Pharmacist-guided pre-emptive pharmacogenetic testing in antidepressant therapy (PrePGx): study protocol for an open-label, randomized controlled trial

Background It is known that only 50% of patients diagnosed with major depressive disorders (MDD) respond to the first-line antidepressant treatment. Accordingly, there is a need to improve response rates to reduce healthcare costs and patient suffering. One approach to increase rates of treatment response might be the integration of pharmacogenetic (PGx) testing to stratify antidepressant drug selection. The goal of PGx assessments is to identify patients who have an increased risk to experience adverse drug reactions or non-response to specific drugs. Especially for antidepressants, there is compiling evidence on PGx influencing drug exposure as well as response. Methods This study is an open-label, randomized controlled trial conducted in two study centers in Switzerland: (1) the Psychiatric Clinic of Solothurn and (2) the Private Clinic Wyss in Münchenbuchsee. Adult inpatients diagnosed with a unipolar moderate or severe depressive episode are recruited at clinic admission and are included in the study. If the adjustment to a new antidepressant pharmacotherapy is necessary, the participants are randomized to either Arm A (intervention group) or Arm B (control group). If no new antidepressant pharmacotherapy is introduced the participants will be followed up in an observational arm. The intervention is the service of pharmacist-guided pre-emptive PGx testing to support clinical decision making on antidepressant selection and dosing. As a comparison, in the control group, the antidepressant pharmacotherapy is selected by the treating physician according to current treatment guidelines (standard of care) without the knowledge of PGx test results and support of clinical pharmacists. The primary outcome of this study compares the response rates under antidepressant treatment after 4 weeks between intervention and control arm. Discussion The findings from this clinical trial are expected to have a direct impact on inter-professional collaborations for the handling and use of PGx data in psychiatric practice. Trial registration ClinicalTrials.govNCT04507555. Registered on August 11, 2020. Swiss National Clinical Trials Portal SNCTP000004015. Registered August 18, 2020.

Alterations in BDNF Protein Concentrations in the Hippocampus do not Explain the Pro-Neurogenic Effect of Citalopram on Adult Neurogenesis

Introduction Brain-derived neurotrophic factor (BDNF) has been implicated in the pro-neurogenic effect of selective serotonin reuptake inhibitors. In this study, we used Tph2 −/− mice lacking brain serotonin to dissect the interplay between BDNF and the serotonin system in mediating the effects of antidepressant pharmacotherapy on adult neurogenesis in the hippocampus. Methods Besides citalopram (CIT), we tested tianeptine (TIA), an antidepressant whose mechanism of action is not well understood. Specifically, we examined cell survival and endogenous concentrations of BDNF following daily injection of the drugs. Results Twenty-one days of CIT, but not of TIA, led to a significant increase in the survival of newly generated cells in the dentate gyrus of wild-type mice, without a significant effect on BDNF protein levels by either treatment. In Tph2 −/− mice, adult neurogenesis was consistently increased. Furthermore, Tph2 −/− mice showed increased BDNF protein levels, which were not affected by TIA but were significantly reduced by CIT. Discussion We conclude that the effects of CIT on adult neurogenesis are not explained by changes in BDNF protein concentrations in the hippocampus.

Cost–Utility Analysis of Mindfulness-Based Cognitive Therapy Versus Antidepressant Pharmacotherapy for Prevention of Depressive Relapse in a Canadian Context: Analyse coût-utilité de la thérapie cognitive basée sur la pleine conscience contre la pharmacothérapie antidépressive pour prévenir la rechute de la dépression en contexte canadien

Objective: Patients suffering from major depressive disorder (MDD) experience impaired functioning and reduced quality of life, including an elevated risk of episode return. MDD is associated with high societal burden due to increased healthcare utilization, productivity losses, and suicide-related costs, making the long-term management of this illness a priority. The purpose of this study is to evaluate the cost-effectiveness of mindfulness-based cognitive therapy (MBCT), a first-line preventative psychological treatment, compared to maintenance antidepressant medication (ADM), the current standard of care. Method: A cost–utility analysis was conducted over a 24-month time horizon to model differences between MBCT and ADM in cost and quality-adjusted life years (QALY). The analysis was conducted using a decision tree analytic model. Intervention efficacy, utility, and costing data estimates were derived from published sources and expert consultation. Results: MBCT was found to be cost-effective compared to maintenance ADM over a 24-month time horizon. Antidepressant pharmacotherapy resulted in 1.10 QALY and $17,255.37 per patient on average, whereas MBCT resulted in 1.18 QALY and $15,030.70 per patient on average. This resulted in a cost difference of $2,224.67 and a QALY difference of 0.08, in favor of MBCT. Multiple sensitivity analyses supported these findings. Conclusions: From both a societal and health system perspective, utilizing MBCT as a first-line relapse prevention treatment is potentially cost-effective in a Canadian setting. Future economic evaluations should consider combined treatment (e.g., ADM and psychotherapy) as a comparator and longer time horizons as the literature advances.

Is there a genuine placebo effect in acute depression treatments? A reassessment of regression to the mean and spontaneous remission

Regression to the mean and spontaneous improvements are rarely considered in interpretations of treatment trials for acute major depression. Here I suggest that regression to the mean and spontaneous remission may account for most improvements seen in placebo groups and also for a large proportion of variance in the acute treatment outcome of both antidepressant pharmacotherapy and psychotherapy. These findings have important implications for the interpretation of active treatments and placebo response in depression trials.