Serotonin syndrome associated with methadone and milk thistle seeds: a case report

Background: Serotonin syndrome is rarely, potentially life threatening condition, associated with use of serotonin acting medications and psychoactive drugs. In the majority of cases the symptoms occur soon after the initiation of a new drug or a change in the dose. Objective: To present a case report and to describe the possible mechanism of development of serotonin syndrome during the interactions between milk thistle seeds and methadone on hepatic cytochrome enzyme system P450. Methods: A case report of a young man on regular therapy with methadone, who develop a serotonin syndrome after ingestion a high dose of milk thistle seeds. Results: Commercial preparations of milk thistle include the extract silibinin, which exhibits no beneficial or harmful drug interactions at normal doses, but at higher concentrations it can lead to dose-dependent effects on methadone metabolism, through inhibition of CYP3A4 and P-glycoprotein. As a result, it may lead to enhanced serotonin re-uptake inhibition and increased serotonin activity. Discussion: Milk thistle is widely used and recommended for detoxification, but it may have serious and life threatening interactions with psychotropic drugs and psychoactive substances when used in high doses

A systematic review of the effects of novel psychoactive substances “legal highs” on people with severe mental illness

Introduction: Novel psychoactive substances (NPS) are synthetic substances that have been developed to produce altered states of consciousness and perceptions. People with severe mental illness (SMI) are more likely to use NPS than people without mental illness, but the short and long-term effects of NPS are largely unknown. Method: We systematically reviewed the literature about the effects of NPS on people with SMI. Results: We included 12 case reports, 1 cross-sectional survey and 1 qualitative study. Participants included mostly males aged between 20 and 35 years. A variety of NPS were used, including synthetic cathinones and herbs such as salvia. The most commonly reported effects of NPS were psychotic symptoms (in some cases novel in form and content to the patients’ usual symptoms) and significant changes in behaviour, including agitation, aggression and violence. Patients’ vital signs; blood pressure, pulse rate and temperature were also commonly affected. Conclusion: NPS potentially have serious effects on people with severe mental illness but our findings have limited generalisability due to a reliance on case studies. There is a paucity of evidence about the long-term effects of these substances. Further research is required to provide a better understanding about how different NPS affect patients’ mental and physical health. PROSPERO Identifier: CRD42015026944 Keywords: legal highs, novel psychoactive substances, psychotic disorders, severe mental illness, schizophrenia, systemati

New/emerging psychoactive substances and associated psychopathological consequences

Submitted 24 November 2018, Revised 18 June 2019, Accepted 26 June 2019, Published online 22 July 2019BackgroundThe present paper provides an updated review of both the large number of new/novel/emerging psychoactive substances (NPS) and their associated psychopathological consequences. Focus was here given on identification of those NPS being commented in specialised online sources and the related short-/long-term psychopathological and medical ill-health effects.MethodsNPS have been identified through an innovative crawling/navigating software, called the 'NPS.Finder®', created in order to facilitate the process of early recognition of NPS online. A range of information regarding NPS, including chemical and street names; chemical formula; three-dimensional image and anecdotally reported clinical/psychoactive effects, were here made available.ResultsUsing the 'NPS.Finder®' approach, a few thousand NPS were here preliminarily identified, a number which is about 4-fold higher than those figures suggested by European and international drug agencies. NPS most commonly associated with the onset of psychopathological consequences included here synthetic cannabinoids/cannabimimetics; new synthetic opioids; ketamine-like dissociatives; novel stimulants; novel psychedelics and several prescription and over-the-counter medicines.ConclusionsThe ever-increasing changes in terms of recreational psychotropics' availability represent a relatively new challenge for psychiatry, as the pharmacodynamics and pharmacokinetics of many NPS have not been thoroughly understood. Health/mental health professionals should be informed about the range of NPS; their intake modalities; their psychoactive sought-after effects; the idiosyncratic psychotropics' combinations and finally, their medical and psychopathological risks.Peer reviewe

An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration

An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration