Accuracy of a single-lead mobile smartphone electrocardiogram for QT interval measurement in patients undergoing maintenance methadone therapy.

STUDY OBJECTIVE: Methadone is associated with QT interval prolongation and torsades de pointes. Expert panel recommendations advocate a pre-methadone electrocardiogram (ECG) and another ECG at 30 days of therapy in patients with risk factors. Some guidelines recommend a pre-methadone ECG and routine ECG monitoring in all methadone patients, but this is controversial due to the resources required. Availability of a convenient, less resource-intensive method of ECG monitoring for patients taking methadone is desirable. The objective of this study was to assess the accuracy of a handheld smartphone ECG (iECG) for QT measurement in patients on maintenance methadone therapy in an urban opioid treatment program. DESIGN: Prospective study. SETTING: Urban opioid treatment program. PATIENTS: n = 115 patients in normal sinus rhythm who were on steady-state maintenance methadone therapy INTERVENTION: Patients (n = 115) underwent a simultaneous 12-lead ECG and a single-lead iECG. MEASUREMENTS AND MAIN RESULTS: The first three QT and RR intervals from lead II of the 12-lead ECG and simulated lead I from the iECG were compared using the Bland-Altman analysis of measurement agreement. Mean [± standard deviation) age was 34 ± 11 years; 71% were female, 75% were white. Compared to the 12-lead ECG, the iECG was associated with a QTc bias of - 0.14 ms (SD = 12 ms, 95% CI = -2.4 to 2.1 ms). The absolute mean difference in QTc between the two methods was 9.5 ± 7.1 ms. For identification of patients with methadone-associated QTc prolongation, the iECG performed moderately well [c-statistic 0.97 (95% CI 0.91-0.99); sensitivity and specificity 75% (95% CI 43-95%) and 99% (95% CI 94-99%), respectively]. The positive and negative likelihood ratios of the iECG for identifying patients with methadone-associated QTc prolongation were 77.25 (95% CI 10.69 to 558.18) and 0.25 (95% CI 0.09 to 0.67), respectively, while the positive and negative predictive values were 90% (95% CI 56-99%) and 97% (95% CI 92-99%), respectively. The accuracy of the iECG for identifying patients with QTc prolongation was 97% (95% CI 91-99%). CONCLUSION: A handheld smartphone ECG is accurate for QT interval measurement in patients taking maintenance methadone therapy, and its performance is moderately good for identifying patients with methadone-associated QTc prolongation.

Methadone-associated QT interval prolongation in patients undergoing maintenance therapy in an urban opioid treatment program.

STUDY OBJECTIVE: Methadone is associated with QT interval prolongation and torsades de pointes. The objective of this study was to (a) determine the incidence of QT interval prolongation among patients on maintenance methadone therapy in an urban opioid treatment program (OTP), (b) compare characteristics of patients who developed methadone-associated QT prolongation with those who did not develop QT prolongation, and (c) investigate the relationship between QT interval prolongation and stereospecific serum methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)] concentrations. DESIGN: Prospective study. SETTING: Urban opioid treatment program (OTP). PATIENTS: n = 93 patients on maintenance methadone therapy in an urban OTP. INTERVENTION: Patients underwent a 12-lead electrocardiogram (ECG) prior to initiating methadone and again during steady-state maintenance methadone therapy. In a subset (n = 43), blood was obtained to determine serum (S)- and (R)-methadone and (S)- and (R)-EDDP concentrations, which were compared in patients who developed Bazett's-corrected QT (QTc) prolongation [≥470 ms (men) or ≥480 ms (women) and/or ≥60 ms lengthening from pretreatment value] with those who did not have QTc prolongation. MEASUREMENTS AND MAIN RESULTS: Mean [± standard deviation (SD)] age was 36 ± 12 years; 73% were female, and 74% were white. QTc prolongation occurred in 14 (15.1%) patients. Patients who developed QTc prolongation were older (41 ± 13 vs. 35 ± 9 years, p = 0.03) and had a longer pre-methadone QTc compared with those who did not have QTc prolongation (429 ± 11 vs. 420 ± 20 ms, respectively, p = 0.02). Serum (S)-methadone concentrations were higher in patients with QTc prolongation compared to patients without prolongation (199 ± 81 vs. 128 ± 68 ng/ml, respectively, p = 0.01), whereas the difference in serum (R)-methadone concentrations between the groups did not reach significance (189 ± 68 vs. 125 ± 60 ng/ml, respectively, p = 0.08). Serum (R)-methadone concentrations correlated with QTc intervals [R2  = 0.15 (95% confidence interval (CI) 0.11-0.62, p = 0.0009)]. The correlation between serum (S)-methadone concentrations and QTc did not reach significance [R2  = 0.08 (95% CI -0.01 to 0.54, p = 0.06)]. Serum (S)-and (R)-EDDP concentrations were not significantly different between the groups and did not significantly correlate with QTc intervals. CONCLUSIONS: Approximately 15% of patients taking maintenance methadone therapy developed QT interval prolongation. Both serum (S)- and (R)-methadone concentrations, but not (S)- or (R)-EDDP, contribute to methadone-associated QT prolongation.

Esketamine: A Novel Option for Treatment-Resistant Depression.

Objective:To review the pharmacology, pharmacokinetics, efficacy, safety, use requirements, and place in therapy of esketamine for treatment-resistant depression (TRD). Data Sources: A comprehensive PubMed search (1966 to October 2019) was conducted using the search terms depression, treatment-resistant, suicide, intranasal, esketamine, and JNJ-54135419. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling, and Clinicaltrials.gov . Study Selection and Data Extraction: All English-language trials evaluating intranasal esketamine for TRD were included and discussed. Data Synthesis: Intranasal esketamine was approved by the US Food and Drug Administration, in conjunction with an oral antidepressant, for treating TRD in adults. Two short-term trials (TRANSFORM-1 and -2) found statistically significant reduction in the Montgomery-Asberg Depression Rating Scale score at day 28 for the fixed 56-mg dose (-4.1; 95% CI = -7.69 to -0.49; P = 0.027 [exploratory]) and flexible-dosed arms (-4.0; 95% CI = -7.31 to -0.64; P = 0.02), though the fixed-dose 84-mg arm (-3.2; 95% CI = -6.88 to 0.45; P = 0.088) of TRANSFORM-1 and TRANSFORM-3 did not (-3.6; 95% CI = -7.2 to 0.07; P = 0.059). Two long-term trials (SUSTAIN-1 and -2) suggested maintenance of response with continued use. Esketamine's adverse effects include dizziness, dysgeusia, somnolence, dissociation, suicidal thoughts and behaviors, and increased heart rate and blood pressure. Relevance to Patient Care and Clinical Practice: Although providing a novel antidepressant mechanism and formulation for TRD, esketamine's role in treatment will likely be limited by cost, administration, and diversion concerns. Conclusion: Intranasal esketamine significantly reduced depression symptoms in TRD, though with tolerability issues.

Evaluation of adherence and persistence with oral versus long-acting injectable antipsychotics in patients with early psychosis.

INTRODUCTION: Despite the theory that long-acting injectable (LAI) antipsychotics should be more likely to improve adherence, reduce gaps in therapy, and prevent relapse compared with oral antipsychotics, there is little published evidence on this issue, specifically in patients with early psychosis. METHODS: Patients with a new diagnosis for a psychotic disorder between July 1, 2013, and August 31, 2014, were retrospectively evaluated during a 12-month duration. The primary outcomes were adherence and persistence. Adherence was determined by proportion of days with medication, and persistence was defined as zero gaps in medication therapy. The secondary outcome was the number of times a psychiatric acute care service was used. Patients were divided into 3 groups based on their antipsychotic prescription history: oral only, LAI only, or both formulations at separate times throughout the study period. RESULTS: Forty-seven patients met inclusion criteria. The average proportions of days with medication were 32%, 76%, and 75% for the oral, LAI, and both formulations groups, respectively (P < .001). For medication persistence, there were 32 patients (91%), 3 patients (75%), and 5 patients (63%) with at least 1 gap in therapy for the oral, LAI, and both formulations groups, respectively (P = .098). For acute care services, there was a median number of zero acute care visits for each of the 3 groups (P = .179). A post hoc subgroup analysis found medication adherence to be statistically different between the oral and LAI groups. DISCUSSION: Long-acting injectable antipsychotics were associated with better adherence compared with oral antipsychotics in patients with early psychosis.