Youth Depression Alleviation: Augmentation with Anti-inflammatory Agent (YoDA-A)

Funding

Government body,NHMRC: National Health and Medical Research Council

Scientific enquiries

Prof Prof. Michael Berk, Professor of Psychiatry

Brief Summary

This study is 12-week acute treatment trial for moderate to severe major depressive disorder (MDD). It is designed to establish whether the use of (i) rosuvastatin or (ii) aspirin, reduces symptom severity and prevents recurrence of depression in young people. In this 3-arm controlled design, add-on therapy to treatment as usual (TAU) with rosuvastatin or aspirin will be compared to placebo. Aims Using a randomised placebo controlled trial, we aim to assess in individuals presenting to specialis .... This study is 12-week acute treatment trial for moderate to severe major depressive disorder (MDD). It is designed to establish whether the use of (i) rosuvastatin or (ii) aspirin, reduces symptom severity and prevents recurrence of depression in young people. In this 3-arm controlled design, add-on therapy to treatment as usual (TAU) with rosuvastatin or aspirin will be compared to placebo. Aims Using a randomised placebo controlled trial, we aim to assess in individuals presenting to specialised early intervention centres with moderate to severe major depression if: 1. 12 weeks treatment with either 10 mg rosuvastatin or 100 mg aspirin treatment reduces severity of depression compared to individuals taking treatment as usual: Primary aim. 2. 12 weeks with either 10 mg rosuvastatin or 100 mg aspirin treatment will improve self-reported symptom burden, quality of life, overall functioning and clinical impression and reduce symptoms of anxiety. 3. There are continued benefits following cessation of trial treatment assessed at 6 months following baseline. 4. whether 12-weeks treatment with 10 mg rosuvastatin or 100 mg aspirin reduces serum markers of inflammation, and 5. whether the reduction in inflammatory and oxidative markers correlates with change in depressive symptomatology Primary Hypothesis 1. 12-weeks of adjunctive rosuvastatin or aspirin treatment will be superior to placebo for reducing symptoms of depression using the Montgomery-Asberg Depression Rating Scale (MADRS). Analysis of rosuvastatin compared with placebo will be conducted separately to aspirin compared with placebo. Changes in MADRS scores in each medication individually are the primary outcomes. Predictors of outcome The study will also aim to explore predictors and moderators of treatment response. Predictors are variables present before treatment that influence a person's response to treatment, regardless of the type of treatment received; whereas moderators differentially predict response to the different treatments. We will explore questions such as whether young people with comorbid substance abuse and borderline personality disorder traits are less likely to respond to treatment overall and less likely to respond to one treatment compared to the other. We will also examine whether baseline cognitive factors predict response to the trial medication.
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Key Inclusion Criteria

- aged of 15 to 25 years inclusive - have a diagnosis of current Major Depressive Disorder (MDD) using Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) - a score on the Montgomery-Asberg Depression Rating Scale of >/=20 - ability to give informed consent and comply with study procedures - female participants are required to use effective contraception if sexually active - established fluency in English - if currently on treatment, that treatment (either pharmacological or psychos .... - aged of 15 to 25 years inclusive - have a diagnosis of current Major Depressive Disorder (MDD) using Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) - a score on the Montgomery-Asberg Depression Rating Scale of >/=20 - ability to give informed consent and comply with study procedures - female participants are required to use effective contraception if sexually active - established fluency in English - if currently on treatment, that treatment (either pharmacological or psychosocial) needs to be stable treatment for at least two weeks prior to enrolment
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Key Exclusion Criteria

- First episode psychosis (at least one positive symptom occurring daily for at least one week, or at least three times per week if the symptom lasts for longer than one hour on each occasion) - SCID-I/P diagnosis of diagnosis of bipolar I or II disorder or alcohol dependence - acute or unstable systemic medical disorder (determined by the treating physician including the review of the routine bloods assessment), including abnormal liver function, thyroid function or haematological findings; or .... - First episode psychosis (at least one positive symptom occurring daily for at least one week, or at least three times per week if the symptom lasts for longer than one hour on each occasion) - SCID-I/P diagnosis of diagnosis of bipolar I or II disorder or alcohol dependence - acute or unstable systemic medical disorder (determined by the treating physician including the review of the routine bloods assessment), including abnormal liver function, thyroid function or haematological findings; or acute or unstable systemic medical disorder, including immune disorders, bleeding disorders (such as haemophillia), significant gastric pathology (e.g. gastric haemorrhage, erosive gastritis or active peptic ulcer disease) and pre-existing cardiac disease - inability to comply with the requirements of informed consent or the study protocol (such as incapacity to consent, determined by the treating physician and research team) - current regular (>weekly) use of statins, aspirin, NSAID’s paracetamol, corticosteroids or any other immunomodulatory agents - Currently taking hypolipidaemics (e.g. gemfibrozil, nicotinic acid; cyclosporine), vitamin K antagonists and other anticoagulants (e.g. warfarin), protease inhibitors (including ritonavir), antacids (within 2 hrs); ketoconazole; spirinolactone; or cimetidine - participants with a history of intolerance or allergy to study medications and those who are currently pregnant or breast feeding will also be excluded
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