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.

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].

Vitamin E and essential polyunsaturated fatty acids supplementation in schizophrenia patients treated with haloperidol.

OBJECTIVES: Previously, oxidative damage has been associated with severity of clinical symptoms and supplementation with antioxidants and essential polyunsaturated fatty acids (EPUFAs) was proposed to have beneficial effects in schizophrenia. We evaluated the effects of supplementation with EPUFAs and vitamin E in patients treated with haloperidol depot injection. DESIGN: This was a double-blind randomized placebo-controlled study with four arms (Placebo, vitamin E, EPUFAs, and vitamin E + EPUFAs). Biomarkers of oxidative stress, neurochemistry, psychopathology, and extrapyramidal symptoms were assessed at baseline and after 4 months. RESULTS: In EPUFAs group of patients, reduced glutathione concentration was increased compared to placebo. Concentration of oxidized glutathione was decreased in patients receiving vitamin E. In addition, compared to placebo a non-significant trend of increased activity of catalase and superoxide dismutase was observed in all three treatment groups. Patients receiving vitamin E experienced less motor retardation. No difference in extrapyramidal symptoms was found. DISCUSSION: Our study indicates that supplementation with vitamin E and EPUFAs may improve the antioxidative defense, especially glutathione system, while there is no major effect on symptoms severity. Supplemental treatment with EPUFAs and vitamin E in schizophrenia patients treated with haloperidol is potentially beneficial and a larger independent study appears warranted.

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.

A population pharmacokinetic evaluation of the influence of CYP2D6 genotype on risperidone metabolism in patients with acute episode of schizophrenia.

The objective of this prospective study was to characterize the metabolism of risperidone to (+)- and (-)-9-hydroxyrisperidone in vivo and to evaluate the influence of CYP2D6 genotype. A population pharmacokinetic modeling approach was used to estimate the interindividual variability of the pharmacokinetic parameters in 50 hospitalized patients with acute episode of schizophrenia. CYP2D6 genotype remarkably influenced the formation clearances of the risperidone metabolites, while creatinine clearance was related to the plasma clearance of 9-hydroxyrisperidone. CYP2D6 genotype was also associated with the average plasma concentration of risperidone active moiety (a sum of all three active compounds). In comparison to the patients with CYP2D6*1/*1 genotype, average steady-state plasma concentration of risperidone active moiety was 3.3- and 1.6-fold higher in poor metabolizers (both alleles nonfunctional; CYP2D6*3 or *4) and intermediate metabolizers (one nonfunctional allele and one allele for diminished enzyme activity; CYP2D6*10 or *41), respectively. Additionally, average plasma concentration of risperidone active moiety was higher in the patients with dystonia (p=0.0066) and parkinsonism (p=0.046). The results of this study imply the potential role of CYP2D6 genotyping in personalizing risperidone therapy in patients with schizophrenia to reduce the incidence of adverse extrapyramidal symptoms.

MDR1 gene polymorphisms and response to acute risperidone treatment.

Polymorphic multidrug resistant protein 1 (MDR1) transports drugs against a concentration gradient across the blood-brain barrier and reduces their accumulation in the brain. MDR1 may therefore influence antipsychotic brain availability contributing to inter-individual differences in treatment response and adverse effects, regardless of plasma concentrations. In the present study we investigated the influence of two common MDR1 polymorphisms on the improvement of psychopathological symptoms and occurrence of extrapyramidal side effects (EPS) in Slovenian schizophrenia patients acutely treated with risperidone. A total of 59 clinically well defined patients with first episode schizophrenia spectrum disorders or after tapering their maintenance treatment were genotyped for MDR1 C3435T and G2677T/A. Steady-state plasma concentrations of risperidone active moiety (sum of risperidone and the 9-hydroxyrisperidone) were determined. G2677T/A and C3435T genotypes were not associated to psychopathological symptoms, efficacy of treatment and risk for parkinsonism. Marginal associations with akathisia (p=0.039 and p=0.042, respectively) and dystonia (p=0.013 and p=0.034, respectively) were observed for both G2677T/A and C3435T genotypes. However, higher AIMS and BARS scores were observed only in heterozygous carriers of G2677T/A and C3435T polymorphisms and there was no tendency of gene-dose effect. The present study does not suggest a major influence of MDR1 G2677T/A and C3435T polymorphisms on treatment response during short-term risperidone therapy in patients with schizophrenia or schizoaffective disorder.

Acute antipyschotic efficacy and side effects in schizophrenia: association with serotonin transporter promoter genotypes.

BACKGROUND: The serotonin transporter (5-HTT) plays an important role in serotonergic neurotransmission. In the present study, we investigated the effects of the 44 bp insertion/deletion polymorphism in the promoter region of 5-HTT gene (5-HTTLPR) on symptomatology of psychosis and clinical response to antipsychotic drugs. METHODS: In total 56 patients acutely treated with haloperidol or risperidone either for the first episode of schizophrenia, schizophreniform or schizoaffective disorders, or for the relapse of these psychotic disorders after tapering their maintenance treatment, were genotyped for the 5-HTTLPR L and S alleles and for the new A/G functional variant within the L alelle (La/g). Psychopathological symptoms were assessed with the Brief Psychiatric Rating Scale (BPRS) and with Clinical Global Impression (CGI) twice: at 8-12 days after the first dose of antipsychotic and after 4 weeks. Extrapyramidal side effects were assessed with the Simpson-Angus Extrapyramidal Side Effects Scale (EPS), the Barnes Akathisia Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS). RESULTS: Age, body mass index (BMI), illness duration, drug type and dosage were considered as covariates when analysing association with genetic variants as they were associated with baseline or final BPRS and CGI scores and/or extrapyramidal side effects. 5-HTTLPR was not associated with baseline and final BPRS and CGI scores or with the CGI% reduction. However, the 5-HTTLPR S allele was associated with a lower improvement in BPRS scores (P=0.022) and this effect was even stronger after pooling subjects with S or Lg containing alleles (P=0.006). We did not observe any effect of 5-HTTLPR on acute antipsychotics side effects. CONCLUSION: Present result supports a contribution of serotonin system to neuroleptics efficacy for the treatment of schizophrenia. The analysis of the La/g functional variant may significantly improve the predictive power of 5-HTTLPR genotyping and represent a step further towards the development of the personalized antipsychotic treatment.

Polymorphisms in dopamine receptor DRD1 and DRD2 genes and psychopathological and extrapyramidal symptoms in patients on long-term antipsychotic treatment.

DRD(1) and DRD(2) receptor gene variants have been associated with clinical aspects of schizophrenia; however only specific features were analyzed in different samples. To assess the complex interaction between genetic and clinical factors, we studied the possible cross-interactions between DRD1 and DRD2 dopamine receptor gene polymorphisms, symptomatology of schizophrenia and schizoaffective disorders, and the occurrence of treatment induced side effects taking into consideration possible clinical confounding variables. One hundred thirty one outpatients in stable remission meeting the DSMIV criteria for schizophrenia spectrum disorders and receiving long-term maintenance therapy with haloperidol, fluphenazine, zuclopenthixole, or risperidone were genotyped for DRD1 A-48G, DRD2 Ins-141CDel, and DRD2 Ser311Cys polymorphisms. Psychopathological symptoms were assessed with the positive and negative syndrome scale for schizophrenia (PANSS). Extrapyramidal side effects were assessed with the Simpson-Angus extrapyramidal side effects scale (EPS), the Barnes Akathisia scale (BARS), and the abnormal involuntary movement scale (AIMS). Drug dosage was included as covariant because it was associated with the severity of symptomatology, akathisia, and parkinsonism. No association was observed for DRD1 and DRD2 polymorphisms and extrapyramidal side effects, or with the other clinical variables considered. Our study suggests that DRD1 and DRD2 variants are not liability factors for tardive dyskinesia.