Transcranial Laser Therapy for Major Depressive Disorder

TLT has previously been evaluated in two large studies of people who have had a stroke. To
date, TLT has been administered to over 550 people who have had a stroke. TLT has also been
used in 10 people with MDD who were taking part in a research study. During this study, TLT
was shown to relieve MDD symptoms without causing too many side effects.

The -Infrared Radiation (NIR) device is also marketed for wrinkles treatment, however it is
experimental for the use in depression. An experimental device means that it is one that has
not been approved by the U.S. Food and Drug Administration (FDA).

During this study, the investigators hope to better find out if NIR TLT is helpful for
treating depression. The investigators will do this by comparing the effects of TLT ("active
treatment") NIR device to a sham treatment (which is an inactive or "pretend" treatment)
device. The sham ("pretend") device looks exactly like the NIR device but will not use a
near-infrared radiation during the study visits. There are two sets of identical devices that
will be used in this study, producing active and sham treatment, respectively. The devices
work exactly the same when you are receiving active treatment and sham treatment, except that
the devices will produce therapeutic transcranial LED energy during the active treatment
sessions but it will not produce this LED energy during the sham treatment sessions.

The investigators hope to enroll about 30 subjects in this study at the Massachusetts General
Hospital Depression Clinical and Research Program.

Inclusion Criteria:

- The subject is at least 18 years of age at screening, but has not had their 66th
birthday.

- SCID diagnosis of major depressive disorder (Structured Clinical Interview for
Diagnostic Statistical Manual-IV)

- HAM-D-17 >14 and < 25

- Women of child-bearing potential must use a double-barrier method for birth control
(e.g. condoms with spermicide) if sexually active.

- Subject Informed Consent obtained in writing in compliance with local regulations
prior to enrollment into this study.

- The subject (and caregiver, if applicable) is willing to participate in this study for
at least 8 weeks.

- Subjects on an antidepressant will need to be on a stable dose for at least six weeks.

Exclusion Criteria:

- The subject is pregnant or lactating.

- The subject failed two or more FDA-approved antidepressants during current episode

- Subjects with less than 2 months MDD symptom free prior to current episode.

- The subject used targeted psychotherapies for depression during current episode
(support therapy or counseling are allowed)

- Substance dependence or abuse in the past 6 months

- Psychotic disorder or psychotic episode (current psychotic episode per SCID
assessment)

- Bipolar affective disorder (per SCID assessment)

- Unstable medical illness, defined as any medical illness which has not been
well-controlled with standard-of-care medications (e.g., insulin for diabetes
mellitus, HCTZ for hypertension)

- Active suicidal or homicidal ideation, as determined by CHRT screening

- The subject has a significant skin condition (i.e., hemangioma, scleroderma,
psoriasis, rash, open wound or tattoo) on the subject's scalp that is found to be
directly below any of the procedure sites.

- The subject has an implant of any kind in the head (e.g. stent, clipped aneurysm,
embolised AVM, implantable shunt - Hakim valve).

- Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study
enrollment (in US: Visudine (verteporfin) - for age related macular degeneration;
Aminolevulinic Acid- for actinic keratoses; Photofrin (porfimer sodium) - for
esophageal cancer, non-small cell lung cancer; Levulan Kerastick (aminolevulinic acid
HCl) - for actinic keratosis; 5-aminolevulinic acid (ALA)- for non-melanoma skin
cancer)