Table 1.
Summary of discussed studies examining demographic and clinical correlates and predictors of rTMS outcome
| Study | Study Design | Sample (N) | rTMS Parameters | Candidate Predictor Variables | Findings |
|---|---|---|---|---|---|
| Berlim, 2014 | Systematic review and meta-analysis | RCTs (29, with data from n=1371 subjects) | All studies included HF rTMS over left DLPFC Specific parameters varied by site. |
Primary diagnosis (i.e., studies with unipolar vs. mixed uni- and bipolar samples), rTMS used as monotherapy vs. augmentation, medication resistance (< vs. ≥ 2 failed antidepressant trials) | rTMS efficacy for samples was not found to differ significantly as a function of baseline medication resistance, rTMS monotherapy vs. augmentation, or primary diagnosis. |
| Brakemeier, 2007 | Open trial | MDD (n=62) or Bipolar II (n=8) | Left DLPFC, 20 Hz, 100% MT ;10 sessions over 2 weeks | Depression severity (HAM-D, BDI); HAM-D factors: psychic depression, loss of motivated behavior, psychosis, anxiety, and sleep disturbances; CORE assessment of psychomotor disturbance; duration of current episode (< vs. ≥ 5 months), medication resistance (y/n), prior antidepressant treatments in the current episode (#) | At baseline, responders differed from non-responders on the following variables: current episode duration, total antidepressant medication trials, medication resistance, CORE agitation, CORE psychomotor retardation, anxiety (HAM-D). Responders and non-responders did not differ significantly at baseline in: gender, age, number of depressive episodes, previous antidepressant treatments, depression severity, psychic depression, loss of motivated behavior, psychosis, sleep disturbance, CORE total score, CORE non-interactiveness. In a multivariable logistic regression, shorter duration of current depressive episode, fewer previous treatment trials, and greater sleep disturbance at baseline were significant predictors of responder status. |
| Brakemeier, 2008 | Open trial (2 sites) | MDD (n= 75) or Bipolar II (n=4) |
Site 1: Left DLPFC, 10 Hz, 1500 pulses per session, 100% MT Site 2: Left DLPFC, 20 Hz, 2000 pulses per session, 100% MT Average of 12.04 ± 2.42 sessions |
Depression severity (HAM-D); HAM-D factors: psychic depression, loss of motivated behavior, psychosis, anxiety, and sleep disturbances; HAM-D subscales: psychomotor retardation and agitation; duration of current episode (< vs. ≥ 5 months), medication resistance (y/n), prior antidepressant treatments in the current episode (#) | At baseline, responders differed from non-responders on current episode duration and medication resistance. Responders and non-responders did not differ significantly at baseline in: gender, age, number of depressive episodes, depression severity, HAM-D factors and subscales. Predictive models fit in Brakemeier et al., 2007 and Fregni et al., 2006 could not be replicated. An exploratory regression model found that lower medication resistance, depressed mood, guilt, and greater psychomotor retardation at baseline predicted greater symptom reduction. |
| Carpenter, 2012 | Naturalistic study | MDD (n = 307) | rTMS delivered over left prefrontal cortex Specific parameters varied by site. |
Baseline depression severity, medication resistance (< vs. ≥ 2 failed antidepressant trials), presence of comorbid anxiety disorder (y/n), gender, age (≤ vs. > 55 years), prior psychiatric hospitalization for depression (y/n) | Lower baseline severity and younger age corresponded to greater treatment benefit. Greater medication resistance had only a “modest” effect on treatment outcome. |
| Ciobanu, 2013 | Naturalistic | MDD (n = 93) | Left prefrontal cortex, 10 Hz, 2000 pulses per session, 90% MT (n = 13) or right prefrontal cortex, 1 Hz, 1200 pulses per session, 90% MT (n = 80) 15 sessions over 3 weeks |
Age (< vs. ≥ 65 years) | Change in depression severity from pre- to post-treatment did not differ between age groups. |
| Conelea, 2017 | Naturalistic | MDD (n = 231) | Left DLPFC, 5 or 10 Hz, 3000 pulses per session, 120% MT Number of sessions varied |
Age (< vs. ≥ 60 years) | Incidence of response or remission did not differ between older and younger patients. Age did not significantly predict depression severity at post-treatment, responder status, or remission status. |
| Figiel, 1998 | Open trial | MDD (n = 53) or bipolar (n = 3) | Left prefrontal cortex, 10 Hz, 500 pulses per session, 110% MT; 5 sessions over 1 weeks | Age, gender, baseline depression severity, mental status | Responders differed significantly from non-responders at baseline in age and depression severity. Responders and non-responders did not differ significantly in gender or mental status at baseline. |
| Fregni, 2006 | Data pooled from 1 open trial and 5 RCTs | MDD (n = 195) | Left DLPFC, high-frequency rTMS; 10 sessions over 2 weeks Specific parameters differed by site |
Age, gender, study site, baseline HAM-D (item and total scores), duration of depression, treatment refractoriness, medication use (y/n), change in HAM-D at post-treatment, rTMS frequency, number of pulses, and rTMS intensity | Younger age and lower treatment refractoriness were found to predict both greater change in depression severity and responder status. |
| Holtzheimer, 2004 | Randomized, controlled trial, blinded, with optional open label crossover | MDD (n = 15) | Left DLPFC, 10 Hz, 1600 pulses per seession, 100% MT; 10 sessions over 2 weeks | Duration of depressive episode (≤ 4 years vs. ≥ 10 years), number of previous antidepressant trials (< vs. ≥ 7) | Combining data from those randomized to active rTMS and those who crossed over to active rTMS following sham, it was found that participants with shorter episode duration had a greater reduction in symptom severity. There was no significant difference in % symptom change for groups with greater or fewer previous antidepressant trials. |
| Kaster, 2018 | Randomized, controlled trial, double blinded | Older adults (60–85 years) with MDD (n = 52) | Deep rTMS over bilateral dorsolateral and ventrolateral prefrontal cortex, 18 Hz, 6012 pulses, 120% MT 20 sessions over 4 weeks |
N/A | Deep TMS was associated with significantly higher rates of remission in late life depression, relative to sham. Remission rates observed appear similar to those reported in younger samples. |
| Levkovitz, 2015 | Randomized, controlled, double-blinded | MDD diagnosis, NITT = 212, NPP - 181 | Prefrontal cortex,18-Hz, 1980 pulses per session, 120% MT. 20 sessions over 4 weeks (followed by 12 weeks of biweekly session) |
Medication resistance (failed 1 or 2 vs. 3+ medication trials in the current episode) | Average slopes of depression severity during the acute treatment phase (HAM-D, baseline to week 5,) were significantly different between active and sham groups for those with lower medication resistance. These slopes were not significantly different between active and sham groups with greater medication resistance. Similarly, rates of remission at week 5 in the low medication resistance group were significantly higher in the active (vs. sham) condition; there was not a significant difference in remission rates in the high medication resistance group. |
| Lisanby, 2009* | Randomized, controlled trial, blinded | MDD (n = 301) | Left DLPFC, 10 Hz, 3000 pulses per session, 120% MT; 20 sessions over 4 weeks | Age, gender, current episode duration, comorbid anxiety disorder, course of illness, medication resistance, employment status, atypical depression, depression severity (MADRS), baseline MT | Within the active TMS arm, shorter duration of current episode and lower medication resistance predicted greater change in depression severity. In the open-label extension, absence of a comorbid anxiety disorder, lower medication resistance, and greater baseline symptom severity predicted better outcome in patients moving from sham to active rTMS. |
| Mosimann, 2004 | Randomized, controlled trial, blinded | Older (age 40–90) patients with TRD (n = 24) | Left DLPFC, 20 Hz, 1600 pulses, 100% MT; 10 sessions over 2 weeks | Age, duration of current depressive episode | Change in depression severity did not correlate with age or current episode duration. No significant differences in antidepressant effects were found between the active and sham conditions. |
| Rostami, 2017 | Naturalistic | Unipolar (n = 102) or bipolar (n = 146) depression | Participants received either:
|
Age, gender, marital status, education level, and individual BDI-II items | No relation was observed between depression type (i.e., unipolar vs. bipolar) and response. Age was the only demographic variable found to significantly predict responder status. Significant clinical predictors of responder status included loss of interest, fatigue, past failure, agitation, pessimism, and irritability. Sadness, appetite problems, and indecisiveness were unique predictors of response in the bipolar subsample and worthlessness and sleep problems were unique predictors of response in unipolar depression. |
BDI = Beck Depression Inventory; HAM-D = Hamilton Depression Rating Scale; HF = high-frequency; MADRS = Montgomery-Asberg Depression Rating Scale; RCT = Randomized Controlled Trial; TMS=transcranial magnetic stimulation; TRD = treatment resistant depression; ITT = Intent to Treat; PP = Per Protocol
*
Significance based on an a priori alpha level of .10.