InTRavenous kEtAmine and immerSive virtUal Reality to Treat dEpression

Depression is the single largest contributor to global disability, and afflicts individuals of all ages, races, genders, and classes. The significant morbidity is associated with depressive disorders relates to myriad direct and indirect financial costs to individuals and society. It also bears significant mortality, as one of the strongest risk factors for suicide.

Depression is also challenging to treat, with standard antidepressant therapy providing remission to only one third of patients, and incompletely improving the condition of another one third. Even when standard therapy is effective, it can take as long as six weeks for improvement of cognitive/emotional symptoms to become apparent. The final one third of patients often undergo a therapeutic odyssey in which various medications are attempted with no measurable benefit. Ultimately these patients receive a diagnosis of treatment-resistant depression (TRD).

Ketamine has emerged as a fast-acting intervention for the treatment of depressive disorders, which can reach maximum efficacy in only 24 hours and persist for 1-2 weeks. Ketamine is safe, well-tolerated, familiar to many providers and has become widely available as a treatment for depression.

Virtual reality (VR), a technology which immerses users in a controlled digital experience, has also recently been recognized for its potential in the treatment of mental health disorders and recent studies have identified similarities in proposed mechanisms for ketamine and VR in the treatment of depression (e.g. the creation of a non-ordinary and non-rigid experiences of consciousness, and the production of evocative or hallucinatory sensory experiences). However, this combination of interventions has not yet been studied.

Here, the investigators propose to study the combined effect of ketamine and VR in the vulnerable adult mental health population undergoing ketamine therapy for treatment-resistant depression (TRD).

In Phase I of the study, participants (N=3-5) will provide feedback to develop the VR software for this study population.

In Phase II, study participants (N=26) will be randomized to control (standard of care ketamine alone, Group I) or intervention (VR + ketamine concurrently (VR-K), Group II) groups to report on protocol feasibility and to inform the development of a definitive trial to assess VR-K treatment efficacy. All participants will receive a typical sub-anesthetic dose of ketamine (0.5mg/kg) infused intravenously (IV) over 45 minutes, and will be monitored by research staff for up to 90 minutes post-procedure. Each participant will receive a total of 4 ketamine treatments, 2 treatments per week for 2 weeks. All patients will continue their baseline antidepressant regimens while engaged in the study, consistent with standard ketamine therapy for TRD. Participants in the intervention group will wear a virtual reality headset at the onset of each standard ketamine therapy session, and will be immersed in a tailor-made virtual environment of positive outdoor scenes to provide relaxation and reprieve from negative thoughts.

Psychometric surveys will be used to assess the effects of both treatment arms on mood and psychiatric outcomes (depression and anxiety symptoms), side effects (sedation, dissociation, vitals), cognitive function, neural activity (EEG), and patient satisfaction with virtual reality.

• Mood and Psychiatric Outcomes - Montgomery-Åsberg Depression Rating Scale (MADRS) [Срок оценки: Baseline, 60 minutes and 24 hours after each treatment, and during 1,2,3-week and 1 and 3 month follow-ups]
• Mood and Psychiatric Outcomes - General Anxiety Disorder-7 (GAD-7) [Срок оценки: Baseline, 60 minutes and 24 hours after each treatment, and during 1,2,3-week and 1 and 3 month follow-ups]
• Mood and Psychiatric Outcomes - Positive and Negative Affect Schedule (PANAS) [Срок оценки: Baseline, 60 minutes and 24 hours after each treatment, and during 1,2,3-week and 1 and 3 month follow-ups]
• Mood and Psychiatric Outcomes - Patient Health Questionnaire (PHQ-9) [Срок оценки: Baseline, 24 hours after each treatment, and during 1,2,3-week and 1 and 3 month follow-ups]
• Mood and Psychiatric Outcomes - Beck Depression Inventory-II (BDI-II) [Срок оценки: Baseline, 24 hours after each treatment, and during 1,2,3-week and 1 and 3 month follow-ups]
• Anti-depressant use [Срок оценки: Baseline, 1 and 3 month follow-ups]
• Ketamine Side Effects - Heart Rate [Срок оценки: Before, continuously during the 45-minute infusion, and up to 60 minutes after each treatment]
• Ketamine Side Effects - Mean Arterial Pressure [Срок оценки: Before, continuously during the 45-minute infusion, and up to 60 minutes after each treatment]
• Ketamine Side Effects - Level of consciousness [Срок оценки: At baseline, once during the 45-minute infusion, and up to 60 minutes after each treatment]
• Ketamine Side Effects - Dissociative Experiences and Psychotomimetic Side Effects [Срок оценки: At baseline, 5-10 minutes after the start of each infusion and 60 minutes after each treatment]
• Ketamine Side Effects - Mystical Experiences Questionnaire (MEQ) [Срок оценки: 60 minutes after each treatment]
• Ketamine Side Effects - Simulator Sickness Questionnaire [Срок оценки: At baseline and 60 minutes after each treatment]