First Episode Bipolar Disorders

First-Episode Bipolar Disorders


Professor Michael Berk


Lisa Henry, Rothanthi Daglas, Craig Macneil, Melissa Hasty, Clare Shelton, Alison Hughes, Melanie Evans, Linda Kader, Aswin Ratheesh, Shilpa Aggarwal, Brendan Murphy, and Murat Yucel.


The First-Episode Bipolar Disorders Unit includes a well-established and integrated team of researchers and clinicians specialised in the identification and treatment of bipolar disorders. The team investigates biological, neuropsychological and psychosocial aspects of bipolar disorders, with its main focus on first-episode mania and psychosis.

The team has also taken a strong role in providing training to clinical staff on biopsychosocial interventions for young people with bipolar disorder. This has included consultation, lectures, and workshops locally, nationally and internationally

Key Achievements

The team continues to publish extensively on research and clinical issues relating to mood disorders.

Current Projects

  • Neuroprotective Properties of Quetiapine versus Lithium in a First Episode Mania Cohort: 12-month Neuroanatomical, Neurochemical and Neuro-cognitive Effects and Preliminary Data of Prophylactic Properties.

The primary purpose of this single blind controlled randomised parallel group design trial is to investigate if treatment with lithium or quetiapine monotherapy, is associated with similar levels of neuroanatomical, biochemical and neurocognitive protection at short-term end points. Two sites are participating in recruiting individuals with first episode bipolar and schizoaffective disorders - Orygen Youth Health (Melbourne Health) and Southern Health. The study is continuing to recruit study participants along with control subjects.

  • Youth Depression Alleviation: Augmentation with Anti-inflammatory Agent (YoDA-A) Proof of principle of the inflammatory and oxidative theory of depression: A treatment study of rosuvastatin and aspirin.

There is now a clear body of recent evidence to support an aetiological role for inflammation and oxidative stress in depression. Depression is a subacute inflammatory state. Inflammation leads to greater oxidative stress, and existing oxidative stress may impact on the inflammatory response. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), such as rosuvastatin, have anti-inflammatory and antioxidant properties, as does aspirin. There is recent evidence that statins enhance psychological well-being, independent of serum cholesterol levels. We have data from three studies both showing a reduction in risk for depression among people taking statins. Similarly, aspirin has been shown to have antidepressant effects in preclinical studies and reduces risk for depression in epidemiological studies.This study is 12-week acute treatment trial for moderate to severe major depressive disorder (MDD), with a 9-month maintenance treatment phase. It is designed to establish whether the use of (i) statins 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. The study primarily aims to assess if in individuals presenting to specialised early intervention centres with moderate to severe major depression, 12-weeks treatment with either rosuvastatin or aspirin reduces severity of depression compared to individuals taking treatment as usual. The study will also examine if either agent reduces the risk of the recurrence of depression, reduces serum markers of inflammation, and whether the reduction in inflammatory and oxidative markers correlates with change in depressive symptomatology.

  • Youth Depression Alleviation: A Randomised Controlled Trial of Cognitive Behavioural Therapy with Fluoxetine or Placebo (YoDA-C)

The study aims to answer an important question in the treatment of moderate-to-severe youth depression: should antidepressant treatment be started as a first-line treatment, concurrent with psychotherapy? Or should psychotherapy alone be commenced first, and medication withheld? The question has taken on increased clinical importance in the wake of recent evidence questioning the effectiveness and safety of antidepressants in young people, and the subsequent development of treatment guidelines that are equivocal in their support of antidepressant medication as first-line treatment. The NHMRC Clinical Practice Guideline (NHMRC CPG) has recently released its recommendations for the treatment of depressed young people up to the age of 25. It calls for more studies of treatment effectiveness for youth depression, and, in particular, for studies that include the 18- to 25-year-old age group. The aim of this proposal is to compare the effectiveness of two interventions for youth with moderate-to-severe major depressive disorder (MDD). Approximately 300 patients aged between 15 and 24 will be randomised to receive either (i) cognitive behavioural therapy (CBT) and fluoxetine, or (ii) CBT and placebo, for 12 weeks in a double-blind, randomised control trial (RCT). This will be the first placebo-controlled study that has examined whether the addition of medication to CBT is an effective strategy for the treatment of youth depression. The primary hypothesis is that young people with moderate-to-severe MDD will show greater improvement after 12 weeks of treatment with CBT and fluoxetine compared to treatment with CBT and placebo.