Optimization, Working Mechanisms and Response Predictors of Bright Light Therapy for Depressive Disorders- a multicenter randomized controlled trial

Bright Light Therapy (BLT) is an effective treatment for seasonal and
non-seasonal depressive disorders, as well as for bipolar depression. Recent
meta-analyses show that BLT effectively reduces depressive symptoms within 5-7
days in approximately 60% of patients with seasonal depression, and in 40% of
other depressive disorders. This effectiveness is comparable to that of
commonly used pharmacological agents, but light therapy seems to work
significantly faster and lead to fewer side effects. Optimization of the
treatment strategy, a better understanding of the working mechanisms, and the
patient characteristics and behaviours that predict treatment response is
needed to increase the effectiveness and useability of BLT in clinical practice
and enable personalized intervention.

This study has the following study aims:
1) Investigate whether treatment context and the addition of chronotherapeutic
and social rhythm interventions improve the efficacy of BLT,
2) examine the role of circadian phase resetting and changes in sleep quality
in the working mechanisms of BLT
3) identify which patient characteristics and behaviours predict treatment
outcomes
4) establish a brain model for the effects of BLT in depression.

A randomized, multicentre, single-blind clinical trial. We will compare three
treatment arms with different BLT administration strategies. Depressive symptom
severity will be assessed by a blind rater at baseline and after BLT. Circadian
rhythm will be assessed using actigraphy data and salivary melatonin
assessment. Ecological momentary assessment will be used to gain insight into
the dynamics of changes in vitality, sleep and affect across treatment.
Predictors of treatment response will be assessed at baseline and include
clinical characteristics, subjective and objective measures of sleep, circadian
parameters (dim light melatonin onset and light-induced melatonin suppression)
and light-related behaviours. MRI will give insight into functional and
structural brain changes after light therapy treatment.

In all arms, patients will receive 10,000 lux BLT in the morning for 30 min/day
on 5 consecutive days. Treatment duration will be one, two or three weeks,
depending on the remittance of depressive symptoms. Participants will be
randomized to receive:

1) BLT in their home environment,
2) BLT in a café setting, supervised by clinical staff and promoting lifestyle
changes and social interaction,
3) Same as arm 2, complemented by BLT timing strategies to optimize and
stabilize sleep-wake patterns and by the use of blue-light blocking glasses in
the evening.

At least 40% of participants are expected to recover from their depressive
episodes. In rare cases, the light therapy might result in mild and
short-lasting side effects, including eyestrain, headache, nausea, irritability
or agitation. A recent meta-analysis reported that the risk of triggering a
manic episode in patients with bipolar disorder after treatment with BLT is not
different from placebo treatment (estimated rate of manic switches: 4.7%). We
expect the benefits to be greater in arm 2 than arm 1 and greatest in arm 3,
with equal amounts of side effects in each arm.