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.

Haloperidol for long-term aggression in psychosis.

BACKGROUND: Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically aggressive behaviour - and both can be prolonged. Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users; it is a frequent cause for admission to inpatient facilities. If people continue to be aggressive it can lengthen hospitalisation. Haloperidol is used to treat people with long-term aggression. OBJECTIVES: To examine whether haloperidol alone, administered orally, intramuscularly or intravenously, is an effective treatment for long-term/persistent aggression in psychosis. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2011 and April 2015). SELECTION CRITERIA: We included randomised controlled trials (RCT) or double blind trials (implying randomisation) with useable data comparing haloperidol with another drug or placebo for people with psychosis and long-term/persistent aggression. DATA COLLECTION AND ANALYSIS: One review author (AK) extracted data. For dichotomous data, one review author (AK) calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. One review author (AK) assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS: We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study (1 RCT, n=110, RR 1.37, CI 0.84 to 2.24, low-quality evidence). Although there were some data for the outcomes listed above, there were no data on most of the binary outcomes and none on service outcomes (use of hospital/police), satisfaction with treatment, acceptance of treatment, quality of life or economics. AUTHORS' CONCLUSIONS: Only one study could be included and most data were heavily skewed, almost impossible to interpret and oflow quality. There were also some limitations in the study design with unclear description of allocation concealment and high risk of bias for selective reporting, so no firm conclusions can be made. This review shows how trials in this group of people are possible - albeit difficult. Further relevant trials are needed to evaluate use of haloperidol in treatment of long-term/persistent aggression in people living with psychosis.

Eight decades of mortality in an English high-security hospital.

BACKGROUND: Psychiatric patients are known to have poorer physical health than the general population and to have premature mortality, but the impact of institutional care on the physical health of patients is less clear. AIMS: This study aimed to compare mortality rates and causes of death between a high-security psychiatric hospital cohort and the general population in England for the periods 1920-1961 and 1972-2000. METHOD: Data were obtained from various clinical and non-clinical archives and death certificates. Standardised mortality ratios were calculated for all causes of patient death for each International Classification of Diseases, 10th Edition category. RESULTS: Mortality rates of men ever resident in Rampton Hospital were similar to those of men in the general population, but women in Rampton Hospital had nearly twice the national death rate. Younger men in the latest time period (1972-2000), however, had a higher mortality rate. Higher mortality rates in the hospital than in the general population were accounted for by infectious and parasitic diseases as well as diseases of the nervous system; rates of neoplasms and diseases of the blood and of circulatory or respiratory diseases were lower among the patients. CLINICAL IMPLICATIONS: Specific-cause mortality rates were compatible with our working hypothesis that the hospital could in some ways pose risks and in other ways be protective. Morbidity and causes of premature death may be environment-specific, so recognition of the types of illness linked to premature death among high-security hospital patients could inform improvements in the physical health of long-stay patients. Further longitudinal studies should be undertaken to monitor trends and inform changes needed to reduce premature mortality. Copyright © 2015 John Wiley & Sons, Ltd.

Pharmacological interventions for those who have sexually offended or are at risk of offending.

BACKGROUND: Sexual offending is a serious social problem, a public health issue, and a major challenge for social policy. Victim surveys indicate high incidence and prevalence levels and it is accepted that there is a high proportion of hidden sexual victimisation. Surveys report high levels of psychiatric morbidity in survivors of sexual offences.Biological treatments of sex offenders include antilibidinal medication, comprising hormonal drugs that have a testosterone-suppressing effect, and non-hormonal drugs that affect libido through other mechanisms. The three main classes of testosterone-suppressing drugs in current use are progestogens, antiandrogens, and gonadotropin-releasing hormone (GnRH) analogues. Medications that affect libido through other means include antipsychotics and serotonergic antidepressants (SSRIs). OBJECTIVES: To evaluate the effects of pharmacological interventions on target sexual behaviour for people who have been convicted or are at risk of sexual offending. SEARCH METHODS: We searched CENTRAL (2014, Issue 7), Ovid MEDLINE, EMBASE, and 15 other databases in July 2014. We also searched two trials registers and requested details of unidentified, unpublished, or ongoing studies from investigators and other experts. SELECTION CRITERIA: Prospective controlled trials of antilibidinal medications taken by individuals for the purpose of preventing sexual offences, where the comparator group received a placebo, no treatment, or 'standard care', including psychological treatment. DATA COLLECTION AND ANALYSIS: Pairs of authors, working independently, selected studies, extracted data, and assessed the risk of bias of included studies. We contacted study authors for additional information, including details of methods and outcome data. MAIN RESULTS: We included seven studies with a total of 138 participants, with data available for 123. Sample sizes ranged from 9 to 37. Judgements for categories of risk of bias varied: concerns were greatest regarding allocation concealment, blinding of outcome assessors, and incomplete outcome data (dropout rates in the five community-based studies ranged from 3% to 54% and results were usually analysed on a per protocol basis).Participant characteristics in the seven studies were heterogeneous, but the vast majority had convictions for sexual offences, ranging from exhibitionism to rape and child molestation.Six studies examined the effectiveness of three testosterone-suppressing drugs: cyproterone acetate (CPA), ethinyl oestradiol (EO), and medroxyprogesterone acetate (MPA); a seventh evaluated two antipsychotics (benperidol and chlorpromazine). Five studies were placebo-controlled; in two, MPA was administered as an adjunctive treatment to a psychological therapy (assertiveness training or imaginal desensitisation). Meta-analysis was not possible due to heterogeneity of interventions, comparators, study designs, and other issues. The quality of the evidence overall was poor. In addition to methodological issues, much evidence was indirect. PRIMARY OUTCOME: recividism. Two studies reported recidivism rates formally. One trial of intramuscular MPA plus imaginal desensitisation (ID) found no reports of recividism at two-year follow-up for the intervention group (n = 10 versus one relapse within the group treated by ID alone). A three-armed trial of oral MPA, alone or in combination with psychological treatment, reported a 20% rate of recidivism amongst those in the combined treatment arm (n = 15) and 50% of those in the psychological treatment only group (n = 12). Notably, all those in the 'oral MPA only' arm of this study (n = 5) dropped out immediately, despite treatment being court mandated.Two studies did not report recidivism rates as they both took place in one secure psychiatric facility from which no participant was discharged during the study, whilst another three studies did not appear directly to measure recividism but rather abnormal sexual activity alone. SECONDARY OUTCOMES: The included studies report a variety of secondary outcomes. Results suggest that the frequency of self reported deviant sexual fantasies may be reduced by testosterone-suppressing drugs, but not the deviancy itself (three studies). Where measured, hormonal levels, particularly levels of testosterone, tended to correlate with measures of sexual activity and with anxiety (two studies). One study measured anxiety formally; one study measured anger or aggression. Adverse events: Six studies provided information on adverse events. No study tested the effects of testosterone-suppressing drugs beyond six to eight months and the cross-over design of some studies may obscure matters (given the 'rebound effect' of some hormonal treatments). Considerable weight gain was reported in two trials of oral MPA and CPA. Side effects of intramuscular MPA led to discontinuation in some participants after three to five injections (the nature of these side effects was not described). Notable increases in depression and excess salivation were reported in one trial of oral MPA. The most severe side effects (extra-pyramidal movement disorders and drowsiness) were reported in a trial of antipsychotic medication for the 12 participants in the study. No deaths or suicide attempts were reported in any study. The latter is important given the association between antilibidinal hormonal medication and mood changes. AUTHORS' CONCLUSIONS: We found only seven small trials (all published more than 20 years ago) that examined the effects of a limited number of drugs. Investigators reported issues around acceptance and adherence to treatment. We found no studies of the newer drugs currently in use, particularly SSRIs or GnRH analogues. Although there were some encouraging findings in this review, their limitations do not allow firm conclusions to be drawn regarding pharmacological intervention as an effective intervention for reducing sexual offending.The tolerability, even of the testosterone-suppressing drugs, was uncertain given that all studies were small (and therefore underpowered to assess adverse effects) and of limited duration, which is not consistent with current routine clinical practice. Further research is required before it is demonstrated that their administration reduces sexual recidivism and that tolerability is maintained.It is a concern that, despite treatment being mandated in many jurisdictions, evidence for the effectiveness of pharmacological interventions is so sparse and that no RCTs appear to have been published in two decades. New studies are therefore needed and should include trials with larger sample sizes, of longer duration, evaluating newer medications, and with results stratified according to category of sexual offenders. It is important that data are collected on the characteristics of those who refuse and those who drop out, as well as those who complete treatment.

Psychological interventions for adults who have sexually offended or are at risk of offending.

BACKGROUND: Sexual offending is a legal construct that overlaps, but is not entirely congruent with, clinical constructs of disorders of sexual preference. Sexual offending is both a social and a public health issue. Victim surveys illustrate high incidence and prevalence levels, and it is commonly accepted that there is considerable hidden sexual victimisation. There are significant levels of psychiatric morbidity in survivors of sexual offences.Psychological interventions are generally based on behavioural or psychodynamic theories.Behavioural interventions fall into two main groups: those based on traditional classical conditioning and/or operant learning theory and those based on cognitive behavioural approaches. Approaches may overlap. Interventions associated with traditional classical and operant learning theory are referred to as behaviour modification or behaviour therapy, and focus explicitly on changing behaviour by administering a stimulus and measuring its effect on overt behaviour. Within sex offender treatment, examples include aversion therapy, covert sensitisation or olfactory conditioning. Cognitive behavioural therapies are intended to change internal processes - thoughts, beliefs, emotions, physiological arousal - alongside changing overt behaviour, such as social skills or coping behaviours. They may involve establishing links between offenders' thoughts, feelings and actions about offending behaviour; correction of offenders' misperceptions, irrational beliefs and reasoning biases associated with their offending; teaching offenders to monitor their own thoughts, feelings and behaviours associated with offending; and promoting alternative ways of coping with deviant sexual thoughts and desires.Psychodynamic interventions share a common root in psychoanalytic theory. This posits that sexual offending arises through an imbalance of the three components of mind: the id, the ego and the superego, with sexual offenders having temperamental imbalance of a powerful id (increased sexual impulses and libido) and a weak superego (a low level of moral probation), which are also impacted by early environment.This updates a previous Cochrane review but is based on a new protocol. OBJECTIVES: To assess the effects of psychological interventions on those who have sexually offended or are at risk of offending. SEARCH METHODS: In September 2010 we searched: CENTRAL, MEDLINE, Allied and Complementary Medicine (AMED), Applied Social Sciences Index and Abstracts (ASSIA), Biosis Previews, CINAHL, COPAC, Dissertation Abstracts, EMBASE, International Bibliography of the Social Sciences (IBSS), ISI Proceedings, Science Citation Index Expanded (SCI), Social Sciences Citation Index (SSCI), National Criminal Justice Reference Service Abstracts Database, PsycINFO, OpenSIGLE, Social Care Online, Sociological Abstracts, UK Clinical Research Network Portfolio Database and ZETOC. We contacted numerous experts in the field. SELECTION CRITERIA: Randomised trials comparing psychological intervention with standard care or another psychological therapy given to adults treated in institutional or community settings for sexual behaviours that have resulted in conviction or caution for sexual offences, or who are seeking treatment voluntarily for behaviours classified as illegal. DATA COLLECTION AND ANALYSIS: At least two authors, working independently, selected studies, extracted data and assessed the studies' risk of bias. We contacted study authors for additional information including details of methods and outcome data. MAIN RESULTS: We included ten studies involving data from 944 adults, all male.Five trials involved primarily cognitive behavioural interventions (CBT) (n = 664). Of these, four compared CBT with no treatment or wait list control, and one compared CBT with standard care. Only one study collected data on the primary outcome. The largest study (n = 484) involved the most complex intervention versus no treatment. Long-term outcome data are reported for groups in which the mean years 'at risk' in the community are similar (8.3 years for treatment (n = 259) compared to 8.4 in the control group (n = 225)). There was no difference between these groups in terms of the risk of reoffending as measured by reconviction for sexual offences (risk ratio (RR) 1.10; 95% CI 0.78 to 1.56).Four trials (n = 70) compared one behavioural programme with an alternative behavioural programme or with wait list control. No meta-analysis was possible for this comparison. For two studies (both cross-over, n = 29) no disaggregated data were available. The remaining two behavioural studies compared imaginal desensitisation with either covert sensitisation or as part of adjunctive drug therapy (n = 20 and 21, respectively). In these two studies, results for the primary outcome (being 'charged with anomalous behaviour') were encouraging, with only one new charge for the treated groups over one year in the former study, and in the latter study, only one new charge (in the drug-only group) over two years.One study compared psychodynamic intervention with probation. Results for this study (n = 231) indicate a slight trend in favour of the control group (probation) over the intervention (group therapy) in terms of sexual offending as measured by rearrest (RR 1.87; 95% CI 0.78 to 4.47) at 10-year follow-up.Data for adverse events, 'sexually anomalous urges' and for secondary outcomes thought to be 'dynamic' risk factors for reoffending, including anger and cognitive distortions, were limited. AUTHORS' CONCLUSIONS: The inescapable conclusion of this review is the need for further randomised controlled trials. While we recognise that randomisation is considered by some to be unethical or politically unacceptable (both of which are based on the faulty premise that the experimental treatment is superior to the control - this being the point of the trial to begin with), without such evidence, the area will fail to progress. Not only could this result in the continued use of ineffective (and potentially harmful) interventions, but it also means that society is lured into a false sense of security in the belief that once the individual has been treated, their risk of reoffending is reduced. Current available evidence does not support this belief. Future trials should concentrate on minimising risk of bias, maximising quality of reporting and including follow-up for a minimum of five years 'at risk' in the community.

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

BACKGROUND: Haloperidol, used alone is recommended to help calm situations of aggression with people with psychosis. This drug is widely accessible and may be the only antipsychotic medication available in areas where resources are limited. OBJECTIVES: To investigate whether haloperidol alone, administered orally, intramuscularly or intravenously, is effective treatment for psychosis-induced agitation or aggression. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (1st June 2011). SELECTION CRITERIA: Randomised controlled  trials (RCTs) involving people exhibiting agitation or aggression (or both) thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes 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. DATA COLLECTION AND ANALYSIS: We independently selected and assessed studies for methodological quality and extracted data. 'Summary of findings' tables were produced for each comparison grading the evidence and calculating, where possible and appropriate, a range of absolute effects. MAIN RESULTS: We included 32 studies comparing haloperidol with 18 other treatments. Few studies were undertaken in circumstances that reflect real world practice, and, with notable exceptions, most were small and carried considerable risk of bias.Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n = 220, risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.95). Dystonia was common (2 RCTs, n = 207, RR 7.49, CI 0.93 to 60.21). Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n = 473, RR 0.78, CI 0.62 to 0.99). More people in the haloperidol group experienced dystonia (2 RCTs, n = 477, RR 6.63, CI 1.52 to 28.86).Despite three larger trials with ziprasidone (total n = 739), data remain patchy, largely because of poor design and reporting. Compared with zuclopenthixol acetate, more people who received haloperidol required more than three injections (1 RCT, n = 70, RR 2.54, CI 1.19 to 5.46).Three trials (n = 205) compared haloperidol with lorazepam. There were no significant differences between the groups with regard to the number of participants asleep at one hour (1 RCT, n = 60, RR 1.05, CI 0.76 to 1.44). However, by three hours, significantly more people were asleep in the lorazepam group compared with the haloperidol group (1 RCT, n = 66, RR 1.93, CI 1.14 to 3.27). There were no differences in numbers requiring more than one injection (1 RCT, n = 66, RR 1.14, CI 0.91 to 1.43).Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n = 67, RR 8.25, CI 0.46 to 147.45; required antiparkinson medication RR 2.74, CI 0.81 to 9.25). Addition of promethazine was investigated in one larger and better graded trial (n = 316). More people in the haloperidol group were not tranquil or asleep by 20 minutes (RR 1.60, CI 1.18 to 2.16). Significantly more people in the haloperidol alone group experienced one or more adverse effects (RR 11.28, CI 1.47 to 86.35). Acute dystonia for those allocated haloperidol alone was too common for the trial to continue beyond the interim analysis (RR 19.48, CI 1.14 to 331.92). AUTHORS' CONCLUSIONS: If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs to offset the adverse effects are available, sole use of haloperidol for the extreme emergency, in situations of coercion, 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. Evidence for use of newer generation antipsychotic alternatives is no stronger than that for older drugs. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries a 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.