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Background Most patients with Posttraumatic Stress Disorder (PTSD) suffer residual symptoms following first-line treatment. Oxidative stress has been implicated in the pathophysiology of PTSD. N-acetylcysteine (NAC) is a precursor of the brain’s primary antioxidant, glutathione, and may diminish oxidative cellular damage. An 8-week pilot study of NAC in veterans with PTSD found that symptoms were significantly reduced in the NAC group compared to placebo. This study aims to confirm these findings with a larger sample in a double-blind, placebo-controlled trial to further explore the efficacy of NAC as an adjunctive therapy in treatment-resistant PTSD. Methods A multicentre, randomised, double-blind, placebo-controlled trial for adult patients who still meet criteria for PTSD following first-line treatment. The intervention comprises either NAC as a fixed dose regime of 2.7 g/day (900 mg three times daily) administered orally for 12 weeks, or placebo. Standard care for PTSD will continue in addition, including other pharmacotherapies. Detailed clinical data will be collected at randomisation and weeks 4, 8, 12, 16, and 64 post-randomisation, with self-report measures completed weekly from baseline to 16 weeks and at 64 weeks post-randomisation. Blood-based biomarkers will be collected at baseline and 12 weeks to assess the mechanism of effect. The primary outcome measure will be change in Clinician-Administered PTSD Scale for DSM-5 at 12 weeks compared with baseline. Secondary outcomes will be change in quality of life, depression, anxiety, substance use and craving, and somatic symptoms. With 126 completed participants (63 per arm), the study is powered at 80% to detect a true difference in the primary outcome measure using a two-tailed analysis with alpha = 0.05, beta = 0.2. Discussion This is the first multicentre, double blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. NAC has an established safety profile, is readily available and easy to administer, and has a favourable tolerability profile, therefore making it an attractive adjunctive therapy. Inclusion of blood analyses to assess potential target engagement biomarkers of oxidative stress and neuroinflammation may help gauge the biological mechanisms of effect of NAC. Trial registration ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004 .

This study used ambulatory polysomnography (PSG) to investigate post-traumatic nightmares of post-traumatic stress disorder (PTSD). The key research question was whether post-traumatic nightmares occur in both rapid eye movement (REM) and non-REM sleep, and if so, whether nightmares in each sleep stage differed in content, phenomenology, and heart rate response. Underlying sleep disorders were investigated in an exploratory way. Thirty-five treatment-seeking veterans, current serving military members, and emergency service personnel undertook full PSG using the Compumedics (Melbourne, Australia) SomtePSG V1 system, during an inpatient psychiatric admission. The PSG recording included an event button to be pressed when a nightmare occurred, allowing us to determine the stage of sleep, changes in heart rate, and associated sleep events. The content and phenomenological features of participants' nightmares were recorded. Of the 35 participants, 29 reported a nightmare during their sleep study, but only 21 pressed the event button and could recall the content of one or more nightmare. This yielded sleep and nightmare data for 24 nightmares. Of the 24, 10 nightmares arose from REM sleep and 14 from non-REM (stages N1 and N2). Seven were accurate trauma replays and 17 were non-replay or a mixture of replay and non-replay. Most nightmares were associated with respiratory or leg movement events and increase in heart rate on awakening. Post-traumatic nightmares of PTSD occur in both REM and non-REM sleep and are commonly associated with other sleep disturbances. These findings have important treatment implications.

Although integral to the early detection and treatment of anorexia nervosa, there is a paucity of clear guidance available for general practitioners (GPs). This paper attempts to bridge the gap between the specialist and generalist literature to assist the busy GP feel confident in identifying and managing these patients. On reading this article it is anticipated the GP will feel well equipped to screen for and provide ongoing treatment to patients who pre-sent with eating disorders, particularly anorexia nervosa. This paper provides guidance for the identification and ongoing management of patients with anorexia nervosa, and supporting their carers. People affected by eating disorders, particularly anorexia nervosa, may deny having a problem, minimise their symptoms and resist treatment yet engage partially with their GP throughout the course of their illness. There are well-validated, quick screening tools that the non-specialist can use to identify patients at high risk of having an eating disorder.