Lithium side effects and toxicity: prevalence and management strategies

Despite its virtually universal acceptance as the gold standard in treating bipolar disorder, prescription rates for lithium have been decreasing recently. Although this observation is multifactorial, one obvious potential contributor is the side effect and toxicity burden associated with lithium. Additionally, side effect concerns assuredly play some role in lithium nonadherence. This paper summarizes the knowledge base on side effects and toxicity and suggests optimal management of these problems. Thirst and excessive urination, nausea and diarrhea and tremor are rather common side effects that are typically no more than annoying even though they are rather prevalent. A simple set of management strategies that involve the timing of the lithium dose, minimizing lithium levels within the therapeutic range and, in some situations, the prescription of side effect antidotes will minimize the side effect burden for patients. In contrast, weight gain and cognitive impairment from lithium tend to be more distressing to patients, more difficult to manage and more likely to be associated with lithium nonadherence. Lithium has adverse effects on the kidneys, thyroid gland and parathyroid glands, necessitating monitoring of these organ functions through periodic blood tests. In most cases, lithium-associated renal effects are relatively mild. A small but measurable percentage of lithium-treated patients will show progressive renal impairment. Infrequently, lithium will need to be discontinued because of the progressive renal insufficiency. Lithium-induced hypothyroidism is relatively common but easily diagnosed and treated. Hyperparathyroidism from lithium is a relatively more recently recognized phenomenon

Cardiometabolic risk indicators in individuals with bipolar disorders: a replication study

Abstract Objectives We recently conducted the first longitudinal study comparing cardiometabolic risk indicators (CMRIs) between a cohort of individuals with bipolar disorders (BDs) and controls from the general population. Here, we sought to validate the findings in that study using an independent case-control sample. Methods We used data from the St. Göran project’s Gothenburg cohort. The BDs group and the control group were examined at baseline and after a median of eight and seven years, respectively. Data collection occurred between March 2009 and June 2022. We used multiple imputation to handle missing data and linear mixed effects model to examine the annual change in CMRIs over the study period. Results The baseline cohort included 407 individuals with BDs (mean age 40 years, 63% women) and 56 controls (mean age 43 years, 54% women). Of those, 63 persons with BDs and 42 controls participated at follow-up. At baseline, individuals with BDs had significantly higher mean values of body mass index (β = 0.14, p = 0.003) than controls. Over the study period, the difference in average annual change between the patient and the control group indicated an increase in patients relative to controls in waist-to-hip ratio (0.004 unit/year, p = 0.01), diastolic (0.6 mm Hg/year, p = 0.048), and systolic (0.8 mm Hg/year, p = 0.02) blood pressure. Conclusions This study replicated the main findings from our previous study and showed that central obesity and measures of blood pressure worsened over a relatively short time in individuals with BDs relative to controls. It is vital for clinicians to monitor CMRIs in persons with BDs and to be proactive in preventing cardiometabolic diseases in this high-risk group

Attempted suicide in bipolar disorder: risk factors in a cohort of 6086 patients.

OBJECTIVE: Bipolar disorder is associated with high risk of self-harm and suicide. We wanted to investigate risk factors for attempted suicide in bipolar patients. METHOD: This was a cohort study of 6086 bipolar patients (60% women) registered in the Swedish National Quality Register for Bipolar Disorder 2004-2011 and followed-up annually 2005-2012. Logistic regression was used to calculate adjusted odds ratios for fatal or non-fatal attempted suicide during follow-up. RESULTS: Recent affective episodes predicted attempted suicide during follow-up (men: odds ratio = 3.63, 95% CI = 1.76-7.51; women: odds ratio = 2.81, 95% CI = 1.78-4.44), as did previous suicide attempts (men: odds ratio = 3.93, 95% CI = 2.48-6.24; women: odds ratio = 4.24, 95% CI = 3.06-5.88) and recent psychiatric inpatient care (men: odds ratio = 3.57, 95% CI = 1.59-8,01; women: odds ratio = 2.68, 95% CI = 1.60-4.50). Further, those with many lifetime depressive episodes were more likely to attempt suicide. Comorbid substance use disorder was a predictor in men; many lifetime mixed episodes, early onset of mental disorder, personality disorder, and social problems related to the primary group were predictors in women. CONCLUSION: The principal clinical implication of the present study is to pay attention to the risk of suicidal behaviour in bipolar patients with depressive features and more severe or unstable forms of the disorder

Sudomotor dysfunction is associated with foot ulceration in diabetes

To examine the relationship between sudomotor dysfunction and foot ulceration (FU) in patients with diabetes. Ninety patients with either Type 1 or Type 2 diabetes [30 without peripheral sensorimotor neuropathy (PN), 30 with PN but without FU and 30 with FU] were recruited in this cross-sectional study. Assessment of PN was based on neuropathy symptom score (NSS), neuropathy disability score (NDS) and vibration perception threshold (VPT). Sudomotor dysfunction was assessed using the sympathetic skin response (SSR). Cardiac autonomic nervous system activity was assessed by the battery of the classical autonomic function tests. Patients with foot ulcers had longer duration of diabetes, higher values of VPT and NDS and lower values of the autonomic functions tests in comparison with the other study groups. Sudomotor dysfunction and cardiac autonomic neuropathy were significantly more common in the FU group. Multivariate logistic regression analysis after adjustment for gender, body mass index, duration of diabetes and glycated haemoglobin (HbA(1c)) demonstrated that the odds ratio (95% confidence intervals) of FU increased with measures of neuropathy such as NDS >= 6 (10.2, 6.2-17.3) and VPT >= 25 volts (19.8, 9.9-47.5), but was also significantly increased with absent SSR (15.3, 5.3-38.4). Sudomotor dysfunction is associated with increased risk of FU and should be included in the screening tests for identification of diabetic patients at risk of ulceration

Pharmacological treatment and risk of psychiatric hospital admission in bipolar disorder

Background Clinical trials have examined the efficacy of drugs to prevent relapse in patients with bipolar disorder, however their design often limits generalization to routine clinical practice. Aims To estimate the effectiveness of drugs used for maintenance treatment in bipolar disorder. Methods We used national registers to identify 35,022 individuals diagnosed with bipolar disorder and information on lithium, valproate, carbamazepine, lamotrigine, quetiapine, and olanzapine treatment from 2006-2009. The main outcome was psychiatric hospitalizations. We used stratified cox regression to compare periods on and off medication within the same individual. Results Medication with lithium, valproate, lamotrigine, olanzapine, and quetiapine was associated with reduced the rates of hospitalization. Lithium was more effective than quetiapine and olanzapine. The effects of specific drugs depended on the polarity of the mood episode. Conclusions Our findings complement results from RCTs, but suggest that lithium is more effective than both quetiapine and olanzapine in routine clinical practice. </p

Pharmacological treatment and risk of psychiatric hospital admission in bipolar disorder

Background Clinical trials have examined the efficacy of drugs to prevent relapse in patients with bipolar disorder, however their design often limits generalization to routine clinical practice. Aims To estimate the effectiveness of drugs used for maintenance treatment in bipolar disorder. Methods We used national registers to identify 35,022 individuals diagnosed with bipolar disorder and information on lithium, valproate, carbamazepine, lamotrigine, quetiapine, and olanzapine treatment from 2006-2009. The main outcome was psychiatric hospitalizations. We used stratified cox regression to compare periods on and off medication within the same individual. Results Medication with lithium, valproate, lamotrigine, olanzapine, and quetiapine was associated with reduced the rates of hospitalization. Lithium was more effective than quetiapine and olanzapine. The effects of specific drugs depended on the polarity of the mood episode. Conclusions Our findings complement results from RCTs, but suggest that lithium is more effective than both quetiapine and olanzapine in routine clinical practice. </p

Psychoeducation for bipolar disorder and risk of recurrence and hospitalization - a within-individual analysis using registry data

Background: The efficacy of psychoeducation for bipolar disorder has been demonstrated in clinical trials, but it is not known if the results translate into effectiveness in routine clinical practice. The aim was to determine the effectiveness of psychoeducation for bipolar disorder in a routine clinical setting. Method: We identified 2819 patients with at least three registrations in the Swedish Quality Assurance Register for Bipolar Disorder. Among those, 402 had not been exposed to psychoeducation at the first visit, but received psychoeducation during any of the following registrations. Using within-individual analyses, the risk of recurrence after having received psychoeducation was compared with the risk prior to psychoeducation. Results: In adjusted within-individuals comparisons, periods after psychoeducation was associated with decreased risks of any recurrence [odds ratio (OR) 0.57, 95% CI 0.42-0.78], (hypo-)manic or mixed episodes (OR 0.54, 95% CI 0.39-0.76), depressive episodes (OR 0.63, 95% CI 0.47-0.86), and inpatient care (OR 0.54, 95% CI 0.33-0.86) relative to periods prior to psychoeducation. There was no association with rates of involuntary sectioning or suicide attempts. Conclusions: The results suggest that psychoeducation for bipolar disorder reduces the risk of mood episodes and inpatient care also when implemented in routine clinical practice