Doses Of Haloperidol Research Articles

Population Pharmacokinetic-Pharmacodynamic Modeling of Haloperidol in Patients With Schizophrenia Using Positive and Negative Syndrome Rating Scale

The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PKPD) model that quantifies the efficacy of haloperidol, accounting for the placebo effect, the variability in exposure-response, and the dropouts. Subsequently, the developed model was utilized to characterize an effective dosing strategy for using haloperidol as a comparator drug in future antipsychotic drug trials. The time course of plasma haloperidol concentrations from 122 subjects and the Positive and Negative Syndrome Scale (PANSS) scores from 473 subjects were used in this analysis. A nonlinear mixed-effects modeling approach was utilized to describe the time course of PK and PANSS scores. Bootstrapping and simulation-based methods were used for the model evaluation. A 2-compartment model adequately described the haloperidol PK profiles. The Weibull and Emax models were able to describe the time course of the placebo and the drug effects, respectively. An exponential model was used to account for dropouts. Joint modeling of the PKPD model with dropout model indicated that the probability of patients dropping out is associated with the observed high PANSS score. The model evaluation results confirmed that the precision and accuracy of parameter estimates are acceptable. Based on the PKPD analysis, the recommended oral dose of haloperidol to achieve a 30% reduction in PANSS score from baseline is 5.6 mg/d, and the corresponding steady-state effective plasma haloperidol exposure is 2.7 ng/mL. In conclusion, the developed model describes the time course of PANSS scores adequately, and a recommendation of haloperidol dose was derived for future antipsychotic drug trials.

Acute intermittent porphyria with psychiatric manifestations: A case report

The porphyrias are a group of eight genetic disorders of heme biosynthesis that result from the deficient activity of a certain enzyme in the biosynthesis pathway. These disorders are separated by symptom manifestation and classified as acute porphyrias and cutaneous porphyrias. One of the acute porphyrias, acute intermittent porphyria (AIP), is caused by a prophobilinogen deaminase deficiency and usually presents as abdominal pain, nausea, constipation, and confusion.

Secondary nonmotor negative symptoms in healthy volunteers after single doses of haloperidol and risperidone: a double‐blind, crossover, placebo‐controlled trial

The effect of antipsychotics (APs) on negative symptoms is controversial. The present study assessed negative symptoms in healthy volunteers without any source of primary negative symptoms after single doses of haloperidol and risperidone. Twenty-five healthy subjects were included in this randomized, placebo-controlled, single-dose (haloperidol 5 mg and risperidone 2.5 mg) crossover and double-blind clinical trial. Negative symptoms were assessed by observer-rated scales and with a self-report scale. Possible confounding effects considered were extrapyramidal symptoms (EPS) and sedative effects. The occupation of striatal dopamine D2 receptors was also determined. Risperidone induced a wide range of negative symptoms such as alogia, blunted affect, avolition/apathy, and attention impairment, whereas haloperidol only induced the avolition/apathy subdomain. Most of the effects of risperidone in healthy volunteers, with the exception of its effects on avolition/apathy, were attributable to AP-induced EPS. Haloperidol did not cause significant EPS after administration. No effect of sedation or psychomotor performance was observed on negative symptoms. Single doses of both haloperidol and risperidone induced nonmotor secondary negative symptoms in healthy volunteers. The clinical findings are especially relevant in view of the impact of negative symptoms on poor functioning. They may help to guide clinicians in their choice of APs (http://clinicaltrials.gov/ct2/show/NCT01259973).

Oxidative stress in schizophrenia patients treated with long-acting haloperidol decanoate

In this study the role of oxidative stress in schizophrenia was investigated by evaluating the relationship of oxidative stress markers with neurochemistry, psychopathology, and extrapyramidal symptoms. Antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and concentrations of malondialdehyde, protein carbonyls, nitrite, nitrate, glutathione, dopamine, noradrenaline, adrenaline, and serotonin were measured in 52 outpatients with DSM-IV diagnosis of schizophrenia treated with haloperidol decanoate. Psychopathology and extrapyramidal symptoms were assessed by positive and negative syndrome scale, global assessment of functioning, abnormal involuntary movement scale, Simpson Angus scale, and Barnes akathisia rating scale. Haloperidol dose was positively correlated with plasma protein carbonyls. Longer duration of illness was associated with decreased levels of glutathione peroxidase. Increased activity of superoxide dismutase was associated with increased levels of catalase, glutathione peroxidase, glutathione reductase and reduced glutathione, and decreased concentration of malondialdehyde, indicating joint action of various antioxidative systems. Increased levels of nitrite and noradrenaline were associated with decreased level of malondialdehyde. Akathisia was greater in patients with decreased catalase activity, indicating involvement of impaired antioxidant defense in developing extrapyramidal symptoms. These results confirm the hypothesis that oxidative stress is involved in pathophysiology of schizophrenia and severity of extrapyramidal symptoms.

Patterns of Opiate, Benzodiazepine, and Antipsychotic Drug Dosing in Older Patients in a Medical Intensive Care Unit

Anecdotal observation suggests that older patients in medical intensive care units receive higher doses of psychoactive medications during evening shifts than day and night shifts. To determine the dosing patterns and total doses of fentanyl, lorazepam, and haloperidol according to nursing shift in a cohort of older patients in a medical intensive care unit. The sample consisted of 309 patients 60 years and older admitted to the medical intensive care unit at Yale-New Haven Hospital, New Haven, Connecticut. Data on time, dosage, and route of administration of the drugs were collected. Data were analyzed by using a Bayesian random effects Poisson model adjusted for individual heterogeneity, excess zero doses, and important clinical covariates. Mean age of the patients was 75 years; 58% received fentanyl, 55% received lorazepam, and 32% received haloperidol. Although dosing with fentanyl did not differ according to shift, doses of both lorazepam and haloperidol were higher during the evening shifts (4 pm to midnight) than during the day or night shifts. Compared with women, men received higher doses of both haloperidol and lorazepam and variability between shifts was greater. In this longitudinal, observational sample of older patients, data indicated a positive association between dose levels of lorazepam and haloperidol during the evening nursing shifts relative to other shifts. Further investigation is needed to determine potential causes and to evaluate the impact on outcomes of sleep deprivation and delirium.

Psychosis, Agitation, and Antipsychotic Treatment in Dementia

Psychosis, Agitation, and Antipsychotic Treatment in Dementia

Haloperidol dose for the acute phase of schizophrenia

Haloperidol is a benchmark, accessible antipsychotic drug against which the effects of newer treatments are gauged. To determine the best range of doses for haloperidol for the treatment of people acutely ill with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (February 2010), which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. We selected studies if they involved people being treated for acute schizophrenia, randomised to two or more dose ranges of non-depot haloperidol, and if they reported clinically meaningful outcomes. For this update, we inspected all citations and independently re-inspected a sample of citations in order to ensure reliable selection. We resolved any disagreement by discussion, and where doubt remained, we acquired the full-text article for further inspection. We then ordered papers, and reliably re-inspected and quality assessed the full reports, and extracted data. For homogeneous dichotomous data, we calculated the risk ratio (RR) with 95% confidence intervals (CI) on an intention-to-treat (ITT) basis. We assumed that people who left the study early or were lost to follow-up had a negative outcome. We calculated mean differences (MD) for continuous outcomes that reported ITT, last observation carried forward (LOCF) data. We excluded data if loss to follow-up was greater than 50%. We included 19 trials with 19 different randomised dose comparisons. No studies reported data on relapse rates or quality of life and only one compared low dose (> 1.5 to 3 mg/day) haloperidol to higher dose ranges. Using standard lower dose (> 3 to 7.5 mg/day) did not result in loss of efficacy (no clinically important improvement in global state, versus standard higher dose (> 7.5 to 15 mg/day, n = 48, 1 RCT, RR 1.09, 95% CI 0.7 to 1.8, very-low-quality evidence); versus high dose (> 15 to 35 mg/day, n = 81, 2 RCTs, RR 0.95, 95% CI 0.8 to 1.2, very-low-quality evidence). Doses of haloperidol in the range of > 3 to 7.5 mg/day had a lower rate of development of clinically significant extrapyramidal adverse effects than higher doses (clinically significant extrapyramidal adverse effects, versus standard higher dose, n = 64, 2 RCTs, RR 0.12, 95% CI 0.01 to 2.1, very-low-quality evidence); versus high dose, n = 144, 3 RCTs, RR 0.59, 95% CI 0.5 to 0.8, very-low-quality evidence; versus very high dose (> 35 mg/day, n = 86, 2 RCTs, RR 0.70, 95% CI 0.5 to 1.1, very-low-quality evidence). None of the other comparisons between dose ranges yielded statistically significant differences, but several, particularly with lower dose ranges, were underpowered to detect clinically meaningful differences. Noresults were conclusive and all were based on small, short studies of limited quality. However, it would be understandable if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the lower dose ranges, especially > 1.5 to 3 mg/day.

Haloperidol for severe anorexia nervosa restricting type with delusional body image disturbance: a nine-case chart review

Here we report on a case series chart review conducted on nine severe and treatment-resistant patients with anorexia nervosa, body mass index < 13 kg/m(2), and a delusional body image disturbance. Patients received low doses of haloperidol during hospitalization. Haloperidol was well tolerated. The delusional body image disturbance and the drive for thinness were subjectively perceived as less intense. BMI increased from the initial 12.2 ± 0.5 to 16.0 ± 1.5 kg/m(2). Mean pulse rate and blood pressure did not change significantly from admission to discharge (66 ± 11.6 bpm; 91/56 mmHg vs 77 ± 12.0 bpm; 102/66 mmHg). Mean of QTc, available from electrocardiograms performed during hospitalization, was 413 ± 38.5 ms (range 342-469 ms). Further investigations are warranted to elucidate clinical usefulness and safety of low doses of haloperidol for patients with treatment-resistant anorexia and delusional body image disturbance.

Opposite effects of typical and atypical anti-psychotic drugs on sensitized dopamine receptors: Sub-chronic low dose Olanzapine exposure reverses sensitization but a similar regimen of low dose haloperidol potentiates sensitization effects

Both typical and atypical antipsychotic drugs are D2 receptor antagonists but yet appear to have markedly different effects upon the induction of dopamine sensitization. This study aims to compare the effects of subchronic regimens of low-dose olanzapine and haloperidol administered to rats previously sensitized to apomorphine. Initially, rats received apomorphine (2.0mg/kg) or vehicle treatments for five consecutive days followed by a conditioning test and an apomorphine challenge test. Next, there was an antipsychotic exposure phase in which three vehicle groups and three apomorphine groups received 10 daily injections of either vehicle, haloperidol (0.03mg/kg) or olanzapine (0.01mg/kg). In the final phase, all groups were given a second conditioning test and apomorphine challenge test. Apomorphine induced sensitization and conditioning effects. Following haloperidol exposure, apomorphine conditioned and sensitization effects were potentiated but, in contrast, olanzapine exposure eliminated apomorphine sensitization effects. In addition, the sensitization induced by apomorphine transformed the low-dose haloperidol treatment into a potent locomotor stimulant treatment. In the vehicle groups, haloperidol and olanzapine exposure effects were equivalent and not different from vehicle treatment. The profound differences observed between typical and atypical antipsychotic exposure in animals with an upregulated dopamine system are consistent with clinical evidence for lower risk of psychomotor disturbances with chronic treatment with atypical antipsychotic. Importantly, the finding that a very low dose of olanzapine reversed sensitization effects suggests that low-dose olanzapine may have clinical utility in a variety of disorders linked to sensitization of the dopamine system.

Quetiapine versus haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial

BackgroundAtypical antipsychotic drugs may have low propensity to induce extrapyramidal side effects in delirious patients. This study aimed to compare the efficacy and tolerability between quetiapine and haloperidol in controlling delirious behavior.MethodsA 7-day prospective, double-blind, randomized controlled trial was conducted from June 2009 to April 2011 in medically ill patients with delirium. Measures used for daily assessment included the Delirium Rating Scale-revised-98 (DRS-R-98) and total sleep time. The Clinical Global Impression, Improvement (CGI–I) and the Modified (nine-item) Simpson– Angus Scale were applied daily. The primary outcome was the DRS-R-98 severity scores. The data were analyzed on an intention-to-treat basis.ResultsFifty-two subjects (35 males and 17 females) were randomized to receive 25–100 mg/day of quetiapine (n = 24) or 0.5–2.0 mg/day of haloperidol (n = 28). Mean (standard deviation) doses of quetiapine and haloperidol were 67.6 (9.7) and 0.8 (0.3) mg/day, respectively. Over the trial period, means (standard deviation) of the DRS-R-98 severity scores were not significantly different between the quetiapine and haloperidol groups (−22.9 [6.9] versus −21.7 [6.7]; P = 0.59). The DRS-R-98 noncognitive and cognitive subscale scores were not significantly different. At end point, the response and remission rates, the total sleep time, and the Modified (nine-item) Simpson–Angus scores were also not significantly different between groups. Hypersomnia was common in the quetiapine-treated patients (33.3%), but not significantly higher than that in the haloperidol-treated group (21.4%).LimitationsPatients were excluded if they were not able to take oral medications, and the sample size was small.ConclusionLow-dose quetiapine and haloperidol may be equally effective and safe for controlling delirium symptoms.Clinical trials registration numberclinicaltrials.gov NCT00954603.

Use of a Geriatric Quality Initiative to Educate Internal Medicine Residents about Delirium and Its Risk Factors.

Delirium is a common and debilitating complication of inpatient care for many older adults, yet internal medicine residents often do not recognize delirium or its risk factors. Integrating geriatric education (eg, delirium recognition) with inpatient quality improvement (QI) is not well tested. We developed an educational pilot program within an ongoing hospital-wide geriatric QI initiative (Global Risk Assessment and Careplan for the Elderly-Acute Care [GRACE-AC]). GRACE-AC modifies the inpatient computerized provider order entry system to meet the needs of vulnerable older adults and uses a bedside care checklist to identify patients with possible delirium and promote delirium prevention by checking on the need for "tethers" (intravenous fluids, Foley catheters, and telemetry). Residents were assessed before and after each inpatient rotation by using anonymous electronic surveys. A total of 167 eligible residents (91%) completed prerotation surveys, and 102 (56%) residents completed postrotation surveys. All but the first rotating resident group received a standardized 2-minute educational in-service orientation. In a comparison of postrotation responses before and after implementation of the in-service, the proportion of residents who reported improvement in their ability to recall which patients had tethers increased from 17% to 52% for intravenous fluids (P = .004), 28% to 75% for Foley catheters (P < .001), and 21% to 50% for telemetry (P = .02). Comparing pre- and postrotation surveys, the proportion of correct responses to questions on haloperidol dosing and the characteristics of delirium increased from 26% to 76% and 31% to 63%, respectively (both P < .001). Our pilot program demonstrated that inpatient geriatric QI initiatives can be successfully merged with a brief educational curriculum.

Are Low Doses of Antipsychotics Effective in the Management of Psychomotor Agitation? A Randomized, Rated-Blind Trial of 4 Intramuscular Interventions

Psychomotor agitation can be associated with a wide range of medical conditions. Although clinical practice advocates the use of several drugs for the management of psychomotor agitation, there are still very few controlled studies comparing the profiles of action and the adverse effects of different drugs that induce tranquilization. The purpose of this study was to compare the efficacy and safety of 4 low-dose pharmacological interventions used to control psychomotor agitation guided by the clinical response. Using a randomized, rated-blind design, 100 agitated patients were assigned to receive 1 of 4 treatments: haloperidol (2.5 mg) + promethazine (25 mg) (HLP + PMZ), haloperidol (2.5 mg) + midazolam (7.5 mg) (HLP + MID), ziprasidone (10 mg) (ZIP), or olanzapine (10 mg) (OLP). Patients were evaluated just before the intervention and after 30, 60, and 90 minutes, using the Agitation-Calmness Evaluating Scale. Adverse effects were assessed within 24 hours after the intervention, using selected items from the UKU Scale (Ugvalg Klinisk Undersgelser Side Effect Scale). According to the clinical indication, medication could be repeated twice after the first injection. Data were analyzed using general linear model with repeated measures and logistic regression. All treatment options promoted a reduction in agitation, without causing excessive sedation, although a lower reduction in agitation was observed with HLP + PMZ and ZIP compared with HLP + MID and OLZ. The need for an additional dose of medication was observed in 22 patients, and only 8 remained agitated during the entire 90-minute period. A higher risk for the development of extrapyramidal symptoms within the following 24 hours was observed with HLP + PMZ. Low doses of haloperidol combined with midazolam can be as effective as olanzapine in reducing psychomotor agitation without increasing the risk of extrapyramidal effects. Because of the higher risk for the occurrence of extrapyramidal symptoms, the combination of haloperidol with promethazine should be considered a second-line treatment option.

Haloperidol Overdosing in the Treatment of Agitated Hospitalized Older People with Delirium: A Retrospective Chart Review from a Community Teaching Hospital

Practice guidelines recommend the use of low dose haloperidol when medication is needed to treat delirium with acute agitation in hospitalized older people. Despite this, high dose haloperidol may frequently be used and result in higher rates of complications. To describe dosages and effects of haloperidol used in the initial treatment of delirium with acute agitation in hospitalized older people, and prescriber use of low and high dose haloperidol. Retrospective chart reviews were performed from June 2008 to May 2009 in a community teaching hospital located in Upland, PA, USA. Patients aged 65 years and older with acute agitated delirium were included. Patients admitted to ICU and those with psychiatric conditions were excluded. Data were collected on haloperidol dosing, responses, sedation, length of stay, and concurrent use of lorazepam. A total of 261 charts of patients who received haloperidol were reviewed and 56 patients met inclusion criteria (14 males, 42 females). The mean age of subjects was 83 years. The recommended starting dose of haloperidol (0.5 mg) was administered to 35.7 % of the patients. An initial dose of more than 1 mg was received by 37.5 % of the patients. The remaining 26.8 % of patients received 1 mg. The relative risk of sedation was significantly greater for subjects receiving more than 1 mg of haloperidol in 24 h. The length of hospitalization was not predicted by haloperidol doses or lorazepam but by the number of days of agitation. Higher than recommended initial doses of haloperidol were frequently used in the treatment of delirium with acute agitation in hospitalized older people. We found no evidence to suggest that higher dosages were more effective in decreasing the duration of agitation or the length of hospital stay. Low dose haloperidol appears to be as effective as and safer than higher doses in the treatment of acute agitation in this older population.

Are "Bath Salts" on Your Differential List? A Case Report of Delirium and Agitation After Use of Illicit Bath Salts

Are "Bath Salts" on Your Differential List? A Case Report of Delirium and Agitation After Use of Illicit Bath Salts

Poster Session III (PIII 1-97) Displayed 7:00 am – 11:00 am Attended 7:00 am – 8:00 am

BACKGROUND: As delirium in critically ill children is increasingly recognized, more children are treated with the antipsychotic drug haloperidol. However, little is known about its safety in this context. The objective of this study was to investigate the incidence and nature of adverse events associated with the use of haloperidol and its possible relationship with dose. METHODS: We identified all patients admitted to the PICU between January 2000 and July 2011 who received haloperidol. Patients were included when haloperidol was prescribed for delirium. Medical and nursing charts were evaluated for a predefined list of known haloperidol adverse events. When a symptom possibly related to haloperidol was identified, the probability of causality was evaluated using the Naranjo score. In addition, each event was evaluated for causality by two clinical pharmacologists and by the Dutch Pharmacovigilance Institute. RESULTS: Fifty-two patients [median age 10.6 (0.3-18.8) yrs] received the drug for treatment of delirium. In six patients (11%) possible adverse events were documented. These included extrapyramidal reactions (n=2), extrapyramidal reactions + hyperpyrexia (n=1), neuroleptic malignant syndrome (n=1), long QT (n=1), and isolated muscle rigidity (n=1). Adverse events were rated as doubtful (n=1), possible (n=2), probable (n=2) and definite (n=1). The median (range) haloperidol dose was similar between patients with and without adverse events [0.03 (0.02-0.06) mg/kg/d vs 0.02 (0.003-0.08) mg/kg/d, p=0.08]. CONCLUSION: To our knowledge, this is the largest pediatric cohort studied for haloperidol-related adverse events. Our study suggests that a significant proportion of patients develop adverse events with haloperidol. As haloperidol adverse events are correlated with dose in adults, our findings suggest that dosing in our pediatric population is suboptimal. Therefore, studies are needed to determine the optimal haloperidol dose for ICU delirium in children.

Dopamine Mediates Testosterone-Induced Social Reward in Male Syrian Hamsters

Adolescent maturation of responses to social stimuli is essential for adult-typical sociosexual behavior. Naturally occurring developmental changes in male Syrian hamster responses to a salient social cue, female hamster vaginal secretions (VS), provide a good model system for investigating neuroendocrine mechanisms of adolescent change in social reward. Sexually naïve adult, but not juvenile, males show a conditioned place preference (CPP) to VS, indicating that VS is not rewarding before puberty. In this series of experiments, the authors examined the roles of testosterone and dopamine receptor activation in mediating the adolescent gain in positive valence of VS. Experiment 1 showed that testosterone replacement is necessary for gonadectomized adult hamsters to form a CPP to VS. Experiment 2 showed that testosterone treatment is sufficient for juvenile hamsters to form a CPP to VS, and that the dopamine receptor antagonist haloperidol blocks formation of a CPP to VS in these animals. Experiments 3 and 4 demonstrated that the disruption of VS CPP with low doses of haloperidol is the result of a reduction in the attractive properties of VS and not attributable to aversive properties of haloperidol. Together, these studies demonstrate that the unconditioned rewarding properties of a social cue necessary for successful adult sociosexual interactions come about as the result of the pubertal increase in circulating testosterone in male hamsters. Furthermore, this social reward can be prevented by dopamine receptor antagonism, indicating that hypothalamic and/or mesocorticolimbic dopaminergic circuits are targets for hormonal activation of social reward.

Bipolar affective disorder preceding frontotemporal dementia in a patient with C9ORF72 mutation: is there a genetic link between these two disorders?

The FTD includes three main clinical syndromes: the behavioural variant (bvFTD), semantic dementia and progressive non-fluent aphasia [1]. For the BvFTD, which is characterized by a rich constellation of psychiatric and behavioural symptoms, the differential diagnosis with psychiatric disorders like schizophrenia and affective disorders, may be challenging [2, 3]. Recently a hexanucleotide repeat expansion in a noncoding region of the C9ORF72 gene has been identified as the cause of chromosome 9p21-linked ALS, FTD and ALS–FTD [4, 5]. We report the case of a man who developed from the age of 42 years an affective disorder characterized by repeated manic and hypomanic episodes. The manic phases were characterized by euphoria, racing thoughts, logorrhea, very high self-esteem, artistic hyperproductivity, little need for sleep. The patient fulfilled the DSM IV criteria for bipolar affective disorder (BPAD) type I [6] and was put on a long term lithium therapy with a good clinical response; during manic phases haloperidol was administered up to the acute episode resolution. The patient worked as a teacher until the age of 57 years. A patient’s maternal uncle developed a parkinsonism at the age of 60. The patient aged 64 presented to our neurological unit because he developed euphoria, impulsivity, logorrhea, sexual disinhibition with his wife, delusional fixed ideas with repetitive behaviours. He was obsessed by the idea of cleaning or putting petrol in his car and spent all day watching sport TV shows. As many of these symptoms were present in the past BPAD episodes, the patient underwent a new psychiatric examination; low doses of haloperidol were started without any improvement, so the therapy was stopped. Later a progressive cognitive impairment appeared. Neuropsychological assessment showed marked attention and executive functions troubles, working memory impairment, anomia and verbal fluency dysfunction. Neurologic examination revealed mild parkinsonism with postural tremor, camptocormia, diffuse bradykinesia and rigidity. Extrapyramidal symptoms arose when the patient was not under antipsychotic treatment. Mutations of TARDBP and PGRN genes were excluded. The patient has been found positive for a GGGGCC hexanucleotide repeat expansion in the first intron of C9ORF72 gene ([70 repeats). Brain MRI showed bilateral frontotemporal atrophy, prominent in frontal areas (Fig. 1). The orbitofrontal cortex was more involved than the dorsolateral prefrontal cortex; moreover there was a significant involvement of the fronto-insula and anterior cingulate gyrus. Perfusion SPECT demonstrated reduction of uptake in the left frontotemporal and right frontoparietal regions (Fig. 1). Structural and functional neuroimaging findings G. Floris G. Borghero A. Cannas F. D. Stefano F. Marrosu Department of Neurology, Azienda Universitaria-Ospedaliera of Cagliari and University of Cagliari, Cagliari, Italy

Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial

BackgroundDelirium is a frequent disorder in intensive care unit (ICU) patients with serious consequences. Therefore, preventive treatment for delirium may be beneficial. Worldwide, haloperidol is the first choice for pharmacological treatment of delirious patients. In daily clinical practice, a lower dose is sometimes used as prophylaxis. Some studies have shown the beneficial effects of prophylactic haloperidol on delirium incidence as well as on mortality, but evidence for effectiveness in ICU patients is limited. The primary objective of our study is to determine the effect of haloperidol prophylaxis on 28-day survival. Secondary objectives include the incidence of delirium and delirium-related outcome and the side effects of haloperidol prophylaxis.MethodsThis will be a multicenter three-armed randomized, double-blind, placebo-controlled, prophylactic intervention study in critically ill patients. We will include consecutive non-neurological ICU patients, aged ≥18 years with an expected ICU length of stay >1 day. To be able to demonstrate a 15% increase in 28-day survival time with a power of 80% and alpha of 0.05 in both intervention groups, a total of 2,145 patients will be randomized; 715 in each group. The anticipated mortality rate in the placebo group is 12%. The intervention groups will receive prophylactic treatment with intravenous haloperidol 1 mg/q8h or 2 mg/q8h, and patients in the control group will receive placebo (sodium chloride 0.9%), both for a maximum period of 28-days. In patients who develop delirium, study medication will be stopped and patients will subsequently receive open label treatment with a higher (therapeutic) dose of haloperidol. We will use descriptive summary statistics as well as Cox proportional hazard regression analyses, adjusted for covariates.DiscussionThis will be the first large-scale multicenter randomized controlled prevention study with haloperidol in ICU patients with a high risk of delirium, adequately powered to demonstrate an effect on 28-day survival.Trial registrationClinicaltrials.gov: NCT01785290.EudraCT number: 2012-004012-66.

1657 – Component structure of the positive and negative syndrome scale (PANSS) in patients with schizophrenia spectrum disorders and predominantly negative syndrome

Aim Earlier studies have examined the symptom dimensions of the PANSS (Positive And Negative Syndrome Scale) in patients with chronic schizophrenia, regardless predominance of symptoms. The aim of this study was to examine the component structure of the PANSS in patients with schizophrenia spectrum disorders and predominantly negative syndrome. Methods Data of PANSS were extracted from a cross-sectional and retrospective multicenter study in 1,704 adult psychiatric outpatients meeting DSM-IV criteria for schizophrenia, schizophreniform or schizoaffective disorder. We used 5 items of the PANSS negative subscale to individually determine the presence of a negative syndrome when the score on all of the 5-items were >3, with no extrapyramidal symptoms, anxiety, or depression and dose of haloperidol, when applicable, ≤15mg/day. Exploratory factor analysis was carried out using principal component analysis to extract domains. Eigenvalues above 1 according with Kaiser K1 rule were applied to extract factors. Items with a loading of ≥ 0.4 were considered to load on a component. Results A total of 307 [61% men, mean age: 41 (SD:12) years] fulfilled criteria for inclusion in the analysis. Principal component analysis of the PANSS revealed four components: positive, negative (all negative items of the original PANSS plus items 15 and 16 of the general psychopathology subscale), mood and disorganization, explained 58% of the total variance. Internal consistency (Cronbach-alpha) of these 4 domains was high: 0.897, 0.874, 0.819 and 0.833, respectively. Conclusions This analysis suggest a four component structure of the PANSS in patients with schizophrenia spectrum disorders and predominantly negative syndrome.

Acute muscle dystonia resulting from medication error: a case report

Acute Muscle Dystonia (AMD) due to medication error is rarely reported in the literature. We are reporting a case of adverse drug reaction due to a single dose of haloperidol. Patient was free from any psychiatric illness and still he developed AMD with use of haloperidol because of medication error. The patient recovered completely from AMD symptoms in one hour after receiving the treatment. This case report intends to improve the awareness among clinicians to be cautious while writing the prescriptions.