LAUSR

Abstract There is a paucity of research, in general, on TRD-LL and on novel approaches and interventional methods for older adults suffering with TRD-LL. Most of the lack of data stems from limited studies on these interventions in older adults since most pharmacotherapy and neuromodulation trials specifically exclude older adults or those with comorbid medical or psychiatric conditions. Broadly, approaches can be divided into those that are FDA approved for depression (but not specifically for TRD-LL) and those that are available and empirically supported but not FDA approved. Among the FDA approved treatments of transcranial magnetic stimulation (all forms of rTMS and dTMS), vagus nerve stimulation (VNS), deep brain stimulation (DBS), and now intranasal ketamine, TMS has been most extensively studied for treatment of late life depression. Newer forms of TMS are also being evaluated in older adults. Though there are extensive data on the use of VNS in TRD, there are no studies in older adults specifically, although a multicenter trial supported by the US Center of Medicare and Medicaid Services, which will recruit adults aged 65 and above, will soon be underway. Published studies in DBS have included older adults but not in appreciable numbers for separate analyses. Studies thus far suggest some benefit in TRD but no specific data for TRD-LL. Most of the published studies of IV ketamine, which is not FDA approved for depression, are limited to case reports which tend to support its use and tolerability in TRD-LL when used as monotherapy or in combination with other interventions. Use of intranasal ketamine, which was recently FDA approved earlier in 2019, in TRD-LL remains anecdotal. Among other approaches with empirical support, but not necessarily FDA approved specific indications, are behavioral interventions (exercise, stress reduction activities), bright light therapy, combination pharmacotherapy (lithium, T3/T4, atypical antipsychotics, psychostimulants, D3 agonists, and opioid analogs), and combination pharmacotherapy and psychotherapy. After briefly reviewing the above interventions, discussion will focus on the clinical assessment of TRD-LL and possible treatment algorithms.