baseline and less than 16. Using
order groups (light first and light last). The com- these criteria, 18.8% (6/32) of the subjects re-
posite Beck scale produced a similar pattern of sponded to light but not placebo, 6.3% (2/32)
results. Table 1 shows the scores broken down responded to placebo but not light, 12.5% (4/32)
into the original and the atypical scales. responded to both treatments, and 62.5% (20/32)
The MANOVA indicated a significant main resporided to neither. Thus, 31.3% (10/32) were
effect of treatment (Wilk’s lambda = 0.342, F = light responders and 18.8% (6/32) were placebo
8.01, df = 6,25, P < 0.001). There was no signifi- responders. Using a l-tailed exact probability test
cant main effect for order groups (Wilk’s lambda (Bishop et al., 1975, p. 258), this difference in
= 0.870, F = 3,28, P = @.264), and no significant proportions was not significant.
order by treatment interaction (Wilk’s lambda = Altering the response criteria, such as requir-
0.764, F = 1.29. df = 6,25, P= 0.298). Planned ing only the 50% reduction in scores or applying
comparisons in the MANOVA indicated that light Terman’s criteria to the 21-item HDRS, did not
and placebo scores were not significantly differ- alter the results. We also examined the response
ent. Pooled scores of light and placebo were rates separately for the light first and light last
significantly different from those at baseline (P < groups and for the first half of the experiment
0.0001). Thus, results indicate that depression and the second half of the experiment (both
diminished with both light and placebo treat- compared to baseline). In none of these addi-
ments, but there was no difference between them tional analyses was there a significant difference
in their antidepressant effects. in response between light and placebo.
216

TABLE 2 Sleep
Self-reported sleep parameters for 32 SAD subjects: weekly During the week before the study (pre-B) sub-
means (SD) in hours past midnight jects woke up later on weekends (or days off)
than weekdays. The average wake-up time on
PRE-B B Ll L2 Pt P2 weekends (or the average of the two latest days)
Wake-up 7.8 6.3 4.4 6.4 6.4 6.4 was 9.0 + 1.5 h, and on weekdays (or the average
(1.4) (0.9) (0.9) (1.0) (0.9) (0.9) of the 5 earliest days) it was 7.2 + 1.4 h. During
Sleep onset 23.i 23.0 22.8 22.9 22.9 23.0
(1.0) (0.9) (0.9) (0.9) (0.9)
the study subjects were required to adhere to a
(1.1)
Totai sleep time 8.9 7.5 7.7 7.6 7.6 7.5 fixed wake-up time, even on weekends. This
(inciuding naps) (1.1) (0.7) (0.7) (0.6) (0.7) (0.6) scheduled wake-up time was earlier than usual in
order to accommodate the 1 h morning treat-
ments. The average scheduled wake-up time was
Expectations 6.4 & 0.9 h. Thus, subjects were required to wake
The mean (+ SD> expectation scores were 18.8 up on average 0.8 h earlier than usual on week-
(&-10.9) for the end of light treatment (L2) and days and 2.6 h earlier on weekends. Table 2
25.8 (+ 13.4) for the end of deactivated ion gen- shows that subjects’ actual wake up time, sleep
erator treatment (P2) (P < 0.01, by a paired t- onset and total sleep time remained relatively
test). Thus, subjects expected to improve with stable during the 5week protocol, with the only
both treatments, and they expected to feel slightly marked change occurring between the pre-B and
better after light treatment (which they knew B weeks. Although subjects woke up earlier, they
would be ‘bright’ light) than after generator treat- did not fall asleep earlier, and thus total sleep
ment (which they knew might be a placebo). time decreased. Although subjects were allowed
However, given our findings the expectation to nap, apparently naps did not compensate for
scores shed no additional light on the results. If the earlier wake-up times. Sleep parameters did
expectations are taken as a partial indicator of not differ between light treatment and placebo
placebo effects, they might be used to explain treatment. Since the placebo produced the same
why one treatment did better than another for changes in sleep schedule as light treatment, it
reasons other than active treatment factors. While fulfilled an important requirement for an accept-
our subjects expected to do somewhat better with able placebo condition.
light than with placebo, in fact, there was no There was a significant correlation between
significant difference in their treatment re- the scheduled wake-up time during the study and
sponses. the change in wake-up time from before the study

TABLE 3
Mean sleep parameters and correlations with clinical response

Mean (SD) Correlations with clinical improvement a

iin hot.&
Ll L2 Pl P2
Light first subjects
Scheduled wake-up time 6.4 (1.0) - 0.36 - 0.42 - 0.08 + 0.06
Wake-up time advance b 0.9 (1.0) -0.65 * -0.58 * -0.14 -t-0.08
Sleep loss c 1.4 (0.9) - 0.35 -0.11 -0.11 -0.04
Light last subjects
Scheduled wake-up time 6.5 (0.9) - 0.09 + 0.23 + 0.00 + 0.03
Wake-up time advance b 0 6 (0.5) + 0.04 + 0.06 +0.38 + 0.27
Sleep loss c 1.3 (1.0) + 0.05 +0.15 +0.27 + 0.39

a Difference between composite HDRS scores (17~item HDRS+7 atypical items) for the indicated week and the baseline week;
b Difference between scheduled wake-up time during the study and average weekday wake-up time in the pre-baseline week;
’ Difference between total sleep time in baseline week and pre-baseline week. * P < 0.05.
%-tailed.
to during the study for the light first subjects
(r = +0.52, P < 0.051, but not for the light last
subjects. This means that there was a tendency
for the light first subjects with the latest sched-
uled wake-up times to have the largest advances
in wake-up time. There was a significant negative
correlation between wake-up time advance and
clinical improvement during light treatment for
the light first group (see Table 3). In other words,
the more these subjects had to advance their
wake-up time, the poorer their antidepressant
re>ponse to light. There was no relationship be-
tween wake-up advance and clinical respclse in
the subjects who received light last. Neither
scheduled wake-up time nor sleep loss was signif-
icantly correlated with antidepressant response.
iscusshn
In this study, both light and placebo produced
significant reductions in depression ratings, but
light was not superior to placebo. Placebo mecha-
nisms are poorly understood, but factors that
contribute to the placebo effect could be atten-
ticn from the research staff and spontaneous
remission. The gradual improvement in depres-
sion ratings over the course of the 5-week study
could be due to both of these factors. Sponta-
neous remission is possible since the natural pho-
toperiod was gradually lengthening, as in most
winter depression studies. However, the experi-
ment was designed to detect any bersfit of light
treatment beyond the gradual improvement due
to placebo effects. Another factor that can con-
tribute to placebo effects is the expectations of
the patients (Brown, 1990; Ross and Olson, 1981).
In this study, the expectation ratings were slightly
better for the light treatment than for the ion
generator treatment, but this difference was not
enough to produce a differential antidepressant
response.
When there is a difference between a putative
active treatment and placebo that does not reach
statistical significance, it is important to ask
whether the sample size was large enough to
detect such a difference should it exist, i.e., was
there enough statistical power. Such calculations
are complicated by crossover designs. However,
we can regard the first three weeks of our proto-
col as a parallel (between groups) design. In that
case, the difference between light and placebo
was so small that even if a very large sample size
produced statistical significance it would be clini-
ca!ly meaningless.
Any difference between an active treatment
and placebo can theoretically be diminished by a
high response rate to the placebo or by a low
response rate to the treatment. Placebo response
rates in antidepressant drug studies range from
0% to 91% (Greenberg and Fisher, 1989). Our
placebo response rate, using the criterion of most
drug studies (a 50% drop in depression ratings),
was 22%. Response rates to low intensity light in
a cross-center analysis of SAD studies ranged
from 0% to 22% (Terman et al., 1989). Our
placebo response rate, using the same joint crite-
ria, was 25%. Thus, our placebo response rate
was not extremely high. Our study did produce a
relatively low response rate to Iight treatment. In
the cross-center analysis (Terman et al., 1989) the
response rate to morning Iight treatment ranged
from 0% to 83%, with an average of 53%. In our
study only 28% of the patients met the same joint
response criteria.
Possible reasons for our low response rate to
light treatment include inadequate ‘dose’ of light
(e.g., duration, intensity, timing), unusual sample
of SAD patients, and the inclusion of a placebo
control group in the study.
Parameters of hight treatment
The most common ‘dose’ of light for therapy
has been about 2500 lux for 2 h. We used a
shorter treatment duration (1 h) to minimize sleep
schedule changes and sleep deprivation, and tried
to compensate by using a higher intensity (about
7000 lux), since there is evidence that duration
and intensity might interact reciprocally (Terman
et al., 1990a). Nevertheless, 1 h might be too
short for that particular intensity. However, there
are studies that used l-h morning light at lower
illuminance than we did which produced better
response rates (Szadoczky et al., 1989; 1991;
Wirz-Justice and Anderson, 1990; Wirz-Justice et
al., 1989). On the other hand, it is possible that
our ‘dose’ was too high. In any case, our particu-
lar light treatment (the specific light box, patient
distance from the box, instructions that it is not
'1S
.
necessary to glance at the lights, duration of
treatment, etc.) has not previously been formally
tested. Therefore, it is possible that our particu-
lar treatment configuration was not adequate.
Another possible reason for our low response
rate to light treatment could be the timing of the
treatment. According to the phase-shift hypothe-
sis (Lewy et al., 1987, 19881, morning light is
antidepressant because it produces a phase ad-
vance of c+cadian rhythms relative to sleep.
Morning light administered at the same local
time, e.g. 6 am, should produce different amounts
of phase advance in different individuals, depend-
ing on the phase of their circadian rhythms. In
the case of individuals with extremely delayed
phases, it could even produce a phase delay. We
chose TV minimize this confound by scheduling
the time of morning treatment relative to the
individual’s habitual sleep schedule, so that phase
shifts might be more consistent among individu-
als. Nevertheless, it is possible that our procedure
produced a range of circadian phase shifts ac-
companied by a range of sleep time shifts resuit-
ing in the ‘wrong’ phase angle between circadian
rhythms and sleep for many subjects.
It is also conceivable that the local time of
light treatment is more important than the circa-
dian time. The mcst common wake-up and treat-
ment time for morning light treatment has been
600 am (Terman et al., 19891, and several proto-
cols required even earlier treatment times such as
5:00 am or a few hours before dawn (Issacs et a;.,
osenthal et al., 1984, 1985). A few treat-
ment studies were structured iikc ours in which
the wake-up time varied somewhat among pa-
tients &Ieiiekson et al., 1986; Terman et al.,
1990a). In our study wake-up times ranged from
4:15 to Y:OOam with the majority (78%) failing
between 5:00 and 7:00 am. Thus our design was
not extremely unusual in terms of wake-up time
and the start of morning light treatment. Never-
theless, it is conceivable that there is a w!ndow of
ideal wake-up times that a substantial portion of
our subjects missed, which could have lowered
our light treatment response.
Sample of SAD patients
Another possible reason for our modest light
treatment response could relate to our sample of
SAD patients. Unlike most other investigatcrs,
we specifically selected those who had the ‘atypi-
cal’ symptoms of increased appetite and sleep in
order to study a more homogeneous popu!ation.
The prevalence of the various atypical symptoms
varies among research centers (Winton and
Checkiey, 1989). Our findings need to be repli-
cated using a broader sample of patients.
We may have selected patients resistant to
light treatment because our subject; had to meet
criteria for current major depression by DSM-
IIIR. Thus, Lhe qualifying symptoms had to be
present ‘nearly every day’ for two weeks. Both
winters during our study contained stretches of
unseasonably warm and sunny days. Patients who
were screened during this type of weather and
whose s;.mptoms completely remitted during such
days did not qualify for our study. Thus, we may
have screened out some cf the most light sensi-
tive patients. Geographical locations where the
winter cloud cover is more constant, such as the
northwestern states, have been considered better
natural ‘laboratories’ for light studies (Avery et
al., lY90). Extremely light sensitive patients could
enter research studies in these locations.
Placebo controls reduce response rates to actiw
treatments
The low response rate to light treatment in our
study could be a function of the inciusion of a
placebo control. The inclusion of a placebo con-
trol lowers the response rate for drugs (Green-
berg and Fisher, 1989; Ross and Olson, 1981;
Shapiro, 1971; Shapiro and Morris, 1978; Smith
et al., 196Y; Wechsier et al., 1965). For example, a
review of 1t!3 antidepressant drug studies
(Wechsler et al., 1965) categorized studies into
those with no control treatment, those that com-
pared two or more different antidepressants and
perhaps a placebo, and those that compared the
drug to a placebo. The percent of studies showing
good improvement rates to the drug decreased
when placebo controls were used. Drug response
rates in the three categories were 57%, 49%, and
23%, respectively. The difference in response
rates has been related to the outcomes that the
patients and staff expected. For further explana-
tion see Eastman (1990b). Another review of an-
tidepressant drug studies showed that the more

stringently controlled the study, the lower the
response rate for the drug (Smith et al., 1969).
The 423 studies were divided into three cate-
gories, those that did not use control groups or
blind techniques, those that used control groups
but no blind techniques, and those that used
control groups and blind techr,iques. The percent
of studies reporting good improvement from the
drug decreased from 58% to 46% to 33% as
design sophistica:ion increased.
A recent review (Terman and Terman, 1991)
provides evidence that a similar principle may
apply to SAD light treatment studies. Studies
were clas+fied, by percent decrease in depression
ratings, into categories ranging from low to strong
response. Only three out of the 8 studies that
included a placebo control (either low illumi-
nznce light or placebo beverage) met the strong
response criterion. On the other hand, seven out
of the 10 studies without a placebo condition
Cwl+h compared two or more different high illu-
minance light treatments) produced a strong re-
sponse. Thus, in these SAD light studies, the
inclusion of a placebo control reduced the re-
sponse rate to the high intensity light treatment.
It is possible that our relatively low response
to light treatment was partially due to the fact
that tie included a placebo control in our design.
Both the patients and staff knew that the patients
might be on a placebo for some of the weeks of
the study. This could lower the overall expecta-
tions of patients and staff, compared to studies in
which patients are given light treatment for all
weeks of the study. We predict that if our light
treatment (same light box, timing, distance, etc.)
were used in an uncontrolled open trial, then the
response rates would be much higher.
We found a negative correlation between
wake-up advance and clinical response to light
treatment for the light first group, but not for the
light last grolrp. In o’iher words, the earlier that
light first subjects had to wake up (relative to
wake-up time before the study), the poorer their
antidepressant :espor?se. For light last subjects
the amount of wake-up advance was not related
to clinical response. One explanation for this
complicated relationship is that patients need
219
time to adjust to their advanced sleep sehedule in
order for morning light to be effective fc.f. Lewy
et a:., 1988). However, another &t&t study of
sleep logs did not find a relationship between the
amount of wake-up tir,le advance ~CXmorning
light and response rates (Wirz-Justice and Ander-
son, 1990). More work needs to be done to deter-
mine whether there is a relationship between
wake-up advance and the antidepressant re-
sponse to light treatment.
Final remarks
In conclusicn, the results show that the mom-
ing light treatment in our study was no mere
effective than a placebo. Possible explanations
inch! ’ 1 :hz use of a sub-optimal ‘dose’ of light
(e.g., i:lcffecrlve intensity or timing), the ssreen-
ing out of light sensitive patients due to unusual
weather, the testing of onlv patients with the
atypical symptoms, and the inclusion of an inert
and plausible placebo control. More work will
have to be done to determine the relative contri-
butions, if any, of these various factors.
Acknowledgements
We thank Larry D. Chait, Ph.D. for suggesting
the placebo control treatment. Louie Fogg, Ph.D.
of Rush-Presb:yterian-St. Luke’s Medical Center
served as a statistical consultant. Some SIGH-
SAD ratings were performed by Jamie K. Lilie,
Ph.D., Cynthia Westegard, M.A., Michael Eas-
ton, M.D. and Paul Sakkas, M.D. Technical assis-
tance was provided by Joy Dunbar, Linda Gallo,
Barbie VcC!uskey, Charles Splete and Alexis
Walker. We thank Karen Stewart, Ph.D. for a
critical reading of this manuscript.
This research was supported by NIMH grant
MH42768.
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