Restless leg syndrome caused by olanzapine: a case series

Restless leg syndrome (RLS) is a common disorder associated with significant distress. We report three cases of drug induced RLS caused by olanzapine. In each case, RLS commenced after initiation of treatment with olanzapine and resolved after ceasing olanzapine. All three patients were subsequently treated with other atypical antipsychotics, risperidone, quetiapine or aripiprazole, without re-emergence of RLS. RLS is associated with central dopaminergic dysfunction. Dopamine agonists and l-dopa reduce the symptoms of RLS, and some agents that block the dopaminergic system aggravate RLS. Greater awareness of potential causes of RLS, and its differentiation from akathisia and illness related agitation might help in reducing the distress associated with it and improving patient compliance.

Dopamine dysregulation syndrome : implications for a dopamine hypothesis of bipolar disorder

Objective: Rational therapeutic development in bipolar is hampered by a lack of pathophysiological model. However, there is a wealth of converging data on the role of dopamine in bipolar disorder. This paper therefore examines the possibility of a dopamine hypothesis for bipolar disorder.

Method: A literature search was conducted using standard search engines Embase, PyschLIT, PubMed and MEDLINE. In addition, papers and book chapters known to the authors were retrieved and examined for further relevant articles.

Results: Collectively, in excess of 100 articles were reviewed from which approximately 75% were relevant to the focus of this paper.

Conclusion: Pharmacological models suggest a role of increased dopaminergic drive in mania and the converse in depression. In Parkinson’s disease, administration of high-dose dopamine precursors can produce a ‘maniform’ picture, which switches into a depressive analogue on withdrawal. It is possible that in bipolar disorder there is a cyclical process, where increased dopaminergic transmission in mania leads to a secondary down regulation of dopaminergic receptor sensitivity over time. This may lead to a period of decreased dopaminergic transmission, corresponding with the depressive phase, and the repetition of the cycle. This model, if verified, may have implications for rational drug development.

Quality of life in restless legs syndrome: A systematic review of clinical trials and a critical review of instruments

Restless legs syndrome (RLS) is a neurological movement disorder characterized by sensory symptoms and motor disturbances. While the underlying cause remains unknown, it is suggested that 20–25% of people with RLS are affected seriously enough to require pharmacological treatment. Dopamine agonists (DAs) are the most common treatment and act by increasing the low levels of dopamine to which RLS is often attributed. A growing literature highlights the debilitating and distressing nature of this condition from the patient's perspective. While sleep problems are most commonly reported, the impact of RLS on quality of life (QOL) is wide ranging, affecting relationships with partners, sex life, family life, social life, leisure activities, friendships, everyday activities, concentration, travel, career/work, sleep, and health.

We conducted a systematic review of clinical trials in which DAs have been evaluated in terms of RLS-specific QOL, i.e. their impact on the QOL of people with RLS, and critically reviewed the development history and measurement properties of RLS-specific QOL instruments.

A systematic search using terms synonymous with RLS, DAs and QOL was conducted using Scopus software, which includes MEDLINE, PsycINFO, EMBASE, and CINAHL. Our search covered publications from 2000 (prior to which RLS-specific QOL measures did not exist) to August 2009. Trials were included in our review if they evaluated DAs for the treatment of adults with RLS and reported evaluation using an RLS-specific QOL measure. We also ran citation searches to identify papers reporting the development history and measurement properties of the identified RLS-specific QOL instruments.

Three measures of RLS-specific QOL have been developed in recent years and are reviewed here: the Restless Legs Syndrome Quality of Life (RLSQOL) questionnaire, the Restless Legs Syndrome Quality of Life Instrument (RLS-QLI), and the Quality of Life Restless Legs Syndrome (QOL-RLS) measure. Critical review indicates that each has limitations (particularly in terms of published developmental history and content validity). Eleven trials of DAs were identified that included assessment of RLS-specific QOL (nine using the RLSQOL and two using the QOL-RLS). In all studies, significant improvements in RLS-specific QOL were observed, although these were mostly short term (12 weeks) and large placebo effects were also noted.

In people with RLS, the use of DAs has been shown to improve RLS-specific QOL. Longer-term, large-scale studies may be needed to confirm these findings and demonstrate statistically significant improvements in RLS-specific QOL at lower doses. Further development of the RLS-specific QOL measures is needed to ensure that the full impact of RLS (and the full benefit of new treatments) on aspects of life identified as important to individuals is captured in future studies.

The suitability of polycystic ovary syndrome-specific questionnaires for measuring the impact of PCOS on quality of life in clinical trials

Objectives: Generic patient-reported outcome (PRO) measures underestimate the impact of polycystic ovary syndrome (PCOS) on quality of life (QoL). The aim of this review was to identify PCOS-specific QoL measures and establish whether their development history and measurement properties support their use in clinical trials.

Methods: A systematic search was conducted using terms synonymous with “PCOS” and “QoL.” Following identification of measures, further searches were undertaken using the questionnaire name and abbreviation to explore its use, development history, and demonstrated measurement properties.

Results: Of 56 abstracts screened, 21 reported using PRO measures. One PCOS-specific QoL measure was identified: the PolyCystic Ovary Syndrome Questionnaire (PCOSQ). Nine papers show that the PCOSQ’s development history is somewhat incomplete, and that it does not have good content validity. The PCOSQ subscales demonstrate acceptable levels of reliability (0.70–0.97) and partial known-groups validity as well as convergent/divergent validity with other PRO instruments. Responsiveness
to change is variable and minimally important differences have not been established.

Conclusions: The PCOSQ is the only condition-specific measure of the impact of PCOS on QoL. Additional research is required to ensure its comprehensiveness, sensitivity, and to guide interpretation prior to including in clinical trials.

Second city syndrome : media reportage of urban rankings

This paper investigates the popularly reported phenomenon of city rankings and, in particular, the category of the ‘second city’ that regularly features as part of this prolific evaluative discourse. Our paper proposes that the category ‘second city’ has a specific analytical value that has to date been underestimated in academic accounts (particularly in the confusing, interchangeable use of ‘second-tier’, ‘secondary’ and ‘second cities’ in the dominant urban studies literature). Instead, we are interested in how second city identifications permeate popular forms of urban comparison in some places.

The example of Melbourne (Australia) is used to investigate how second city identities are historically sustained through evaluative media representations. In particular we examine how, through their reportage of various world city rankings, metropolitan newspapers reveal and articulate a ‘second city consciousness’. How do media institutions, and more specifically, media reports, frame these urban rankings in such a way to confirm Melbourne’s similarity to other globalised places (i.e. proposing its status as a ‘world city’), yet also as a city also marked by a particular historical specificity? And how do they draw on already existing popular and political traditions of urban comparison? This article will identify and analyse the role of newspapers in perpetuating both formal and informal urban comparisons.