Efficacy of Electronic Cognitive Behavioral Therapy Application to Treat Major Depressive Disorder

This is a prospective, randomized, comparator-controlled, two-arm, parallel group study to
examine the safety and efficacy of eCBT Mood, a handheld, computerized, electronic cognitive
behavioral therapy (CBT) application, in patients with major depressive disorder (MDD). The
study will involve 100 patients with mild to moderate MDD randomly assigned to daily use of
either a CBT application focused on depression ('eCBT Mood'; MindApps, llc) or a
comparator-controlled group using a mood monitoring application ('Mood Tracker'; GP
International). This study design and duration of the study is consistent with other studies
employing comparator-controlled designs in the study of CBT interventions, including
computerized CBT interventions, among patients with MDD (e.g., Andrews et al., 2010;
McKendree-Smith et al., 2003).

After being screened to ensure that the patients meet the required diagnostic, depression
severity, and other inclusion criteria, patients will be randomly assigned (1:1) to use
either eCBT Mood, a computer application running on the Apple® iPhone™ or iPod Touch®
handheld computer platforms. The application includes: (1) a psychoeducation module on the
relationships among thoughts, feelings, and behaviors, (2) a 6-item daily depression
assessment with the option to e-mail the summary score and suicidal ideation assessment
response to a 3rd party, (3) a negative automatic thought identification module, (4) a
feelings and thoughts log, (5) a module enabling the user to challenge their negative
automatic thoughts, (6) an assessment and challenge module regarding core beliefs which
underlie many automatic thoughts, (7) optional compliance reminders to use the application
or take medicines, and (8) links to behavioral science-based online content regarding MDD
from PsychCentral (see www.psychcentral.com). In contrast, the comparator control condition
will use Mood Tracker, which is also a a computer application running on the Apple iPhone or
iPod Touch handheld computer platforms. This application enables users to rate their mood
using expressive faces on a daily basis, log about their daily feelings, and also has an
option enabling an e-mail to be sent to a 3rd party regarding their daily mood ratings.

Throughout the 8-week study period, patients will complete both in-person and
telephone-based assessments of their depression severity, mood, frequency of negative
automatic thoughts, and safety assessments.

Inclusion Criteria:

- Male or female patients between the ages of 18 and 65 at the date of consent.

- Diagnosis of MDD consistent with the DSM-IV-TR as assessment by the Mini
International Neuropsychiatric Interview (MINI).

- Owns and has access to an iPhone or iPod Touch capable of downloading and running
either eCBT or the comparator mood monitoring application.

- At the screening and visits, must exhibit mild to moderate MDD with scores between 17
and 34 on the MADRS, inclusive. Subjects with scores >34 on the MADRS will be
referred by the Study Investigator for alternative psychotherapeutic and/or
pharmacological care for their depression.

- Note that no subjects are to be discontinued from any pharmacotherapies used to treat
depression solely for the purpose of qualifying for this study. Be willing and able
to refrain from the following therapies for the duration of the study:

- All approved pharmacotherapies for MDD, including serotonin reuptake inhibitors,
serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, tricyclic
and tetracyclic antidepressants, bupropion, mood stabilizers, and adjunctive
antipsychotics.

- Medical device therapies for depression, including transcranial magnetic stimulation,
vagal stimulation, electroconvulsive shock therapy, and others.

- Beginning any type of group or individual psychotherapy.

- Beginning another clinical trial for major depressive disorder or other condition.

- Patients' primary language must be English.

- Subject is willing and has an understanding and ability to fully comply with study
procedures and restrictions defined in this protocol.

Exclusion Criteria:

- Depression severity, as measured by either:

- Clinician judgment that the patient's depression is too severe to make self-help
resource a viable treatment option.

- Depression severity as measured by a scores >34 on the MADRS.

- Clinician assessed high risk of suicide or self-harm.

- Intellectual disability or physical limitation that would prevent use of the
computerized handheld intervention.

- Comorbid psychopathology where the primary disorder is not depression.

- Within the past 3 months has had a course of treatment with psychotherapy or
pharmacotherapy for depression.