Funding was not received.

Late-life depression affects 2-8% of seniors and causes high rates of caregiver distress and risk of suicide. To exacerbate the problem, antidepressants, the cornerstone of therapy, are resistant in 55-80% of this population. Hence, this group of patients is labeled as having treatment-resistant late-life depression (TR-LLD).

Non-pharmacological interventions like meditation could offer significant benefits as augmentation strategies to improve response rate of antidepressants in TR-LLD. One such breath-based meditation intervention called Sudarshan Kriya Yoga is of interest based on highly significant preliminary data in adult patients with treatment-resistant depression, its scalability and relatively low cost to learn this lifelong skill.

Thirty patients diagnosed with TR-LLD will learn this intervention over 5 consecutive days by a certified para-professional trainer. This will be followed by 3 weekly 90 min follow-up sessions and then bimonthly sessions for 8 more weeks. SKY consists of a series of breathing techniques, including Sudarshan Kriya (SK), a sequential rhythm-specific breathing exercise. Participants will be asked to practice this technique for 25-30 minutes daily over the next 11 weeks. The investigators will collect clinical as well as feasibility outcome measures. The investigators will also explore if it is feasible to assess the antioxidant Glutathione (GSH) in the brain using a sophisticated magnetic resonance spectroscopy. The investigators suspect that GSH levels are reduced in TR-LLD and they will improve with SKY.

RECRUITMENT AND CONSENT:

Patients will be recruited from Victoria Hospital, London Health Sciences Centre or Parkwood Mental Health, St. Joseph's Health Care London. Patients will be screened and recruited after giving valid consent.

STUDY INTERVENTION (Sudarshan Kriya Yoga, SKY):

The 30 recruited TR-LLD participants will be invited to attend training sessions on SKY. The SKY program is a highly structured and standardized mind-body resilience building program. Through SKY breathing, interactive discussions, journaling, yoga and guided meditations, the workshop builds a framework for resilience and empowerment, and develops self-awareness, connectedness and community, and a positive outlook. This is a minimally invasive treatment and is not routinely available as standard of care. SKY involves rhythmic, cyclical forms of breathing in which there are no pauses between inhalation and exhalation. The breathing practices of this program include: (a) a three-stage Pranayama with Ujjayi, also called Victory Breath or Ocean Breath (b) Bhastrika or Bellow's Breath and (c) Sudarshan Kriya (SK) or the Rhythmic Breath Technique.

SKY will be consistently taught to the participants by two instructors from The Art of Living Foundation, an international humanitarian and charitable organization. SKY training will take place in a group-format with group sizes varying between 4-6 participants. The investigators will conduct these training sessions in an appropriately sized and accessible community hall in London, Ontario. SKY training involves attending a 5-day course that teaches the basic principles of SKY over 2.5-3 hour daily sessions. These will be followed by once weekly follow up sessions (90 min/wk) for 3 weeks and then bimonthly sessions (every 2 weeks) for the next 8 weeks. In addition, participants will be asked to practice SKY at home daily (25 min/day) throughout the duration of the study period and log practice frequency and any other noteworthy observations in a log sheet that will be provided to them.

MENTAL HEALTH ASSESSMENTS:

Participants will be screened for eligibility using criteria described below , the Anti-Depressant Treatment History Form, and if applicable an MRI pre-screening checklist. Prior to the start of the intervention, trained raters will meet with eligible participants to obtain demographic information. Participants will complete baseline measures of depression, comorbid anxiety, quality of life and caregiver burden. Specifically, the following scales will be administered: Hamilton Depression Rating Scale (HAM-D 17 item version), Geriatric Anxiety Inventory, European Quality of Life (EQ-5D-5L) and the Zaritz Caregiver burden. The abovementioned scales will be administered again at three other time points, weeks 4, 8 and 12.

MRI:

Seven healthy control participants will be recruited by advertising via flyers in waiting areas of the clinic. In addition, spouses and other family members accompanying the patient, who appear to be of eligible age, will be offered a letter of information about this research study. All thirty recruited TR-LLD participants will also be offered the option of participating in the MRI portion of the study in addition to the study activities described above. Our goal is to recruit 13 TR-LLD to complete MRI scans.

All MRI participants will complete the MRI screening questionnaire. Control participants will additionally be asked to complete a Mini Neuropsychiatric Interview (MINI) to confirm an absence of any mental health diagnosis. Both control and TR-LLD participants who are eligible to take part in the MRI portion of the study will be asked to attend a one-hour appointment at the Western Centre for Functional and Metabolic Mapping at University Hospital campus of LHSC. Control participants will attend only one such appointment, while TR-LLD participants will be asked to attend one MRI visit pre-intervention and one MRI visit post-intervention. The Research Coordinator or Research Assistant will accompany participants to the MRI visit, while the MRI analysis itself will be completed by an in-house MRI technician at the Western Centre for Functional and Metabolic Mapping.

The investigators will conduct semi-structured interviews by trained raters on study completers as well as drop outs. If a participant consented to be part of the study but then decided against participation at any point, he/she will be offered the opportunity to identify any problems with our approach by participating in a short interview conducted by a trained research assistant.

Inclusion Criteria:

• 60-80 years of age
• major depressive disorder, as per the results of an interview by a trained rater using the Structured Clinical Interview for DSM-5 and subsequently confirmed by the psychiatrist
• Mild to moderate depression as confirmed by a score on the HAM-D 17 between 8 and 23
• Have failed at least two trials of antidepressants, given at adequate doses for adequate duration during the current episode
• Able to follow verbal instructions and sit without physical discomfort for 45 minutes
• Willing and able to attend at least 75% of all Sudarshan Kriya Yoga (SKY) sessions
• Willing to dedicate 25-30 minutes/day to SKY practice at home
• Low risk of suicide based on a clinical initial interview and during follow-up interviews at weeks 4, 8 and 12.

Exclusion Criteria:

• Uncontrolled hypertension, seizure disorder, psychosis, substance abuse, or dementia
• Currently participating in other similar studies or currently practicing any type of formal meditation, mindfulness or breathing techniques
• A major surgery within 6 weeks prior to commencement of or scheduled during, the study intervention
• A traumatic brain injury
• Any contraindications to MRI will also be excluded
• Healthy control participants must have no significant mental health issues, or contraindications to MRI.