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Background Primary care is a major access point for the initial treatment of depression, but the management of these patients is far from optimal. The lack of time in primary care is one of the major difficulties for the delivery of evidence-based psychotherapy. During the last decade, research has focused on the development of brief psychotherapy and cost-effective internet-based interventions mostly based on cognitive behavioral therapy (CBT). Very little research has focused on alternative methods of treatment for depression using CBT. Thus, there is a need for research into other therapeutic approaches. Objective This study aimed to assess the effectiveness of 3 low-intensity, internet-based psychological interventions (healthy lifestyle psychoeducational program [HLP], focused program on positive affect promotion [PAPP], and brief intervention based on mindfulness [MP]) compared with a control condition (improved treatment as usual [iTAU]). Methods A multicenter, 4-arm, parallel randomized controlled trial was conducted between March 2015 and March 2016, with a follow-up of 12 months. In total, 221 adults with mild or moderate major depression were recruited in primary care settings from 3 Spanish regions. Patients were randomly distributed to iTAU (n=57), HLP (n=54), PAPP (n=56), and MP (n=54). All patients received iTAU from their general practitioners. The main outcome was the Spanish version of the Patient Health Questionnaire-9 (PHQ-9) from pretreatment (time 1) to posttreatment (time 2) and up to 6 (time 3) and 12 (time 4) months’ follow-up. Secondary outcomes included the visual analog scale of the EuroQol, the Short-Form Health Survey (SF-12), the Positive and Negative Affect Schedule (PANAS), and the Pemberton Happiness Index (PHI). We conducted regression models to estimate outcome differences along study stages. Results A moderate decrease was detected in PHQ-9 scores from HLP (β=–3.05; P=.01) and MP (β=–3.00; P=.01) compared with iTAU at posttreatment. There were significant differences between all intervention groups and iTAU in physical SF-12 scores at 6 months after treatment. Regarding well-being, MP and PAPP reported better PHI results than iTAU at 6 months post treatment. PAPP intervention significantly decreased PANAS negative affect scores compared with iTAU 12 months after treatment. Conclusions The low-intensity, internet-based psychological interventions (HLP and MP) for the treatment of depression in primary care are more effective than iTAU at posttreatment. Moreover, all low-intensity psychological interventions are also effective in improving medium- and long-term quality of life. PAPP is effective for improving health-related quality of life, negative affect, and well-being in patients with depression. Nevertheless, it is important to examine possible reasons that could be implicated for PAPP not being effective in reducing depressive symptomatology; in addition, more research is still needed to assess the cost-effectiveness analysis of these interventions. Trial Registration ISRCTN Registry ISRCTN82388279; http://www.isrctn.com/ISRCTN82388279 International Registered Report Identifier (IRRID) RR2-10.1186/s12888-015-0475-0

Mindfulness-Based Interventions (MBIs) present positive effects on mental health in diverse populations. However, the detailed associations between MBIs and biomarkers in patients with psychiatric disorders remain poorly understood. The aim of this study was to examine the effects of MBIs on biomarkers in psychiatric illness used to summarise the effects of low-grade inflammation. A systematic review of PubMed, EMBASE, PsycINFO, and the Cochrane Library was conducted. Effect sizes (ESs) were determined by Hedges’ g and the number needed to treat (NNT). Heterogeneity was evaluated. A total of 10 trials with 998 participants were included. MBIs showed significant improvements in the event-related potential amplitudes in attention-deficit hyperactivity disorder, the methylation of serotonin transporter genes in post-traumatic stress disorder, the salivary levels of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) in depression, and the blood levels of adrenocorticotropic hormone (ACTH), IL-6, and TNF-α in generalised anxiety disorder. MBIs showed low but significant effects on health status related to biomarkers of low-grade inflammation (g = −0.21; 95% confidence interval (CI) –0.41 to −0.01; NNT = 8.47), with no heterogeneity (I2 = 0; 95% CI 0 to 79). More trials are needed to establish the impact of MBIs on biomarkers in psychiatric illness.