Virtual Reality Behavioral Activation: An Intervention for Major Depressive Disorder
Phase: NA
Conditions: Major Depressive Disorder, MDD, Depression
Sponsor: Stanford University

NCT04268316 
 
February 25, 2020 
 
 
 
 
 
 
 
 
 
 
Virtual Reality Behavioral Activation: An Intervention for Major Depressive Disorder 
 
Protocol ID: 53483 
 
Protocol Director: 
Margot Paul, M.S. 
 
Academic Sponsor: 
Kim Bullock, M.D. 
 
Other Personnel: 
Jeremy Bailenson, Ph.D. 
 
 
Research Site: 
Stanford School of Medicine, Department of Psychiatry & Behavioral Sciences 
401 Quarry Rd, Palo Alto, CA 94304 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Funding: This study has no institutional funding and no funding has been or will be sought.  
 
1. Purpose of the Study and Background 
 
1.1 Purpose of the Study 
 
The primary aims of this study are to assess the feasibility, acceptability, and tolerability of a 
virtual reality (VR) behavioral activation (BA) treatment for individuals diagnosed with major 
depressive disorder (MDD). The secondary aim of this study is to explore the efficacy of using 
VR to deliver BA therapy to a clinical MDD population. 
 
The primary hypothesis of this study is that VR is an acceptable, feasible, and safe way to deliver 
a BA intervention for individuals diagnosed with MDD. Acceptability will measure the 
participant’s desire to continue using the VR treatment after the study ends, the participant’s 
satisfaction with the VR treatment, the participant's use of the headset, and the participant’s 
acceptance of VR treatment. Feasibility will look at how well VR can integrate into the BA 
therapy. Tolerability will measure simulator sickness and agitation while using the VR headset. 
 
A secondary hypothesis is that VRBA will have stronger effects than BA treatment as usual or a 
waitlist control in treating individuals with MDD due to increased homework compliance. This is 
due to the research that has illustrated that homework compliance is one of the strongest 
predictors of treatment outcomes for BA. This hypothesis will be assessed by running t-tests 
comparing the change in PHQ-9 scores at timepoints across the three study arms.  
 
This study will also comment on the following questions: Can one successfully deliver BA 
without the movement component, simulating just the experience of pleasure/ mastery? Does 
VRBA lead people to want to engage in real-life activities? Is the active ingredient of BA 
emotion or movement? Movement during the VRBA will be measured with the headset.  
 
1.2 Study Significance 
 
Little to no research has been done to elucidate the role of VR technology in lieu of real-world 
behavioral activation. This study will lay the groundwork for future studies to examine the role 
that VR may play in improving mood in clinical populations that are unable to perform real-
world behavioral activation because of physical and/or psychological limitations. 
 
1.3 Background 
 
Major depressive disorder (MDD) is one of the most common mental disorders in the United 
States. The lifetime prevalence of MDD is estimated to be 12% (Kessler et al., 2011) and it is the 
11th greatest cause of disability and mortality in the world (Murray et al., 2012). Current 
treatment includes both cognitive behavioral therapy (CBT) and pharmacological intervention. 
There is strong evidence for the efficacy of a very simple type of CBT for depression that 
requires no active cognitive abilities from participants and can be delivered by primary care 
providers. This type of therapy is called Behavioral Activation (BA) (Dimidjian et al., 2011). 
Research has shown BA to be more effective than cognitive therapy alone and equivalent to 

medication for treating depression in participants (Dimidjian et al., 2006; Scogin et al., 2005; 
Spates, Pagoto, & Kalata, 2006). However, many participants are unable to complete BA therapy 
due to lack of access to trained providers, physical constraints, diminished motivation, or 
geographical or financial reasons. Increasing access to mental health care using technology such 
as a Virtual BA therapy may provide a solution to these barriers. 
  
Behavioral Activation encourages participants to change their moods by changing behavior and 
increasing sensory stimulation and positive emotions. BA therapy begins with monitoring a 
participant’s current activity and identifying positive activities that can be added into the 
participant’s daily schedule. These pleasant activities can be as simple as soaking in a bathtub, 
going to the mall, lying on the beach, or going fishing. These activities are then scheduled into 
the participant’s daily routine, and progress is tracked. The list of activities is modified as 
necessary and challenges and barriers are problem‐solved for each participant. 
  
Virtual Reality (VR) technology now allows one to create and experience realistic and 
immersive virtual environments in which people can move around freely and interact with their 
surroundings. Compared to other mediums, VR is a very effective tool for eliciting feelings of 
presence: the user’s subjective feeling of being inside a virtual environment. In part because of 
its ability to elicit presence, VR has been leveraged to deliver mental health interventions, 
including exposure‐based therapies for participants with anxiety. VR is ideal for exposure 
therapy because participants are realistically immersed in a feared environment that is tailored to 
match their specific phobias (Maples‐Keller, Runnell, Kim, & Rothbaum, 2017). For similar 
reasons, VR may also be ideal for delivering BA therapy: individuals can be immersed in 
environments that evoke strong feelings of enjoyment, mastery, and pleasure. These 
environments can be tailored to match each individual’s list of ideal, positive activities. VR may 
also be ideal for delivering BA because it makes an incredibly wide range of activities easily and 
immediately accessible and can include pleasurable activities that may be impossible to complete 
in the real world (e.g. scuba-diving the Great Barrier Reef). 
  
Within a clinical MDD population, VR-BA may be especially ideal for individuals who lack the 
motivation to engage in real-world BA. In this setting, VR-BA may either replace or act as a 
steppingstone to real-world BA. Standardizing and operationalizing a BA treatment to be self‐
administered may also be a cost-effective way of preventing and treating MDD. This may be 
especially important in areas where access to care is a problem for MDD treatment. 
 
1.4 References 
 
Angst, F., Stassen, H. H., Clayton, P. J., & Angst, J. (2002). Mortality of participants with mood 
disorders: follow‐up over 34‐48 years. Journal of Affective Disorders, 68. 167‐181. 
  
Birckhead, B., Khalil, C., Liu, X., Conovitz, S., Rizzo, A., Danovitch, I., ... & Spiegel, B. (2019). 
Recommendations for Methodology of Virtual Reality Clinical Trials in Health Care by an 
International Working Group: Iterative Study. JMIR mental health, 6(1), e11973. 
  

Brent, D. A., Moritz, G., Bridge, J., Perper, J., & Canobbio, R. (1996). The impact of adolescent 
suicide on siblings and parents: A longitudinal follow‐up. Suicide and Life‐Threatening 
Behavior, 26(3), 253‐259. 
  
Dimidjian, S., Hollon, S. D., Dobson, K. S., Schmaling, K. B., Kohlenberg, R. J., Addis, M. E. 
… Jacobson, N. S. (2006). Randomized trial of behavioral activation, cognitive therapy, and 
antidepressant medication in the acute treatment of adults with major depression. Journal of 
Consulting and Clinical Psychology, 74(4), 658‐670. 
  
Kessler, R. C., Ormel, J., Petukhova, M., McLaughlin, K. A., Green, J. G., Russo, L.  
J. …Ustun, T. B. (2011). Development of Lifetime Comorbidity in the World Health 
Organization World Mental Health Surveys. Arch Gen Psychiatry. 68(1). 90‐100 
  
Linke, S., Wojciak, J., & Day, S. (2002). The impact of suicide on community mental health 
teams: Findings and recommendations. Psychiatric Bulletin, 26(2), 50‐52. 
  
MacPhillamy, D. J., & Lewinsohn, P. M. (1982). The pleasant events schedule: Studies on 
reliability, validity, and scale intercorrelation. Journal of Consulting and Clinical Psychology, 
50(3), 363. 
  
Maples‐Keller, J., Bunnell, B., Kim, S. J., & Rothbaum, B. (2017). The use of virtual reality 
technology in the treatment of anxiety and other psychiatric disorders. Harvard Review of 
Psychiatry, 25(3), 103‐113. 
  
Murray, C. J., Vos, T., Lozano, R., Naghavi, M., Flaxman, A. D., Michaud, C. … Memish, Z. A. 
(2012). Disability‐adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990‐
2010: a systematic analysis for the global burden of disease study 2010. The Lancet, 380(9859). 
2197‐ 2223. 
  
Parikh, S. V., Segal. Z. V., Grigoriadis, S., Ravindran, A., Kennedy, S. H., Raymond,  
L., & Patten, S. B. (2009). Canadian network for mood and anxiety treatments (CANMAT) 
clinical guidelines for the management of major depressive disorder in adults. II. Psychotherapy 
alone or in combination with antidepressant medication. Journal of Affective Disorders, 117, 
515‐525. 
  
Scogin, F., Scogin, D., Hanson, A., Stump, J., & Coates, A. (2005). Evidence‐based 
psychotherapies for depression in older adults. Clinical Psychology: Science and Practice. 12. 
222‐237. 
  
Spates, C. R., Pagoto, S. L., & Kalata, A. (2006). A qualitative and quantitative review of 
behavioral activation treatment of major depressive disorder. The Behavior Analyst Today, 7(4), 
508‐521. 
  
Thompson, L. W., Gallagher, D., & Breckenridge, J. S. (1987). Comparative effectiveness of 
psychotherapies for depressed elders. Journal of Consulting and Clinical Psychology, 55(3), 385‐ 
390. 

 
2. Criteria for Subject Selection 
 
2.1 Number of Subjects: 30  
 
2.2 Gender of Subjects: All genders will be included and accepted in the study.  
 
2.3 Age of Subjects: Participants must be over the age of 18 years old.  
 
2.4 Racial and Ethnic Origin: No enrollment restrictions based on race or ethnicity. 
2.5 Inclusion Criteria:  
1. Participant must meet DSM V criteria for MDD  
2. 18 years of age or older  
3. English speaking  
2.6 Exclusion criteria  
1. Substance Use Disorders in past year 
2. Any psychosis or bipolar I disorder 
3. Any seizure in the last 6 months or untreated epilepsy 
4. Current suicidal urges and intent 
5. Current nonsuicidal self-injury or parasuicidal behavior 
3. Methods and Procedures 
3.1 Procedure 
Participants will be recruited from the clinic waitlist or through the study flyer. A total of 30 
participants will be recruited, about 10 participants per study arm. These participants will be 
given the contact information of the protocol director. Upon reaching out to the protocol director, 
an informational phone script will be read to determine study eligibility and subject interest.  
 
If subjects are interested and present with symptoms of depression, they will be invited to 
Stanford School of Medicine, Department of Psychiatry & Behavioral Sciences for an intake 
session. This session will include obtaining informed consent, the Mini International 
Neuropsychiatric Interview, and completing the demographic questionnaire. If subjects meet 
study eligibility, they will be randomized into either the VRBA, BA treatment as usual, or 
waitlist control arm of the study using 5 opaque, concealed envelopes in sets of 6 to preserve 
balance throughout the study. Participants will have a 1 in 3 chance of being randomized into 
each group. Participants will then be scheduled for their first treatment appointment.  
 
The VR intervention will follow the protocol for Behavioral Activation (BA). Participants in the 
BA treatment as usual or VRBA arms of the study will meet with their clinician once per week 
for 50 minutes to receive BA therapy. These participants will complete the PHQ-9 at the 

beginning of each session. If item 9 is endorsed, a risk assessment will be completed in real-time 
and appropriate actions will be taken.  
 
In the first session, psychoeducation around the connection between behavior and mood will be 
discussed. Participants will then be introduced to BA. Participants will consider activities they 
enjoy as well as be provided with an activity list. Participants will be asked to select at least four 
activities that are highly enjoyable to schedule into their upcoming week. The VRBA 
participants will be required to choose VR activities for the week and the BA treatment as usual 
participants will be required to choose real-life activities to participate in. The VR participants 
will complete an activity in VR during session, in order to learn how to use the headset, which 
they will take home. Each time the participant finishes an activity in VR, he/she will be asked to 
complete a questionnaire assessing “spatial presence,” “simulator sickness,” “agitation measure,” 
and acceptability. Participants will also be asked to rate their mood on a scale of 1-10 (1=worst 
they ever felt; 10=best they ever felt) before and after their chosen activity. During session 2 and 
3, clinicians will check in regarding goal attainment, work on barriers to completion of activities, 
assess depression scores, and introduce a new activity goal. During session 4, the treatment and 
skills will be reviewed, and feedback will be attained.  
 
The participants randomized to the waitlist control group will be administered the PHQ-9 via 
phone on a weekly basis for four weeks. If item 9 is endorsed, a risk assessment will be 
conducted in real-time, and proper measures will be taken in accordance with risk. After the four 
weeks are completed, these participants will be given the option to simply remain on the clinic 
waitlist or choose to partake in 4 weeks of VRBA or BA treatment as usual. Only the data during 
their time as a waitlist control will be used in the study.  
 
4. Data Safety Monitoring Plan 
 
As this is a case series within standard of care procedures, steps to minimize risks to the 
confidentiality of identifiable information will be taken as with all HIPPA compliant services 
delivered at the Clinic. Data will all be labeled with the participants' assigned ID number. 
Protected Health Information will be kept separate from data and ID numbers in a Stanford 
University School of Medicine encrypted database to which only the PI and research assistants 
will have access. Psychological effects of study participation or breeches in confidentiality will 
be monitored and discussed at research meetings. There is a slight risk of motion sickness so 
participants will be closely monitored while immersed in the virtual scene, and if there is any 
discomfort they will be removed from the virtual environment. Participants are free to 
discontinue participation at any time. Any situation requiring medical attention will be promptly 
provided. 
 
Given that participants enrolled are clinically depressed, suicidal ideation will be assessed each 
session. If it is revealed that a participant is expressing suicidal ideation, the clinician will 
conduct a thorough risk assessment in real time and a safety plan will be created. If it is 
determined the participant is an imminent danger to themselves, the clinician will initiate a 5150 
hold and walk the participant to the hospital. 
 
5. Preliminary unpublished data: There is no preliminary data to date.