Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) is an effective treatment for major depressive disorder (MDD). However, there is a considerable degree of heterogeneity in randomized clinical trials of rTMS, for instance pertaining to patient characteristics such as age and degree of treatment refractoriness. Increased age and higher levels of refractoriness both predict lower antidepressant efficacy of rTMS in patients with MDD. We hypothesized that rTMS trials that recruited patients who had previously failed fewer treatment attempts find stronger treatment effects and we examined how many failed medication trials were required to meet each study’s definition of treatment refractoriness.
Fourty six trials (N = 2028 patients) reported on the level of treatment refractoriness in their sample. The minimum number of failed medication trials used to define treatment refractoriness ranged from ≥ 1 to ≥ 3; one trial provided a range of 1–4 failed medication trials to define treatment refractoriness . Most patients (38.2%) participated in studies which used ≥ 2 failed medication trials as inclusion criterion. No study with medication-naïve patients was found and only three studies included non treatment-refractory patients (n = 41; 2.4%). We did not find significant subgroup differences in terms of response rates between trials with different criteria used to define treatment refractoriness (Q5 = 9.05, p = 0.11). Although this test might be underpowered. Differences in treatment efficacy depending on the study inclusion criteria cannot be acertained due to a lack of studies in low treatment refractory or medication-nnaïve patients. In light of the benign tolerability profile of rTMS, future trials should investigate the efficacy of rTMS in non-treatment refractory depression.