Intravenous dantrolene in hypermetabolic syndromes: a survey of the U.S. Veterans Health Administration database.

BACKGROUND: Intravenous dantrolene is often prescribed for hypermetabolic syndromes other than the approved indication of malignant hyperthermia (MH). To clarify the extent of and indications for dantrolene use in conditions other than MH, we sought to document current practices in the frequency, diagnoses, clinical characteristics and outcomes associated with dantrolene treatment in critical care settings. METHODS: Inpatients receiving intravenous dantrolene from October 1, 2004 to September 30, 2014 were identified retrospectively in the U.S. Veterans Health Administration national database. Extracted data included; diagnoses of hypermetabolic syndromes; triggering drugs; dantrolene dosages; demographics; vital signs; laboratory values; in-hospital mortality; complications; and lengths of stay. Frequency and mortality of patients who did not receive dantrolene were obtained in selected diagnoses for exploratory comparisons. RESULTS: Dantrolene was administered to 304 inpatients. The most frequent diagnoses associated with dantrolene treatment were neuroleptic malignant syndrome (NMS; N = 108, 35.53%) and sepsis (N = 47, 15.46%), with MH accounting for only 13 (4.28%) cases. Over half the patients had psychiatric comorbidities and received psychotropic drugs before dantrolene treatment. Common clinical findings in patients receiving dantrolene included elevated temperature (mean ± SD; 38.7 ± 1.3 °C), pulse (116.33 ± 22.80/bpm), respirations (27.75 ± 9.58/min), creatine kinase levels (2,859.37 ± 6,646.88 IU/L) and low pO2 (74.93 ± 40.16 mmHg). Respiratory, renal or cardiac failure were common complications. Mortality rates in-hospital were 24.01% overall, 7.69% in MH, 20.37% in NMS and 42.55% in sepsis, compared with mortality rates in larger and possibly less severe groups of unmatched patients with MH (5.26%), NMS (6.66%), or sepsis (41.91%) who did not receive dantrolene. CONCLUSIONS: In over 95% of cases, dantrolene administration was associated with diagnoses other than MH in critically-ill patients with hypermetabolic symptoms and medical and psychiatric comorbidities. Exploratory survey data suggested that the efficacy and safety of dantrolene in preventing mortality in hypermetabolic syndromes other than MH remain uncertain. However, randomized and controlled studies using standardized criteria between groups matched for severity are essential to guide practice in using dantrolene.

Effect of Varenicline on Tardive Dyskinesia: A Pilot Study.

OBJECTIVE: Although evidence implicates striatal cholinergic impairment as a mechanism underlying tardive dyskinesia, trials of nonspecific cholinergic agents have been inconclusive. As a partial agonist at specific nicotinic receptor subtypes, varenicline reduces drug-induced dyskinesias in animal models suggesting promise as a treatment for tardive dyskinesia. METHODS: Three schizophrenia patients with tardive dyskinesia who were smokers underwent an open trial of varenicline. After a 2-week baseline, subjects received varenicline 1 mg twice daily. Changes from baseline on the Abnormal Involuntary Movement Scale were measured after a 4-week varenicline stabilization period, and 6 weeks after the smoking quit date in one patient. RESULTS: Varenicline had no effect on mean Abnormal Involuntary Movement Scale scores after 4 weeks. Although smoking decreased after 4 weeks on varenicline and diminished further in one patient after 10 weeks, this also appeared to have no effect on ratings of tardive dyskinesia. CONCLUSION: In contrast to animal models, no significant change in tardive dyskinesia occurred in response to varenicline replacement in three schizophrenia patients. Further investigations of cholinergic mechanisms in tardive dyskinesia are worthwhile as agents for specific cholinergic targets become available for treatment. In addition, treatment trials of tardive dyskinesia should control for smoking status, while patients on antipsychotics receiving nicotine replacement therapies for smoking should be studied further for changes in movement.

Correlates of the Abnormal Involuntary Movement Scale in Veterans With Tardive Dyskinesia.

PURPOSE/BACKGROUND: To add to limited evidence on the Abnormal Involuntary Movement Scale (AIMS) as a measure of tardive dyskinesia (TD) in clinical practice settings, the characteristics and correlates of AIMS scores were assessed. METHODS/PROCEDURES: Veterans with schizophrenia/schizoaffective, bipolar, or major depressive disorders receiving antipsychotics and at least 1 AIMS score during October 1, 2014, to September 30, 2015, were identified. Tardive dyskinesia was determined by the International Classification of Diseases, Ninth Revision, Clinical Modification, codes. Correlates of AIMS scores were examined using χ or t tests. Odds ratios and ß parameters with 95% confidence intervals for categorical and continuous variables associated with AIMS scores were derived from a multivariate logistic and linear regression, respectively. FINDINGS/RESULTS: Among 7985 veterans receiving antipsychotics, only 4706 (58.9%) had at least 1 AIMS examination. Of these, 229 (4.9%) were diagnosed with possible TD. The mean total AIMS scores and AIMS awareness/incapacitation scores were significantly higher for patients with TD (both P < 0.0001). Comparing diagnostic threshold criteria of AIMS ratings, only 17.5% to 37.1% of veterans with TD were successfully identified. Among TD patients, 21.4% had a total score of moderate-severe and 15.3% had ratings of at least mild movements in 2 or more body regions. In the regression analyses, being older, African-American, having schizophrenia/schizoaffective disorder, and receiving antipsychotics or benztropine significantly increased the severity of AIMS scores. Higher AIMS scores were not predictive of outcomes other than marital status in socioeconomic or healthcare domains. IMPLICATIONS/CONCLUSIONS: Although the AIMS is essential for TD research, its value in clinical practice without training and oversight remains unclear. Efforts to adapt screening procedures to clinical needs may be worthwhile.

Cumulative Burden of Illness in Veterans With Tardive Dyskinesia and Serious Mental Disorders.

PURPOSE/BACKGROUND: To inform cost-benefit decisions for veterans, the risk of tardive dyskinesia (TD) and its impact on comorbidities and outcomes were assessed. METHODS/PROCEDURES: In a retrospective study, veterans with schizophrenia/schizoaffective, and bipolar and major depressive disorders receiving antipsychotics during the period October 1, 2014, to September 30, 2015, were identified. Tardive dyskinesia was determined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Correlates of TD were examined using χ or t tests. Odds ratios (ORs) and ß parameters with 95% confidence intervals (CIs) for categorical and continuous variables associated with TD were derived from a multivariate logistic and linear regression, respectively. FINDINGS/RESULTS: Among 7985 veterans, 332 (4.2%) were diagnosed as having possible TD. The odds of having TD were higher for older veterans (OR, 1.04; 95% CI, 1.03-1.05; P < 0.0001) and veterans with schizophrenia/schizoaffective disorder (OR, 1.54; 95% CI, 1.23-1.91; P < 0.0001) or diabetes (OR, 1.64; 95% CI, 1.30-2.06; P < 0.0001). Veterans with TD received more antipsychotic prescriptions (mean ± SD, 18.4 ± 30.3 vs 13.3 ± 26.4; P = 0.003) and days of supply (233.9 ± 95.4 vs 211.4 ± 102.0; P < 0.0001). They were more likely to have received 2 or more antipsychotics (27.1% vs 19.7%, P = 0.0009) and benztropine (OR, 2.25: 95% CI 1.73-2.91; P < 0.0001). Veterans with TD had a higher Charlson Comorbidity Index score (ß = 0.32; SE, 0.09; 95% CI, 0.14-0.49; P = 0.0003) and higher odds of any medical hospitalization (OR, 1.45; 95% CI, 1.07-1.95; P = 0.001). IMPLICATIONS/CONCLUSIONS: The diagnosis of possible TD was associated with older age, schizophrenia/schizoaffective disorder, medical comorbidity, and hospitalization. Tardive dyskinesia may be a marker for patients at risk of adverse health care outcomes and diminished quality of life.

Socioeconomic Disparities and Metabolic Risk in Veterans with Serious Mental Illness.

Socioeconomic disparities were assessed in predicting metabolic risk among veterans with serious mental illness. Veterans with schizophrenia, schizoaffective, or bipolar disorders were identified in VISN 4 facilities from 10/1/2010 to 9/30/2012. Differences between patients with and without metabolic syndrome were compared using t-tests, Chi square tests and multivariate logistic regressions. Among 10,132 veterans with mental illness, 48.8% had metabolic syndrome. Multivariate logistic regression analysis confirmed that patients with metabolic syndrome were significantly more likely to be older, male, African-American, married, and receiving disability pensions but less likely to be homeless. They were more likely to receive antipsychotics, antidepressants, or anticonvulsants. Bivariate cross-sectional analysis revealed that patients with metabolic syndrome had higher rates of coronary artery disease, cerebrovascular disease, and mortality, and that metabolic syndrome was more often associated with emergency visits and psychiatric or medical hospitalizations. Demographics, socioeconomic status and medications are independent predictors of metabolic syndrome and should be considered in broader screening of risk factors in order to provide preventive interventions for metabolic syndrome.