Use of synthetic cannabinoids in patients with psychotic disorders: case series.

An increasing number of synthetic cannabinoids have become available on the black market in recent years, and health professionals have seen a corresponding increase in use of these compounds among patients with psychiatric disorders. Unfortunately, there is almost no research available in the literature on this topic, and what little exists is based on case reports of individuals without psychiatric disorders. Synthetic cannabinoids are functionally similar to, but structurally different from, delta-9-tetrahydrocannabinol, the active principle in cannabis, and are problematic for many reasons. The psychotropic action of synthetic cannabinoids in patients with schizophrenia is unpredictable, with very diverse clinical presentations. These drugs can be much more potent than delta-9-tetrahydrocannabinol, they are readily available and difficult to detect. The gold standard for identification of synthetic cannabinoids is gas chromatography with mass spectrometry, but even this is difficult because new formulations of these designer drugs are constantly emerging. In this manuscript, we provide an overview and discussion of synthetic cannabinoids and present four cases of patients with synthetic cannabinoid intoxication who were hospitalized in our intensive psychiatric unit at the time of intoxication. All patients had a history of schizophrenia and had been hospitalized several times previously. While hospitalized, they smoked an unknown substance brought in by a visitor, which was then confirmed using gas chromatography with mass spectrometry to be the synthetic cannabinoid AM-2201. Our patients experienced predominantly psychiatric adverse clinical effects. We observed the appearance of new psychotic phenomena, without exacerbation of their previously known psychotic symptoms, as well as the occurrence or marked worsening of mood and anxiety symptoms. Despite several similar reactions, and even though they ingested the same exact substance, the clinical picture differed markedly between individual patients. We assume that the acute effects of synthetic cannabinoids in patients with schizophrenia would be different from those in persons without psychotic disorders. The reasons for this difference could be the actual symptomatology of the presenting disorder, the impact of psychopharmacotherapy, individual patient differences and probably many, as yet unknown, factors. The long-term consequences of synthetic cannabinoid use on preexisting psychotic disorders are unclear.

Incidence, Severity and Characteristics of Patients' Aggression in Acute Psychiatric Wards: Data from a Slovenian National Survey.

Aim: To evaluate the incidence, severity and characteristics of aggressive behaviour in patients hospitalized in acute psychiatric wards, as well as the association between patient characteristics and the incidence of recurrent aggressive behaviour. Methods: A multicentre prospective study included all twelve acute wards in Slovenian psychiatric hospitals with a total capacity of 232 beds. Over five consecutive months, data on the number of treatment episodes involving aggressive behaviour and the number of aggressive incidents, their severity and characteristics were obtained using the Staff Observation Aggression Scale-Revised (SOAS-R). Patient- and event-based incident rates of verbal and physical aggression were calculated. The association between patient characteristics and recurrent aggressive behaviour was analysed. Patient characteristics data were extracted from hospital databases. Results: 3,190 treatment episodes were included during a 5-month period. Aggressive behaviour was observed in 13.4% of treatment episodes, and 922 aggressive incidents were recorded, which resulted in 3.98 incidents per 100 occupied bed days and 9.48 incidents per bed per year. 74.1% of incidents were severe, and more than half of incidents included physical aggression. 75.5% of incidents were directed against medical staff. 5.9% of treatment episodes were involved in multiple aggressive incidents. Compared to patients with single incidents, patients with recurrent aggression had a less frequent main diagnosis of substance use disorders and a longer duration of hospitalization. Conclusion: Monitoring the frequency and characteristics of aggressive behaviour allows comparisons with other studies and, more importantly, it is necessary for planning and assessing the effectiveness of preventative aggression management strategies.

An expert review of clozapine in Eastern European countries: Use, regulations and pharmacovigilance.

OBJECTIVES: To compare the prevalence, regulations, and pharmacovigilance practices of clozapine use in Eastern European countries (except Russia). METHODS: Questionnaires and data from administrative databases (2016 and 2021), package inserts and national guidelines were collected from 21 co-authors from 21 countries. Reports of clozapine adverse drug reactions (ADRs) sent to the global pharmacovigilance database (VigiBase™) were analyzed from introduction to December 31, 2022. RESULTS: Clozapine prescription among antipsychotics in 2021 varied six-fold across countries, from 2.8 % in the Czech Republic to 15.8 % in Montenegro. The utilization of antipsychotics in both 2016 and 2021 was highest in Croatia, and lowest in Serbia in 2016, and Montenegro in 2021, which had half the defined daily dose (DDD)/1000/day compared to the Croatian data. From 2016 to 2021, the prevalence of antipsychotic use increased in almost all countries; the proportion of clozapine use mainly remained unchanged. Differences were detected in hematological monitoring requirements and clozapine approved indications. Only a few national schizophrenia guidelines mention clozapine-induced myocarditis or individual titration schemes. The VigiBase search indicated major underreporting regarding clozapine and its fatal outcomes. By comparison, the United Kingdom had less than half the population of these Eastern European countries but reported to VigiBase more clozapine ADRs by 89-fold and clozapine fatal outcomes by almost 300-fold. CONCLUSION: Clozapine is under-utilized in Eastern European countries. Introducing individualized clozapine treatment schedules may help to maximize clozapine benefits and safety. Major improvement is needed in reporting clozapine ADRs and fatal outcomes in Eastern European countries.

Effectiveness of De-Escalation in Reducing Aggression and Coercion in Acute Psychiatric Units. A Cluster Randomized Study.

Objective: Most guidelines for the management of aggressive behavior in acute psychiatric patients describe the use of de-escalation as the first-choice method, but the evidence for its effectiveness is inconsistent. The aim of the study was to assess the effect of verbal and non-verbal de-escalation on the incidence and severity of aggression and the use of physical restraints in acute psychiatric wards. Methods: A multi-center cluster randomized study was conducted in the acute wards of all psychiatric hospitals in Slovenia. The research was carried out in two phases, a baseline period of five consecutive months and an intervention period of the same five consecutive months in the following year. The intervention was implemented after the baseline period and included training in verbal and non-verbal de-escalation techniques for the staff teams on experimental wards. Results: In the baseline study period, there were no significant differences in the incidence of aggressive behavior and physical restraints between the experimental and control groups. The incidence rates of aggressive events, severe aggressive events, and physical restraints per 100 treatment days decreased significantly after the intervention. Compared to the control group, the incidence rate of aggressive events was 73% lower in the experimental group (IRR = 0.268, 95% CI [0.221; 0.342]), while the rate of severe events was 86% lower (IRR = 0.142, 95% CI [0.107; 0.189]). During the intervention period, the incidence rate of physical restraints due to aggression in the experimental group decreased to 30% of the rate in the control group (IRR = 0.304, 95% CI [0.238; 0.386]). No reduction in the incidence of restraint used for reasons unrelated to aggression was observed. After the intervention, a statistically significant decrease in the severity of aggressive incidents (p < 0.001) was observed, while the average duration of restraint episodes did not decrease. Conclusion: De-escalation training is effective in reducing the incidence and severity of aggression and the use of physical restraints in acute psychiatric units. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT05166278].

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

Abstract 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.