Early effects predict trajectories of response to esketamine in treatment-resistant depression.

BACKGROUND: The efficacy of esketamine in treatment-resistant depression (TRD) has been confirmed. However, its administration is expensive and restrictive, with limited knowledge on how long the treatment should be continued. Predicting the treatment outcome would benefit patients and alleviate the global treatment cost. We aimed to define distinct trajectories of treatment response and assess their predictability. METHODS: In this longitudinal study, two independent samples of patients with unipolar or bipolar TRD were treated with esketamine in real-world settings. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) before each esketamine administration. Latent class analyses were used to define trajectories of response. RESULTS: In the original sample (N = 50), we identified two classes whose trajectories depicted response and non-response, respectively. The model was validated in the confirmatory sample (N = 55). Class membership was influenced by a few baseline characteristics such as concomitant benzodiazepine medication, number of depressive episodes or polarity. On the other hand, after only two esketamine administrations, the MADRS score predicted the 90-day trajectory of response with an accuracy of 80 %. LIMITATIONS: This observational study is not placebo-controlled. Therefore, its results and their generalizability need to be confirmed in experimental settings. CONCLUSIONS: After the first administrations of esketamine, the MADRS score has a good capacity to predict the most plausible trajectory of response. While thresholds and their predictive values need to be confirmed, this finding suggests that clinicians could base on MADRS scores their decision to discontinue treatment because of poor remaining chances of treatment response.

Repetitive Transcranial Magnetic Stimulation (rTMS) in Post-Traumatic Stress Disorder: Study Protocol of a Nationwide Randomized Controlled Clinical Trial of Neuro-Enhanced Psychotherapy "TraumaStim".

The use of high-frequency Transcranial Magnetic Stimulation (HF-rTMS) of the right dorsolateral prefrontal cortex (DLPFC) in treating Post-traumatic Stress Disorder (PTSD) is currently regarded as a level B intervention (probable effectiveness). HF-rTMS has attracted interest as a neuromodulation therapeutic method for PTSD. Prolonged exposure and reactivation therapy are also regarded as first-line treatments for PTSD. Randomized controlled clinical studies examining the effectiveness of several HF-rTMS sessions coupled with psychotherapy have not yet been completed. In total, 102 patients with refractory PTSD will be randomly assigned (1:1) to reactivation therapy, in addition to either active HF-rTMS (20 Hz) or sham HF-rTMS, for 12 sessions in a nationwide, multicenter, double-blind controlled trial. The impact on PTSD symptoms and neurocognitive functioning will be assessed. The primary outcome is the PTSD severity score measured based on the Clinician-Administered PTSD Scale (CAPS-5) at one month. If this additional therapy is successful, it may strengthen the case for regulatory authorities to approve this additional technique of treating PTSD. Additionally, it expands the field of neurostimulation-assisted psychotherapy.