Psychosis-induced Aggression Research Articles

Is haloperidol alone (rapid tranquilization) an effective and safe treatment for psychosis-induced aggression or agitation?

Is haloperidol alone (rapid tranquilization) an effective and safe treatment for psychosis-induced aggression or agitation?

Add-on benzodiazepines for psychosis-induced aggression.

In severely psychotic, violent patients, add-on benzodiazepines are often prescribed with antipsychotic agents. We examined aggression, suicidality, and self-harm among psychotic patients treated with antipsychotic monotherapy, compared with those treated with add-on benzodiazepines, during the first 2 weeks of psychiatric hospitalization to clarify the association of add-on benzodiazepines and aggression. Electronic medical records of 400 patients consecutively admitted to Abarbanel Mental Health Center from 2012 to 2014 for psychosis, and remained hospitalized for at least 2 weeks were evaluated. Violence toward staff, patients, and property, physical restraints, seclusion, self-harm, and suicidal thoughts, were examined. Falls and referrals to general hospital indicated adverse medication effects, and were recorded. No significant between-group differences were found for sex, age, psychiatric diagnosis, compulsory admissions, antipsychotic dosages, number of previous hospitalizations, or hospitalization days were detected. Maximum dosage for antipsychotics in the monotherapy group did not reveal a statistically significant difference from the add-on benzodiazepine group (2.2 ± 1.4 vs. 2.2 ± 1.3, respectively), expressed in defined daily dose. There were no between-group differences in frequency of any violent event, incidence of self-harm, suicidal thoughts, frequency of falls, and/or referrals to a general hospital. Addition of benzodiazepines might be unnecessary. Benzodiazepine addition to antipsychotic drugs for patients with severe psychosis should be with caution.

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

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

In people with psychosis-induced aggression or agitation, how does aripiprazole compare with placebo or other antipsychotics?

In people with psychosis-induced aggression or agitation, how does aripiprazole compare with placebo or other antipsychotics?

Benzodiazepines for Psychosis-Induced Aggression or Agitation.

Benzodiazepines for Psychosis-Induced Aggression or Agitation.

Risperidone for psychosis-induced aggression or agitation (rapid tranquillisation).

Risperidone for psychosis-induced aggression or agitation (rapid tranquillisation).

Aripiprazole (intramuscular) for psychosis-induced aggression or agitation (rapid tranquillisation).

People experiencing psychosis may become aggressive. Antipsychotics, such as aripiprazole in intramuscular form, can be used in such situations. To evaluate the effects of intramuscular aripiprazole in the treatment of psychosis-induced aggression or agitation (rapid tranquillisation). On 11 December 2014 and 11 April 2017, we searched the Cochrane Schizophrenia Group's Study-based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. All randomised controlled trials (RCTs) that randomised people with psychosis-induced aggression or agitation to receive either intramuscular aripiprazole or another intramuscular intervention. We independently inspected citations and, where possible, abstracts, ordered papers and re-inspected and quality assessed these. We included studies that met our selection criteria. At least two review authors independently extracted data from the included studies. We chose a fixed-effect model. We analysed dichotomous data using risk ratio (RR) and the 95% confidence intervals (CI). We analysed continuous data using mean differences (MD) and their CIs. We assessed risk of bias for included studies and used GRADE to create 'Summary of findings' tables. Searching found 63 records referring to 21 possible trials. We could only include three studies, all completed over the last decade, with 885 participants, of which 707 were included for quantitative analyses in this systematic review. Due to limited comparisons, small size of trials and a paucity of investigated and reported 'pragmatic' outcomes, evidence was mostly graded as low or very low quality. No trials reported useful data for one of our primary outcomes of tranquil or asleep by 30 minutes. Economic outcomes were also not reported in the trials.When compared with placebo, fewer people in the aripiprazole group needed additional injections compared to the placebo group (2 RCTs, n = 382, RR 0.69, 95% CI 0.56 to 0.85, very low-quality evidence). Clinically important improvement in agitation at two hours favoured the aripiprazole group (2 RCTs, n = 382, RR 1.50, 95% CI 1.17 to 1.92, very low-quality evidence). The numbers of non-responders after the first injection also favoured aripiprazole (1 RCT, n = 263, RR 0.49, 95% CI 0.34 to 0.71, low-quality evidence). Although no effect was found, more people in the aripiprazole compared to the placebo group experienced adverse effects (1 RCT, n = 117, RR 1.51, 95% CI 0.93 to 2.46, very low-quality evidence).Aripiprazole required more injections compared to haloperidol (2 RCTs, n = 477, RR 1.28, 95% CI 1.00 to 1.63, very low-quality evidence), with no significant difference in agitation (2 RCTs, n = 477, RR 0.94, 95% CI 0.80 to 1.11, very low-quality evidence), and similar non-responders after first injection (1 RCT, n = 360, RR 1.18, 95% CI 0.78 to 1.79, low-quality evidence). Aripiprazole and haloperidol did not differ when taking into account the overall number of people that experienced at least one adverse effect (1 RCT, n = 113, RR 0.91, 95% CI 0.61 to 1.35, very low-quality evidence).Compared to aripiprazole, olanzapine was better at reducing agitation (1 RCT, n = 80, RR 0.77, 95% CI 0.60 to 0.99, low-quality evidence) and had a more favourable effect on global state change scores (1 RCT, n = 80, MD 0.58, 95% CI 0.01 to 1.15, low-quality evidence), both at two hours. No differences were found in terms of experiencing at least one adverse effect during the 24 hours after treatment (1 RCT, n = 80, RR 0.75, 95% CI 0.45 to 1.24, very low-quality evidence). However, participants allocated to aripiprazole experienced less somnolence (1 RCT, n = 80, RR 0.25, 95% CI 0.08 to 0.82, low-quality evidence). The available evidence is of poor quality but there is some evidence aripiprazole is effective compared to placebo and haloperidol, but not when compared to olanzapine. However, considering that evidence comes from only three studies, caution is required in generalising these results to real-world practice. This review firmly highlights the need for more high-quality trials on intramuscular aripiprazole in the management of people with acute aggression or agitation.

Benzodiazepines for psychosis-induced aggression or agitation.

Benzodiazepines for psychosis-induced aggression or agitation.

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

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. 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. 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. Randomised controlledtrials (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. 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. 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). 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.

De-escalation techniques for psychosis-induced aggression or agitation.

Aggression is a disposition, a willingness to inflict harm, regardless of whether this is behaviourally or verbally expressed and regardless of whether physical harm is sustained.De-escalation is a psychosocial intervention for managing people with disturbed or aggressive behaviour. Secondary management strategies such as rapid tranquillisation, physical intervention and seclusion should only be considered once de-escalation and other strategies have failed to calm the service user. To investigate the effects of de-escalation techniques in the short-term management of aggression or agitation thought or likely to be due to psychosis. We searched Cochrane Schizophrenia Group's Study-Based Register of Trials (latest search 7 April, 2016). Randomised controlled trials using de-escalation techniques for the short-term management of aggressive or agitated behaviour. We planned to include trials involving adults (at least 18 years) with a potential for aggressive behaviour due to psychosis, from those in a psychiatric setting to those possibly under the influence of alcohol or drugs and/or as part of an acute setting as well. We planned to include trials meeting our inclusion criteria that provided useful data. We used the standard methodological procedures expected by Cochrane. Two review authors inspected all abstracts of studies identified by the search process. As we were unable to include any studies, we could not perform data extraction and analysis. Of the 345 citations that were identified using the search strategies, we found only one reference to be potentially suitable for further inspection. However, after viewing the full text, it was excluded as it was not a randomised controlled trial. Using de-escalation techniques for people with psychosis induced aggression or agitation appears to be accepted as good clinical practice but is not supported by evidence from randomised trials. It is unclear why it has remained such an under-researched area. Conducting trials in this area could be influenced by funding flow, ethical concerns - justified or not - anticipated pace of recruitment as well the difficulty in accurately quantifying the effects of de-escalation itself. With supportive funders and ethics committees, imaginative trialists, clinicians and service-user groups and wide collaboration this dearth of randomised research could be addressed.

Droperidol for psychosis-induced aggression or agitation.

Droperidol for psychosis-induced aggression or agitation.

Benzodiazepines for psychosis-induced aggression or agitation.

Acute psychotic illness, especially when associated with agitated or violent behaviour, can require urgent pharmacological tranquillisation or sedation. In several countries, clinicians often use benzodiazepines (either alone or in combination with antipsychotics) for this outcome. To estimate the effects of benzodiazepines, alone or in combination with antipsychotics, when compared with placebo or antipsychotics, alone or in combination with antihistamines, to control disturbed behaviour and reduce psychotic symptoms. We searched the Cochrane Schizophrenia Group's register (January 2012), inspected reference lists of included and excluded studies and contacted authors of relevant studies. We included all randomised clinical trials (RCTs) comparing benzodiazepines alone or in combination with any antipsychotics, versus antipsychotics alone or in combination with any other antipsychotics, benzodiazepines or antihistamines, for people with acute psychotic illnesses. We reliably selected studies, quality assessed them and extracted data. For binary outcomes, we calculated standard estimates of relative risk (RR) and their 95% confidence intervals (CI) using a fixed-effect model. For continuous outcomes, we calculated the mean difference (MD) between groups. If heterogeneity was identified, this was explored using a random-effects model. We included 21 trials with a total of n = 1968 participants. There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo, although there was a higher risk of no improvement in people receiving placebo in the medium term (one to 48 hours) (n = 102, 1 RCT, RR 0.62, 95% CI 0.40 to 0.97, very low quality evidence). There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics (n = 308, 5 RCTs, RR 1.10, 95% CI 0.85 to 1.42, low quality evidence); however, people receiving benzodiazepines were less likely to experience extrapyramidal effects (EPS) in the medium term (n = 536, 8 RCTs, RR 0.15, 95% CI 0.06 to 0.39, moderate quality of evidence). Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results. When comparing combined benzodiazepines/antipsychotics (all studies compared haloperidol) with the same antipsychotics alone (haloperidol), there was no difference between groups in improvement in the medium term (n = 155, 3 RCTs, RR 1.27, 95% CI 0.94 to 1.70, very low quality evidence) but sedation was more likely in people who received the combination therapy (n = 172, 3 RCTs, RR 1.75, 95% CI 1.14 to 2.67, very low quality evidence). However, more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine (n = 60,1 RCT, RR 25.00, 95% CI 1.55 to 403.99, very low quality evidence) or ziprasidone (n = 60, 1 RCT, RR 4.00, 95% CI 1.25 to 12.75 very low quality evidence). When haloperidol and midazolam were compared with olanzapine, there was some evidence the combination was superior in terms of improvement, sedation and behaviour. The evidence from trials for the use of benzodiazepines alone is not good. There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects. Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects. Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify. Much more high quality research is needed in this area.

Review: limited evidence on effects of haloperidol alone for rapid tranquillisation in psychosis-induced aggression

Review: limited evidence on effects of haloperidol alone for rapid tranquillisation in psychosis-induced aggression

Loxapine inhaler for psychosis-induced aggression or agitation

Loxapine inhaler for psychosis-induced aggression or agitation

Quetiapine for psychosis-induced aggression or agitation

Quetiapine for psychosis-induced aggression or agitation

P02-18 - Systematic review: chlorpromazine for psychosis induced aggression or agitation

ObjectivesTo examine the effects of chlorpromazine for psychosis-induced aggression or agitation.MethodWe searched the Cochrane Schizophrenia Group Trials Register (2008) for randomised control trials or double blind trials implying randomisation, comparing chlorpromazine with another drug or placebo for people thought to be acutely aggressive due to psychotic illness. For selected studies we extracted data and calculated relative risks (RR) and 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effects model.Results118 studies were identified, two met inclusion criteria. One compared oral chlorpromazine with oral thioridazine and one intramuscular chlorpromazine with intramuscular haloperidol.Those allocated chlorpromazine did not remain on medication (RR 2.00 CI 0.94 to 4.26), or stay in hospital (RR 1.87 CI 0.70 to 4.95) longer than those allocated thioridazine. No differences were found for adverse effects.Those allocated chlorpromazine were no more likely to have one (RR 3.00 CI 0.13 to 68.26), 2-4 (RR 0.90 CI 0.52 to 1.55) or 5+ (RR 0.75 CI 0.20 to 2.79) injections than those allocated haloperidol. Two patients allocated chlorpromazine had, serious hypotension (RR 5.00 CI 0.26 to 96.13), one developed status epilepticus (RR 3.00 CI 0.13 to 68.26), no one allocated haloperidol had these effectsConclusionOverall the quality of evidence is limited and dated. Chlorpromazine was just as effective as similar medicines, but it may be associated with more side effects. Where better, more evaluated drugs are available it may be best to avoid using chlorpromazine. Carefully designed clinical trials are urgently needed.

Aripiprazole for psychosis-induced aggression or agitation

Aripiprazole for psychosis-induced aggression or agitation

Evidence for pharmacological management of psychosis-induced aggression: 4 RCTs, > 1200 randomised, > 98% follow-up

Evidence for pharmacological management of psychosis-induced aggression: 4 RCTs, > 1200 randomised, > 98% follow-up