Clozapine blood level assessment using a point-of-care device: feasibility and reliability.

Background: Therapeutic drug monitoring (TDM) is useful to assess clozapine adherence and optimize treatment. However, analysis of venous blood levels by liquid chromatography tandem mass spectrometry (LC-MS/MS) is often logistically complicated and process time is prolonged. Objective: To assess the feasibility and reliability of a new point-of-care device, (MyCare™ Insite), using capillary blood for clozapine therapeutic monitoring. Methods: Matched venous and capillary blood samples were collected from patients treated with clozapine on a stable dose. Samples were analyzed by LC-MS/MS and MyCare Insite Clozapine Test. Clozapine plasma levels were compared between methods using linear regression model. Both patients and treatment team completed questionnaires about the feasibility of blood sampling. Results: Of the total sample (44 patients, 61% males, mean age 43 ± 12 years), mean daily clozapine dose was 293 ± 134 mg/day. Linear regression model demonstrated high correlation with R 2 = 0.83 (p < 0.0001) and mean difference of 26 ± 162 ng/ml. More than 60% of the patients found the clozapine TDM to be important. Most of the participants (58%) favored the capillary sampling and 11% claimed that testing method would affect their adherence to TDM. Moreover, a larger portion (72%) strongly preferred to be tested at the office rather than at the lab. Conclusions: The point-of-care device offers an accessible and satisfactory measurement of clozapine blood levels. Both patients and healthcare providers reported preference for capillary sampling as well as for the in-office TDM procedure. The immediate results provided by the device can facilitate rapid and informed clinical decisions and therefore improve clozapine treatment outcomes.

New approaches to antipsychotic medication adherence - safety, tolerability and acceptability.

INTRODUCTION: Antipsychotic pharmacotherapy is considered a first-line treatment in schizophrenia-related disorders and is associated with favorable prognosis and lower mortality rates. However, low adherence rates present a major clinical challenge. In this paper, we will review contemporary approaches to improve adherence to antipsychotic treatment, considering their mechanism of action, safety, tolerability and acceptability. AREAS COVERED: Novel pharmacological delivery methods included different routes of administration of registered medications (such as intramuscular clozapine preparation and transdermal asenapine), modifications of existing compounds (such as 3-monthly injectable formulation of paliperidone palmitate), and increased interest in oral long-acting medication formulations (such as with penfluridol). In addition, we reviewed innovative technology to monitor adherence, based on the use of electronic digital medicine systems and ingestible sensors. EXPERT OPINION: All of these diverse approaches were clinically relevant in enhancing treatment adherence and found to be safe and tolerable. The place of each approach is predicated on a personalized approach in each patient, and future research could usefully use large comparative studies to establish robust treatment guidelines. The implementation of new and varied approaches to antipsychotic treatment adherence is welcomed and have the potential to make a significant impact on morbidity in this often difficult-to-treat population.

Metabolic predictors for mortality among patients treated with long-term clozapine - A longitudinal study.

Clozapine is the only antipsychotic compound indicated for refractory-schizophrenia. However, it is associated with emergent metabolic dysregulation and cardiovascular risk which may lead to mortality. In this study we aimed to explore predictors for mortality in a large cohort of schizophrenia patients treated with long-term clozapine, using the electronic medical records of the largest health care provider in Israel. Among 27,929 patients diagnosed with schizophrenia, 1817 were prescribed clozapine during the years 2012-2014. We compared patients who survived (n=1705) and patients who died (n=112) during the 3-year follow-up period. Socio-demographic background, cardiovascular morbidity, medication prescriptions and health-care utilization were compared between groups. Cox proportional hazard models were used to assess the association of variables with survival. Chronic hypertension was found to be the only metabolic factor associated with significant hazard ratio (HR) for mortality (HR: 1.55 95% CI: 1.03-2.34). Moreover, those who died had more prevalent ischemic heart disease (14% vs 3%, p<0.005) as well as more frequent hospitalizations (0.01±0.02 vs 0.11±0.18 average per month, p<0.005), for longer periods (2.22±9.87 vs 20.38±33.76 days per month, p<0.005). Among those who died, less patients received prescriptions of statins for hyperlipidemia (13.7% vs. 52.9% in survivors, p<0.005) and hypoglycemics for diabetes mellitus (16.3% vs. 67.1% in survivors, p<0.005). Inadequate treatment of metabolic syndrome, under chronic clozapine treatment, was found to be an independent predictor for mortality. Adequate rigorous regimen for diagnosis and treatment of metabolic risk factors, especially hyperlipidemia and diabetes mellitus, might lower complications rate and prolong life expectancy among this population.

Patterns of cannabis use and clinical correlates among individuals with Major Depressive Disorder and Bipolar Disorder.

BACKGROUND: Major Depressive Disorder (MDD) and Bipolar Disorder (BPD) are the most severe mood disorders globally. Previous reports indicate high co-occurrence of cannabis use and cannabis use disorders (CUDs) associated with both disorders, yet studies comparing patterns of cannabis use between individuals with MDD and BPD are scarce. METHODS: Data were drawn from Wave 1 (2001-2002) of the National Epidemiologic survey on Alcohol and Related Conditions (NESARC). Cannabis users who qualified for a diagnosis of past-year MDD (N=217) were compared to those with BPD (N=168) in frequency and daily dose of cannabis use, rates of comorbid psychiatric disorders including specific criteria of CUDs, treatment utilization and suicidality. RESULTS: Among past-year cannabis users, individuals with BPD reported using cannabis more frequently and smoking more joints per day compared to those with MDD. They were also more likely to suffer from comorbid personality disorders and qualify for specific CUD-criteria, including use in physically hazardous situations and unsuccessful efforts to control substance use. CONCLUSIONS: Our results indicate that individuals with BPD may present more intensive patterns of cannabis use compared to those with MDD. This may have potential effects on the course of BPD and should be further explored in longitudinal studies.