Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder: A Randomized Clinical Trial.

Importance: Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression. Objective: To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019. Interventions: Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo. Main Outcomes and Measures: Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide. Results: The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group. Conclusions and Relevance: In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities. Trial Registration: ClinicalTrials.gov Identifier: NCT01928446.

Suicide Risk in Bipolar Disorder: A Brief Review.

Bipolar disorders (BDs) are prevalent mental health illnesses that affect about 1-5% of the total population, have a chronic course and are associated with a markedly elevated premature mortality. One of the contributors for the decreased life expectancy in BD is suicide. Accordingly, the rate of suicide among BD patients is approximately 10-30 times higher than the corresponding rate in the general population. Extant research found that up to 20% of (mostly untreated) BD subjects end their life by suicide, and 20-60% of them attempt suicide at least one in their lifetime. In our paper we briefly recapitulate the current knowledge on the epidemiological aspects of suicide in BD as well as factors associated with suicidal risk in BD. Furthermore, we also discuss concisely the possible means of suicide prevention in BD.

Candidate reference measurement procedures for chloride, potassium, sodium, calcium, magnesium, and lithium by inductively coupled plasma (isotope dilution) sector field mass spectrometry (ICP-(ID) SFMS) in serum.

BACKGROUND: Standardization of the measurement of electrolyte concentrations in serum is of considerable interest for quality assurance in patient care. To promote the ongoing process of standardization we developed candidate reference measurement procedures of highest metrological order for Cl, K, Na, Ca, Mg, and Li using ICP-(ID) SFMS. METHODS: Serum samples were diluted with 4 mmol/L nitric acid and were spiked with the internal standard for quantification, separately for each analyte. The samples were introduced in the ICP-SFMS device by continuous infusion using a peristaltic pump. The measurement results were compared with reference measurement procedure values obtained by atom absorption spectroscopy, flame emission spectroscopy, and coulometry. The measurement accuracy and precision was calculated by analyzing certified reference materials and EQAS samples. RESULTS: The mean coefficient of variation (CV) of the ICP-MS procedures for the serum samples was 0.65% for Cl, 0.46% for K, 0.51% for Na, 0.77% for Ca, 0.78% for Mg, and 0.58% for Li. The mean bias from target values of NIST certified reference materials was +0.85% for Cl, -0.46% for K, +0.68% for Na, -0.21% for Ca, +0.27% for Mg, and -0.39% for Li. CONCLUSIONS: Candidate reference measurement procedures for 6 electrolytes were developed by high performance magnetic sector field ICP-MS fulfilling the requirements of ISO 15193:2009 for reference measurement procedures with traceability to SI according to ISO 17511:2003 and can be used for setting target values in EQAS and for certification of reference materials.

Evaluation of three first-generation ion-selective electrode analyzers for lithium: systematic errors, frequency of random interferences, and recommendations based on comparison with flame atomic emission spectrometry.

Ion-selective electrode analyzers for measuring lithium (Li/ISE) in serum became available in early 1987. We compared results for patients' samples from three of them vs results from flame atomic emission spectrometry (FAES). Within-run and day-to-day imprecision ranged from 0.01 to 0.03 mmol/L and 0.01 to 0.04 mmol/L, respectively. Comparing Li/ISE results (y) with the FAES results (x) gave the following equations: y = 1.063x - 0.035 for AMDEV's Lytening 2, y = 1.020x + 0.038 for NOVA's Model 11, and y = 1.030x - 0.027 for AVL's Model 985. Unexplained positive errors greater than 0.2 mmol/L were observed for two of the 90 patients' samples, but only a few additional excessively high values were seen in 3000 patients' samples run subsequently (Lytening 2). Causes of error in clinical Li/ISE measurements are still unclear; simply characterizing them as "matrix effects" does not correct the underlying analytical problem. An increase in pH from loss of CO2 gave low results on two of the three Li/ISE analyzers but did not change FAES results. Trimethylammonium bicarbonate used in a reconstitution solution caused extremely high Li/ISE results but did not change FAES results. Performance specifications to help reduce and correct these errors are recommended.

Creep of posterior dental composites.

The creep of microspecimens of posterior dental composites was studied using a torsional creep apparatus. Shear stresses were maintained for 3 h and recovery was followed for 50 h. Creep curves were obtained at 21, 37, and 50 degrees C and four torque levels. The effect of conditioning the specimens in water up to 8 weeks was studied. The posterior composites exhibited linear viscoelastic behavior at low deformations. They had higher shear moduli and greater resistance to creep than conventional and microfilled composites. In aging experiments, maximum shear moduli occurred when specimens were 48 h to 1 week old. Subsequent softening was attributed to water absorption. Residual strain was highest when the composites were stressed within 24 h of initiating polymerization. Residual strain was very low in specimens 48 h to 8 weeks of age.