Journal of Affective Disorders 227 (2018) 90–96

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Journal of Affective Disorders

journal homepage: www.elsevier.com/locate/jad

Research paper

Clinical efficacy, onset time and safety of bright light therapy in acute T
bipolar depression as an adjunctive therapy: A randomized controlled trial
Tian-hang Zhoua, Wei-min Danga,1, Yan-tao Maa, Chang-qing Hub, Ning Wangc, Guo-yi Zhangd,
Gang Wangb, Chuan Shia, Hua Zhange, Bin Guoc, Shu-zhe Zhoua, Lei Fengb, Shu-xia Genga,
⁎
Yu-zhen Tongd, Guan-wen Tangc, Zhong-kai Hed, Long Zhenb, Xin Yua,
a
Peking University Sixth Hospital, Peking University Institute of Mental Health, the Key Laboratory of the Ministry of Health (Peking University), National Clinical
Research Center for Mental Disorders, Beijing, China
b
Mood Disorders Center, Beijing Anding Hospital, Capital Medical University & China Clinical Research Center for Mental Disorders Center of Depression, Beijing Institute
for Brain Disorders, Beijing, China
c
Beijing Huilongguan Hospital, Peking University, Beijing, China
d
School of physics, Peking University, Beijing, China
e
Peking University Third Hospital, Beijing, China

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Bright light therapy (BLT) is an effective treatment for seasonal affective disorder and non- seasonal
Bright light therapy depression. The efficacy of BLT in treating patients with bipolar disorder is still unknown.
Bipolar depression Aims: The aim of this study is to examine the efficacy, onset time and clinical safety of BLT in treating patients
Clinical efficacy with acute bipolar depression as an adjunctive therapy (trial registration at ClinicalTrials.gov: NCT02009371).
Onset time
Methods: This was a multi-center, single blind, randomized clinical trial. Seventy-four participants were ran-
domized in one of two treatment conditions: BLT and control (dim red light therapy, dRLT). Sixty-three parti-
cipants completed the study (33 BLT, 30 dRLT). Light therapy lasted for two weeks, one hour every morning. All
participants were required to complete several scales assessments at baseline, and at the end of weeks 1 and 2.
The primary outcome measures were the clinical efficacy of BLT which was assessed by the reduction rate of
HAMD-17 scores, and the onset time of BLT which was assessed by the reduction rate of QIDS-SR16 scores. The
secondary outcome measures were rates of switch into hypomania or mania and adverse events.
Results: 1) Clinical efficacy: BLT showed a greater ameliorative effect on bipolar depression than the control,
with response rates of 78.19% vs. 43.33% respectively (p < 0.01). 2) Onset day: Median onset day was 4.33 days
in BLT group. 3) BLT-emergent hypomania: No participants experienced symptoms of hypomania. 4) Side ef-
fects: No serious adverse events were reported.
Conclusion: BLT can be considered as an effective and safe adjunctive treatment for patients with acute bipolar
depression.

1. Background
Bipolar disorder (BD) is a common severe mental illness which is
characterized by recurrent episodes of depression and mania/hypo-
mania (American Psychiatric Associasion (APA), 2013). The estimated
lifetime prevalence of BD in general population worldwide was around
1.0% (Clemente et al., 2015), and higher with broader diagnostic cri-
teria (Zimmermann et al., 2009). A recent meta-analysis has reported
the estimated point, 12-month and lifetime prevalence of BD in China
were 0.09%, 0.17% and 0.11% (Zhang et al., 2017). BD is a disabling
illness which has been the 12th leading cause of disability worldwide
across (Ferrari et al., 2016), which imposes a great burden to patients
and the whole society because of its marked functional impairment
(Sole et al., 2012; Vieta et al., 2013).
Depressive episode is an important clinical stage of BD. Studies have
shown that BD patients spend significantly more time with depressive
symptoms than with mood elevation/mixed symptoms (De Dios et al.,
2010). Depressive symptoms are associated with greater social im-
pairments compared with mania/ hypomania (Bonnin et al., 2010).
Furthermore, suicide or suicide attempts mostly occur in the depressive

⁎
Correspondence to: Institute of Mental Health, Peking University, Peking University Institute of Mental Health, No. 51, Huayuanbeilu Rd, Haidian District, Beijing 100191, China.
E-mail address: yuxin@bjmu.edu.cn (X. Yu).
1
This author contributed equally to this study and share first authorship.

http://dx.doi.org/10.1016/j.jad.2017.09.038
Received 22 January 2017; Received in revised form 20 July 2017; Accepted 23 September 2017
Available online 25 September 2017
0165-0327/ © 2017 Elsevier B.V. All rights reserved.
T.-h. Zhou et al.
episode of BD (Hauser et al., 2013). However, depressive episode of BD
are still not well controlled by current treatments (Forte et al., 2015;
Swartz et al., 2012).
Because of limited research, the clinical evidence is insufficient to
support clinical guidelines to make a clear recommendation for bipolar
depression (Frye, 2011; Yatham et al., 2013). Medications currently
used for the treatment of bipolar depression are frequently partially
effective, leaving residual depressive symptoms which are liable to re-
lapse (Geddes et al., 2009; Greil et al., 2012). Side effects induced by
mood stabilizers and antipsychotics which are a most important reason
for poor treatment compliance also cannot be ignored (Barraco et al.,
2012; Selle et al., 2014). Therefore there is a clear need for an effective
adjunctive treatment with less risk of severe side effects. Bright light
therapy (BLT) has been proposed as a promising choice.
Although the efficacy of BLT in treating depression has gradually
been recognized, the mechanism of BLT is still in the stage of hypoth-
esis. Light signals are captured by melanopsin-containing retinal cells
on retina and transduced to electrical signals. The retinohypothalamic
tract delivers these signals to suprachiasmatic nuclei (SCN) which can
regulate biologic rhythm (Hattar et al., 2003). The function of SCN is
impacted by the dose and duration of light explosion (Zeitzer et al.,
2005). Melatonin directly regulates SCN through melatonin receptors
on SCN (Macchi and Bruce, 2004; Stehle et al., 2003), while the func-
tional leaf of SCN is controlled by serotonergic neurons located in raphe
nuclei (Moore and Speh, 2004).
Several controlled trials have shown the safety and efficacy of BLT
for seasonal affective disorder (SAD) (Melrose, 2015; Nussbaumer et al.,
2015; Rohan et al., 2015). BLT has been approved as a first-line treat-
ment for SAD by American Psychiatric Association (APA) (Terman,
2007). The application of BLT in non- seasonal depression (NSD) has
been increasing, but the efficacy is controversial (Martiny et al., 2005;
Niederhofer and von Klitzing, 2012; Tuunainen et al., 2004). BLT has
been approved as a supplementary treatment for NSD by APA (Terman,
2007). A recent meta-analysis including 881 participants from 20 RCTs
demonstrated a beneficial effect of BLT in the treatment of NSD
[standardized mean difference in depression score: −0.41(95%CI:
−0.64~−0.18)], while the overall quality of evidence is poor due to
high risk of bias and inconsistency (Perera et al., 2016).
The efficacy of BLT in bipolar depression has been explored in many
studies (Benedetti et al., 2005; Papatheodorou and Kutcher, 1995; Sit
et al., 2007), but seldom in randomized clinical trials (Dauphinais et al.,
2012). In a recent published randomized sham-controlled (negative
ion) trial, Chojnacka at al has examined the efficacy and safety of
morning BLT in the treatment of patients with a depressive episode in
bipolar and unipolar disorder (Chojnacka et al., 2016). Though overall
improvement in depressive symptoms, both response and remission
rates were significantly higher in BLT group. We hypothesized that BLT
would have a beneficial effect on depressive symptoms in patients with
acute bipolar depression and may have a faster onset time.
2. Methods
2.1. Design
This study was one of the capital health research and development
of special programs in Beijing, China (SF2011-4024-03), and part of
Beijing Municipal pooling funds on Science and technology achieve-
ments transformation and industrialization project
(Z121100006112057). This was a multi-center, single-blind, controlled,
parallel group study conducted in three tertiary referral centers in
Beijing. This study was approved by the Ethics Committee of the Peking
University Institute of Mental Health in December 2012 [No.
2012(47)]. The design for this study is presented in Fig. 1.
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Journal of Affective Disorders 227 (2018) 90–96
2.2. Participants
Seventy-four participants who met all inclusion/exclusion criteria
were recruited from December 2013 to March 2015. Participants were
volunteers, aged 18–65, and signed written informed consent. All met
clinical criteria for Bipolar disorder, depressed phase. All met clinical
criteria for Bipolar disorder, depressed phase. The diagnosis of patient
was verified by a review of medical record. Participants were required
to be on a stable psychotropic medication for at least 2 weeks prior to
enrollment, and to have a total score of 17 or more on the Hamilton
Depression Scale with 17 items (HAMD-17) at baseline visits (Sharp,
2015; Tang and Zhang, 1984).
Participants were excluded from the study if they had a diagnosis of
any other Axis I disorder according to DSM-IV criteria or a score of12 or
more on the Young Mania Rating Scale (YMRS) at either screening or
baseline (Young et al., 1978; Zhang, 1998). The other main exclusion
criteria were having been treated with Transcranial Magnetic Stimu-
lation (TMS) or Modified Electroconvulsive Therapy (MECT) in the 3
months prior to screening, a significant suicide risk, a history of sub-
stance abuse or dependency in the 6 months prior to screening, and
being regarded by investigators as being an unsuitable candidate for the
protocol. Participants were also excluded if they had an ocular disorder
or they were taking a photosensitizing agent, which made it potentially
unsafe to undergo BLT. Women who were pregnant, lactating or plan-
ning to become pregnant were also excluded.
Since this is the first controlled trial of BLT and dRLT for treatment
of bipolar depression in China and there are few data about the effect
size of the two interventions, the sample size could not be estimated on
the basis of statistical considerations. The preliminary results obtained
from our first 20 participants, with 10 in BLT group and 10 in dRLT
group. Preliminary results showed that the effective rate of BLT and
dRLT was 80% and 40% respectively. We assumed the loss rate was
20%, so a total sample size of 32 in each group was considered ade-
quate for this exploratory study.
2.3. Interventions
The participants were randomized to the intervention (BLT) and
placebo (dim Red Light Therapy, dRLT) arm on receipt of the completed
consent form using an automated permuted block randomization with a
block size of 10 and an allocation ratio of 1:1. Trained raters from each
center who had passed consistent training for many research projects
before and who remained blind to allocated treatments evaluated each
participant using the HAMD-17, YMRS, Clinical Global Impression
(CGI) (Forkmann et al., 2011; Wu, 1984) and Side Effects Rating Scale
(SERS) of Asberg (Asberg et al., 1970; Qian et al., 2015), at baseline
visit (V0), the end of week 1 (V1) and the end of week 2 (V2). A
modified self-administered questionnaire, the 16-item Quick Inventory
of Depressive Symptomatology, Self-report (QIDS-SR16) (Liu et al.,
2017; Rush et al., 2003)，which was used to measure the onset day of
BLT was required in the first week daily. Both senior investigators who
conducted the statistical analyses and wrote up the results were masked
to the code throughout the study and at the time of data analyses.
During the study, research staff who were not blind to treatment
assignment were responsible for treatment management. All partici-
pants were required to be on a mood stabilizer or a combination of
mood stabilizers judged by their clinicians to be sufficient. Participants
were prohibited from taking any antidepressant medications during the
study. No change in the dosage of any psychotropic medication was
allowed. Benzodiazepines were allowed at up to 2 mg of lorazepam-
equivalents per day.
In order to balance expectations, participants were told that both
BLT and dRLT have been found to be effective in treating some forms of
depression, although this had not been well studied in bipolar depres-
sion. The study design was presented as a comparison of different light
therapies.
T.-h. Zhou et al. Journal of Affective Disorders 227 (2018) 90–96

Fig. 1. Study design.

Definite Research Protocol

Recruitment: November 2013

to March 2015

HAMD-17
YMRS Baseline assessment (V0)
SERS CGI

Randomization

Arm 1: BLT Arm 2: dRLT

At the end of Week 1 (V1): HAMD-17, YMRS, Week 1:

SERS and CGI QIDS-SR16

Treatment phase

At the end of Week 2 (V2): HAMD-17, YMRS,

SERS, and CGI

Data analysis

2.4. Treatment devices and procedures
Light therapy was administered by light boxes made by School of
Physics, Peking University. The BLT device measures 60 × 80 × 10 cm,
with a 100% UV filter and several 180-watt Light-Emitting Diodes
(LED) bulbs of 10000-Kelvin color temperature. The dRLT device is in
the same shape. Light boxes were placed on a tabletop. The heights of
light boxes were adjusted to make sure the center of the box was at eye
level. 5000 lx at 100 cm setting in the BLT device and less than 100 lx in
the dRLT device were used. According to Terman's results (Terman
et al., 2001), the antidepressant effect of light is potentiated by early-
morning administration in circadian time. Participants whose face fully
exposed without staring into the light were treated every morning for
1 h between 6:30 a.m. to 9:00 a.m. during the 2-week treatment phase
of this trial.
2.5. Outcome measures
The primary outcome measure of this trial was clinical efficacy and
the onset day of BLT. Clinical efficacy of BLT was measured by HAMD-
17 at V2. Responders were defined as those participants with a decrease
in HAMD-17 score (V2) of 50% or more from baseline. The onset day
was defined as the day when a decrease in QIDS-SR16 score of 50% or
more from baseline occurred. The secondary outcome measures were
rates of switches into hypomania or mania which were measured by
YMRS and adverse events which were measured by SERS.
2.6. Statistical methods
Data analyses were conducted using SPSS version 17.0. Basic de-
scriptive statistics including the mean, standard deviation, variance and
range were calculated for primary, secondary and demographic vari-
ables. Differences in measurement data were compared with t-test for
those data with normal distributions, and non- parametric tests for
ratings that did not exhibit normal distributions. Differences in cate-
gorical data were compared with chi square test. Logistic regression
analysis was applied to assess the relationship between possible pre-
dictors and BLT efficacy. Odds ratio and 95% confidence intervals were
applied to measure the degree of association.

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T.-h. Zhou et al. Journal of Affective Disorders 227 (2018) 90–96

Fig. 2. Participants’ flow diagram.

Assessed for eligibility
(N=220)

Excluded (N=146)
Not meeting inclusion criteria
(N = 110)
Declined to participate (N = 36)

RandomizationÄN=74Å

BLTÄn=37Å dRLTÄn=37Å

Discontinued interventionÄn=4Å Discontinued interventionÄn=7Å

Refused interventionÄn=2Å Refused interventionÄn=1Å
Perceived lack of efficacy Perceived lack of efficacy
Än=1Å n=4
Failed to returnÄn=1Å Invalid evaluationÄn=2Å

Analysed Analysed
n=33 n=30

3. Results Table 2
Comparison of HAMD-17 score between 2 groups.
The participants’ flow diagram for the study is presented in Fig. 2.
BLT(n = 33) dRLT(n = 30) p
220 participants were assessed for eligibility and 74 participants were
recruited to the trial. 63participants completed the study (33 BLT, Baseline 20.39 ± 2.18 19.30 ± 2.59 0.08
30dRLT) and returned full questionnaire data for analyses. Table 1 End of 1st week 13.45 ± 4.24 13.93 ± 3.18 0.62
listed demographics and clinical characteristics of participants in BLT End of 2nd week 8.61 ± 3.41 10.53 ± 3.22 0.03*
Score reducing 11.79 ± 3.23 8.77 ± 3.44 < 0.01*
and dRLT groups. Patients received the first-line pharmacho- therapy
for bipolar depression, namely quetiapine (200 mg~600 mg), valproate p < 0.05.
(500 mg~1500 mg) and lithium carbonate (500 mg~1500 mg) or joint.
The type and dosage of drugs used in two groups were balanced. Main Table 3
mood stabilizers include quetiapine (36.36% in BLT group vs. 36.67% Repeated measures ANOVA of changes in HAMD-17 score between 2 groups over time
in dRLT group), quetiapine combined with sodium valproate(30.30% in tests of within-subjects effects.
BLT group vs. 33.33% in dRLT group), and quetiapine combined with
Source Type IV sum of df Mean square F Sig
squares
Table 1
Baseline demographic and clinical characteristics of the group. Time
Greenhouse- 3362.68 1.78 1892.24 371.34 < 0.001
BLT(n = 33) dRLT(n = 30) t/χ2 p Geisser
Huynh-Feldt 3362.68 1.86 1811.15 371.34 < 0.001
Age, years: mean ± sd 35.09 ± 14.19 39.73 ± 13.53 −1.33 0.19 Lower-bound 3362.68 1.00 3362.68 371.34 < 0.001
Gender: M/F 13/20 16/14 0.73 0.39 Time*Group
Marital status: 15/16/2 10/18/2 0.98 0.61 Greenhouse- 71.76 1.78 40.38 7.92 0.001
Single/Married/Divorced Geisser
Education: 8/10/15 15/8/7 5.13 0.08 Huynh-Feldt 71.76 1.86 38.65 7.92 0.001
Primary school and lower/ Lower-bound 71.76 1.00 71.76 7.92 0.007
Middle school/College Error (Time)
and higher Greenhouse- 552.39 108.40 5.096
Outpatient/Inpatient 22/11 6/24 12.03 0.01* Geisser
Course of disease, month: 48 (6240) 54 (6, 288) 0.42 0.68 Huynh-Feldt 552.39 113.26 4.877
M (min, max) Lower-bound 552.39 61.00 9.056
HAMD-17 score: mean ± sd 20.39 ± 2.59 19.30 ± 2.18 1.81 0.08
YMRS score: M (min, max) 0 (0,6) 0 (0,6) 1.18 0.24
CGI, severity of illness: M 5 (4,6) 5 (4,6) 1.00 0.92
(min, max)

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T.-h. Zhou et al. Journal of Affective Disorders 227 (2018) 90–96

lithium(15.15% in BLT group vs. 13.33% in dRLT group). There were 4. Discussion
no statistically significant difference between two groups (p = 0.98).
(Tables 2, 3). BLT has been widely used in the treatment of SAD and NSD, and its
clinical efficacy has been confirmed by a number of clinical studies
(Baxendale et al., 2013; Brouwer et al., 2015; Martensson et al., 2015).
3.1. Primary outcome
The use of BLT for treating bipolar depression was still in the ex-
ploratory stage. Although many studies have attempted to investigate
The participants treated with BLT demonstrated a significantly im-
the efficacy of BLT in the treatment of bipolar depression, there has
provement in response to treatment compared with patients treated
been no consistent conclusion yet (Benedetti et al., 2005;
with dRLT at the end of this trial. The total score of HAMD-17 were
Papatheodorou and Kutcher, 1995; Sit et al., 2007). The results of a
both significantly decreased after 2 weeks of this trial (p < 0.01). At the
recent controlled trial have shown no statistically significant differences
end of this trial, the total score of HAMD-17 in the BLT group was
in any outcome measures at study end point for patients with bipolar
significantly lower than dRLT group (p = 0.03). The mean end point
depression treated with morning BLT compared with the control group
HAMD-17 score showed 57.82% reduction from baseline for BLT and
(Dauphinais et al., 2012).
45.44% for dRLT. 78.79% of participants (n = 26) of BLT group were
Our study has shown that there was a significant difference (p =
responders, while the response rate was 43.33% in the dRLT group (n
0.01) in the ameliorating effects of depressive symptoms (in terms of
= 13). The response rates were significantly different between two
HAMD-17 reduction rate) among patients with bipolar depression
groups (p < 0.01).
treated with morning BLT combine with first- line drug therapy com-
Mauchly's test indicated that the assumption of sphericity had been
pared with the control group treated with dRLT combine with first-line
violated, χ2 (2) = 8.04, p = 0.02, therefore degrees of freedom were
drug therapy after 2 week treatment phase. This is by far the first
corrected using Greenhouse-Geisser estimates of sphericity (ε = 0.89).
randomized controlled trial to show the clinical efficacy of BLT in the
The results show that there was significant effect of HAMD score on the
treatment of bipolar depression compared with the control group
time, F (1.78, 40.38) = 7.92, p = 0.01. These results suggested that the
(particular kind of dRLT placebo) as an adjust treatment.
total score of HAMD-17 in the BLT group was significantly lower than
Patients’ expectation towards the treatment has become a general
dRLT group over time during the study period.
problem for clinical research among depression patients. Rutherford
Since outpatient/inpatient ratio in BLT and dRLT groups was sig-
and colleagues have found that patients’ expectation had a significant
nificantly different at baseline, the effect of outpatient versus inpatient
improve impact on the antidepressant effect (Rutherford et al., 2013).
status on treatment efficacy was further explored. 64.29% of partici-
Research on BLT have found similar consequences, that is high ex-
pants (n = 18) in outpatients were responders, while the response rate
pectations can improve the efficacy of BLT in treating patients with
was 60.00% in inpatients (n = 21). There were no statistically sig-
depression (Eastman, 1990; Knapen et al., 2014). In order to balance
nificant difference (p = 0.93). Previous studies have indicated that
patients’ expectations, patients from the control group were treated
gender is a predictor of clinical efficacy of light therapy (Roecklein
with dRLT which is in the same device and environment, but with no
et al., 2012). The effect of gender on BLT efficacy was then further
antidepressant effects in this trial.
discussed. We found that 76.47% of female participants (n = 26) were
BLT has been considered as a rapid onset treatment. 50–65% SAD
responders, while the response rate was 44.83% in male participants (n
patients can achieve remission within 1 week treatment (Terman and
= 13). The difference was statistically significant (p = 0.02).
Terman, 2005). Researches on BLT treating patients with bipolar de-
Results from single factor analysis showed that group (BLT vs.
pression have shown that most patients can achieve remission with 2
dRLT) and gender were two influence factors of the clinical efficacy of
week BLT (Papatheodorou and Kutcher, 1995; Sit et al., 2007). This is
light therapy. Multivariate Logistic regression analysis was done to
the first study using QIDS-SR16 to measure the onset time of BLT. We
explore risk factors of effectiveness. Results showed that gender and
found the median onset time of BLT combined with first-line drug
group were 2 independent factors (OR BLT/dRLT = 4.69, 95%CI: 1.47,
therapy for patients with acute bipolar depression was about 4 days,
14.94,p = 0.01; ORF/M = 3.94, 95%CI: 1.22, 12.16,p = 0.02).
which was consistent with previous studies.
The onset day was defined as the day when a decrease in QIDS-SR16
Treatment-emergent hypomania or mania is well known to be as-
score of 50% or more from baseline occurred. Total score of QIDS-SR 16
sociated with antidepressant medication for bipolar depression
was 12.41 (3, 24) at baseline visit and 8.77 (3, 15) at the end of the first
(Biernacka et al., 2012; Daray et al., 2010; Mundo et al., 2006). The
week. 9 patients from BLT group responded to BLT within 2 weeks. The
switch rate has become lower since newer antidepressant agents and
longest time was 6 days (2 cases) and the shortest time was 2 days (1
mood stabilizers used together, yet it remains problematic (Post et al.,
case) recorded in this study. The median onset time was 4.33 days.
2006; Viktorin et al., 2014). In this study, only 2 cases developed ir-
There were no responders in the dRLT group during first week (mea-
ritability at the end of the trial. Compared with the control group, the
sured by QIDS) in this trial.
light therapy used in this study were considered not to increase the risk
of switch rate.
3.2. Secondary outcome Emergent hypomania under light therapy has occurred in previous
related studies (Leibenluft et al., 1995; Papatheodorou and Kutcher,
Participants from both groups did not experience symptoms of hy- 1995; Sit et al., 2007). The rate of light therapy-emergent hypomania in
pomania during this trial. One participant from each group developed our study was lower than previous studies, which may be attributable to
irritability, with an increase in YMRS score to 10 in BLT group and 8 in sufficient mood stabilizers. We recommend that further use of BLT for
dRLT group. One participant from each group had an increase in YMRS patients with bipolar depression should combine with mood stabilizers
score to 5. There were no statistically significant differences in the rate in order to control the switch rate.
of hypomania as measured by YMRS between the BLT and dRLT groups BLT was given by a fluorescent light box with a diffusing shield in
(p = 0.60). many studies before. Nausea, vomiting, dizziness, headache and vision
No serious adverse events were reported. New adverse events oc- damage were noted as possible side effects due to full-spectrum fluor-
curred in BLT group including 1 dizziness, 1 fatigue and 2 sleep dis- escent (Botanov and Ilardi, 2013; Leichtfried et al., 2010). A number of
turbance compared with the dRLT group. Most adverse events were fluorescent lamps were needed to achieve a sufficient light intensity,
mild-to-moderate and responded to treatment adjustments when in- which can produce a higher temperature and also a certain security
dicated. There were no statistically significant differences in adverse risk. Light-Emitting Diodes (LED), which is low heat radiation, energy
events as measured by SERS between BLT and dRLT groups (p = 0.98). consumption and more environmental friendly, was used in this study.

94
T.-h. Zhou et al.
The LED wavelength range can be adjusted in accordance with the re-
quirements and the peak wavelength is more stable (Tridente and De
Luca, 2012). No serious adverse events were reported. According to this
study, LED was recommended as a proper device for further BLT re-
searches.
There are some major limitations of this study. Firstly, 2 weeks is
too short of duration to assess depression outcomes in BD, which is a
major limitation. Secondly, we did not measure the seasonality scores
and use Morningness-Eveningness Questionnaire to measure biological
rhythm which may affect the efficacy of light therapy. Thirdly, since it
is difficult to enroll a large number of participants in our settings, we
did not control the drug distribution and outpatient/inpatient strictly,
which may have some effects on the final efficacy of light therapy. Last
but not least, the clinical assessments of all participants were not
comprehensive. Clinical related information, including bipolar sub-
types, were not recorded accordingly.
5. Conclusion
Bright Light therapy combined with first-line drug medication
showed certain efficacy, faster onset time and did not increase the rate
of switch into hypomania and side effects compared with simple drug
treatments for patients with acute bipolar depression. Bright Light
therapy can be considered as an effective and safe adjunctive treatment
choice for acute bipolar depression according to our study.
Acknowledgements
Funding for this study was provided by Beijing Municipal
Commission of Health and Family Planning (SF2011-4024-03). The
funding sources played no further role in the study design; in the col-
lection, analysis and interpretation of data; in the writing of the report,
or in the decision to submit the report for publication. We thank Dr.
Huali Wang and Dr. Yanbo Yuan from Peking University Institute of
Mental Health, for their helpful comments for study design. We thank
Dr. Yuqing Song, Dr. Yue Zhu, Dr. Huijun Zhang, Dr. Zhiying Li and Dr.
Huimin Gao from Peking University Institute of Mental Health, for their
help in recruiting patients. We thank Haijuan Zhang, LPN, Jianghua Li,
LPN, and other nurses from Peking University Institute of Mental
Health, for their helpful support. We also thank Xiaozhen Lv, Ph D,
from Peking University Institute of Mental Health, for data analyses and
helpful comments.
Future directions
Further trials would be needed to establish a therapeutic effect in
this population. Patients with bipolar depression are in a high hetero-
geneity. Further work for patients in homogeneity, such as similar
general characteristics, seasonal pattern and sleep- wake cycle, might
help to elucidate the mechanism that may underlie this clinical re-
sponse.
Funding source
This study was one of the Capital Health Research and Development
of Special Programs in Beijing, China (SF2011-4024-03), and part of
Beijing Municipal pooling funds on Science and Technology
Achievements Transformation and Industrialization Project
(Z121100006112057).
Conflict of interests
All authors have completed the Unified Competing Interest form at
www.icmje.org/coi_disclosure.pdf (available on request from the cor-
responding author) and declare that (1) none of the authors have re-
ceived support from the shoe factory for the submitted work; (2) none
95
Journal of Affective Disorders 227 (2018) 90–96
of the authors have relationships with the shoe factory that might
pertain to the submitted work in the previous 3 years; (3) the authors'
spouses, partners, or children have no financial relationships that may
be relevant to the submitted work; and (4) all of the authors have non-
financial interests that may be relevant to the submitted work.
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