Risk factors for coercion length at psychiatric hospitals in Israel: Relationship with staff.

Background: Coercive interventions continue to be applied frequently in psychiatric care when patients are at imminent risk of harming themselves and/or others. Aim: The purpose of this study was to demonstrate the relationship between the length of coercion and a variety of factors, including the sociodemographic background of patients, their diagnoses and the characteristics of hospital staff. Methods: This is a one-year cross-sectional retrospective study, including records of 298 patients who underwent restraint and/or seclusion interventions in male acute, closed wards in two psychiatric hospitals in Israel. Results: A higher proportion of academic nurses to nonacademic nurses on duty leads to a shorter coercion time (P < 0.000). The number of male staff on duty, without any relation to their level of education, also leads to the shortening of the coercion time. Conclusion: The presence of registered, academic female nurses, male staff on duty and the administration of medication before coercive measures can reduce the length of restriction.

Efficacy of oral versus long-acting antipsychotic treatment in patients with early-phase schizophrenia in Europe and Israel: a large-scale, open-label, randomised trial (EULAST).

BACKGROUND: Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. METHODS: EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. FINDINGS: Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 247 patients, 72 (29%) patients completed the study and 175 (71%) met all-cause discontinuation criteria. In the combined LAI treatment arm of 264 patients, 95 (36%) completed the study and 169 (64%) met the all-cause discontinuation criteria. Cox regression analyses showed that treatment discontinuation for any cause did not differ between the two combined treatment groups (hazard ration [HR] 1·16, 95% CI 0·94-1·43, p=0·18). No significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (log rank test χ2=1·87 [df 1]; p=0·17). During the study, 121 psychiatric hospitalisations occurred in 103 patients, and one patient from each of the LAI groups died; the death of the patient assigned to paliperidone was assessed to be unrelated to the medication, but the cause of other patient's death was not shared with the study team. 86 (25%) of 350 participants with available data met akathisia criteria and 70 (20%) met parkinsonism criteria at some point during the study. INTERPRETATION: We found no substantial advantage for LAI antipsychotic treatment over oral treatment regarding time to discontinuation in patients with early-phase schizophrenia, indicating that there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice. FUNDING: Lundbeck and Otsuka.

[LONG-ACTING INJECTABLE ANTIPSYCHOTICS IN SCHIZOPHRENIA].

INTRODUCTION: Long-acting injectable antipsychotics (LAI AP) were mainly developed with the intention to improve adherence to treatment in schizophrenia patients and to reduce the high rates of relapses and re-hospitalizations due to treatment discontinuation. Several studies comparing LAI AP with oral antipsychotics in schizophrenia have been performed, in which RCTs (considered to be the 'gold standard' for clinical trial design) generally show no benefit for LAI AP over oral drugs, whereas observational studies do. The more pragmatic the study design, the more likely it is to show a benefit for LAI AP versus oral therapy. Seeing that the percentage of patients who are currently being treated with LAI AP is far from the percentage of non-adherent patients, it can be argued that LAI AP are significantly underused. LAI AP formulations of antipsychotics have traditionally been used for those patients with schizophrenia with the most severe symptoms, poorest compliance, most hospitalizations, and poorest outcomes, namely at the latter stages of their illness. However, an increasing number of authors suggest that early-phase patients may have the most to gain from LAI AP, at a time when their disorder is most treatable and when avoidance of recurrences and re-hospitalizations may lead to the greatest benefits. To prove the advantage of LAI AP versus oral antipsychotics, there has been an evolution to a new type of clinical trial design that combines some of the best features of both naturalistic "real life" studies and RCTs, namely pragmatic RCT. Currently, there is an ongoing trial in Israel and European countries (the EULAST study) that is an example of this kind of "new" clinical trial design. EULAST is a pragmatic randomized open label cohort study that includes a naturalistic type of follow-up among schizophrenic patients who are early in the disease course. Hopefully, it will dispel doubts concerning the advantages of LAI AP versus oral antipsychotics and will help clinicians to optimize patient's outcomes.

New insights into tardive dyskinesia genetics: Implementation of whole-exome sequencing approach.

Tardive dyskinesia (TD) is an adverse movement disorder induced by chronic treatment with antipsychotics drugs. The contribution of common genetic variants to TD susceptibility has been investigated in recent years, but with limited success. The aim of the current study was to investigate the potential contribution of rare variants to TD vulnerability. In order to identify TD risk genes, we performed whole-exome sequencing (WES) and gene-based collapsing analysis focusing on rare (allele frequency < 1%) and putatively deleterious variants (qualifying variants). 82 Jewish schizophrenia patients chronically treated with antipsychotics were included and classified as having severe TD or lack of any abnormal movements based on a rigorous definition of the TD phenotype. First, we performed a case-control, exome-wide collapsing analysis comparing 39 schizophrenia patients with severe TD to 3118 unrelated population controls. Then, we checked the potential top candidate genes among 43 patients without any TD manifestations. All the genes that were found to harbor one or more qualifying variants in patients without any TD features were excluded from the final list of candidate genes. Only one gene, regulating synaptic membrane exocytosis 2 (RIMS2), showed significant enrichment of qualifying variants in TD patients compared with unrelated population controls after correcting for multiple testing (Fisher's exact test p = 5.32E-08, logistic regression p = 2.50E-08). Enrichment was caused by a single variant (rs567070433) due to a frameshift in an alternative transcript of RIMS2. None of the TD negative patients had qualifying variants in this gene. In a validation cohort of 140 schizophrenia patients assessed for TD, the variant was also not detected in any individual. Some potentially suggestive TD genes were detected in the TD cohort and warrant follow-up in future studies. No significant enrichment in previously reported TD candidate genes was identified. To the best of our knowledge, this is the first WES study of TD, demonstrating the potential role of rare loss-of-function variant enrichment in this pharmacogenetic phenotype.

Patient-centered Approach in Closed Psychiatric Wards: The Curative Power of Relaxing Music Chosen by Patients.

BACKGROUND: Psychiatry is changing as medicine adopts a patient-centered approach. This model of care places greater emphasis on the patients' involvement in determining the goals of their treatment and the nature of their care. This study offers a non-verbal patient-centered intervention by using relaxing music chosen by patients in a closed psychiatric ward to achieve reduction in levels of stress and psychomotor agitation. METHOD: Participants, patients in closed wards, entered a seclusion room whenever they showed psychomotor agitation, overwhelming stress or physical and verbal aggression. While in the seclusion room, participants in the research group (n=24) were exposed to relaxing music of their choice whereas the comparative group (n=28) did not receive any sensory stimulation. The participants filled out the Visual Analogue Scale to measure their emotional state before and after this experience while the staff filled out the Behavioral Activity Rating Scale. RESULTS: Results show significantly higher emotional calm and prominent reduction in psychomotor agitation among the research group in comparison with the comparative group. CONCLUSIONS: Relaxing music chosen by patients has a positive effect on their emotional state and behavioral activity and may therefore serve as an alternative sensory intervention before patients reach violent situations that require restraint.

Overcrowding in Psychiatric Wards is Associated With Increased Risk of Adverse Incidents.

OBJECTIVE: To study the association between bed occupancy in psychiatric wards and rate of adverse incidents (AIs) including aggressive behavior and falls. METHODS: This is a retrospective study analyzing bed occupancy and AIs' data in 4 closed wards in a state psychiatric hospital in Israel over a 20-month period. Ward-level daily records were extracted from the hospital's electronic admission-discharge and AI registries, creating a log of 609 days for each of the 4 wards. Relationships between gross and net bed occupancy and AIs rate were calculated, in general and for each ward and type of incidents. RESULTS: Average gross occupancy was 106±14.8% and net occupancy was 96.4±15.6%. Gross occupancy >100% was recorded in 51% of days. Net occupancy was higher on days with at least 1 incident than on no-incident days (98.6±14.8% vs. 95.7±15.7%, P<0.0001). AIs occurred in 18.6% of days in the lowest occupancy quadrant (up to 85% occupancy), compared with 26.7% of days in the highest occupancy quadrant (106% and above). Moreover, aggressive behavior-type incidents were significantly lower in the lowest occupancy quadrant days compared with the highest occupancy quadrant (8.3% vs. 14.1%, P<0.01). Evidence of a dose-response effect of bed occupancy on AIs rate was found. CONCLUSIONS: Overoccupancy is prevalent in psychiatric wards and is associated with an increased rate of aggressive AIs and falls. Policy makers should be convinced about the necessity to reduce overcrowding in psychiatric wards and to improve safety of inpatient facilities.

A multicenter, add-on randomized controlled trial of low-dose d-serine for negative and cognitive symptoms of schizophrenia.

BACKGROUND: Observations that antagonists of the N-methyl-d-aspartate (NMDA) receptor of glutamatergic neurons can mimic symptoms of schizophrenia have raised the hope that NMDA agonists can improve symptoms. On the basis of encouraging results of trials in which NMDA agonists were added to antipsychotics, we conducted an adequately powered randomized controlled trial adding d-serine, an NMDA modulator, to antipsychotics. METHOD: This study was a 195-patient, multicenter, double-blind, randomized, placebo-controlled, 16-week trial of d-serine 2 g/d as an add-on treatment to antipsychotics. Subjects had DSM-IV schizophrenia or schizoaffective disorder and were inpatients or outpatients stabilized on antipsychotics, with persistent negative symptoms. The primary outcome measures were changes in negative symptoms and cognition as measured by the Scale for the Assessment of Negative Symptoms (SANS) and the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery, respectively. The study was performed between 2003 and 2007. RESULTS: Mean total Positive and Negative Syndrome Scale scores at baseline were 75.5. Subjects receiving d-serine and placebo improved in scores on the SANS and MATRICS, but no significant differences were observed between groups: improvement on SANS was 11.4% for d-serine vs 14.8% for placebo, F1,147=1.18, P=.32; and improvement on MATRICS was 6.8% for d-serine vs 6.1% for placebo, F1,125=0.96, P=.39, respectively. d-Serine was well tolerated. DISCUSSION: This study did not find a significant difference between drug and placebo. However, the results are limited by a relatively large placebo response and somewhat lower-achieved doses than in prior studies. Future studies will administer higher doses and will attempt to affect the NMDA receptor using other mechanisms, such as agonists of the presynaptic metabotropic glutamate 2/3 receptor or glycine reuptake inhibitors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00138775.

[Non-urgent compulsory hospitalization].

The Israel Mental Health Law of 1991 gave authority to the regional psychiatrist to give orders of compulsory hospitalization - urgent and non-urgent. The non-urgent Hospitalization Order applies to conditions of non-immediate danger, in which potential for significant damage or harm to the patient or others is expected. Authority is granted to the District Psychiatric Committee as a body of appeal (before the Hospitalization Order is carried out) and as a tribunal to decide upon continuation after the first two weeks of hospitalization. This article aims to stress the main problems encountered by psychiatrists regarding management and treatment under the Non-Urgent Compulsory Hospitalization Order: 1) Postponing hospitalization or releasing a patient for 24 hours, in order to launch an appeal before receiving any treatment, may facilitate clinical deterioration. The ambiguous waiting period could enhance anxiety, acting out and dangerousness. 2) The article discusses clinical and legal aspects of compulsory hospitalization - both urgent and non-urgent. The diverse problematic issues will be elaborated through three clinical cases, and, when clinically indicated, proposals raised for possible solutions in converting an urgent compulsory order to a non-urgent compulsory order.

[Multisensory environmental intervention (snoezelen) as a preventive alternative to seclusion and restraint in closed psychiatric wards].

UNLABELLED: Seclusion and restraint, unfortunately, still remain a routine practice in closed psychiatric wards worldwide and in Israel. These practices often lead to distress, traumatized patients, and further increase the negative view and stigmatization of psychiatric treatment and, most especially, psychiatric hospitalization. Multisensory environmental intervention, Snoezelen, combines sensory integration theory with a client-oriented approach. Snoezelen treatment calms and relaxes agitative patients giving them a feeling of dignity, initiative and freedom of choice. The Snoezelen room is a high-tech, multisensory environment that includes music, light of fiber optic strands, calming image projections, vibrations of bubbles tubes, and soothing smells. After 30 to 40 minutes of exposure to Snoezelen, agitative patients in our closed ward reported substantial reduction of their distress level and, outwardly, appeared less agitated and displayed less aggressive and hostile behavior. Foremost, since the beginning of the multisensory environmental interventions in the closed wards, a statistically significant reduction in the number of restraints and seclusions has occurred in the closed male section in comparison to the closed female section, where snoezelen has not been administered (P < 0.05). IN CONCLUSION: Snoezelen is an innovative and preventative alternative to seclusion and restraint in closed psychiatric settings. It produces a calming effect on agitative patients, reduces the length of time and number of seclusions and restraints, and diminishes the stigma against psychiatric treatment and hospitalization.

[Legal involvement in psychiatric care].

In an amendment to the law regarding the treatment of the Mental Health patient in 1991, authority was given to the regional psychiatrists' committee to oversee compulsory orders for psychiatric hospitalization and compulsory orders for outpatient psychiatric treatment--and the extension of these orders. On 1st of June 2002 a pilot study was started in the Jerusalem region, in which mental health patients were to be represented by lawyers employed by the Ministry of Justice. The pilot study began as an initiative of the Ministry of Justice, in agreement with the Ministry of Health. We describe 3 cases which demonstrate that the procedure of legal representation lacks the necessary balance between medical and legal considerations. The decision of the regional psychiatrists' committee or the court is liable to worsen the patients' mental health status and even to accelerate aggression towards self or others. In rare cases a premature discharge based on legal considerations rather than medical evaluation may result in suicide, as demonstrated in one of the vignettes. The article discusses the unbalanced approach of legal versus medical consideration, preference of "liberty" over health and the "wish" of the patient rather than his well-being. The article considers the unbalanced approach of the legal system to appeals of therapists against the decision of the regional psychiatrists' committee, where prosecutors of the state decided an appeal of this kind over the staff treating the patient has no precedence. That was presented as justification that it should be rejected. A pilot study compared between patients discharged from compulsory hospitalization through regional psychiatrists' committee or court and patients discharged on a medical basis without legal interference. The study showed a shorter stay in the community in the first group (42%) compared to 75% stay in the community in the second group, after six months. We are of the opinion that the current provision of legal assistance is lacking the necessary balance between medical and legal considerations; the 'wish for freedom' as a default, although illogical, is within the new system of legal aid, and is more considerate and important than the 'best interests' of the patient and his health.

Comparison between two legal indications for compulsory outpatient treatment in Israel.

The aim of the present study was to compare the outcome of two legal indications for Compulsory Outpatient Treatment (COT) in Israel (a) as an alternative to compulsory hospitalization (CH) and (b) as a follow-up to CH. Demographic, clinical and legal measurements based on 326 COT orders issued in the Jerusalem and Southern district of Israel were compared according to the two legal provisions for COT contained in the Treatment of Mental Patients Law (1991). The COT order was found to be more effective when used as an alternative to CH (53.1%) than when it was used following CH (38.8%), p = 0.002. In the former case, there were fewer schizophrenic patients, fewer hospitalizations, fewer visits to psychiatric emergency services and longer remissions. Our results point to the influence of the legal indications on the efficacy of the COT order and help define the target population.