Joe Reilly

Renal failure in lithium-treated bipolar disorder: a retrospective cohort study.

Objective Lithium users are offered routine renal monitoring but few studies have quantified the risk to renal health. The aim of this study was to assess the association between use of lithium carbonate and incidence of renal failure in patients with bipolar disorder. Methods This was a retrospective cohort study using the General Practice Research Database (GPRD) and a nested validation study of lithium exposure and renal failure. A cohort of 6360 participants aged over 18 years had a first recorded diagnosis of bipolar disorder between January 1, 1990 and December 31, 2007. Data were examined from electronic primary care records from 418 general practices across the UK. The primary outcome was the hazard ratio for renal failure in participants exposed to lithium carbonate as compared with non-users of lithium, adjusting for age, gender, co-morbidities, and poly-pharmacy. Results Ever use of lithium was associated with a hazard ratio for renal failure of 2.5 (95% confidence interval 1.6 to 4.0) adjusted for known renal risk factors. Absolute risk was age dependent, with patients of 50 years or older at particular risk of renal failure: Number Needed to Harm (NNH) was 44 (21 to 150). Conclusions Lithium is associated with an increased risk of renal failure, particularly among the older age group. The absolute risk of renal failure associated with lithium use remains small.

Personality disorder prevalence in psychiatric outpatients: a systematic literature review.

INTRODUCTION A systematic literature review of studies measuring the prevalence of personality disorder in community secondary care is needed to identify both the met and unmet needs and plan services accordingly. METHODS PsycINFO, MEDLINE and EMBASE databases were searched using NHS Evidence. Only studies assessing overall personality disorder prevalence within help-seeking, outpatient populations were included. Papers were excluded for focusing solely on the prevalence of specific personality disorders or comorbid prevalence within specific populations. RESULTS A total of 269 papers were identified. Nine papers met criteria and were critically appraised, showing a high level of heterogeneity with regards to methods, inclusion criteria, source of information, time of assessment, instruments used and overall quality of research. Prevalence estimates in Europe varied between 40% and 92%, were more consistently approximated between 45% and 51% in the USA and differed significantly in the two Asian studies: 1.07% (India) and 60% (Pakistan). CONCLUSIONS The prevalence of personality disorder in community mental health care appears to be substantial, but better estimates will only emerge from high quality studies with greater consistency of method. Implementing screening tools within outpatient or community services may result in high rates of personality disorder identification, with both clinical and service implications.

Lithium and chronic kidney disease

Lithium use is associated with renal disorder and renal failure; this article offers guidance on monitoring, drug interactions, and when to consider stopping the drug

Balancing harms in support of recovery

Abstract Background: Harm in mental health has traditionally been viewed as “unambiguous” and measured in terms of suicide, self-harm, self-neglect and violence. In order to develop an organisational patient safety strategy, one Trust engaged with service users, carers and senior clinicians and managers in order to understand how they define harm. Aim: To explore the meaning of harm in a mental health and learning disabilities setting. Method: This paper describes the outcome of service improvement work with service users, carers, senior clinicians and managers at one Trust to determine what harm meant to them. Results: Harm is a concept which is broader than elements currently seen within organisational patient safety metrics and clinical risk assessments. Conclusions: Taking into account the diverse feedback received about what constitutes harm, a more inclusive definition emerges which could be incorporated into a new framework for risk management, balancing risk of harms across multiple dimensions. This approach has the potential to bring together consideration of the risk and recovery agendas.

Psycho-education with problem solving (PEPS) therapy for adults with personality disorder: A pragmatic multi-site community-based randomised clinical trial

BackgroundImpairment in social functioning is a key component of personality disorder. Therefore psycho-education and problem solving (PEPS) therapy may benefit people with this disorder. Psycho-education aims to educate, build rapport, and motivate people for problem solving therapy. Problem solving therapy aims to help clients solve interpersonal problems positively and rationally, thereby improving social functioning and reducing distress. PEPS therapy has been evaluated with community adults with personality disorder in an exploratory trial. At the end of treatment, compared to a wait-list control group, those treated with PEPS therapy showed better social functioning, as measured by the Social Functioning Questionnaire (SFQ). A definitive evaluation is now being conducted to determine whether PEPS therapy is a clinically and cost-effective treatment for people with personality disorderMethodsThis is a pragmatic, two-arm, multi-centre, parallel, randomised controlled clinical trial. The target population is community-dwelling adults with one or more personality disorder, as identified by the International Personality Disorder Examination (IPDE). Inclusion criteria are: Living in the community (including residential or supported care settings); presence of one or more personality disorder; aged 18 or over; proficiency in spoken English; capacity to provide informed consent. Exclusion criteria are: Primary diagnosis of a functional psychosis; insufficient degree of literacy, comprehension or attention to be able to engage in trial therapy and assessments; currently engaged in a specific programme of psychological treatment for personality disorder or likely to start such treatment during the trial period; currently enrolled in any other trial. Suitable participants are randomly allocated to PEPS therapy plus treatment as usual (TAU) or TAU only. We aim to recruit 340 men and women. The primary outcome is social functioning as measured by the SFQ. A reduction (i.e., an improvement) of 2 points or more on the SFQ at follow-up 72 weeks post-randomisation is our pre-specified index of clinically significant change. Secondary outcomes include a reduction of unscheduled service usage and an increase in scheduled service usage; improved quality of life; and a reduction in mental distress.DiscussionPEPS therapy has potential as an economical, accessible, and acceptable intervention for people with personality disorder. The results from this randomised controlled trial will tell us if PEPS therapy is effective and cost-effective. If so, then it will be a useful treatment for inclusion in a broader menu of treatment options for this group of service users.Trial RegistrationInternational Standard Randomised Controlled Trial Number - ISRCTN70660936

Are mood stabilisers helpful in treatment of borderline personality disorder

Borderline personality disorder is a severe mental health problem that affects around 1% of people.1 It is characterised by intense unstable relationships, impulsivity, and chronic feelings of emptiness.2 Affective instability is also a core symptom, with marked fluctuations in mood, which may switch rapidly from hopelessness and despair to feeling irritable, angry, and out of control. People with this condition have high rates of deliberate self harm and a rate of suicide that is 20 times that of the general population.3 Although psychological treatments have been shown to improve the mental health of people with borderline personality disorder,4 many people do not engage with such treatments, and as many as half of those who do engage drop out before treatment has been completed.5 People with borderline personality disorder are more likely to experience mood disorders, including bipolar affective disorder.6 7 Differentiating between borderline personality disorder and bipolar affective disorder can be difficult. Changes in mood are much more frequent among people with borderline personality disorder, and such patients are more likely to report feelings of anger, in contrast to elated mood reported by people with bipolar disorder.8 Affective instability among people with borderline personality disorder has led to interest in the role of mood stabilisers (sodium valproate, lamotrigine, topiramate, carbamazepine, and lithium) as a potential treatment. However, the evidence base for the use of these drugs in people with this condition is poor, and considerable uncertainty exists about whether they should be used in clinical practice. Current guidance from the National Institute for Health and Care Excellence (NICE) states that drug treatments should “not be used for borderline personality disorder or for the individual symptoms or behaviour associated with the disorder.”9 By contrast, American guidelines state that mood stabilisers should be considered …

Psychoeducation and Problem Solving (PEPS) Therapy for Adults With Personality Disorder: A Pragmatic Randomized-Controlled Trial

We compared psychoeducation and problem solving (PEPS) therapy against usual treatment in a multisite randomized-controlled trial. The primary outcome was social functioning. We aimed to recruit 444 community-dwelling adults with personality disorder; however, safety concerns led to an early cessation of recruitment. A total of 154 people were randomized to PEPS and 152 to usual treatment. Follow-up at 72 weeks was completed for 68%. PEPS therapy was no more effective than usual treatment for improving social functioning (adjusted difference in mean Social Functioning Questionnaire scores = -0.73; 95% CI [-1.83, 0.38]; p = 0.19). PEPS therapy is not an effective treatment for improving social functioning of adults with personality disorder living in the community.

Safety profile of lamotrigine in overdose

Background: Lamotrigine is an anticonvulsant as well as a mood stabilizer. Apart from its established use in the treatment of epilepsy, there has been an expansion of its use in the treatment of mental disorders. Patients with epilepsy as well as those with mental disorders are at increased risk of deliberate drug overdoses. An evidence base for the safety profile of lamotrigine in overdose is an essential tool for prescribers. The objective of this study was to carry out a narrative synthesis of the existing evidence for the safety profile of lamotrigine in overdose. Methods: A systematic search was conducted of EMBASE (1974 to December 2015), MEDLINE (1946 to December 2015), PsycINFO (1806 to December 2015) and CINAHL (1981 to December 2015) databases. Studies were included in which there was a deliberate or accidental single drug overdose of lamotrigine, with its toxic effects described. Studies that did not involve an overdose were excluded. A narrative synthesis of the described toxic effects was carried out. Results: Out of 562 articles identified, 26 studies were included, mainly in the form of case reports and series. The most commonly described toxic effects of lamotrigine were on the central nervous system, specifically seizures, movement disorders and reduced consciousness. Other toxic effects included QTc interval and QRS complex prolongations, hypersensitivity reactions, serotonin syndrome as well as rhabdomyolysis possibly due to seizures and/or agitation. Deaths were recorded in two studies, with cardiovascular and neurological toxic effects described. Conclusions: Even though lamotrigine has been reported to be well tolerated, there is a risk of toxic effects which can be life threatening in overdose. This needs to be borne in mind when prescribing to patients at an increased risk of deliberate drug overdose.

Tumor and plasma met levels in non-metastatic prostate cancer

Objective To measure Met protein content in prostate biopsies guided by fused magnetic resonance and ultrasound imaging, and to measure soluble Met (sMet) protein concentration in plasma samples from patients presenting evidence of prostate cancer. Patients and Methods 345 patients had plasma samples drawn prior to image-guided biopsy of the prostate. Of these, 32% had benign biopsies. Of the 236 that were positive for prostate adenocarcinoma (PCa), 132 treated by total prostatectomy had Gleason scores of 6 (17%), 7, (55%), 8 (16%), or 9–10 (12%). 23% had evidence of local invasion. Plasma samples were also obtained from 80 healthy volunteers. Tissue Met and plasma sMet were measured by two-site immunoassay; values were compared among clinically defined groups using non-parametric statistical tests to determine significant differences or correlations. Results PCa tumor Met correlated significantly with plasma sMet, but median values were similar among benign and malignant groups. Median plasma sMet values were also similar among those groups, although both medians were significantly above normal. Median Met content in primary PCa tumors and sMet concentrations were independent of Gleason score, final pathologic stage and age. Conclusion Plasma sMet is not predictive of PCa or its severity in patients with organ-confined or locally invasive disease. Quantitative analysis of Met protein content and activation state in PCa tumor biopsy samples was highly feasible and may have value in follow-up to genomic and/or transcriptomic-based screens that show evidence of oncogenically relevant MET gene features that occur at relatively low frequency in non-metastatic PCa.

Psychoeducation with problem-solving (PEPS) therapy for adults with personality disorder: a pragmatic randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of a manualised intervention to improve social functioning.

BACKGROUND If effective, less intensive treatments for people with personality disorder have the potential to serve more people. OBJECTIVES To compare the clinical effectiveness and cost-effectiveness of psychoeducation with problem-solving (PEPS) therapy plus usual treatment against usual treatment alone in improving social problem-solving with adults with personality disorder. DESIGN Multisite two-arm, parallel-group, pragmatic randomised controlled superiority trial. SETTING Community mental health services in three NHS trusts in England and Wales. PARTICIPANTS Community-dwelling adults with any personality disorder recruited from community mental health services. INTERVENTIONS Up to four individual sessions of psychoeducation, a collaborative dialogue about personality disorder, followed by 12 group sessions of problem-solving therapy to help participants learn a process for solving interpersonal problems. MAIN OUTCOME MEASURES The primary outcome was measured by the Social Functioning Questionnaire (SFQ). Secondary outcomes were service use (general practitioner records), mood (measured via the Hospital Anxiety and Depression Scale) and client-specified three main problems rated by severity. We studied the mechanism of change using the Social Problem-Solving Inventory. Costs were identified using the Client Service Receipt Inventory and quality of life was identified by the European Quality of Life-5 Dimensions questionnaire. Research assistants blinded to treatment allocation collected follow-up information. RESULTS There were 739 people referred for the trial and 444 were eligible. More adverse events in the PEPS arm led to a halt to recruitment after 306 people were randomised (90% of planned sample size); 154 participants received PEPS and 152 received usual treatment. The mean age was 38 years and 67% were women. Follow-up at 72 weeks after randomisation was completed for 62% of participants in the usual-treatment arm and 73% in the PEPS arm. Intention-to-treat analyses compared individuals as randomised, regardless of treatment received or availability of 72-week follow-up SFQ data. Median attendance at psychoeducation sessions was approximately 90% and for problem-solving sessions was approximately 50%. PEPS therapy plus usual treatment was no more effective than usual treatment alone for the primary outcome [adjusted difference in means for SFQ -0.73 points, 95% confidence interval (CI) -1.83 to 0.38 points; p = 0.19], any of the secondary outcomes or social problem-solving. Over the follow-up, PEPS costs were, on average, £182 less than for usual treatment. It also resulted in 0.0148 more quality-adjusted life-years. Neither difference was statistically significant. At the National Institute for Health and Care Excellence thresholds, the intervention had a 64% likelihood of being the more cost-effective option. More adverse events, mainly incidents of self-harm, occurred in the PEPS arm, but the difference was not significant (adjusted incidence rate ratio 1.24, 95% CI 0.93 to 1.64). LIMITATIONS There was possible bias in adverse event recording because of dependence on self-disclosure or reporting by the clinical team. Non-completion of problem-solving sessions and non-standardisation of usual treatment were limitations. CONCLUSIONS We found no evidence to support the use of PEPS therapy alongside standard care for improving social functioning of adults with personality disorder living in the community. FUTURE WORK We aim to investigate adverse events by accessing centrally held NHS data on deaths and hospitalisation for all PEPS trial participants. TRIAL REGISTRATION Current Controlled Trials ISRCTN70660936. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 52. See the NIHR Journals Library website for further project information.