ABSTRACT
Background: Initial randomised controlled trials (RCTs) showed that prophylactic azithromycin in pregnant women improved maternal and neonatal outcomes; however, the recent evidence did not show any benefit to neonatal survival. There is conflicting evidence over the role of azithromycin prophylaxis in antenatal and intrapartum periods. We explored whether azithromycin prophylaxis in pregnant women improves maternal and neonatal outcomes. Methods: For this systematic review and meta-analysis registered on PROSPERO [CRD42023411093], we searched seven databases (PubMed, Scopus, Embase, Cochrane Library, EBSCOHost, ProQuest, and Web of Science) and clinical trial registries until 04/23/2024, for RCTs evaluating antenatal/intrapartum azithromycin prophylaxis against placebo/routine care in pregnant women. The primary outcome was neonatal mortality. Intrapartum and antenatal administration were assessed separately. We used random-effects meta-analysis. The risk of bias was assessed using the Cochrane RoB 2 tool. The GRADE approach was used to evaluate the certainty of the evidence. Findings: Screening 2161 records retrieved 20 RCTs (56,381 participants). Intrapartum azithromycin may make little or no difference to neonatal mortality [5 RCTs, 44,436 participants; Risk Ratio (RR): 1.02, 95% CI 0.86-1.20, I 2 = 0%, very low certainty], and maternal mortality [3 RCTs, 44,131 participants, RR: 1.26, 0.65-2.42, I 2 = 0%, low certainty]. Similarly, antenatal azithromycin may have little or no effect on neonatal mortality [3 RCTs; 5304 participants; RR: 0.74, 0.35-1.56, I 2 = 43%, very-low certainty] and maternal mortality [3 RCTs; 8167 participants RR: 1.62, 0.67-3.91, I 2 = 0%, low certainty]. There is no data on long-term adverse outcomes and antimicrobial resistance. Interpretation: Low to very low certainty evidence suggests that intrapartum or antenatal azithromycin prophylaxis in pregnant women might not reduce maternal or neonatal mortality. Funding: None.
ABSTRACT
BACKGROUND: Major depressive disorder is often resistant to first-line treatment, with around 30% failing to respond to traditional therapy. Treatment-resistant depression results in prolonged hospitalization and healthcare costs. Anti-inflammatory drugs have shown promising results in depression not responding to initial therapy. Minocycline has anti-inflammatory properties and crosses the blood-brain barrier. It has demonstrated varied results in several randomized controlled trials (RCTs). METHODS: We assessed the efficacy of minocycline compared to placebo in depression not responding to one first-line antidepressant via a systematic review and meta-analysis. We performed a comprehensive literature search across PubMed, Cochrane, and Scopus for RCTs. We visualized the results using forest plots and drapery plots. We assessed and explored heterogeneity using I2, prediction interval, and meta-regression. Then, we rated the certainty of the evidence. RESULTS: Four RCTs revealed a non-significant difference in depression severity [-3.93; 95% CI: -16.14 to 8.28], rate of response [1.15; 0.33-4.01], and rate of remission [0.94; 0.44-2.01]. However, the reduction in depression severity is significant at a trend of Pâ <â .1. The high between-study heterogeneity (I2â =â 78%) for depression severity could be answered by meta-regression (Pâ =â .02) for the duration of therapy. CONCLUSION: There is no significant difference with minocycline compared to placebo for depression not responding to first-line antidepressant therapy. However, the treatment response varies with treatment duration and patients' neuroinflammatory state. Thus, larger and longer RCTs, especially in diverse disease subgroups, are needed for further insight. This is needed to allow greater precision medicine in depression and avoid elevated healthcare expenditure associated with hit-and-trial regimens. REGISTRATION: CRD42023398476 (PROSPERO).