Kristina Fritz

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders

Objectives: To provide guidance for the management of mood disorders, based on scientific evidence supplemented by expert clinical consensus and formulate recommendations to maximise clinical salience and utility. Methods: Articles and information sourced from search engines including PubMed and EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (MDC) (e.g., books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Information was reviewed and discussed by members of the MDC and findings were then formulated into consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous successive consultation and external review involving: expert and clinical advisors, the public, key stakeholders, professional bodies and specialist groups with interest in mood disorders. Results: The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (Mood Disorders CPG) provide up-to-date guidance and advice regarding the management of mood disorders that is informed by evidence and clinical experience. The Mood Disorders CPG is intended for clinical use by psychiatrists, psychologists, physicians and others with an interest in mental health care. Conclusions: The Mood Disorder CPG is the first Clinical Practice Guideline to address both depressive and bipolar disorders. It provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus. Mood Disorders Committee: Professor Gin Malhi (Chair), Professor Darryl Bassett, Professor Philip Boyce, Professor Richard Bryant, Professor Paul Fitzgerald, Dr Kristina Fritz, Professor Malcolm Hopwood, Dr Bill Lyndon, Professor Roger Mulder, Professor Greg Murray, Professor Richard Porter and Associate Professor Ajeet Singh. International expert advisors: Professor Carlo Altamura, Dr Francesco Colom, Professor Mark George, Professor Guy Goodwin, Professor Roger McIntyre, Dr Roger Ng, Professor John O’Brien, Professor Harold Sackeim, Professor Jan Scott, Dr Nobuhiro Sugiyama, Professor Eduard Vieta, Professor Lakshmi Yatham. Australian and New Zealand expert advisors: Professor Marie-Paule Austin, Professor Michael Berk, Dr Yulisha Byrow, Professor Helen Christensen, Dr Nick De Felice, A/Professor Seetal Dodd, A/Professor Megan Galbally, Dr Josh Geffen, Professor Philip Hazell, A/Professor David Horgan, A/Professor Felice Jacka, Professor Gordon Johnson, Professor Anthony Jorm, Dr Jon-Paul Khoo, Professor Jayashri Kulkarni, Dr Cameron Lacey, Dr Noeline Latt, Professor Florence Levy, A/Professor Andrew Lewis, Professor Colleen Loo, Dr Thomas Mayze, Dr Linton Meagher, Professor Philip Mitchell, Professor Daniel O’Connor, Dr Nick O’Connor, Dr Tim Outhred, Dr Mark Rowe, Dr Narelle Shadbolt, Dr Martien Snellen, Professor John Tiller, Dr Bill Watkins, Dr Raymond Wu.

Mood disorders: neurocognitive models

In recent years, a number of neurocognitive models stemming from psychiatry and psychology schools of thought have conceptualized the pathophysiology of mood disorders in terms of dysfunctional neural mechanisms that underpin and drive neurocognitive processes. Though these models have been useful for advancing our theoretical understanding and facilitating important lines of research, translation of these models and their application within the clinical arena have been limited—partly because of lack of integration and synthesis. Cognitive neuroscience provides a novel perspective for understanding and modeling mood disorders. This selective review of influential neurocognitive models develops an integrative approach that can serve as a template for future research and the development of a clinically meaningful framework for investigating, diagnosing, and treating mood disorders.

Pharmacological management of unipolar depression

To be used in conjunction with ‘Psychological management of unipolar depression’ [Lampe et al. Acta Psychiatr Scand 2013;127(Suppl. 443):24–37] and ‘Lifestyle management of unipolar depression’ [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38–54]. To provide clinically relevant recommendations for the use of pharmacological treatments in depression derived from a literature review.

Differential engagement of the fronto-limbic network during emotion processing distinguishes bipolar and borderline personality disorder.

Differential engagement of the fronto-limbic network during emotion processing distinguishes bipolar and borderline personality disorder

The Lithium Battery: assessing the neurocognitive profile of lithium in bipolar disorder.

OBJECTIVE The aim of the present study was to characterize the neurocognitive effects of lithium in bipolar disorder to inform clinical and research approaches for further investigation. METHODS Key words pertaining to neurocognition in bipolar disorder and lithium treatment were used to search recognized databases to identify relevant literature. The authors also retrieved gray literature (e.g., book chapters) known to them and examined pertinent articles from bibliographies. RESULTS A limited number of studies have examined the effects of lithium on neurocognition in bipolar disorder and, although in some domains a consistent picture emerges, in many domains the findings are mixed. Lithium administration appears to reshape key components of neurocognition - in particular, psychomotor speed, verbal memory, and verbal fluency. Notably, it has a sophisticated neurocognitive profile, such that while lithium impairs neurocognition across some domains, it seemingly preserves others - possibly those vulnerable to the effects of bipolar disorder. Furthermore, its effects are likely to be direct and indirect (via mood, for example) and cumulative with duration of treatment. Disentangling the components of neurocognition modulated by lithium in the context of a fluctuating and complex illness such as bipolar disorder is a significant challenge but one that therefore demands a stratified and systematic approach, such as that provided by the Lithium Battery. CONCLUSIONS In order to delineate the effects of lithium therapy on neurocognition in bipolar disorder within both research and clinical practice, a greater understanding and measurement of the relatively stable neurocognitive components is needed to examine those that indeed change with lithium treatment. In order to achieve this, we propose a Lithium Battery-Clinical and a Lithium Battery-Research that can be applied to these respective settings.

Individualized management of unipolar depression

The recommendations for the management of clinical depression in this supplement are spread across three papers which together, provide clinically pertinent advice in regards to pharmacological and psychological treatment and lifestyle interventions. The Clinical Practice Recommendations (CPR) for depression (1), published in 2009, put forward a formulaic approach for the assessment and management of unipolar (major) non-psychotic depression. Its simplicity and style ensured widespread implementation, especially in settings where there are considerable constraints of time and resources, such as primary care. In secondary and tertiary specialist settings, clinicians have more time to assess patients, but at the same time, usually deal with more complex presentations. In these instances, the management of depression usually necessitates a more individual and tailored approach to achieve an optimal outcome. Therefore, building on the CPR for depression, the recommendations in this supplement address in greater depth key aspects of managing clinical depression, and have been developed with experienced clinicians in mind (2). Separate articles, written by specialists with clinical expertise, address the main components of clinical management, Pharmacological management of unipolar depression (3), Psychological management of unipolar depression (4), and Lifestyle management of unipolar depression (5). Fundamental principles and strategies for successful management which form the foundation for subsequent recommendations are outlined in this brief introductory paper. Depression is a complex and heterogeneous condition that has multiple causes and variegated manifestations (6). Described both dimensionally and categorically (7), the unitary model that comprises mild, moderate, and severe depression is the framework we have chosen to elaborate upon so as to assist clinicians in tailoring clinical management. This severity-based schema is widely used by both specialists and general practitioners partly because in most clinical settings, the ‘subtypes’ of depression, such as melancholic and psychotic depression, are relatively uncommon. Early childhood experiences, in particular, psychological adversity (8–11), genetic vulnerability, and any number of medical conditions (12–14) can contribute to the pathogenesis of depression, making a single identifiable etiology a rarity. The interplay between psychological, biological, and lifestyle/social factors, and their influence on the development of depression, is not well understood, but within each factor, there are aspects that are important for diagnosis and treatment (15). Most cases of clinical depression necessitate lifelong management; thus, a chronic disease model should be adopted. The key issues that need to be considered within this model include education about the identification of early warning signs, the role of psychological interventions, the need for effective pharmacotherapy, the benefits of general medical health, and the importance of lifestyle changes.

Getting depression clinical practice guidelines right: time for change?

As part of a series of papers [‘Chronobiology of mood disorders’ Malhi & Kuiper. Acta Psychiatr Scand 2013;128(Suppl. 444):2–15; and ‘Its time we managed depression: The emerging role of chronobiology’ Malhi et al. Acta Psychiatr Scand 2013;128(Suppl. 444):1] examining chronobiology in the context of depression, this article examines recent western clinical practice guidelines (CPGs) for the treatment of depression with respect to the recommendations they make, in particular as regards chronobiological treatments, and briefly considers the implications of their methodology and approach.

Metabolite profiles in the anterior cingulate cortex of depressed patients differentiate those taking N-acetyl-cysteine versus placebo

Background: Increased oxidative stress is thought to contribute to the pathophysiology of major depressive disorder (MDD), which is in part due to diminished levels of glutathione, the primary anti-oxidant of the brain. Oral administration of N-acetyl-cysteine (NAC) replenishes glutathione and has therefore been shown to reduce depressive symptoms. Proton magnetic spectroscopy (1H-MRS) that allows quantification of brain metabolites pertinent to both MDD and oxidative biology may provide some novel insights into the neurobiological effects of NAC, and in particular metabolite concentrations within the anterior cingulate cortex (ACC) are likely to be important given the key role of this region in the regulation of affect. Objective: The aim of this study was to determine whether the metabolite profile of the ACC in MDD patients predicts treatment with adjunctive NAC versus placebo. Methods: This study was nested within a multicentre, randomized, double-blind, placebo-controlled study of MDD participants treated with adjunctive NAC. Participants (n = 76) from one site completed the spectroscopy component at the end of treatment (12 weeks). Spectra from a single-voxel in the ACC were acquired and absolute concentrations of glutamate (Glu), glutamate-glutamine (Glx), N-acetyl-aspartate (NAA) and myo-inositol (mI) were obtained. Binary logistic regression analysis was performed to determine whether metabolite profiles could predict NAC versus placebo group membership. Results: When predicting group outcome (NAC or placebo), Glx, NAA and mI were a significant model, and had 75% accuracy, while controlling for depression severity and sex. However, the Glu, NAA and mI profile was only predictive at a trend level, with 68.3% accuracy. For both models, the log of the odds of a participant being in the NAC group was positively related to NAA, Glx and Glu levels and negatively related to mI levels. Conclusion: The finding of higher Glx and NAA levels being predictive of the NAC group provides preliminary support for the putative anti-oxidative role of NAC in MDD.

Maintaining mood stability in bipolar disorder: a clinical perspective on pharmacotherapy

Bipolar disorder is defined by its poles, elevated mood or irritability characterises mania, and marked low mood and lack of energy typifies depression. Treatment of these acute states is necessary for the patients well-being but the major management challenge lies in reducing the frequency and severity of relapses and recurrences, and maintaining healthy mood. Typically, patients with bipolar disorder experience a recurrence every 17–30 months and have multiple episodes over the course of the illness.1 Successful management of this chronic, recurrent illness ultimately depends on maintaining long-term mood stability and preventing further episodes of depression and mania. It is therefore, all the more remarkable that maintenance therapies have received sparse attention; this is partly because longitudinal research is difficult to design and conduct. Therefore, clinicians often have to draw on experience regarding the long-term use of medications. This paper outlines the options for long-term pharmacotherapy of bipolar disorder and addresses common clinical questions regarding administration, drawing on a synthesis of current evidence for maintenance agents. To identify relevant evidence for the long-term pharmacological management of bipolar disorder electronic database searches were conducted using Summon (the University of Sydneys cross-search engine), OvidSP (including PubMed and PsycINFO) and Cochrane reviews. Searches were limited to the past 7 years. In addition existing systematic reviews were carefully scrutinised and their bibliographies drawn on to identify additional studies of note which were appraised alongside recent clinical trials. This review primarily included studies that were randomised, placebo-controlled, blinded, non-enriched and of sufficient duration to be regarded as maintenance therapy. Studies that did not meet all these principal requirements, such as those with external validity in non-randomised settings, were also reviewed cautiously and their findings were considered with limitations. Their impact in determining treatment decisions was moderated accordingly. The need to institute this process reflects the paucity of …

Agitation for recognition by DSM-5 mixed features specifier signals fatigue?

Australian & New Zealand Journal of Psychiatry, 49(6) Recently, the Diagnostic and Statistical Manual of Mental Disorders–Fifth Edition (DSM-5) introduced the mixed features specifier to describe the coterminous occurrence of manic and depressive symptoms (American Psychiatric Association [APA], 2013). Three symptoms from the opposing pole of the illness are needed to attach this specifier to an episode of hypomania, mania or depression. This means that a mixed mood state can occur in a variety of contexts with different symptom patterns defining mixed features (Malhi, 2013). However, the exclusion by DSM-5 of key symptoms as potential mixed features, on the assumption that they lack discrimination, has been challenged (Malhi et al., 2014), and an important clinical question as to which symptoms best define a mixed state remains unanswered (Reinares et al., 2015). Clinically, mixed features are likely to be nuanced by the context within which they arise, such that mixed features occurring in depression (Mixed Depression) will likely differ from those that occur in mania/ hypomania (Mixed Mania). Naturally, this presupposes that mixed mood states occur at the intersection of processes that underpin mania/hypomania and depression resulting in an admixture of symptoms from seemingly disparate poles. To investigate this, we prospectively compared patients with mixed features occurring in the context of depression or mania. A total of 72 consecutive admissions to a specialist Mood Disorders Unit (Northside Clinic – a private adult inpatient facility in Sydney) were assessed during the first week of their inpatient stay. Patients were defined as having a major depressive or manic/ hypomanic episode in accordance with DSM-5 and designated as having mixed features if they reported three or more symptoms from the opposite pole of illness – including the three excluded symptoms in DSM-5, distractibility, psychomotor agitation and irritability. Diagnosis was assigned following a comprehensive clinical assessment at the time of admission using DSM diagnostic criteria, an in-depth review by an experienced consultant and a further appraisal in an extensive multidisciplinary review involving up to 10 clinicians and three psychologists within the first week of admission. A total of 61 patients met criteria for major depressive disorder (MDD), and of these, 10 reported experiencing symptoms of mania and met criteria for Mixed Depression (depression with mixed features). The remaining 51 patients reported only depressive symptoms. An additional 11 patients met criteria for a manic episode and also reported experiencing depressive symptoms, and were therefore designated as having Mixed Mania (mania with mixed features). The profile of symptoms endorsed by the two mixed features groups was compared using a series of chisquare analyses. Among the symptoms of depression, only two symptoms distinguished the mixed groups (refer to Figure 1(a) and Table 1). Patients with Mixed Depression endorsed fatigue/loss of energy (80%) significantly more frequently than those with Mixed Mania (27%). Conversely, psychomotor agitation was significantly more common in those with Mixed Mania (91%) as compared to those with Mixed Depression (50%). In contrast to depressive symptoms, virtually all the Agitation for recognition by DSM-5 mixed features specifier signals fatigue?