Cannabinoid levels description in a cohort of patients with chronic and neuropathic pain treated with Cannabis decoction: A possible role of TDM.

The phytocomplex of Cannabis is made up of approximately 500 substances: terpeno-phenols metabolites, including Δ-9-tetrahydrocannabinol and cannabidiol, exhibit pharmacological activity. Medical Cannabis has several pharmacological potential applications, in particular in the management of chronic and neuropathic pain. In the literature, a few data are available concerning cannabis pharmacokinetics, efficacy and safety. Thus, aim of the present study was the evaluation of cannabinoid pharmacokinetics in a cohort of patients, with chronic and neuropathic pain, treated with inhaled medical cannabis and decoction, as a galenic preparation. In this study, 67 patients were enrolled. Dried flower tops with different THC and CBD concentrations were used: Bedrocan® medical cannabis with THC level standardized at 19% and with a CBD level below 1%, Bediol® medical cannabis with THC and CBD level standardized at similar concentration of 6.5% and 8%, respectively. Cannabis was administered as a decoction in 47 patients and inhaled in 11 patients. The blood withdrawn was obtained before the new dose administration at the steady state and metabolites plasma concentrations were measured with an UHPLC-MS/MS method. Statistically significant differences were found in cannabinoids plasma exposure between inhaled and oral administration of medical cannabis, between male and female and cigarette smokers. For the first time, differences in cannabinoid metabolites exposures between different galenic formulations were suggested in patients. Therapeutic drug monitoring could be useful to allow for dose adjustment, but further studies in larger cohorts of patients are required in order to confirm these data.

Vitamin D impact in affecting clozapine plasma exposure: A potential contribution of seasonality.

Schizophrenia affects approximately 24 million people worldwide and clozapine is the most effective antipsychotic drug. Nevertheless, its use in therapy is limited due to adverse effects.Therapeutic drug monitoring is a clinical tool useful to reduce the clozapine toxicity. In the literature, papers showed how psychiatric disorders could be associated with low vitamin D levels, but a few studies focusing on its role in affecting clozapine exposure are available. A TDM repository was analyzed: clozapine and vitamin D levels measured with liquid chromatography were considered. 1261 samples obtained from 228 individuals were evaluated: 624 patients (49.5%) showed clozapine plasma levels in therapeutic range (350-600 ng/mL). Clozapine toxic plasma levels (>1000 ng/mL) were more present in winter (p = 0.025), compared to other seasons. Concerning vitamin D, a sub-analysis of 859 samples was performed: 326 (37.81%) were deficient ( ng/mL), 490 (57.12%) had insufficient concentrations (10-30 ng/mL), while 43 (5.02%) had sufficient (>30 ng/mL) levels. A correlation between vitamin D and clozapine plasma levels (p = 0.007, Pearson coefficient=0.093) was observed. The role of seasonal variation in clozapine plasma exposure in psychiatric patients treated with clozapine was suggested. Further studies in larger cohorts are needed in order to clarify these aspects.

Effect of long-acting injectable antipsychotics on hospitalizations and global functioning in schizophrenia: a naturalistic mirror-image study.

Background: Partial adherence to antipsychotics is the most common cause of relapses and rehospitalization in patients with schizophrenia (SZ), leading to higher health care costs and psychosocial disability. The use of long-acting injectable (LAI) antipsychotics may improve therapeutic continuity and adherence to treatment. Objective: To assess the effectiveness of switching from oral antipsychotics (OAs) to long-acting antipsychotics. Methods: This 1-year mirror-image study evaluated the effect of switching from OAs to LAIs on the reduction of psychiatric hospitalizations and the improvement of global functioning in patients with schizophrenia. Differences in outcomes between second-generation (SGA) LAIs and first-generation (FGA) LAIs were also analyzed. Results: In all, 166 patients were included: 32.5% treated by FGA-LAIs and 67.5% by SGA-LAIs. There was an overall reduction of 71% in the average number of hospital admissions and an overall improvement of 29.3% in the Global Assessment of Functioning (GAF) score between the previous 12 months and the 12 months following the switching to LAIs. Patients who switched to SGA-LAIs had no significant differences in hospitalization occurrences but a significant improvement in GAF scores when compared with patients who switched to FGA-LAIs. Conclusion: Our results suggest that using LAIs could be the most adequate treatment choice for SZ patients with a high risk of relapse and low adherence rate. Patients with poorer social functioning may be ideal candidates for SGA-LAIs treatment. Our findings may be of particular interest from a clinical and health care management perspective.

A new UHPLC-MS/MS method for cannabinoids determination in human plasma: A clinical tool for therapeutic drug monitoring.

Cannabinoid derivates have been largely used for different medical purpose. In the literature, several methods capable of separating THC and its principles metabolites are described, although Δ8- and Δ9-THC separation has not been completely achieved. THC metabolism has not been fully understood and metabolites plasma distribution in healthy and pathological patients remains to further deepen. The aim of this study was the validation of UHPLC-MS/MS method for the quantification of 10 cannabinoids in human plasma, as important tool for improving clinical efficacy of cannabis administration. Obtained results were in accordance with recommendations of ICH Harmonised Guideline for bioanalytical method validation, showing a good linearity, optimal accuracy as well as satisfactory results in terms of intra-day and inter-day precision and matrix effect. Furthermore, blood sampling study was performed to investigate the better collection method. Optimal separation of Δ-9-tetrahydrocannabinol (Δ9-THC), Δ8-tetrahydrocannabinol (Δ8-THC) was obtained. The present method showed optimal linearity and satisfactory results in terms of specificity and selectivity. Recovery was between 92.0% and 96.5% for all analytes. The matrix-effect showed good performance; no carry over was observed. Cannabinoid metabolites present in higher plasma concentrations were: 11-Hydroxy-Δ9-tetrahydrocannabinol, 11-Nor-9carboxy-Δ9-tetrahydrocannabinol and THC-COOH-glucuronide. Method performance makes it suitable for routine purposes and a potential tool for therapeutic ranges definition. The present work will be used to test several samples in a long-term clinical study, paving the way for further future works.

A case report and literature review of cognitive malingering and psychopathology.

Malingering of cognitive difficulties constitutes a major issue in psychiatric forensic settings. Here, we present a selective literature review related to the topic of cognitive malingering, psychopathology and their possible connections. Furthermore, we report a single case study of a 60-year-old man with a long and ongoing judicial history who exhibits a suspicious multi-domain neurocognitive disorder with significant reduction of autonomy in daily living, alongside a longtime history of depressive symptoms. Building on this, we suggest the importance of evaluating malingering conditions through both psychiatric and neuropsychological assessment tools. More specifically, the use of Performance Validity Tests (PVTs)-commonly but not quite correctly considered as tests of "malingering"-alongside the collection of clinical history and the use of routine psychometric testing, seems to be crucial in order to detect discrepancies between self-reported patient's symptoms, embedded validity indicators and psychometric results.

Treatment response and tolerability with once-monthly paliperidone palmitate initiated shortly after hospital admission in patients with schizophrenia.

OBJECTIVES: Partial or non-adherence in patients with schizophrenia is common and increases the risk of relapse. This study explored safety, tolerability and treatment outcomes in patients hospitalised for an exacerbation of schizophrenia initiated on maintenance treatment of once-monthly paliperidone palmitate (PP1M). METHODS: A 6-week, observational cohort study of patients initiated on PP1M within 3 weeks after hospital admission. RESULTS: Overall, 367 patients were documented, 85.8% with paranoid schizophrenia subtype. Mean time from hospital admission to PP1M initiation was 9.4 ± 7.7 days. Treatment-emergent adverse events were reported by 22.9% of patients. From baseline to endpoint, significant improvements were observed in psychotic symptoms (Brief Psychiatric Rating Scale total score mean change -19.3 ± 12.6, P < .0001) and functioning (Personal and Social Performance scale total score mean change 14.3 ± 12.4, P < .0001). Overall, 6.0% of patients were very or extremely satisfied with their prior antipsychotic medication at baseline compared with 47.2% very or extremely satisfied with PP1M treatment at endpoint. CONCLUSIONS: Initiating PP1M in patients with exacerbated schizophrenia shortly after hospital admission was well tolerated and resulted in statistically significant and clinically relevant improvements in symptoms and patient functioning, suggesting that patients may benefit from early initiation of PP1M during their hospital stay.