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Background: Stopping long-term (>12 months) antidepressant use can be difficult due to unpleasant withdrawal symptoms. Many people do not recognise withdrawal symptoms or understand how to minimise them while safely discontinuing antidepressants. To address the gaps, the authors developed the 'Redressing long-term antidepressant use' (RELEASE) resources, comprising a medicines information brochure, a decision aid, and drug- specific hyperbolic tapering protocols. Aim: To explore patients' acceptability of the RELEASE resources to optimise their use and impact. Design and setting: A think-aloud interview study among adults with lived experience of long-term antidepressant use conducted in south-east Queensland, Australia, between November 2021 and June 2022. Method: Participants were purposively sampled from general practices and interviewed face-to-face or via videoconferencing. Participants verbalised their thoughts, impressions, and feelings while engaging with each resource. Interviews were analysed using a deductive coding framework, including codes related to acceptability and optimisation. Interviews were analysed in a series of four tranches, with iterative modifications made to resources after each tranche. Results: Participants (n = 14) reported the resources to be relevant, informative, motivational, and usable. Participants' comments informed modifications, including changes to wording, content order, and layout. Several participants expressed frustration that they had not had these resources earlier, with one reporting the information could have been 'life changing'. Many commented on the need for these resources to be widely available to both patients and doctors. Conclusion: The RELEASE resources were found to be acceptable, useful, and potentially life changing. The effectiveness of these consumer-informed resources in supporting safe cessation of long-term antidepressants is currently being tested in general practice. [ABSTRACT FROM AUTHOR]

Background: Many people experience withdrawal symptoms when they attempt to stop antidepressants. Withdrawal symptoms are readily misconstrued for relapse or ongoing need for medication, contributing to long-term use (> 12 months). Long-term antidepressant use is increasing internationally yet is not recommended for most people. Long-term use is associated with adverse effects including weight gain, sexual dysfunction, lethargy, emotional numbing and increased risk of falls and fractures. This study aims to determine the effectiveness of two multi-strategy interventions (RELEASE and RELEASE+) in supporting the safe cessation of long-term antidepressants, estimate cost-effectiveness, and evaluate implementation strategies. Methods: Design: 3-arm pragmatic cluster randomised controlled trial effectiveness-implementation hybrid type-1. Setting: primary care general practices in southeast Queensland, Australia. Population: adults 18 years or older taking antidepressants for longer than 1 year. Practices will be randomised on a 1.5:1:1 ratio of Usual care:RELEASE:RELEASE+. Intervention: RELEASE for patients includes evidence-based information and resources and an invitation to medication review; RELEASE for GPs includes education, training and printable resources via practice management software. RELEASE+ includes additional internet support for patients and prescribing support including audit and feedback for GPs. Outcome measures: the primary outcome is antidepressant use at 12 months self-reported by patients. Cessation is defined as 0 mg antidepressant maintained for at least 2 weeks. Secondary outcomes: at 6 and 12 months are health-related quality of life, antidepressant side effects, well-being, withdrawal symptoms, emotional numbing, beliefs about antidepressants, depressive symptoms, and anxiety symptoms; and at 12 months 75% reduction in antidepressant dose; aggregated practice level antidepressant prescribing, and health service utilisation for costs. Sample size: 653 patients from 28 practices. A concurrent evaluation of implementation will be through mixed methods including interviews with up to 40 patients and primary care general practitioners, brief e-surveys, and study administrative data to assess implementation outcomes (adoption and fidelity). Discussion: The RELEASE study will develop new knowledge applicable internationally on the effectiveness, cost-effectiveness, and implementation of two multi-strategy interventions in supporting the safe cessation of long-term antidepressants to improve primary health care and outcomes for patients. Trial registration: ANZCTR, ACTRN12622001379707p. Registered on 27 October 2022. [ABSTRACT FROM AUTHOR]

Oxidized lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids, collectively known as oxylipins, are bioactive signaling molecules that play diverse roles in human health and disease. Supplementation with n-3 docosahexaenoic acid (DHA) during pregnancy has been reported to decrease the risk of preterm birth in singleton pregnancies, which may be due to effects of DHA supplementation on oxylipins or their precursor n-6 and n-3 fatty acids. There is only limited understanding of the levels and trajectory of changes in plasma oxylipins during pregnancy, effects of DHA supplementation on oxylipins and unesterified fatty acids, and whether and how oxylipins and their unesterified precursor fatty acids influence preterm birth. In the present study we used liquid chromatography-tandem mass spectrometry to profile oxylipins and their precursor fatty acids in the unesterified pool using plasma samples collected from a subset of pregnant Australian women who participated in the ORIP (Omega-3 fats to Reduce the Incidence of Prematurity) study. ORIP is a large randomized controlled trial testing whether daily supplementation with n-3 DHA can reduce the incidence of early preterm birth compared to control. Plasma was collected at study entry (≈pregnancy week 14) and again at ≈week 24, in a subgroup of 48 ORIP participants-12 cases with spontaneous preterm (<37 weeks) birth and 36 matched controls with spontaneous term (≥40 weeks) birth. In the combined preterm and term pregnancies, we observed that in the control group without DHA supplementation unesterified AA and AA-derived oxylipins 12-HETE, 15-HETE and TXB2 declined between weeks 14-24 of pregnancy. Compared to control, DHA supplementation increased unesterified DHA, EPA, and AA, DHA-derived 4-HDHA, 10-HDHA and 19,20-EpDPA, and AA-derived 12-HETE at 24 weeks. In exploratory analysis independent of DHA supplementation, participants with concentrations above the median for 5-lipoxygenase derivatives of AA (5-HETE, Odds Ratio (OR) 8.2; p = 0.014) or DHA (4-HDHA, OR 8.0; p = 0.015) at 14 weeks, or unesterified AA (OR 5.1; p = 0.038) at 24 weeks had higher risk of spontaneous preterm birth. The hypothesis that 5-lipoxygenase-derived oxylipins and unesterified AA could serve as mechanism-based biomarkers predicting spontaneous preterm birth should be evaluated in larger, adequately powered studies., Competing Interests: Declaration of Competing Interest Dr. Makrides reports receiving advisory board fees, paid to her institution, from Fonterra Co-operative Group and Nestlé Nutrition Institute; and Dr. Gibson, receiving advisory board fees from Fonterra Co-operative Group and holding a patent (WO20 13/10 40 25 A1) on stabilizing and analyzing fatty acids in a biologic sample stored on solid media, owned by Adelaide Research and Innovation, the University of Adelaide, and licensed to Xerion. These disclosures are outside the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)