Holding steady: age-related effects on treatment response during rtms treatment of depression

Introduction Outcomes of repetitive Transcranial Magnetic Stimulation (rTMS) for treatment-resistant depression vary widely across published studies, with several different mood rating scales being used to assess response and remission. Though prior work has suggested diminished response to rTMS in older populations, it has not been well-characterized or examined across multiple rating scales in a large dataset. To this end, we compared the abilities of three self-report scales (Inventory of Depressive Symptomatology 30-item [IDS], Patient Health Questionnaire 9-item [PHQ], and Profile of Mood States 30-item [POMS]) and the observer-rated Hamilton Depression Rating Scale 17-item (HDRS) to detect symptom change during naturalistic rTMS treatment in subjects under and over age 55. Methods 805 subjects (269 age 55 or older, 536 under age 55) with nonpsychotic MDD completed a six-week course of rTMS treatment with weekly self-report and observer ratings. Response and remission rates were determined in both age groups, with response defined as at least 50% reduction in scale score and remission defined as HDRS<7, IDS<14, PHQ<5, or POMS reduction of at least 75% (empirically defined). A broader definition of response and remission were then empirically defined, with criteria based on the number of scales demonstrating response or remission (with rates examined based on a minimum of one, two, or three scales). Correlations between scales in both age groups were examined with Kendall's t, and Cox models examined the effects of baseline scale scores and early symptom improvement as predictors of remission. Results All scales detected significant improvement during treatment, with correlations of Kendall's t=0.69-0.88 among self-report instruments and t=0.36-0.52 between self-report and observer-rated instruments (p<0.001) for age >=55, and t=0.73-0.85 among self-report instruments and t=0.54-0.56 between self-report and observer-rated instruments (p<0.001) for age <55. Response/remission rates varied widely across instruments: highest was PHQ (59/43% for >=55, 52%/30% for <55), followed by POMS (52%/28% for >=55, 47%/26% for <55), IDS (41%/26% for >=55, 40%/26% for <55), and HDRS (33%/22% for >=55, 37%/19% for <55). Higher baseline severity was associated with lower likelihood of remission across all scales (Hazard Ratio 0.84-0.97) and response across self-rated scales except PHQ (HR 0.98-0.99) (p<0.05). Greater improvement by session 10 predicted remission (HR 1.52-2.58, p<0.001) and response (HR 1.51-3.24, p<0.001) across all scales. Age did not interact with either baseline severity or early improvement to affect likelihood of response or remission. Broadening outcomes based on the minimum number of scales meeting response/remission criteria yielded the following rates: 60%/42% if age>=55 and 54%/35% if age<55 for at least one scale, 42%/28% if age>=55 and 42%/26% if age<55 for at least two scales, and 23%/18% if age>=55 and 22%/18% if age<55 for at least three scale. Using any single scale conferred 7-27% risk if age>=55 and 5-27% if age<55 for not detecting response/remission detected by another scale (lowest with PHQ and highest with HDRS). Conclusions All instruments detected improvement (including early improvement) with rTMS treatment, but degree of improvement varied notably. Use of any single scale conferred a significant risk of not detecting response/remission detected on another. Interestingly, though prior work has suggested diminished response and remission rates to rTMS with age, these data suggest response and remission rates are similar across the lifespan. These findings suggest caution in comparing degree of improvement across studies using different scales, regardless of age, and that accurate assessment of symptom burden over treatment may require multiple instruments. This research was funded by This project was made possible by the Ryan Family Fund for TMS Research. The authors would like to thank the Ryan Family for their generous support of innovative approaches to depression treatment and of groundbreaking TMS technology; their contributions have advanced the university's education and research missions. The research described was also supported by NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR001881. This material is also based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-2034835. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.