17. SAINT FOR TREATMENT-RESISTANT DEPRESSION: REAL WORLD FINDINGS

Introduction

Among older adults with major depressive disorder who receive pharmacologic treatment, it has been estimated that at least one-third do not respond to at least two adequate trials of antidepressants—i.e., the definition of treatment-resistant depression currently used by the FDA when considering indications for new therapies. Although electroconvulsive therapy (ECT) is a highly effective intervention for severe depression or depression with psychotic features, its use in older adults can be limited due to concerns for adverse side effects, including anterograde and retrograde amnesia, and increased risks in individuals with cardiovascular or neurologic comorbidities.

Repetitive transcranial magnetic stimulation (rTMS), particularly in the form of intermittent theta-burst stimulation (iTBS), has emerged as a promising non-invasive alternative for treatment of depression. The novel Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, which recently received FDA clearance, consists of ten daily high-dose sessions of iTBS targeting the left dorsolateral prefrontal cortex (DLPFC), which enables treatment time to be condensed into five days, rather than the typical four to six week course of conventional rTMS. The protocol also utilizes functional connectivity (fcMRI)-guided, personalized, algorithmic targeting of the region of the left DLPFC that is identified as being the most anticorrelated with the subgenual anterior cingulate cortex.

In the initial clinical trials, the SAINT protocol demonstrated impressive results, with over 80% of patients achieving remission in the open-label trial, and 50-80% meeting remission criteria at some point during the four week follow-up period in the randomized sham-controlled trial. However, studies evaluating the efficacy of SAINT in the geriatric population remain absent. Furthermore, real-world patient populations need to be treated to better gauge the effectiveness of this treatment outside of clinical trials.

Methods

The University of Arkansas for Medical Sciences (UAMS), through its Interventional Psychiatry Program, was the first site in the United States to offer SAINT to patients in a clinical setting. We received patient referrals from all over the United States, as well as, locally, with the majority being self-referrals. After a comprehensive psychiatric evaluation, patients were offered SAINT TMS if they met criteria for treatment resistant MDD without psychotic features and had no contraindications for the MRI or procedure. A resting-state fMRI was obtained for each patient in the Brain Research Institute housed within the psychiatry department at UAMS. The fMRI data was then uploaded to Magnus Medical to develop a personalized treatment target within the left DLPFC for each patient.

Each patient received ten sessions a day for 5 consecutive days. Each session lasted 10min and there was a minimum of 50min rest between sessions. Patients received 18,000 pulses per day and a total of 90,000 by the end of the treatment series. All treatments were delivered on a MagVenture MagPro X100 system (MagVenture A/S, Denmark) equipped with a MagVenture Cool-B65 A/P coil set to deliver iTBS 1800 pulse pattern at stimulation strength of 90% motor threshold. The stimulation strength was also corrected to account for individual differences in cortical depth of the treatment.

Results

A total of 10 patients (mean age = 64 years, range: 33 to 79; 6 female, 4 male) have completed the SAINT treatment protocol at UAMS at the time of this writing. Of the 10 patients treated to date, 8 were 60 years or older (mean age = 71 years) which made up our older adult cohort. Using the Maudsley Staging method, all patients met criteria for at least “moderate” treatment resistant depression (i.e., mean score = 10, scale range 3-15). On average, patients had failed between five to seven antidepressant medications, eight of ten had failed augmentation strategies, and two had failed ECT. The mean MOCA score was 26.7 for our older adult cohort. Severity of depressive symptoms and response to treatment was measured with both the PHQ-9 and the GDS-15. Among the older adult cohort, the mean baseline GDS-15 was 11 and the mean baseline PHQ-9 was 14.5. At the end of day 5, the mean GDS was 6.63, and the mean PHQ-9 was 9.63. Using the GDS, a total of four patients met criteria for either response or remission. Using the PHQ-9, a total of 2 patients met criteria for remission by treatment day 5, and 1 additional patient went on to meet criteria for remission on follow up 2 weeks later. No serious adverse effects were reported, with the most commonly reported side effects of the procedure being fatigue and mild to moderate headache.

Conclusions

Even in a patient population that included significantly treatment-resistant older adults, the SAINT protocol appears to offer promise for at least a portion of these patients. Further work is needed to further define inclusion and exclusion criteria for SAINT, to identify patients who may be at risk of relapse, and to develop maintenance or re-treatment protocols. To date, SAINT is covered only by traditional Medicare, or patients must pay out-of-pocket. The benefits of SAINT in terms of short duration of treatment, relatively low side effect burden, and effectiveness suggest that this treatment should be more broadly accessible to older adults with treatment-resistant depression.