No antidepressant effects of low intensity transcranial pulsed electromagnetic fields for treatment resistant depression

Background: Noninvasive neurostimulation with transcranial Pulsed Electromagnetic Fields (tPEMF) may be a promising method for treatment resistant depression (TRD). Studies shown substantial improvement of depressive symptoms in patients with TRD, but there is no information on long-term antidepressant effects. The aim of this study was to investigate the short- and long-term efficacy of tPEMF in participants with TRD. Methods: Eligible participants with TRD in this sham-controlled double-blind multicenter trial were randomly assigned to five weeks either daily active or sham tPEMF. Severity of depression and anxiety was assessed preand directly post-treatment and five and fifteen weeks post-treatment. Primary outcome was change on the 17item Hamilton depression rating scale directly post-treatment. Secondary outcome was change on the Hamilton17 during follow-up and change on the Inventory of Depressive Symptomatology Self-Report and the Beck Anxiety Index. Results: Of the 55 included participants, 50 completed the treatment protocol. Depressive symptoms improved over time in both groups. The improvement continued until the last follow-up measure. There was no difference in outcome between the active and the sham group on change in depression post-treatment or on any secondary measure. Conclusion: Treatment with this type of active tPEMF was not superior to sham in patients with TRD. This is in contrast to a previous study using a similar design and power calculation, but a higher magnetic field strength, that reported improvement of depression after treatment with tPEMF compared to sham. An important limitation of our study was the fact that no different dosing regimens were tried

The Relationship between Insomnia and the Pathophysiology of Major Depressive Disorder: An Evaluation of a Broad Selection of Serum and Urine Biomarkers

Insomnia exhibits a clinically relevant relationship with major depressive disorder (MDD). Increasing evidence suggests that insomnia is associated with neurobiological alterations that resemble the pathophysiology of MDD. However, research in a clinical population is limited. The present study, therefore, aimed to investigate the relationship between insomnia and the main pathophysiological mechanisms of MDD in a clinical sample of individuals with MDD. Data were extracted from three cohorts (N = 227) and included an evaluation of depression severity (Quick Inventory of Depressive Symptomatology, QIDS-SR16) and insomnia severity (QIDS-SR16 insomnia items) as well as serum and urine assessments of 24 immunologic (e.g., tumour necrosis factor α receptor 2 and calprotectin), neurotrophic (e.g., brain-derived neurotrophic factor and epidermal growth factor), neuroendocrine (e.g., cortisol and aldosterone), neuropeptide (i.e., substance P), and metabolic (e.g., leptin and acetyl-L-carnitine) biomarkers. Linear regression analyses evaluating the association between insomnia severity and biomarker levels were conducted with and without controlling for depression severity (M = 17.32), antidepressant use (18.9%), gender (59.0% female; 40.5% male), age (M = 42.04), and the cohort of origin. The results demonstrated no significant associations between insomnia severity and biomarker levels. In conclusion, for the included biomarkers, current findings reveal no contribution of insomnia to the clinical pathophysiology of MDD

Validity of the Maudsley Staging Method in Predicting Treatment-Resistant Depression Outcome Using the Netherlands Study of Depression and Anxiety

OBJECTIVE: We investigated if the degree of treatment resistance of depression, as measured by the Maudsley Staging Method (MSM), is predictive of a worse depression outcome by using a large naturalistic cohort of depressed patients. METHODS: 643 subjects from the general population, primary care, and secondary care who suffered from current depressive disorder were included from the Netherlands Study of Depression and Anxiety baseline assessment. The diagnostic criterion was major depressive disorder (MDD) in the last month, based on the Composite Interview Diagnostic Instrument (CIDI), or a CIDI diagnosis of MDD in the past 6 months with an Inventory of Depressive Symptomatology Self-Report score > 24 at baseline. In these subjects, composite scores of the MSM, based on duration, severity, and treatment history of current episode, were determined retrospectively. We then determined if the MSM score prospectively predicted the 2-year course of depression after baseline. The primary outcomes were percentage of follow-up time spent in a depressive episode and being "mostly depressed" (≥ 50% of the follow-up) between baseline and 2-year follow-up. RESULTS: The MSM predicted "percentage of follow-up time with depression" (P < .001) and was associated with being "mostly depressed" (OR = 1.40; 95% CI, 1.23-1.60; P < .001). These effects were not modified by having received treatment. CONCLUSIONS: The current study shows that the MSM is a promising tool to predict worse depression outcomes in depressed patients. In this study that adds to previous work, we show the applicability of MSM in a wider range of primary and secondary care patients with depression