The science and practice of lithium therapy

Introduction: Despite more that 60 years of clinical experience, the effective use of lithium for the treatment of mood disorder, in particular bipolarity, is in danger of becoming obsolete. In part, this is because of exaggerated fears surrounding lithium toxicity, acute and long-term tolerability and the encumbrance of life-long plasma monitoring. Recent research has once again positioned lithium centre stage and amplified the importance of understanding its science and how this translates to clinical practice.

Objective: The aim of this paper is to provide a sound knowledge base as regards the science and practice of lithium therapy.

Method: A comprehensive literature search using electronic databases was conducted along with a detailed review of articles known to the authors pertaining to the use of lithium. Studies were limited to English publications and those dealing with the management of psychiatric disorders in humans. The literature was synthesized and organized according to relevance to clinical practice and understanding.

Results: Lithium has simple pharmacokinetics that require regular dosing and monitoring. Its mechanisms of action are complex and its effects are multi-faceted, extending beyond mood stability to neuroprotective and anti-suicidal properties. Its use in bipolar disorder is under-appreciated, particularly as it has the best evidence for prophylaxis, qualifying it perhaps as the only true mood stabilizer currently available. In practice, its risks and tolerability are exaggerated and can be readily minimized with knowledge of its clinical profile and judicious application.

Conclusion: Lithium is a safe and effective agent that should, whenever indicated, be used first-line for the treatment of bipolar disorder. A better understanding of its science alongside strategic management of its plasma levels will ensure both wider utility and improved outcomes.

Treatment and outcomes of an Australian cohort of outpatients with bipolar 1 or schizoaffective disorder over twenty-four months : implications for clinical practice

Background The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with ‘real-world’ treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication.

Methods Participants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale – Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data.

Results On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts.

Conclusions Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.

Mania : diagnosis and treatment recommendations

This article provides recommendations for the diagnosis and treatment of mania, which characterizes bipolar I disorder (BD I). Failure to detect mania leads to misdiagnosis and suboptimal treatment. To diagnose mania, clinicians should include a detailed mood history within their assessment of patients presenting with depression, agitation, psychosis or insomnia. With regards to treatment, by synthesizing the findings from recent treatment guidelines, and reviewing relevant literature, this paper has distilled recommendations for both acute and long-term management. Antimanic agents including atypical antipsychotics and traditional mood stabilizers are employed to reduce acute manic symptoms, augmented by benzodiazepines if needed, and in refractory or severe cases with behavioural and/or psychotic disturbance, electroconvulsive therapy may occasionally be necessary. Maintenance/prophylaxis therapy aims to reduce recurrences/relapse, for which the combination of psychological interventions with pharmacotherapy is beneficial as it ensures adherence and monitoring of tolerability.

Effects of N-acetyl cysteine on cognitive function in bipolar disorder

Aims

Bipolar disorder is characterized by progressive changes in cognition with declines in executive functioning, memory and sustained attention. Current pharmacotherapies for bipolar disorder target mood symptoms but have not addressed these cognitive changes resulting in euthymic individuals who still experience cognitive deficits. N-acetyl cysteine (NAC) has been shown to have effects on antioxidant status, glutamate transmission, inflammation and neurogenesis. Adjunctive treatment with NAC improves the symptoms experienced by those with bipolar disorder, particularly depression, and it was hypothesized that cognition may also be improved following NAC treatment.
Methods

As part of a larger randomized, double-blind, placebo-controlled trial, participants in the current report were tested at baseline and 6 months to assess changes in cognitive function following either 2000 mg of NAC daily or placebo.
Results

This study failed to find changes in cognitive function following treatment with NAC compared to placebo.
Conclusions

While an important pilot study, this study had a small sample size and included a limited battery of cognitive tests. Further investigations on the effects of NAC on cognitive performance in bipolar disorder are required.

The determinants of happiness

Measures of mood happiness are increasingly used to assess the development and progress of nations. The limitations of this approach are, however, considerable. Within developed nations population happiness is quite resistant to change, despite major improvements in the objective standard of living. The reason, we propose, is that levels of subjective wellbeing are psychologically managed for each person, to be held around their genetically determined 'set-point'. This homeostatic management system acts to keep people feeling normally positive about them self, and so resists change. Thus, the search for 'happiness determinants' in the form of objective circumstances is often unrewarding in normally functioning samples. Due to homeostatic resistance, changes in objective variables will have weak effects on mood happiness. If large changes in mood happiness are found, they can be attributed to homeostatic failure and represent pathology.

The contribution of job and partner satisfaction to the homeostatic defense of subjective wellbeing

Two studies investigate subjective wellbeing (SWB) homeostasis. The first investigates the contribution of job satisfaction (JS) and partner satisfaction (PS) to the homeostatic defense of SWB. The extant model of homeostasis does not include either variable. The second study investigates the relationship between Homeostatically Protected Mood (HPMood) and other factors involved in the homeostatic model. It has been proposed that HPMood is the basic, biologically determined, positive mood that saturates SWB and other related variables, and forms the basis of the SWB set-point. Thus, if HPMood is an individual difference and it perfuses other homeostatic variables, then HPMood should be responsible for much of the shared variance between such variables. Two comparative samples are involved. One is a group of 171 Hong Kong Chinese recruited through convenience sampling. The other is a group of 343 Australians recruited via a general population survey. Results indicate that both JS and PS predict significant variance in Global Life Satisfaction beyond the existing factors in the homeostatic model. It is also found that, after controlling for the effect of HPMood, the strength of correlations between SWB and other homeostatic variables is significantly diminished. The implications of these findings are discussed.

Intergenerational effects of the Holocaust : subjective well-being in the offspring of survivors

Offspring of Holocaust survivors have been the subject of much research into how traumatic events affect future generations. This study considers the effects of the Holocaust on the well-being rather than trauma of offspring of Holocaust survivors in Australia. 285 Jewish participants completed a questionnaire to measure components of subjective well-being. Analyses revealed that offspring of Holocaust survivors reported lower general positive mood than non-OHS. This result was limited to offspring of Holocaust survivors with two survivor parents. These findings imply that effects of the Holocaust are transmitted to nonclinical offspring of Holocaust survivors and that the number of survivor parents is a crucial determinant in understanding these transgenerational outcomes.

A sentiment-aware approach to community formation in social media

Participating in a community exemplifies the aspect of sharing, networking and interacting in a social media system. There has been extensive work on characterising on-line communities by their contents and tags using topic modelling tools. However, the role of sentiment and mood has not been studied. Arguably, mood is an integral feature of a text, and becomes more significant in the context of social media: two communities might discuss precisely the same topics, yet within an entirely different atmosphere. Such sentiment-related distinctions are important for many kinds of analysis and applications, such as community recommendation. We present a novel approach to identification of latent hyper-groups in social communities based on users’ sentiment. The results show that a sentiment-based approach can yield useful insights into community formation and metacommunities, having potential applications in, for example, mental health—by targeting support or surveillance to communities with negative mood—or in marketing—by targeting customer communities having the same sentiment on similar topics.

The impact of statins on psychological wellbeing : a systematic review and meta-analysis

Background : Cholesterol-lowering medications such as statins have anti-inflammatory and antioxidant properties, which may be beneficial for treating depression and improving mood. However, evidence regarding their effects remains inconsistent, with some studies reporting links to mood disturbances. We aimed to conduct a meta-analysis to determine the impact of statins on psychological wellbeing of individuals with or without hypercholesterolemia.

Methods : Articles were identified using medical, health, psychiatric and social science databases, evaluated for quality, and data were synthesized and analyzed in RevMan-5 software using a random effects model.

Results : The 7 randomized controlled trials included in the analysis represented 2,105 participants. A test for overall effect demonstrated no statistically significant differences in psychological wellbeing between participants receiving statins or a placebo (standardized mean difference (SMD) = -0.08, 95% CI -0.29 to 0.12; P = 0.42). Sensitivity analyses were conducted to separately analyze depression (n = 5) and mood (n = 2) outcomes; statins were associated with statistically significant improvements in mood scores (SMD = -0.43, 95% CI -0.61 to -0.24).

Conclusions : Our findings refute evidence of negative effects of statins on psychological outcomes, providing some support for mood-related benefits. Future studies could examine the effects of statins in depressed populations.

Aspirin : a review of its neurobiological properties and therapeutic potential for mental illness

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- 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.

Integrating psychologists into the Canadian health care system : the example of Australia

Canada and Australia share many similarities in terms of demographics and the structure of their health systems; however, there has been a divergence in policy approaches to public funding of psychological care. Recent policy reforms in Australia have substantially increased community access to psychologists for evidence-based treatment for high prevalence disorders. In Canada, access remains limited with the vast majority of consultations occurring in the private sector, which is beyond the reach of many individuals due to cost considerations. With the recent launch of the Mental Health Commission of Canada, it is timely to reflect on the context of the current Canadian and Australian systems of psychological care. We argue that integrating psychologists into the publicly-funded primary care system in Canada would be feasible, beneficial for consumers, and cost-effective.

Adult attachment insecurities are associated with obsessive compulsive disorder

Objectives.  Obsessive compulsive disorder (OCD) is one of the most disabling and highly prevalent anxiety disorders (ADs). Current cognitive models of OCD implicate views about the self and world in the maintenance of the disorder. However, little research has focused on issues that may lead to vulnerability to such views. In particular, a person's attachment insecurities (attachment anxiety, avoidance) may be important risk factors increasing the likelihood of such non-adaptive perceptions (Doron & Kyrios, 2005).

Design.  Participants meeting criteria for OCD were compared with cohorts meeting criteria for other ADs and healthy controls on a range of measures including adult attachment, OC symptoms, cognitions, and mood.

Methods.  Diagnosis of the clinical groups was established using the Anxiety Disorders Interview Schedule for DSM-IV (Brown, Di Nardo, & Barlow, 1994). The clinical relevance of attachment insecurities was ascertained by comparing their prevalence in an OCD sample (N= 30), an ADs sample (N= 20), and a community sample (N= 32). Results.  Attachment anxiety was significantly higher in individuals with OCD, even when controlling for depression.

Conclusions.  Addressing attachment anxiety in individuals presenting with OCD may be important for enhancing therapeutic outcomes. However, findings are based on cross-sectional data that preclude conclusions relating to causal influence.