The management of bipolar disorder in primary care : a review of existing and emerging therapies

Recent evidence suggests that the prevalence of bipolar disorder is as much as fivefold higher than previously believed, and may amount to nearly 5% of the population, making it almost as common as unipolar major depression. It is, therefore, not unrealistic to assume that primary care or family physicians will frequently encounter bipolar patients in their practice. Such patients may present with a depressive episode, for a variety of medical reasons, for longer-term maintenance after stabilization, and even with an acute manic episode. Whatever the reason, a working knowledge of current trends in the acute and longer-term management of bipolar disorder would be helpful to the primary care physician. In addition, an understanding of important side-effects and drug interactions that occur with drugs used to treat bipolar disorder, which may be encountered in the medical setting, are paramount. This paper will attempt to review existing and emerging therapies in bipolar disorder, as well as their common drug interactions and side-effects.

The validity and internal structure of the bipolar depression rating scale (BDRS): data from a clinical trial of N-acetylcysteine as adjunctive therapy in bipolar disorder

Background: The phenomenology of unipolar and bipolar disorders differ in a number of ways, such as the presence of mixed states and atypical features. Conventional depression rating instruments are designed to capture the characteristics of unipolar depression and have limitations in capturing the breadth of bipolar disorder.

Method: The Bipolar Depression Rating Scale (BDRS) was administered together with the Montgomery Asberg Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) in a double-blind randomised placebo-controlled clinical trial of N-acetyl cysteine for bipolar disorder (N = 75).

Results: A factor analysis showed a two-factor solution: depression and mixed symptom clusters. The BDRS has strong internal consistency (Cronbach's alpha = 0.917), the depression cluster showed robust correlation with the MADRS (r = 0.865) and the mixed subscale correlated with the YMRS (r = 0.750).

Conclusion: The BDRS has good internal validity and inter-rater reliability and is sensitive to change in the context of a clinical trial.

Health-related quality of life and functioning in bipolar disorder : the impact of pharmacotherapy

Bipolar disorder has a major deleterious impact on many aspects of a patient's functioning and health-related quality of life. Although the formal measurement of these deficits has been neglected until recently, many well-designed trials now include an assessment of functioning and health-related quality of life using one or more rating scales. This review describes recent developments in the measurement of functioning and health-related quality of life in bipolar disorder, and discusses the evidence that medications that improve symptoms in bipolar disorder also offer clinically relevant benefits in functioning and health-related quality of life. Direct comparisons of the benefits of medications including atypical antipsychotics are problematic due to differences in trial populations, study durations and rating scales. Data from quetiapine trials indicate that this medication offers prompt and sustained improvement of functioning in patients with mania and enhancement of health-related quality of life in patients with bipolar depression, to accompany the significant improvements in mood episodes.

The safety of medications for the treatment of bipolar disorder during pregnancy and the peurperium

Risks associated with pharmacological treatment of bipolar disorder are heightened during reproductive events. Treatments need to be planned with the mutual agreement of both the treating physician and the patient and tailored to the needs of the individual so as to minimise risk while providing adequate treatment. Conventional treatments have all been associated with teratogeny in first trimester exposure, lithium with cardiac malformation and valproate and carbamazepine with neural tube malformations. There have been an insufficient number of first trimester exposures to the newer anticonvulsant mood stabilisers, lamotrigine and oxcarbazepine, to determine whether there is a safety advantage in switching to these agents. Increasingly, atypical antipsychotics are being suggested as useful agents for the treatment of bipolar disorder. While not known to be teratogenic, there are other reproductive safety concerns associated with these agents. Bipolar disorder patients may be prescribed antidepressants, and many of these agents are associated with a low safety risk during reproductive events, however data regarding use of these agents are currently equivocal. Adverse outcomes from inadequate pharmacological prophylaxis have been documented for both the mother and the baby. Risks and benefits need to be carefully balanced based on an accurate review of the evidence.

Olanzapine / fluoxetine combination for treatment resistant depression : efficacy and clinical utility

Antidepressant monotherapy is a first-line treatment for depression; however, not all sufferers will adequately respond to treatment. When treating a patient with treatment-resistant depression, the clinician needs to consider all factors which may contribute to an inadequate response to an antidepressant. These include accuracy of diagnosis and medication adherence, as well as the patient’s personality, lifestyle, life events and social circumstances. If it is determined that treatment resistance is due to failure of efficacy of antidepressant monotherapy, then an augmentation strategy using an atypical antipsychotic may be considered. Treatment using olanzapine/fluoxetine combination (OFC) is one of many options. Four randomized, acute-phase trials have suggested OFC is useful for reducing Montgomery–Åsberg Depression Rating Scale scores after inadequate response to antidepressant monotherapy. OFC has been useful at doses of olanzapine/fluoxetine 6/25, 6/50, 12/25 and 12/50 mg/day, with 1/5 mg/day suggested to be an ineffective dose. Treatment with OFC has been associated with some side effects, including weight gain and the metabolic syndrome, somnolence, dry mouth, increased appetite and headache. Treatment decisions therefore need to be made to balance the risks and benefits.

Combination pharmacotherapy in unipolar depression

It is estimated that between 60 and 80% of those with major depressive disorder do not achieve full symptomatic remission from first-line antidepressant monotherapy. Residual depressive symptoms substantially impair quality of life and add to the risk of recurrence. It is now clear that depression would benefit from more vigorous treatment, in order to ameliorate its disease burden. While there are established algorithms in situations of treatment resistance, the use of combination pharmacotherapy in unipolar depression is a relatively under-investigated area of treatment and may be an effective and tolerable strategy that maximizes the available resources. This paper reviews the current evidence for combination pharmacotherapy in unipolar depression and discusses its clinical applications.

Ecological notes on the East Gippsland burrowing crayfish Engaeus orientalis, including burrow structure and associated fauna

Despite Australia having a high diversity of freshwater crayfish species, the ecology of many of these species remains poorly known, particularly burrowing crayfish of the genus Engaeus. Biological information on colour, behaviour, burrow structure, associated burrow fauna and habitat of the East Gippsland Burrowing Crayfish Engaeus orientalis obtained during incidental observations in 2007 and 2008 is provided. The burrow structure took the form of radiating runways under a rock slab, while the burrow location was in a semi-disturbed site away from water. Both are atypical for this species.

Aiming for change by degrees

Our federal Education Minister believes too many Australians are falling through the cracks, writes Joanna Mather.

Addressing a group of doctoral graduates in Melbourne recently, federal Education Minister Julia Gillard used Barack Obama's election victory in the US to drive home the social and economic imperatives for getting more poor and disadvantaged Australians into universities.

Manipulating Islam and democracy in Iraq’s ‘Pluralised Authoritarianism’

With the realisation that the initial motives for the 2003 invasion of Iraq – Saddam’s alleged stockpile of Weapons of Mass Destruction (WMD) and his links to Al-Qaeda – were grievous intelligence errors the Bush administration, with varying degrees of success, were able to spin the war’s rasion d’etre and redefine the parameters of victory. A central tenet of this approach was to begin speaking about democracy as if it had always been one of the aims of the war itself. For the first few years, the effort to democratise Iraq appeared to gain some credible momentum: a complex array of political, religious and ethno-sectarian factions formed political parties and civil society movements; uncensored news was enthusiastically consumed across the nation; Iraqi citizens took to the streets to protest key government decisions; and millions of Iraqis voted in relatively free and fair national elections (Davis, 2004, 2007, Isakhan, 2008, 2011b). Central to each of these developments were various Iraqi religious establishments – but especially those of the Shia Arab population of Iraq – who saw no distinction between their Islamic faith and the notion of democracy. Not surprisingly, a body of literature has emerged which has been very optimistic about Iraq’s engagement with both ‘Islam’ and ‘democracy’ in the post-Baathist period, while acknowledging the challenges it faces in creating a stable, egalitarian and democratic society (Al-Musawi, 2006, Cole, 2006, Davis, 2005, Dawisha, 2009, Isakhan, 2011a, Stansfield, 2007).

However, there have been virtually no studies which have sought to question this optimism in the light of more recent events. Addressing this lacuna, this paper documents the last few years (2006- 2011) which have seen many elements within the Iraqi political elite – most notably the Maliki government and his State of Law Coalition (SLC) – demonstrate what has been referred to in literature on other Arab states alternatively as ‘liberalised autocracy’ (Brumberg, 2002), ‘semi-authoritarianism’ (Ottaway, 2003) or ‘pluralised authoritarianism’ (Posusney and Angrist, 2005). That is to say, that these states consolidate their incumbency while putting in place measures that can be considered more or less liberal. To do this, the regime actually utilises (and controls) nominally democratic mechanisms such as elections, media freedoms, political opposition and civil society as part of their strategy to retain power. Of particular interest here are the ways in which the Maliki government – and Shia Arab Iraqi political factions more broadly – have manipulated both ‘Islam’ and ‘democracy’ towards such ‘pluralised authoritarianism’.

The Liam Jurrah story : from Yuendumu to the MCG

Known as the 'Warlpiri Warrior,' the 'Jurrahcane' and 'Cougar,' Liam Jurrah is a rising star of the AFL, known for his startling displays of skill, artistry and the 'deadly' impact of his football ability. But despite Liam's prodigious talent, he is a relative newcomer to the AFL. This book tells the incredible journey travelled by Liam, a fully initiated Warlpiri man, from the remote Aboriginal desert community of Yuendumu to the MCG, as the first of his kind to play football at an elite level. Along the way the book describes how the author and his family came to understand and treasure the richness of Liam's Warlpiri culture.

Effects of exercise on the isoelectric patterns of erythropoietin

Objectives: Recombinant erythropoietin has a strong impact on aerobic power and is therefore one of the most potent doping agents in endurance sports. The anti-doping control of this synthetic hormone relies on the detection, in the urine, of its isoelectric pattern, which differs from that of the corresponding natural hormone, the latter being typically more acidic than the former. However, a small number of natural urinary patterns, referred to as atypical patterns, are less acidic than the dominant form. Based on anecdotal evidence, the occurrence of such patterns seems to be related to particular strenuous exercises. This study aimed to demonstrate this relation using a strenuous exercise protocol.

Design: Seven athletes took part in a training protocol including a series of supramaximal short-duration exercises. Urine and blood samples were collected throughout the protocols.

Settings: World Cycling Center, Aigle, Switzerland, and research laboratories.

Participants: Seven top-level athletes (cyclists) were involved in this study.

Main Outcome Measures: Erythropoietin (EPO) isoelectric patterns were obtained by submitting blood and urine samples to isoelectric focusing. Additional protein dosages were performed.

Results: Supramaximal short-duration exercises induced the transformation of typical urinary natural EPO patterns into atypical ones. None of the obtained atypical patterns fulfilled the 3 criteria mandatory for reporting an adverse analytical finding. Serum EPO patterns were not affected by the exercises that caused the transformation of urinary patterns.

Conclusion: An exercise-induced transient renal dysfunction is proposed as a hypothetic explanation for these observations that rely on parallel investigations of proteinuria in the same samples.

Brief report : maltreatment in childhood and body concerns in adulthood

Objective: We examined the relationship between maltreatment in childhood and body concerns in adulthood.

Method: A community sample of 156 women and 143 men completed measures of maltreatment – frequency of sexual abuse, physical abuse, physical neglect, emotional abuse and emotional neglect – in childhood. They also reported current dissatisfaction with body weight and shape and drive for thinness and drive for muscle.

Results and conclusions: Childhood maltreatment was associated with drive for muscle in women and body dissatisfaction and drive for thinness in men. The results provide some evidence that adverse conditions in childhood can be associated with gender-atypical body concerns in adulthood.

Nef binds p6* in gagpol during replication of human immunodeficiency virus type 1

The atypical Nef protein (NefF12) from human immunodeficiency virus type 1 strain F12 (HIV-1F12) interferes with virion production and infectivity via a mysterious mechanism. The correlation of these effects with the unusual perinuclear subcellular localization of NefF12 suggested that the wild-type Nef protein could bind to assembly intermediates in late stages of viral replication. To test this hypothesis, Nef from HIV-1NL4-3 was fused to an endoplasmic reticulum (ER) retention signal (NefKKXX). This mutant NefKKXX protein recapitulated fully the effects of NefF12 on Gag processing and virion production, either alone or as a CD8 fusion protein. Importantly, the mutant NefKKXX protein also localized to the intermediate compartment, between the ER and the trans-Golgi network. Furthermore, Nef bound the GagPol polyprotein in vitro and in vivo. This binding mapped to the C-terminal flexible loop in Nef and the transframe p6* protein in GagPol. The significance of this interaction was demonstrated by a genetic assay in which the release of a mutant HIV-1 provirus lacking the PTAP motif in the late domain that no longer binds Tsg101 was rescued by a Nef.Tsg101 chimera. Importantly, this rescue as well as incorporation of Nef into HIV-1 virions correlated with the ability of Nef to interact with GagPol. Our data demonstrate that the retention of Nef in the intermediate compartment interferes with viral replication and suggest a new role for Nef in the production of HIV-1.

Description of systenobythere gen. nov. (Ostracoda, Crustacea) from the late miocene of southeastern Australia with comments on its problematical taxonomic and palaeoecological affinities

A new ostracod genus and species, Systenobythere archboldi, is described from late Miocene open neritic strata of southeastern Australia. Specimens occur in argillaceous glauconitic sands deposited in offshore continental shelf settings that were periodically influenced by coastal upwelling. Systenobythere archboldi possesses an adductor muscle scar pattern typical of the Bythocytheridae, but has a pentodont hinge and sieve-type normal pore canals atypical of this family.