ObjectivesTo systematically review the efficacy and safety of anti-inflammatory agents for patients with major depressive disorders.MethodsWe searched the literature to identify potentially relevant randomised controlled trials (RCTs) up to 1 January 2019. The primary outcome was efficacy, measured by mean changes in depression score from baseline to endpoint. Secondary outcomes included response and remission rates and quality of life (QoL). Safety was evaluated by incidence of classified adverse events. Heterogeneity was examined using the I2 and Q statistic. Pooled standard mean differences (SMDs) and risk ratios (RRs) were calculated. Subgroup meta-analyses were conducted based on type of treatment, type of anti-inflammatory agents, sex, sponsor type and quality of studies.ResultsThirty RCTs with 1610 participants were included in the quantitative analysis. The overall analysis pooling from 26 of the RCTs suggested that anti-inflammatory agents reduced depressive symptoms (SMD −0.55, 95% CI −0.75 to −0.35, I2=71%) compared with placebo. Higher response (RR 1.52, 95% CI 1.30 to 1.79, I2=29%) and remission rates (RR 1.79, 95% CI 1.29 to 2.49, I2=41%) were seen in the group receiving anti-inflammatory agents than in those receiving placebo. Subgroup analysis showed a greater reduction in symptom severity in both the monotherapy and adjunctive treatment groups. Subgroup analysis of non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins and minocyclines, respectively, disclosed significant antidepressant effects for major depressive disorder (MDD). For women-only trials, no difference in changes of depression severity was found between groups. Subanalysis stratified by sponsor type and study quality led to the same outcomes in favour of anti-inflammatory agents in both subgroups. Changes of QoL showed no difference between the groups. Gastrointestinal events were the only significant differences between groups in the treatment periods.ConclusionsResults of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with MDD and are reasonably safe.
Background: Migraine is one of the most common neurological disorders that leads to disabilities. However, the conventional drug therapy for migraine might be unsatisfactory at times. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibody (CGRP mAb) for the preventive treatment of episodic migraine, and provide high-quality clinical evidence for migraine therapy. Methods: A systematic electronic database search was conducted to identify the potentially relevant studies. Two independent authors performed data extraction and quality appraisal. Mean difference (MD) and risk ratio (RR) were pooled for continuous and dichotomous data, respectively. The significance levels, weighted effect sizes and homogeneity of variance were calculated. Results: Eleven high-quality randomized control trials that collectively included 4402 patients were included in this meta-analysis. Compared to placebo group, CGRP mAb therapy resulted in a reduction of monthly migraine days [weighted mean difference (WMD) = − 1.44, 95% CI = (− 1.68,− 1.19)] and acute migraine-specific medication days [WMD = − 1.28, 95% CI = (− 1.66,− 0.90)], with an improvement in 50% responder rate [RR = 1.51, 95% CI = (1.37,1.66)]. In addition, the adverse events (AEs) and treatment withdrawal rates due to AEs were not significantly different between CGRP mAb and placebo groups. Similar efficacy and safety results were obtained for erenumab, fremanezumab, and galcanezumab in subgroup analysis. Conclusions: The current body of evidence reveals that CGRP mAb is an effective and safe preventive treatment for episodic migraine.
Herein, we developed a photolabile spherical nucleic acid (PSNA) for carrier-free and near-infrared (NIR) photocontrolled self-delivery of small-interfering RNA (siRNA) and antisense oligonucleotide (ASO). PSNA comprised a hydrophilic siRNA shell with a hydrophobic core containing a peptide nucleic acid-based ASO (pASO) and NIR photosensitizer (PS). The incorporation of a singlet oxygen (1O2)-cleavable linker between the siRNA and pASO allowed on-demand disassembly of PSNA in tumor cells once 1O2 was produced by the inner PS upon NIR light irradiation. The generated 1O2 could also concurrently promote lysosomal escape of the released siRNA and pASO to reach cytosolic targets. Both in vitro and in vivo results demonstrated that, under NIR light irradiation, PSNA could suppress hypoxia inducible factor-1α (HIF-1α) and B-cell lymphoma 2 (Bcl-2) for gene therapy (GT), which further combined photodynamic therapy (PDT) favored by the released PS to inhibit tumor cell growth. Given its carrier-free, NIR-sensitive, designable, and biocompatible merits, PSNA represents a promising self-delivery nanoplatform for cancer therapy.
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