Centre for Youth Mental Health - Research Publications
Permanent URI for this collection
Search Results
1 - 8 of 8
-
ItemThe SMILES trial: an important first step(BMC, 2018-12-28)The SMILES trial was the first intervention study to test dietary improvement as a treatment strategy for depression. Molendijk et al. propose that expectation bias and difficulties with blinding might account for the large effect size. While we acknowledge the issue of expectation bias in lifestyle intervention trials and indeed discuss this as a key limitation in our paper, we observed a strong correlation between dietary change and change in depression scores, which we argue is consistent with a causal effect and we believe unlikely to be an artefact of inadequate blinding. Since its publication, our results have been largely replicated and our recent economic evaluation of SMILES suggests that the benefits of our approach extend beyond depression. We argue that the SMILES trial should be considered an important, albeit preliminary, first step in the field of nutritional psychiatry research.
-
ItemAspirin: a review of its neurobiological properties and therapeutic potential for mental illness(BMC, 2013-03-18)There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory 'braking signals', including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor-α and interleukin (IL)--6, but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders.
-
ItemThe addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): study protocol for a randomised control trial(BMC, 2014-11-04)BACKGROUND: The aim of the Youth Depression Alleviation-Combined Treatment (YoDA-C) study is to determine whether antidepressant medication should be started as a first-line treatment for youth depression delivered concurrently with psychotherapy. Doubts about the use of medication have been raised by meta-analyses in which the efficacy and safety of antidepressants in young people have been questioned, and subsequent treatment guidelines for youth depression have provided only qualified support. METHODS/DESIGN: YoDA-C is a double-blind, randomised controlled trial funded by the Australian government's National Health and Medical Research Council. Participants between the ages of 15 and 25 years with moderate to severe major depressive disorder will be randomised to receive either (1) cognitive behavioural therapy (CBT) and fluoxetine or (2) CBT and placebo. The treatment duration will be 12 weeks, and follow-up will be conducted at 26 weeks. The primary outcome measure is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) after 12 weeks of treatment. The MADRS will be administered at baseline and at weeks 4, 8, 12 and 26. Secondary outcome measures will address additional clinical outcomes, functioning, quality of life and safety. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ID: ACTRN12612001281886 (registered on 11 December 2012).
-
ItemDeserves a hearing? A case report of remitting tinnitus with N-acetyl cysteine(IN HOUSE PUBLICATIONS, 2013-07)
-
ItemYouth Depression Alleviation-Augmentation with an anti-inflammatory agent (YoDA-A): protocol and rationale for a placebo-controlled randomized trial of rosuvastatin and aspirin(WILEY, 2018-02)AIM: There is growing support for the role of inflammation and oxidative stress in the pathophysiology of major depressive disorder (MDD). This has led to the development of novel strategies targeting inflammation in the treatment of depression. Rosuvastatin and aspirin have well-documented, anti-inflammatory and antioxidant properties. The aim of the Youth Depression Alleviation: Augmentation with an anti-inflammatory agent (YoDA-A) study is to determine whether individuals receiving adjunctive anti-inflammatory agents, aspirin and rosuvastatin experience a reduction in the severity of MDD compared with individuals receiving placebo. METHODS: YoDA-A is a 12-week triple-blind, randomized controlled trial funded by the National Health and Medical Research Council, Australia. Participants aged 15-25, with moderate-to-severe MDD, are allocated to receive either 10 mg/day rosuvastatin, 100 mg/day aspirin, or placebo, in addition to treatment as usual. Participants are assessed at baseline and at weeks 4, 8, 12 and 26. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: The study is planned to be completed in 2017. At date of publication, 85 participants have been recruited. CONCLUSION: Timely and targeted intervention for youth MDD is crucial. Given the paucity of new agents to treat youth MDD, adjunctive trials are not only pragmatic and 'real-world', but additionally aim to target shortfalls in conventional medications. This study has the potential to first provide two new adjunctive treatment options for youth MDD; aspirin and rosuvastatin. Second, this study will serve as proof of principle of the role of inflammation in MDD.
-
ItemThe Efficacy of Adjunctive N-Acetylcysteine in Major Depressive Disorder: A Double-Blind, Randomized, Placebo-Controlled Trial(PHYSICIANS POSTGRADUATE PRESS, 2014-06)OBJECTIVE: Major depressive disorder (MDD) is one of the most common psychiatric disorders, conferring considerable individual, family, and community burden. To date, treatments for MDD have been derived from the monoamine hypothesis, and there is a paucity of emerging antidepressants, especially with novel mechanisms of action and treatment targets. N-acetylcysteine (NAC) is a redox-active glutathione precursor that decreases inflammatory cytokines, modulates glutamate, promotes neurogenesis, and decreases apoptosis, all of which contribute to the neurobiology of depression. METHOD: Participants with a current episode of MDD diagnosed according to DSM-IV-TR criteria (N = 252) were treated with NAC or placebo in addition to treatment as usual for 12 weeks and were followed to 16 weeks. Data were collected between 2007 and 2011. RESULTS: The omnibus interaction between group and visit for the Montgomery-Asberg Depression Rating Scale (MADRS), the primary outcome measure, was not significant (F₁,₅₂₀.₉ = 1.98, P = .067), and the groups did not separate at week 12 (t₃₆₀.₃ = -1.12, P = .265). However, at week 12, the scores on the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) differed from placebo (P = .03). Among participants with a MADRS score ≥ 25, NAC separated from placebo at weeks 6, 8, 12, and 16 (P < .05). Additionally, the rate of change between baseline and week 16 was significant (t₂₂₁.₀₃ = -2.11, P = .036). NAC treatment was superior to placebo at week 16 for secondary readouts of function and clinical impression. Remission and response were greater in the NAC group at week 16, but not at week 12. The NAC group had a greater rate of gastrointestinal and musculoskeletal adverse events. CONCLUSIONS: Being negative at the week 12 end point, and with some positive secondary signals, the study provides only limited support for the role of NAC as a novel adjunctive therapy for MDD. These data implicate the pathways influenced by NAC in depression pathogenesis, principally oxidative and inflammatory stress and glutamate, although definitive confirmation remains necessary. TRIAL REGISTRATION: www.anzctr.org.au Identifier: ACTRN12607000134426.
-
ItemMaintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial(BMC, 2012-08-14)BACKGROUND: N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. METHOD: The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. RESULTS: There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. CONCLUSIONS: There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. TRIAL REGISTRATION: The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).
-
ItemA pilot randomized, double-blind, placebo-controlled study of granisetron in the treatment of sexual dysfunction in women associated with antidepressant use(LIPPINCOTT WILLIAMS & WILKINS, 2004-05)A pilot study was conducted to evaluate the usefulness of granisetron for the treatment of antidepressant induced sexual dysfunction in women. Twelve women with antidepressant induced sexual dysfunction (AISD) were assigned granisetron (n=5) or placebo (n=7) in a 14-day randomized, double-blind, placebo-controlled study. One participant in the granisetron group did not complete the study. Participants were assessed at baseline, day 7 and day 14 using the Feiger Sexual Function and Satisfaction Questionnaire and the Arizona Sexual Experience Scale. No statistical differences were measured at baseline or at endpoint between the granisetron or placebo group. This study did not produce evidence supporting the usefulness of granisetron in AISD.