Apparent Lack of Benefit of Combining Repetitive Transcranial Magnetic Stimulation with Internet-Delivered Cognitive Behavior Therapy for the Treatment of Resistant Depression: Patient-Centered Randomized Controlled Pilot Trial.

Background: Treatment-resistant depression (TRD) is considered one of the major clinical challenges in the field of psychiatry. An estimated 44% of patients with major depressive disorder (MDD) do not respond to two consecutive antidepressant therapies, and 33% do not respond to up to four antidepressants. Over 15% of all patients with MDD remain refractory to any treatment intervention. rTMS is considered a treatment option for patients with TRD. Likewise, iCBT is evidence-based, symptom-focused psychotherapy recommended for the treatment of TRD. Objective: This study aimed to evaluate the initial comparative clinical effectiveness of rTMS treatment with and without iCBT as an innovative intervention for the treatment of participants diagnosed with TRD. Methods: This study is a prospective two-arm randomized controlled trial. Overall, 78 participants diagnosed with TRD were randomized to one of two treatment interventions: rTMS sessions alone and rTMS sessions plus iCBT. Participants in each group were made to complete evaluation measures at baseline, and 6 weeks (discharge) from treatment. The primary outcome measure was baseline to six weeks change in mean score for the 17-item Hamilton depression rating scale (HAMD-17). Secondary outcomes included mean baseline to six-week changes in the Columbia suicide severity rating scale (CSSRS) for the rate of suicidal ideations, the QIDS-SR16 for subjective depression, and the EQ-5D-5L to assess the quality of health in participants. Results: A majority of the participants were females 50 (64.1%), aged ≥ 40 39 (50.0%), and had college/university education 54 (73.0%). After adjusting for the baseline scores, the study failed to find a significant difference in the changes in mean scores for participants from baseline to six weeks between the two interventions under study on the HAMD-17 scale: F (1, 53) = 0.15, p = 0.70, partial eta squared = 0.003, CSSRS; F (1, 56) = 0.04 p = 0.85, partial eta squared = 0.001, QIDS-SR16 scale; F (1, 53) = 0.04 p = 0.61, partial eta squared = 0.005, and EQ-5D-VAS; F (1, 51) = 0.46 p = 0.50, and partial eta squared = 0.009. However, there was a significant reduction in means scores at week six compared to baseline scores for the combined study population on the HAMD-17 scale (42%), CSSRS (41%), QIDS-SR16 scale (35%), and EQ-VAS scale (62%). Conclusion: This study did not find that combined treatment of TRD with rTMS + iCBT (unguided) was superior to treatment with rTMS alone. Our findings do not support the use of combined treatment of rTMS + iCBT for the management of TRD disorders.