Rispridone for psychosis-induced aggression or agitation (rapid tranquilisation) (review)

BackgroundAggressive, agitated or violent behaviour due to psychosis constitutes an emergency psychiatric treatment where fast‐acting interventions are required. Risperidone is a widely accessible antipsychotic that can be used to manage psychosis‐induced aggression or agitation. ObjectivesTo examine whether oral risperidone alone is an effective treatment for psychosis‐induced aggression or agitation. Search methodsWe searched the Cochrane Schizophrenia Group's Study‐Based Register of Trials (up to April 2017); this register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records into the register. Selection criteriaRandomised controlled trials (RCTs) comparing rapid use of risperidone and other drugs, combinations of drugs or placebo for people exhibiting aggression or agitation (or both) thought to be due to psychosis. Data collection and analysisWe independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR) and for continuous data we calculated mean difference (MD), all with 95% confidence intervals (CI) and used a fixed‐effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce a ’Summary of findings’ tables. Main resultsThe review now contains data from nine trials (total n = 582) reporting on five comparisons. Due to risk of bias, small size of trials, indirectness of outcome measures and a paucity of investigated and reported 'pragmatic' outcomes, evidence was graded as very‐low quality. None of the included studies provided useable data on our primary outcome 'tranquillisation or asleep' by 30 minutes, repeated need for tranquillisation or any economic outcomes. Data were available for our other main outcomes of agitation or aggression, needing restraint, and incidence of adverse effects. Risperidone versus haloperidol (up to 24 hours follow‐up) For the outcome, specific behaviour ‐ agitation, no clear difference was found between risperidone and haloperidol in terms of efficacy, measured as at least 50% reduction in the Positive and Negative Syndrome Scale ‐ Psychotic Agitation Sub‐score (PANSS‐PAS) (RR 1.04, 95% CI 0.86 to 1.26; participants = 124; studies = 1; very low‐quality evidence) and no effect was observed for need to use restraints (RR 2.00, 95% CI 0.43 to 9.21; participants = 28; studies = 1; very low‐quality evidence). Incidence of adverse effects was similar between treatment groups (RR 0.94, 95% CI 0.54 to 1.66; participants = 124; studies = 1; very low‐quality evidence). Risperidone versus olanzapine One small trial (n = 29) reported useable data for the comparison risperidone versus olanzapine. No effect was observed for agitation measured as PANSS‐PAS endpoint score at two hours (MD 2.50, 95% CI ‐2.46 to 7.46; very low‐quality evidence); need to use restraints at four days (RR 1.43, 95% CI 0.39 to 5.28; very‐low quality evidence); specific movement disorders measured as Behavioural Activity Rating Scale (BARS) endpoint score at four days (MD 0.20, 95% CI ‐0.43 to 0.83; very low‐quality evidence). Risperidone versus quetiapine One trial reported (n = 40) useable data for the comparison risperidone versus quetiapine. Aggression was measured using the Modified Overt Aggression Scale (MOAS) endpoint score at two weeks. A clear difference, favouring quetiapine was observed (MD 1.80, 95% CI 0.20 to 3.40; very‐low quality evidence). No evidence of a difference between treatment groups could be observed for incidence of akathisia after 24 hours (RR 1.67, 95% CI 0.46 to 6.06; very low‐quality evidence). Two participants allocated to risperidone and one allocated to quetiapine experienced myocardial ischaemia during the trial. Risperidone versus risperidone + oxcarbazepine One trial (n = 68) measured agitation using the Positive and Negative Syndrome Scale ‐ Excited Component.(PANSS‐EC) endpoint score and found a clear difference, favouring the combination treatment at one week (MD 2.70, 95% CI 0.42 to 4.98; very low‐quality evidence), but no effect was observed for global state using Clinical Global Impression ‐ Improvement (CGI‐I) endpoint score at one week (MD ‐0.20, 95% CI ‐0.61 to 0.21; very‐low quality evidence). Incidence of extrapyramidal symptoms after 24 hours was similar between treatment groups (RR 1.59, 95% CI 0.49 to 5.14; very‐low quality evidence). Risperidone versus risperidone + valproic acid Two trials compared risperidone with a combination of risperidone plus valproic acid. No clear differences between the treatment groups were observed for aggression (MOAS endpoint score at three days: MD 1.07, 95% CI ‐0.20 to 2.34; participants = 54; studies = 1; very low‐quality evidence) or incidence of akathisia after 24 hours: RR 0.75, 95% CI 0.28 to 2.03; participants = 122; studies = 2; very low‐quality evidence). Authors' conclusionsOverall, results for the main outcomes show no real effect for risperidone. The only data available for use in this review are from nine under‐sampled trials and the evidence available is of very low quality. This casts uncertainty on the role of risperidone in rapid tranquillisation for people with psychosis‐induced aggression. High‐quality pragmatic RCTs are feasible and are needed before clear recommendations can be drawn on the use of risperidone for psychosis‐induced aggression or agitation

On the potential distortions of highly cited papers in emerging research fields: A critical appraisal

Citation-based metrics are increasingly used as a proxy to define representative, considerable, or significant papers. We challenge this belief by taking into account factors that may play a role in providing citations to a manuscript and whether/how those highly cited studies could shape a scientific field. A different approach to summarisation of relevant core publications within a topic is proposed

Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation)

Background Haloperidol used alone is recommended to help calm situations of aggression or agitation for people with psychosis. It is widely accessible and may be the only antipsychotic medication available in limited-resource areas. Objectives To examine whether haloperidol alone is an effective treatment for psychosis-induced aggression or agitation, wherein clinicians are required to intervene to prevent harm to self and others. Search methods We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (26th May 2016). This register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. Selection criteria Randomised controlled trials (RCTs) involving people exhibiting aggression and/or agitation thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes of interest included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We included trials meeting our selection criteria and providing useable data. Data collection and analysis We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR), for continuous data we calculated mean difference (MD), and for cognitive outcomes we derived standardised mean difference (SMD) effect sizes, all with 95% confidence intervals (CI) and using a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce 'Summary of findings' tables which included our pre-specified main outcomes of interest. Main results We found nine new RCTs from the 2016 update search, giving a total of 41 included studies and 24 comparisons. Few studies were undertaken in circumstances that reflect real-world practice, and, with notable exceptions, most were small and carried considerable risk of bias. Due to the large number of comparisons, we can only present a summary of main results. Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n=220, RR 0.88, 95% CI 0.82 to 0.95, very low-quality evidence) and experienced dystonia (2 RCTs, n=207, RR 7.49, 95% CI 0.93 to 60.21, very low-quality evidence). Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n=473, RR 0.78, 95% CI 0.62 to 0.99, low-quality evidence). More people in the haloperidol group experienced dystonia (2 RCTs, n=477, RR 6.63, 95% CI 1.52 to 28.86, very low-quality evidence). Four trials (n=207) compared haloperidol with lorazepam with no significant differences with regard to number of participants asleep at one hour (1 RCT, n=60, RR 1.05, 95% CI 0.76 to 1.44, very low-quality of evidence) or those requiring additional injections (1 RCT, n=66, RR 1.14, 95% CI 0.91 to 1.43, very low-quality of evidence). Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n=67, RR 8.25, 95% CI 0.46 to 147.45, very low-quality of evidence). Addition of promethazine was investigated in two trials (n=376). More people in the haloperidol group were not tranquil or asleep by 20 minutes (1 RCT, n=316, RR 1.60, 95% CI 1.18 to 2.16, moderate-quality evidence). Acute dystonia was too common in the haloperidol alone group for the trial to continue beyond the interim analysis (1 RCT, n=316, RR 19.48, 95% CI 1.14 to 331.92, low-quality evidence). Authors' conclusions Additional data from new studies does not alter previous conclusions of this review. If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs are available, sole use of haloperidol for extreme emergency could be considered unethical. Addition of the sedating promethazine has support from better-grade evidence from within randomised trials. Use of an alternative antipsychotic drug is only partially supported by fragmented and poor-grade evidence. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries risk of additional harm. After six decades of use for emergency rapid tranquillisation, this is still an area in need of good independent trials relevant to real world practice

The reMAP project: A retrospective, 15-year register study on inpatient care for youth with mental disorders

Aim: We aimed to characterize youth hospitalization trends in a psychiatric inpatient unit from a large, public university hospital with a broad catchment area in Milan, Italy. Methods: Hospitalization data of patients with an age at admission 64 35 were retrospectively retrieved over a time span of 15 years. The sample was comprised of 1982 admissions to a psychiatric ward, aggregated into ICD-10 diagnostic clusters and then analysed. We investigated the epidemiological trends with a focus on age at admission, gender, nationality and hospitalization rates, length of stay and \u201crevolving door\u201d readmissions within a year. Results: Hospitalization rates increased for eating Disorders and decreased for nonaffective psychotic disorders; median length of stay generally decreased; hospitalization rates for foreign youth increased, in particular for those diagnosed with nonaffective psychotic disorders, personality disorders, and substance-related and addictive disorders. The revolving door phenomenon was also associated with nonaffective psychoses and neurodevelopmental disorders, while found to increase for eating disorders. Conclusions: Hospitalization patterns reflect the general increase of foreign youth in the suburban tissue of a large metropolitan area like Milan. However, our data might underestimate the constant growth of mental health problems in foreign youth due to a generally lower access to services. Novel pharmacological treatments and early intervention programs might explain the decrease of hospitalization duration and hospitalization rate for youth with non-affective psychoses. The observed increase in hospitalization for young patients with eating disorders sustains the development of adequate policies tailored towards specialty wards

Asenapine in the Treatment od Acute Mania : a Real-World Observational Study with 6 Months Follow-up

Asenapine is a second-generation antipsychotic with a unique pharmacological profile that was recently approved for the treatment of moderate/severe manic episodes. Real-world data on rapidity of action in inpatient settings are lacking. The aims of the current real-world observational study were to evaluate: (i) short-term efficacy of asenapine after 7 days (T0-T1) in patients hospitalized for a manic episode in the course of bipolar I disorder or schizoaffective disorder (group A), (ii) differences in length of stay (LoS), and (iii) rehospitalization compared to a control population (group B) with a 6-month follow-up. Twenty patients were included in each group. The mean total Young Mania Rating Scale score decreased by 12.6 (SD \ub110.3; t(17) = 5.2, P < 0.005), implying a mean 37.8% improvement. A statistically significant reduction was observed for all Young Mania Rating Scale items, except for \u201csexual interest.\u201d The mean total BPRS score decreased by 17.2 (SD \ub114.9; t(17) = 4.9, P < 0.005). A statistically significant reduction was observed for several items, including \u201cconceptual disorganization,\u201d \u201cgrandiosity,\u201d \u201cunusual thought content,\u201d and \u201cexcitement\u201d. Length of stay was 17.9 (SD \ub19.0) days for group A and 14.7 (SD \ub112.7) days for group B; the result of the Kruskal-Wallis test showed no significant differences (\u3c72 = 2.199, P = 0.138). Despite a high discontinuation rate, only 17.7% of patients in group Awere rehospitalized in the following 6 months compared to 41.2% of those in group B (relative risk = 0.43, 95% confidence interval, 0.13\u20131.39). Findings from this small, preliminary study at least partially support the results of previous trials, confirming effectiveness and tolerability in the context of comorbidity and polypsychopharmacology

Efficacy of Triple Chronotherapy in unipolar and bipolar depression: A systematic review of the available evidence

Background Given the strong relationship between circadian rhythm disruption and mood regulation, combined chronotherapeutic approaches have been proposed for mood disorders. However, a comprehensive review of the available evidence on the efficacy of such interventions for depression is lacking. Aim To systematically review available literature on Triple Chronotherapy (Sleep Deprivation \u2013 Sleep Phase Advance \u2013 Bright Light Therapy) for depressive symptoms in Major Depression and Bipolar Depression. Methods We followed the PRISMA statement for systematic reviews to conduct a web-based search on PubMed, Scopus and Embase using a list of selected keywords relevant to depression and chronotherapy. Results After title and abstract screening of the 321 records retrieved, 25 potentially eligible studies were assessed at full-text screening. Nineteen studies were excluded for failure to match inclusion criteria. Six records of Triple Chronotherapy in addition to conventional treatment, published between 2009 and 2018, were included in the revision. All studies reported significant improvements on HAM\u2013D scores at the end of treatment, with 50% to 84% response rates. Efficacy of treatment was confirmed on follow-up by three studies, with 58% to 61% response rates. Remission rates varied from 33,3% to 77%. Reported side effects were negligible across studies. Limitations Available trials are very few and only one included a control group treated with a daily exercise program. Conclusions The limited literature suggests that Triple chronotherapy might be a safe and effective addition to conventional antidepressant interventions, although well\u2013designed, randomized controlled trials are needed

Dream content and intrusive thoughts in Obsessive-Compulsive Disorder

Although central to any exhaustive theory of human subjectivity, the relationship between dream and waking consciousness remains uncertain. Some findings suggest that dream consciousness can be influenced by severe disorders of thought content. The suppression of unwanted thoughts has been shown to influence dream content in healthy individuals. In order to better define this phenomenon, we evaluated the persistence of obsessive/compulsive themes across the dream and waking cognition of OCD patients and in a control group of healthy subjects. Participants were administered a shortened version of the Thematic Apperception Test to produce a waking fantasy narration, and were trained to keep a dream diary. Dream and waking narrative contents were analyzed in order to recognize obsessive/compulsive themes, and to calculate Mean Dream Obsession/Compulsion (MDO, MDC) and Mean TAT Obsession/Compulsion (MTO, MTC) parameters. No differences were found between the two populations in terms of MDO, MDC, MTO, nor MTC. Density of obsessive and compulsive themes were significantly higher in dream reports than in waking narratives for both groups. No correlation was observed between MDO/MDC scores and Y-BOCS obsession/compulsion scores in the OCD group. These findings strengthen the discontinuity hypothesis, suggesting that ruminative aspects of cognition are somehow interrupted during dream activity

La Triple Chronotherapy come approccio per la riduzione della sintomatologia depressiva e dell&apos;intenzionalit&#224; suicidaria in pazienti ospedalizzati : Protocollo di studio di un Trial randomizzato controllato

Background: Depressive disorders are a relevant burden for public health due to their prevalence and high levels of associated disability and mortality. Recent studies suggest that the combination of multiple chronotherapuetic interventions may reveal effective in the rapid improvement of depressive symptoms. Objectives: This paper describes the protocol of a study that aims to test the efficacy of a triple chronotherapy intervention (combined total sleep deprivation, light therapy and sleep phase advance) in the improvement of depressive symptoms in individuals diagnosed with unipolar or bipolar depression. Methods: A randomized controlled trial will be conducted in patients hospitalized with a unipolar or bipolar depression at the Servizio Psichiatrico di Diagnosi e Cura inpatient unit of the San Paolo - ASST Santi Paolo e Carlo Hospital in Milan, Italy. Individuals will be randomly assigned to the intervention (triple chronotherapy add-on to standard pharmacological treatment) or to the "control" group (standard pharmacological treatment). Results: Enrolment began in December 2018 and will end in October 2020, or at any earlier point in which the expected sample size will be reached. The study protocol has already been approved by the local ethics committee and is registered as EudraCT 2019-000892-18. Outcome analyses aim to verify whether triple chronotherapy produces a rapid and stable improvement in depressive symptoms in individuals hospitalized for an acute unipolar or bipolar depressive episode