IM Haloperidol Research Articles

Denial of Pregnancy in a Patient With a History of Pseudocyesis

Denial of pregnancy is a condition in which a pregnant patient does not believe she is pregnant. This case describes a 23-year-old Caucasian female, with a past psychiatric history of pseudocyesis, stimulant use disorder, and schizophrenia, who was admitted to the inpatient psychiatric unit for the treatment of psychosis, suicidal thoughts, and homicidal ideation. During her hospitalization, an intrauterine pregnancy was confirmed with three serum quantitative human chorionic gonadotropin (hCG) levels and a transabdominal ultrasound. Despite definitive evidence of pregnancy, the patient reported it was impossible she was pregnant and stated she had not had intercourse for more than a year. The patient was treated with IM haloperidol decanoate and PO haloperidol. Care was coordinated with the obstetrics team to ensure the patient and her fetus received adequate prenatal care. After acute stabilization, the patient was discharged with close follow-up. This case presentation describes one of the few documented cases of pregnancy denial in a patient with a history of pseudocyesis. Additionally, this case highlights the ethical issues associated with the treatment of pregnancy denial patients. Additional studies are necessary to fill in the gaps in the literature on this unique condition.

Angioedema with haloperidol - case report

IntroductionHaloperidol is a high-potency first generation antipsychotic and one of the most frequently used antipsychotic medications. It is a potent central antagonist of type 2 dopamine receptors, with low alpha 1 adrenergic activity and has no antihistamine or anti-cholinergic activity. It is a widely used drug with proven efficacy. Angioedema is a very rare side effect, occurring in <1% of cases.ObjectivesCase report and reflection on its etiologyMethodsA Pubmed search was performed with the MeSH terms “haloperidol” and “Anaphylactic reactions”. Relevant articles obtained from the respective bibliographic references were also consulted.ResultsThe following case describes the development of angioedema in a patient with an acute confusional syndrome on the second haloperidol IM administration for symptomatic control of agitation. Angioedema has been reported as an adverse effect of various antipsychotics such as clozapine, risperidone, ziprazidone and chlorpromazine, however, resulting from haloperidol administration is rare.ConclusionsIn long-term formulations sensitization testing is especially important but a single prior administration is not sufficient, a second controlled administration is essential to avoid this kind of fatal reactions.

Intramuscular midazolam, olanzapine, or haloperidol for the management of acute agitation: A multi-centre, double-blind, randomised clinical trial.

BackgroundThe safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated.MethodsA pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18–75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam (n = 56), olanzapine (n = 54), or haloperidol (n = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118).FindingsOf 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine (p = 0·03) and haloperidol (p = 0·002). Adverse event rates were similar across the three arms. Dystonia (n = 1) and cardiac arrest (n = 1) were reported in the haloperidol group.InterpretationMidazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects.FundingResearch Grants Council, Hong Kong.

Dopamine dilemma: case report of treating psychosis in patient with retinitis pigmentosa

ABSTRACTRetinitis Pigmentosa is a rare inherited degenerative eye disease affecting the retinal pigment epithelium (RPE), in which mutation of rhodopsin leads to severe visual impairment, and legal blindness. The D4 receptors are abundant within the rods of the retina and dopamine release is the primary feedback mechanism preventing retinal degeneration by the unopposed action of melatonin. Here, we present a 50-year-old female patient with schizophrenia and retinitis pigmentosa who was admitted to an inpatient unit for an acute psychotic exacerbation with agitation and persecutory delusions. Patient initially was administered IM haloperidol since she refused oral form, but she eventually was compliant to oral Haloperidol with eventual reduction in daily dose to 5mg/d with treatment response and good tolerability including no change in visual acuity. The treatment of psychosis in patients with retinitis pigmentosa is challenging and requires consideration of the potential D4 receptor effects associated wi...

Manifestations and treatment of central nervous system complications associated with synthetic cathinone (“bath salts”) toxicities

INTRODUCTION "Bath Salts" or synthetic cathinone derivatives have made waves during the past several years in the designer drug market as a new trend in drugs of abuse. Natural cathinones are psychoactive chemicals that have been historically consumed by chewing Khat, or Catha edulis, leaves and shoots in regions of Africa and the Arabian Peninsula. Traditionally, Khat has been utilized to increase alertness and enhance euphoria as CNS stimulants commonly used by religious leaders and militant factions. The pharmacologic effects of synthetic cathinones have been noted to be similar to cocaine, amphetamines, and 3,4-methylenedioxy-Nmethylamphetamine (MDMA/ecstasy) although each have their own unique profile. There are at least 12 different known synthetic cathinones that are currently available but 4-methylmethcathinone (mephedrone), 3,4methylenedioxypyrovalerone (MDPV), and 3,4methylenedioxymethcathinone (methylone) are three of the more common analogues. The DEA added mephedrone, methylone and MDPV to the list of Schedule 1 substances as part of the Control Substances Act in September 2011. This was an emergency scheduling and has not yet been made permanent. The other 9+ synthetic cathinones remain unscheduled.

Current rapid tranquillisation documents in the UK: a review of the drugs recommended, their routes of administration and clinical parameters influencing their use

BackgroundDespite not being underpinned by a strong evidence base, rapid tranquillisation is frequently the intervention of choice for dealing with violent and aggressive behaviour in psychiatric hospitals. This is the second of a two-part review of recommendations set out in UK trusts' adult rapid tranquillisation documents. In this article we focus on the drugs recommended, their routes of administration and clinical parameters influencing their use.MethodA review of adult rapid tranquillisation documents currently in use in NHS or HSC trusts providing adult mental health services in the UK.ResultsA total of 45 rapid tranquillisation documents met the inclusion criteria and were examined. Sixteen drugs were recommended, via four separate routes of administration. Beyond the use of oral and IM lorazepam, haloperidol and olanzapine there was no consensus as to which drugs should be used for rapid tranquillisation in adults. Eleven clinical decision-making parameters were identified that influenced the selection of drugs for IM administration. However, the wide variation and sometimes absence of advice surrounding these parameters was concerning.Conclusions and implications for clinical practiceThe results of this review demonstrate that there is a need to rationalise rapid tranquillisation and develop consensus guidelines that allow for evidence based decision-making tools.

Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses.

Medication used for acute aggression in psychiatry must have rapid onset of effect, low frequency of administration and low levels of adverse effects. Zuclopenthixol acetate is said to have these properties. To estimate the clinical effects of zuclopenthixol acetate for the management of acute aggression or violence thought to be due to serious mental illnesses, in comparison to other drugs used to treat similar conditions. We searched the Cochrane Schizophrenia's Group Trials Register (July 2011). We supplemented this by citation searching and personal contact with authors and relevant pharmaceutical companies. All randomised clinical trials involving people thought to have serious mental illnesses comparing zuclopenthixol acetate with other drugs. Two review authors extracted and cross-checked data independently. We calculated fixed-effect relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. We analysed by intention-to-treat. We used mean differences (MD) for continuous variables. We found no data for the primary outcome, tranquillisation. Compared with haloperidol, zuclopenthixol acetate was no more sedating at two hours (n = 40, 1 RCT, RR 0.60, 95% CI 0.27 to 1.34). People given zuclopenthixol acetate were not at reduced risk of being given supplementary antipsychotics (n = 134, 3 RCTs, RR 1.49, 95% CI 0.97 to 2.30) although additional use of benzodiazepines was less (n = 50, 1 RCT, RR 0.03, 95% CI 0.00 to 0.47). People given zuclopenthixol acetate had fewer injections over seven days compared with those allocated to haloperidol IM (n = 70, 1 RCT, RR 0.39, 95% CI 0.18 to 0.84, NNT 4, CI 3 to 14). We found no data on more episodes of aggression or harm to self or others. One trial (n = 148) reported no significant difference in adverse effects for people receiving zuclopenthixol acetate compared with those allocated haloperidol at one, three and six days (RR 0.74, 95% CI 0.43 to 1.27). Compared with haloperidol or clotiapine, people allocated zuclopenthixol did not seem to be at more risk of a range of movement disorders (< 20%). Three studies found no difference in the proportion of people getting blurred vision/dry mouth (n = 192, 2 RCTs, RR at 24 hours 0.90, 95% CI 0.48 to 1.70). Similarly, dizziness was equally infrequent for those allocated zuclopenthixol acetate compared with haloperidol (n = 192, 2 RCTs, RR at 24 hours 1.15, 95% CI 0.46 to 2.88). There was no difference between treatments for leaving the study before completion (n = 522, RR 0.85, 95% CI 0.31 to 2.31). One study reported no difference in adverse effects and outcome scores, when high dose (50-100 mg/injection) zuclopenthixol acetate was compared with low dose (25-50 mg/injection) zuclopenthixol acetate. Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most of the small trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis, or in preventing adverse effects than intramuscular haloperidol, and neither seemed to have a rapid onset of action. Use of zuclopenthixol acetate may result in less numerous coercive injections and low doses of the drug may be as effective as higher doses. Well-conducted pragmatic randomised controlled trials are needed.

P-574 - High cpk levels in plasma- but not NMS? follow up study of 70 patients in urgent psychiatry

Creatin phosphokinaze enzymes showed high levels when happened infarctus myocardii,rhabdomyolises, and neurolept malignant syndome. NMS is life threatening neurological disorder often caused as adverse reaction of use neuroleptics. its usually presented with high body temperature over 38C,rigidity of muscles, confussion or altered consciousness,autonomic imbalance,cpk eleveted plasma levels and diaphoresis known as sweat shock. NMS can ger peak of intensitiy in as little as 3 days if not threated and can lead to death. In our study we traced levels of cpk, crp, liver enzmes among 70 patients after admission in urgent psychiatry nad the same parametars after one month. Among all patients, the first group 10 persons dg as f20,during admission had gor one amp of haloperidol im plus one amp lorazapam im. CPk were 4500 to 5000, the second group dg as f25, 40 persons got the same therapy. cpk were 2600 to 3000, the third group dg f 18, heroin iv addicts tried ts with tablets but not neuroleptics and cpk were 5000 to 6000,crp 70, hepatitis b.c.many scars on their skin were noticed. After one month on intensive treatment in the first group cpk levels falled to 450, in the second group cpk normalized, and in the third group cpk stayed extremly high as were at start. We diddnt observed other symptoms of NMS, just cpk. so. the question are what exactly means high levels of cpk in psychiatry without using neuroleptics? these patients had been got therapy,as mentioned just one day, the first day of admission. Concluson 10%sch are sensitive.

Haloperidol Dosing Strategies in the Treatment of Delirium in the Critically-Ill

Delirium is the most common mental disturbance in critically-ill patients and results in significant morbidity and mortality. Haloperidol is a preferred agent for the treatment of delirium in this population because of its rapid onset of action and lack of hemodynamic effects. Despite its widespread use in the critical care setting, most of the relevant data are obtained from case series or extrapolated from non-critically-ill populations. This review provides an overview of haloperidol pharmacokinetics and a comprehensive summary of the evidence for various haloperidol dosing regimens in the treatment of delirium in critically-ill patients. A comprehensive literature search was conducted in Medline, Embase, and International Pharmaceutical Abstracts with "haloperidol", "delirium", "agitation", "critically-ill", and "intensive care" as keywords. Studies involving haloperidol for delirium prophylaxis, non-critical care settings, and terminally-ill subjects were excluded. Eleven studies were identified: four with intermittent IV haloperidol, four with continuous IV infusion haloperidol, two with oral/enteral haloperidol, and one with IM haloperidol. All of the case reports, case series, and descriptive studies have shown a benefit with haloperidol, but publication bias is likely present. Only three studies were controlled studies, but all had small sample sizes and methodological flaws. Randomized, double-blind, active-comparator trials of haloperidol with allocation concealment are needed. Subsequent research should focus on using validated delirium screening and assessment scales for more objective identification and measurement of delirium outcomes.

Characteristics and Mortality Among Hospitalized Patients Treated with Intramuscular Antipsychotics: Analysis of a United States Hospital Database

Mortality rates across matched cohorts of hospitalized patients treated with IM olanzapine, haloperidol, and/or ziprasidone in a hospital database were compared. Using propensity score matching, matched cohorts of IM olanzapine- (N=2,984) and IM haloperidol-treated patients (N=2,984) and IM olanzapine- (N=2,876) and IM ziprasidone-treated patients (N=2,876) were obtained. The study outcome was in-hospital death within 2 days of administering IM antipsychotic. Incidence of death was not statistically different between olanzapine-ziprasidone cohorts (OR=1.21, 95% CI 0.92-1.59). The olanzapine cohort demonstrated a significantly lower death incidence than the haloperidol cohort (OR=0.73, 95% CI 0.57-0.93; p=.011). The results suggest that patients treated with IM olanzapine do not have a significantly greater risk of death than patients treated with IM haloperidol or IM ziprasidone.

P03-364 Comparison of intramuscular ziprasidone and haloperidol for acute psychotic agitation in an emergency room

ObjectivesTo compare the efficacy and safety of the intramuscular formulations of ziprasidone and haloperidol in treating agitation in schizophrenic patients attended in an emergency room.MethodConsecutive patients were alternatively assigned to receive 20 mg of IM ziprasidone or 10 mg of IM haloperidol. Efficacy measures were improvement in Behavioral Activity Rating Scale (BARS), in the sum of five items of the Positive and Negative Syndrome Scale that focused on agitation (PANSS-A) and scores on the Clinical Global Impression improvement scale (CGI-I), obtained 45 minutes and 2 hours after the IM medication. Tolerability assessments included changes in ECG, monitoring of vital signs and register of adverse events.ResultsFinally 18 patients (13 men, mean age 40.8 ±10.2) were included in the analysis of data. At arrival in the emergency room, there were no differences between ziprasidone (Z) and haloperidol (H) groups in age, mean QTc length, mean BARS and mean PANSS-A scores. Analyzing the global sample there was an improvement in agitation scores. No significant differences were found between the groups in change of BARS and PANSS-A scores, in CGI-I scores or in the variation of the length of QTc interval at two hours. No serious adverse events were reported.ConclusionsIn spite of the small sample size, both treatments ziprasidone IM and haloperidol IM seems to be similarly effective for the management of psychotic agitation in the emergency room. Both were well tolerated. Lengthening of QTc interval due to ziprasidone IM had not been found in our sample.

Naturalistic study of intramuscular ziprasidone versus conventional agents in agitated elderly patients: Retrospective findings from a psychiatric emergency service

The newer atypical antipsychotics have gained prominence as first-line oral agents to treat severe agitation, but their use in the psychiatric emergency service (PES) setting has been limited because of the unavailability of parenteral formulations. The advent of parenteral formulations of atypical antipsychotics, beginning with ziprasidone in 2002, might afford an alternative treatment option. The objective of this article was to determine the effectiveness and tolerability of IM ziprasidone usedto treat agitation in elderly patients. In this data analysis, the PES database at the Department of Psychiatry and Behavioral Science, Schoolof Medicine, State University of New York, Stony Brook, New York, was searched for records of patients aged ≥65 years who received a single 20-mg dose of IM ziprasidone for the treatment of acute agitation. Efficacy data from these patients were compared with those from an age- and gender-matched sample that received conventional treatment (CT group) with IM haloperidol, with or without lorazepam. Data were also included from a previous naturalistic outcomes study to determine the effectiveness and tolerability of IM ziprasidone in patients treated at the PES at Stony Brook. Additional records were identified using a search of pharmacy and restraint records for PES-treated geriatric patients who received IM ziprasidone over a 2.5-year period beginning in late 2002, when IM ziprasidone became available. In some patients in the ziprasidone group, the effects of the drug on agitation were assessed prospectively by blinded psychiatrists using the Behavioural Activity Rating Scale (BARS) (1 — difficult or unable to arouse to 7 — violent, requires restraint). Also included in the analysis were data concerning use of rescue medication (oral or parenteral) other than the study drug within 2 hours of initial treatment, restraint time, and adverse events (changes in vital sign measurements and electrocardiography [ECG]). The database revealed 15 patients who received ziprasidone (9 men, 6 women; age range, 65–87 years) and 20 patients who were included in the CT sample (13 men, 7 women; age range, 65–88 years). In the 6 cases rated on the BARS, the mean (SE) baseline score was high (6.8 [0.1]), with a decrease to 4.0 (0.4) ( P < 0.05) at 45 minutes after study drug administration and to 2.8 (0.4) ( P < 0.01) at 120 minutes. Rescue medication was needed in 4 ziprasidone cases and 2 CT cases ( P = NS), and mean (SE) restraint times did not vary significantly between groups (ziprasidone [n = 12], 85 [15] minutes; CT [n = 17], 83 [12] minutes). No clinically significant effects on blood pressure or heart rate were noted, and no cardiac or other adverse events were reported. ECG results with ziprasidone (n = 3) or CT (n = 6) were unremarkable. The results of this data analysis of the effects of IM ziprasidone suggest that this agent was similarlyeffective compared with CT and was well tolerated in this geriatric population with acute agitation presenting to a PES. Ziprasidone might be an effective, well-tolerated treatment option for acute agitation in elderly patients presenting to a PES.

Olanzapine IM or velotab for acutely disturbed/agitated people with suspected serious mental illnesses.

People presenting with agitated or violent behaviour thought to be due to severe mental illness may require urgent pharmacological tranquillisation. Several preparations of olanzapine, an antipsychotic drug, are now being used for management of such agitation. To estimate the effects of intramuscular, oral-velotab, or standard oral olanzapine compared with other treatments for controlling aggressive behaviour or agitation thought to be due to severe mental illness. We searched the Cochrane Controlled Trials Register (Issue 1, 2002), The Cochrane Schizophrenia Group's Register (November 2004) and reference lists. We contacted authors of trials and the manufacturers of olanzapine. Randomised clinical trials comparing oral-velotab or intramuscular, or standard oral olanzapine to any treatment, for agitated or aggressive people with severe mental illnesses. We reliably selected, quality assessed and data extracted studies. For binary outcomes we calculated a fixed effects Risk Ratio (RR) and its 95% Confidence Interval (CI) with a weighted Number Needed to Treat/Harm statistic (NNT/H). For continuous outcomes, we preferred endpoint data to change data and synthesised non-skewed data from valid scales using a weighted mean difference (WMD). Four trials compared olanzapine IM with IM placebo (total n=769, 217 allocated to placebo). Fewer people given olanzapine IM had 'no important response' by 2 hours compared with placebo (4 RCTs, n=769, RR 0.49 CI 0.42 to 0.59, NNT 4 CI 3 to 5) and olanzapine IM was as acceptable as placebo (2 RCTs, n=354, RR leaving the study early 0.31 CI 0.06 to 1.55). When compared with placebo, people given olanzapine IM required substantially fewer additional injections following the initial dose (4 RCTs, n=774, RR 0.48 CI 0.40 to 0.58, NNT 4 CI 4 to 5). Olanzapine IM did not seem associated with extrapyramidal effects (4 RCT, n=570, RR experiencing any adverse event requiring anticholinergic medication in first 24 hours 1.27 CI 0.49 to 3.26). Two trials compared olanzapine IM with haloperidol IM (total n=482, 166 allocated to haloperidol). Studies found no differences between olanzapine IM and haloperidol by 2 hours for the outcome of 'no important clinical response' (2 RCTs, n= 482, RR 1.00 CI 0.73 to 1.38) neither was there a difference for needing repeat IM injections (2 RCTs, n=482, RR 0.99 CI 0.71 to 1.38). More people on haloperidol experienced akathisia over the five day oral period compared with olanzapine IM (1 RCT, n=257, RR 0.51 CI 0.32 to 0.80, NNT 6 CI 5 to 15) and fewer people allocated to olanzapine IM required anticholinergic medication by 24 hours compared with those given haloperidol IM (2 RCTs, n= 432, RR 0.20 CI 0.09 to 0.44, NNT 8 CI 7 to 11). Two trials compared olanzapine IM with lorazepam IM (total n=355, 119 allocated to lorazepam). For the outcome of 'no important clinical response' , there was no difference between people given olanzapine IM and those allocated to lorazepam at 2 hours (2 RCTs, n=355, RR 92 CI 0.66 to 1.30) but fewer people allocated to olanzapine IM required additional injections by 24 hours compared with those on lorazepam IM (2 RCTs, n=355, RR 0.68 CI 0.49 to 0.95, NNT 10 CI 6 to 59). People receiving IM olanzapine were less likely to experience any treatment emergent adverse events, than those on lorazepam (1 RCT, n=150, RR at 24 hours 0.62 CI 0.43 to 0.89, NNT 5 CI 4 to 17) and over the same time period there were no clear differences in the use of anticholinergic medication between groups (1 RCT, n=150, RR 1.16 CI 0.38 to 3.58).No studies reported outcomes related to hospital and service use. Nor did any report on issues of satisfaction with care or suicide, self-harm or harm to others. No studies evaluated the oro-dispersable form of olanzapine. Data relevant to the effects of olanzapine IM are taken from some studies that may not be considered ethical in many places, all are funded by a company with a pecuniary interest in the result. These studies often poorly report outcomes that are difficult to interpret for routine care. Other important outcomes are not recorded at all. Nevertheless, olanzapine IM probably has some value in helping manage acute aggression or agitation, especially where it is necessary to avoid some of the older, better, known treatments. Olanzapine causes fewer movement disorders than haloperidol and more than lorazepam. The value of the oro-dipersable velotab preparation is untested in trials. There is a need for well designed, conducted and reported randomised studies in this area. Such studies are possible and, we argue, should be designed with the patient groups and clinicians in mind. They should report outcomes of relevance to the management of people at this difficult point in their illness.

Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses.

Medication used for acute aggression in psychiatry must have rapid onset of effect, low frequency of administration and low levels of adverse effects. Zuclopenthixol acetate is said to have these properties. To estimate the clinical effects of zuclopenthixol acetate for the management of acute aggression or violence thought to be due to serious mental illnesses, in comparison to other drugs used to treat similar conditions. We supplemented past searches of Current Controlled Trials (10/2000), the Cochrane Library (1997) and MEDLINE (1966-1997) and appeals for unpublished data with an update search of the Cochrane Schizophrenia Group's Register of trials (September 2003). All randomised clinical trials involving people thought to have serious mental illnesses comparing zuclopenthixol acetate with other drugs. Data were extracted independently by two reviewers and cross-checked. We calculated fixed effects relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. Where possible, the number needed to treat/harm statistic (NNT/H) was calculated. We analyzed by intention-to-treat. Mean differences were used for continuous variables. We found no data for the primary outcome, tranquilisation. Compared with haloperidol, zuclopenthixol acetate was no more sedating at two hours (n=40, 1 RCT, RR 0.60 CI 0.27 to 1.34). People given zuclopenthixol acetate were not at reduced risk of being given supplementary antipsychotics (n=134, 3 RCTs, RR 1.49 CI 0.97 to 2.30) although additional use of benzodiazepines was less (n=50, 1 RCT, RR 0.03 CI 0.00 to 0.47, NNT 2 CI 2 to 4). People given zuclopenthixol acetate had fewer injections over seven days compared with those allocated to haloperidol IM (n=70, 1 RCT, RR 0.39 CI 0.18 to 0.84, NNT 4 CI 3 to 14). We found no data on more episodes of aggression or harm to self or others. One trial (n=148) reported no significant difference in adverse effects for people receiving zuclopenthixol acetate compared with those allocated haloperidol at one, three and six days (RR 0.74 CI 0.43 to 1.27). Compared with haloperidol or clotiapine, people allocated zuclopenthixol did not seem to be at more risk of a range of movement disorders (<20%). Three studies found no difference in the proportion of people getting blurred vision/ dry mouth (n=192, 2 RCTs, RR at 24 hours 0.90 CI 0.48 to 1.70). Similarly dizziness was equally infrequent for those allocated zuclopenthixol acetate compared with haloperidol (n=192, 2 RCTs, RR at 24 hours 1.15 CI 0.46 to 2.88). There was no difference between treatments for leaving the study before completion (n=522, RR 0.85 CI 0.31 to 2.31). Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis, or in preventing adverse effects than intramuscular haloperidol, and neither seemed to have a rapid onset of action. Well-conducted pragmatic randomised controlled trials are needed.

Single oral doses of risperidone plus lorazepam are as effective as IM haloperidol plus IM lorazepam for the acute treatment of psychotic agitation,

Single oral doses of risperidone plus lorazepam are as effective as IM haloperidol plus IM lorazepam for the acute treatment of psychotic agitation,

Oral risperidone + lorazepam versus IM haloperidol + lorazepam in the emergency treatment of acute psychosis in schizophrenia and schizoaffective disorder

Oral risperidone + lorazepam versus IM haloperidol + lorazepam in the emergency treatment of acute psychosis in schizophrenia and schizoaffective disorder

Droperidol for acute psychosis.

People with acute psychotic illnesses, especially when associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone neuroleptic, is used for this purpose in several countries. To estimate the effects of droperidol when compared to other treatments for controlling disturbed behaviour and reducing psychotic symptoms for people with suspected acute psychotic illnesses. The Cochrane Controlled Trials Register (Issue 2, 2000), The Cochrane Schizophrenia Group's Register (May 2000), EMBASE (1980-2000), MEDLINE (1966-2000), PASCAL (1973-2000) and PsycLIT (1970-2000) were methodically searched. Twenty-one other databases were also searched as part of a broader project and this composite database was searched for this review. This was supplemented by hand searching reference lists, contacting industry and relevant authors. Randomised clinical trials comparing droperidol to any treatment, for people with suspected acute psychotic illnesses, such as schizophrenia, schizoaffective disorder, mixed affective disorders, manic phase of bipolar disorder or brief psychotic episode. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants were lost to follow up. For binary outcomes, standard estimations of risk ratio (RR) and their 95% confidence intervals (CI) were calculated. Where possible, weighted number needed to treat or harm statistics (NNT, NNH), and their 95% confidence intervals (CI), were also calculated. Only two clearly relevant randomised trials with usable data were identified. One additional study was included but focused on outcomes at 30 days rather than a few hours. One small (n=41) randomised trial compared droperidol (10mg IV) with placebo IV and found that people allocated to droperidol were significantly less likely to need additional haloperidol injections in the first few minutes (n=41, RR 0.37 CI 0.2 to 0.7, NNT 2 CI 1 to 10) than those given placebo. By 90 minutes this difference was still evident but not statistically significant (RR 0.46 CI 0.2 to 1.2). When 5mg IM droperidol was compared to 5mg IM haloperidol people given droperidol were again less likely to need additional injections by 30 minutes, than those given haloperidol, but this result did not quite reach conventional levels of statistical significance (n=27, RR 0.45 CI 0.2 to 1.01). One person out of 16 given haloperidol experienced a mild dystonic reaction, and none of the 11 people allocated to droperidol were reported to have experienced adverse effects. This is an important and surprisingly under-researched area. Use of droperidol for the emergency situation is currently justified on experience rather than evidence from well conducted and reported randomised trials.

Prolactin responses to im haloperidol in drug-naive and drug-experienced schizophrenic patients

SummaryThe prolactin (PRL) responses to 5 mg im haloperidol were assessed in the drug-free state and after one month treatment with neuroleptics in 14 male schizophrenic patients who had never received drug treatment, and in 20 male patients who had discontinued their neuroleptic treatment for periods of two months to one year. Drug experienced patients showed lower PRL increases after acute haloperidol (mean 31.7 ng/ml) than drug-naive patients (mean responses 43.4 ng/ml). After treatment with neuroleptics in doses appropriate for the best clinical response, the baseline PRL levels were similar in the two groups, and im haloperidol did not cause any further PRL increases. The results provide evidence that after discontinuation of neuroleptics, the hypothalamic-pituitary dopamine receptors are subsensitive, and remain in that state for long periods of time.

Droperidol versus haloperidol for chemical restraint of agitated and combative patients

To compare two related pharmacological agents used for the chemical restraint of agitated and combative patients. A randomized, double-blind, prospective study was carried out in patients requiring physical restraint in a university hospital emergency department. Sixty-eight violent or agitated adult patients whom the attending physician believed would benefit from chemical restraint to protect the patient and staff and to expedite evaluation. Twenty-one participants were administered 5 mg haloperidol IM; 26 were administered 5 mg droperidol IM; 12 were administered haloperidol IV; and nine were administered 5 mg droperidol IV. All patients were rated on a five-point combativeness scale at five, ten, 15, 30, and 60 minutes after the study drug was given. Vital signs also were recorded at these times. IM droperidol decreased combativeness significantly more than IM haloperidol at ten (P = .006), 15 (P = .01), and 30 (P = .04) minutes. There was no significant difference between the two drugs when given by the IV route (beta at the 5% confidence level, P = .78). In equal IM doses (5 mg), droperidol results in more rapid control of agitated patients than haloperidol, without any increase in undesirable side effects.

Neurotensin-induced miosis: The role of dopaminergic pathways

In this study we investigated the role that dopaminergic pathways play in the miotic effect exerted by neurotensin after intracameral administration. Neurotensin was injected into the anterior chamber (AC) at a dose of 30 μg to 4 groups of albino rabbits which had previously undergone the following treatment: a) desmethylimipramine IM and, after 30 min, 6-hydroxydopamine IV 7 days prior to the neurotensin administration; b) haloperidol IM for 15 days; c) haloperidol AC 10 minutes before the neurotensin administration. Our data confirm previous observations regarding the miotic activity of neurotensin and suggest that the dopaminergic system plays an important role in the miotic effect of neurotensin.