Lithium for acute mania.

BACKGROUND: Bipolar disorder is a common condition associated with high morbidity; developing efficacious, safe treatments is therefore essential. Lithium is an effective maintenance treatment for bipolar disorder. It acts as mood stabiliser and reduces the risk of suicide. However, evidence assessing the efficacy of lithium in the treatment of acute mania is less robust. Current evidence-based guidelines cite multiple anti-dopaminergic and mood-stabilising agents as initial treatments: more definite evidence is needed to decide if lithium should be the first-line therapy. OBJECTIVES: 1. To assess the effects of lithium in comparison with placebo or other active treatment in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder.2. To review the acceptability and tolerability of treatment with lithium in comparison with placebo or other active treatments in alleviating the acute symptoms of a manic or mixed episode in people with bipolar disorder. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, and PsycINFO. We also searched the World Health Organization trials portal (ICTRP) and ClinicalTrials.gov. We checked the reference lists of all included studies and relevant systematic reviews. We have incorporated studies from searches to 18 May 2018 into the current analyses. SELECTION CRITERIA: Prospective randomised controlled studies comparing lithium with placebo or alternative drug treatment in treatment of acute mania. We included anyone with bipolar disorder, male and female, of any age. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted data and assessed methodological quality. We used odds ratios (ORs) to analyse binary efficacy outcomes, and mean differences (MDs) or standardised mean differences (SMDs) for continuously distributed outcomes. We used a fixed-effect model unless heterogeneity was moderate or substantial, in which case we used a random-effects model. We used Review Manager 5 to analyse data. We assessed the certainty of evidence for individual outcomes using the GRADE approach. MAIN RESULTS: We found 36 randomised controlled studies comparing lithium with placebo, one of 12 drugs, or electroconvulsive therapy for treatment of acute mania. Studies included male and female participants (n = 4220), of all ages, who all fitted criteria for a manic episode within the context of a diagnosis of bipolar disorder.Risk of bias was variable; 12 studies had a high risk of bias in one domain and 27 gave inadequate information on randomisation leading to an 'unclear' rating for selection bias.Lithium versus placeboHigh-certainty evidence found that lithium was an effective treatment for acute mania and was more effective than placebo at inducing a response (OR 2.13, 95% confidence interval (CI) 1.73 to 2.63; participants = 1707; studies = 6; I2 = 16%; high-certainty evidence), or remission (OR 2.16, 95% CI 1.73 to 2.69; participants = 1597; studies = 5; I2 = 21%; high-certainty evidence).Lithium was more likely than placebo to cause tremor (OR 3.25, 95% CI 2.10 to 5.04; participants = 1241; studies = 6; I2 = 0%; high-certainty evidence), and somnolence (OR 2.28, 95% CI 1.46 to 3.58; participants = 1351; studies = 7; I2 = 0%; high-certainty evidence).There was insufficient evidence to determine the effect of lithium for all-cause dropouts (OR 0.76; 95% CI 0.46 to 1.25; participants = 1353; studies = 7; I2 = 75%; moderate-certainty evidence), and weight gain (OR 1.48, 95% CI 0.56 to 3.92; participants = 735, studies = 3; I2= 51%; moderate-certainty evidence).Lithium versus antipsychotics or mood stabilisersFor the outcome of inducing a response, there was only very low-certainty evidence regarding lithium compared to haloperidol (MD -2.40, 95% CI -6.31 to 1.50; participants = 80; studies = 3; I2 = 95%), quetiapine (OR 0.66, 95% CI 0.28 to 1.55; participants = 335; studies = 2; I2 = 71%), and carbamazepine (SMD 0.21, 95% CI -0.18 to 0.60; participants = 102; studies = 3; I2 = 0%).Lithium was probably less likely to induce a response than olanzapine (OR 0.44, 95% CI 0.20 to 0.94; participants = 180; studies = 2; I2 = 0%; moderate-certainty evidence).Lithium may be less likely to induce a response than risperidone (MD 7.28, 95% CI 5.22 to 9.34; participants = 241; studies = 3; I2 = 49%; low-certainty evidence).There was no evidence of a difference between lithium and valproate (OR 1.22, 95% CI 0.87 to 1.70; participants = 607; studies = 5; I2 = 22%; moderate-certainty evidence).There was moderate-certainty evidence that lithium was more effective than topiramate at treating acute mania (OR 2.28, 95% CI 1.63 to 3.20; participants = 660; studies = 1).Data on adverse events for these comparisons contained too few studies to provide high-certainty evidence. AUTHORS' CONCLUSIONS: This systematic review indicates that lithium is more effective than placebo as a treatment for acute mania but increases the risk for somnolence and tremor. Limited evidence suggests little or no difference between lithium and other mood stabilisers (valproate, carbamazepine) or antipsychotics (risperidone, quetiapine, haloperidol). Olanzapine may be an exception, as it is probably slightly more effective than lithium. There is uncertain evidence that risperidone may also be more effective than lithium. Lithium is probably more effective at treating acute mania than topiramate. When compared to placebo, lithium was more likely to cause adverse events. However, when compared to other drugs, too few studies provided data on adverse effects to provide high-certainty evidence. More, rigorously designed, large-scale studies are needed to definitively conclude if lithium is superior to other interventions in treating acute mania.

Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data.

BACKGROUND: Lithium is a widely used and highly effective treatment for mood disorders, but causes poorly characterised adverse effects in kidney and endocrine systems. We aimed to analyse laboratory information system data to determine the incidence of renal, thyroid, and parathyroid dysfunction associated with lithium use. METHODS: In a retrospective analysis of laboratory data from Oxford University Hospitals National Health Service Trust (Oxfordshire, UK), we investigated the incidence of renal, thyroid, and parathyroid dysfunction in patients (aged ≥18 years) who had at least two creatinine, thyrotropin, calcium, glycated haemoglobin, or lithium measurements between Oct 1, 1982, and March 31, 2014, compared with controls who had not had lithium measurements taken. We used survival analysis and Cox regression to estimate the hazard ratio (HR) for each event with lithium use, age, sex, and diabetes as covariates. FINDINGS: Adjusting for age, sex, and diabetes, presence of lithium in serum was associated with an increased risk of stage three chronic kidney disease (HR 1·93, 95% CI 1·76-2·12; p<0·0001), hypothyroidism (2·31, 2·05-2·60; p<0·0001), and raised total serum calcium concentration (1·43, 1·21-1·69; p<0·0001), but not with hyperthyroidism (1·22, 0·96-1·55; p=0·1010) or raised adjusted calcium concentration (1·08, 0·88-1·34; p=0·4602). Women were at greater risk of development of renal and thyroid disorders than were men, with younger women at higher risk than older women. The adverse effects occurred early in treatment (HR <1 for length of treatment with lithium). Higher than median lithium concentrations were associated with increased risk of all adverse outcomes. INTERPRETATION: Lithium treatment is associated with a decline in renal function, hypothyroidism, and hypercalcaemia. Women younger than 60 years and people with lithium concentrations higher than median are at greatest risk. Because lithium remains a treatment of choice for bipolar disorder, patients need baseline measures of renal, thyroid, and parathyroid function and regular long-term monitoring. FUNDING: None.

Lithium toxicity profile: a systematic review and meta-analysis.

BACKGROUND: Lithium is a widely used and effective treatment for mood disorders. There has been concern about its safety but no adequate synthesis of the evidence for adverse effects. We aimed to undertake a clinically informative, systematic toxicity profile of lithium. METHODS: We undertook a systematic review and meta-analysis of randomised controlled trials and observational studies. We searched electronic databases, specialist journals, reference lists, textbooks, and conference abstracts. We used a hierarchy of evidence which considered randomised controlled trials, cohort studies, case-control studies, and case reports that included patients with mood disorders given lithium. Outcome measures were renal, thyroid, and parathyroid function; weight change; skin disorders; hair disorders; and teratogenicity. FINDINGS: We screened 5988 abstracts for eligibility and included 385 studies in the analysis. On average, glomerular filtration rate was reduced by -6·22 mL/min (95% CI -14·65 to 2·20, p=0·148) and urinary concentrating ability by 15% of normal maximum (weighted mean difference -158·43 mOsm/kg, 95% CI -229·78 to -87·07, p<0·0001). Lithium might increase risk of renal failure, but the absolute risk was small (18 of 3369 [0·5%] patients received renal replacement therapy). The prevalence of clinical hypothyroidism was increased in patients taking lithium compared with those given placebo (odds ratio [OR] 5·78, 95% CI 2·00-16·67; p=0·001), and thyroid stimulating hormone was increased on average by 4·00 iU/mL (95% CI 3·90-4·10, p<0·0001). Lithium treatment was associated with increased blood calcium (+0·09 mmol/L, 95% CI 0·02-0·17, p=0·009), and parathyroid hormone (+7·32 pg/mL, 3·42-11·23, p<0·0001). Patients receiving lithium gained more weight than did those receiving placebo (OR 1·89, 1·27-2·82, p=0·002), but not those receiving olanzapine (0·32, 0·21-0·49, p<0·0001). We recorded no significant increased risk of congenital malformations, alopecia, or skin disorders. INTERPRETATION: Lithium is associated with increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain. There is little evidence for a clinically significant reduction in renal function in most patients, and the risk of end-stage renal failure is low. The risk of congenital malformations is uncertain; the balance of risks should be considered before lithium is withdrawn during pregnancy. Because of the consistent finding of a high prevalence of hyperparathyroidism, calcium concentrations should be checked before and during treatment. FUNDING: National Institute for Health Research Programme Grant for Applied Research.

First do no harm: iatrogenic maintaining factors in anorexia nervosa.

The aim of this paper is to reflect on the way that we as clinicians may play an inadvertent role in perpetuating eating disordered behaviour. This is considered within the theoretical framework of Schmidt and Treasures' maintenance model of anorexia nervosa (AN). The model includes four main domains; interpersonal factors, pro-AN beliefs, emotional style and thinking style. Interpersonal reactions are of particular relevance as clinicians (as with family members) may react with high expressed emotion and unknowingly encourage eating disorder behaviours to continue. Hostility in the form of coercive refeeding in either a hospital or outpatient setting may strengthen conditioned food avoidance and pessimism may hamper motivation to change. Negative schema common to eating disorders, for example low self-esteem, perfectionism and striving for social value may augment existing or initiate new eating disorder behaviour. Services can become a reinforcing influence by providing an overly protective, palliating environment which ensures safety, security and acceptance whilst reducing loneliness and isolation. This stifles the need for an individual to develop their own sense of responsibility, autonomy and independence allowing avoidance to dominate. Furthermore, the highly structured environment of inpatient care supports the rigid attention to detail and inflexibility that is characteristic of people with eating disorders, and allows these negative behaviours to thrive. Careful planning of service provision, reflective practice, supervision and regular team feedback is essential to prevent iatrogenic harm.

Atypical antipsychotics and anorexia nervosa: a review.

BACKGROUND: There is currently mixed opinion regarding the value of using atypical antipsychotics to treat anorexia nervosa (AN). AIMS: To evaluate the literature on the use of atypical antipsychotics in AN. METHOD: A review of all studies and clinical guidelines published before September 2009 involving use of an atypical antipsychotic in patients with AN. Analysis is by narrative synthesis. RESULTS: Forty-three publications or study protocols were found, including four randomized-controlled trials, five open-label trials and 26 case reports. The most studied drugs were olanzapine, quetiapine and risperidone. Atypical antipsychotics appear safe and there is some evidence of positive effects on depression, anxiety and core eating disordered psychopathology in patients with anorexia nervosa. Currently there is insufficient evidence to confirm atypical antipsychotics enhance weight gain in this setting. CONCLUSIONS: Further high quality evidence is needed in this area in order to provide practical guidance to clinicians. However, the main challenge is to persuade adequate numbers of AN patients to participate in research trials.

Longitudinal mood monitoring in bipolar disorder: Course of illness as revealed through a short messaging service.

BACKGROUND: Online self-monitoring of mood can be used to investigate differences in course patterns across patient groups. This study explored the feasibility of remote symptom capture with True Colours, a self-rated online mood monitoring tool completed on a weekly basis. METHODS: Participants with bipolar disorder (N = 297) completed weekly depression and mania questionnaires over an average of 27.5 months (range 1 -81 months). Subgroups defined by sex, age, and bipolar I vs. II status were compared on time in various mood states, number of episodes, and week-to-week mood variability. RESULTS: Compliance with weekly questionnaires was generally high (median, 92% of weeks). Mood symptoms occurred for an average of 55.4% of weeks across the follow-up period. Females spent more time with hypomanic/manic and depressive symptoms and had more depressive episodes compared to males. Younger participants were found to experience more hypomanic/manic episodes and showed greater variability in mood symptoms than older participants. No significant differences in mood symptoms or variability were observed between bipolar I and II patients. LIMITATIONS: This was a naturalistic study with a heterogeneous cohort, and did not include a control group. True Colours does not identify mood fluctuations that may occur in the days between weekly assessments. CONCLUSIONS: Monitoring moods through an online tool is both feasible and informative regarding course of illness in patients with bipolar disorder. Interventions aiming to reduce mood variability and manic/hypomanic episodes in the early phases of bipolar disorder may enhance the long-term symptomatic course of the illness.

The feasibility and effectiveness of Catch It, an innovative CBT smartphone app.

BACKGROUND: The widespread use of smartphones makes effective therapies such as cognitive-behavioural therapy (CBT) potentially accessible to large numbers of people. AIMS: This paper reports the usage data of the first trial of Catch It, a new CBT smartphone app. METHOD: Uptake and usage rates, fidelity of user responses to CBT principles, and impact on reported negative and positive moods were assessed. RESULTS: A relatively modest proportion of people chose to download the app. Once used, the app tended to be used more than once, and 84% of the user-generated content was consistent with the basic concepts of CBT. There were statistically significant reductions in negative mood intensity and increases in positive mood intensity. CONCLUSIONS: Smartphone apps have potential beneficial effects in mental health through the application of basic CBT principles. More research with randomised controlled trial designs should be conducted. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

New patient assessment in old age psychiatry: the importance of risk assessment.

Aims and method In recent years, the role of non-medical community mental health team (CMHT) clinicians has widened to include new patient assessments. It is unclear whether all professionals have the skills and confidence to undertake these to a high quality. This project investigated which professionals are doing new assessments, evaluated their quality and explored the assessors' unmet training needs. The study was based on the data extracted from electronic notes and a complete audit cycle in South Oxfordshire Older Adults CMHT; this was a cross-sectional study across Oxfordshire older adults services. Results Most new assessments (72.4%) were done by non-medical clinicians; the majority were missing important information, especially relating to medications and risk assessment. Only 75% of assessors felt at least 'partially confident' to do assessments and found them stressful, with 86% keen to undertake further training. Clinical implications Simple measures such as an assessment form, a programme of training seminars and adequate supervision, delivered to all CMHT clinicians, can ensure high-quality assessment in diverse clinical environments.

Hyponatremia-induced change in mood mimicking late-onset bipolar disorder.

OBJECTIVE: Hyponatremia and bipolar disorder are rarely considered to have common features. This report describes a case of hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) presenting as late-onset bipolar disorder and discusses the evidence linking hyponatremia to mood disorders. METHOD: Case report and review of published literature. RESULTS: This case provides evidence that mood changes identical to those seen in bipolar disorder may be caused by hyponatremia at a variety of concentrations. CONCLUSIONS: Further research is required to determine causes of SIADH in psychiatric patients with symptomatic hyponatremia and to elucidate the mechanism by which hyponatremia causes changes in mood. In older patients presenting with new-onset bipolar disorder, a physical etiology must always be excluded.