Rebecca F. McKnight

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.

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.

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.

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.

ACP Journal Club: cognitive-behavioral therapy improved response and remission at 6 and 12 months in treatment-resistant depression.

Source Citation Wiles N, Thomas L, Abel A, et al. Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the ...

Short- and Midterm Side Effects of Lithium Therapy

Lithium is a widely used and effective treatment for mood disorders. In the short term, patients may experience transitory gastrointestinal (GI) side effects or mild tremor, whilst a proportion of patients develop a reversible nephrogenic diabetes insipidus. Endocrine disorders—goitre, hypothyroidism, hyperthyroidism, hyperparathyroidism and weight gain—may occur in the long term. Exacerbation or development of skin and hair conditions due to lithium therapy has been reported in the literature, but good quality evidence is still needed to verify this association. Regular monitoring whilst taking lithium is essential to identify patients at risk of developing adverse effects and to provide safe and effective treatment.