Oral Haloperidol Research Articles

Recurrent Episodes of Hypothermia With Psychiatric Medications

Recurrent Episodes of Hypothermia With Psychiatric Medications

Co-administration of haloperidol and drugs affecting the angiotensin pathway: effect on the extrapyramidal system

The present study investigates the extrapyramidal effects of co-administration of enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin receptor blocker) with haloperidol in mice. Enalapril/losartan (as a suspension in 1% gum acacia) was administered by oral gavage and haloperidol was administered as an intraperitoneal injection to all the animals for seven days. Catalepsy was measured 30 min after the administration of haloperidol (1 mg/kg i.p.) on days 1 and 7. Observations on day 1 constituted the acute study (single dose administration) and observations on day 7, constituted the chronic study (repeated dose administration). Both acute and chronic administration of enalapril/losartan produced an increase in the duration of haloperidol induced catalepsy at the highest dose (20 mg/kg). Enalapril produced a more pronounced increase in the duration of catalepsy as compared to losartan on both acute and chronic administration. Results of our study suggest that co-administration of anti-psychotics and drugs affecting the angiotensin system can lead to an increase in motor side effects and therefore should be used with caution in patients with these co-morbid conditions.

The horse with stripes: a case of anti-NMDA receptor encephalitis.

The horse with stripes: a case of anti-NMDA receptor encephalitis.

The Horse With Stripes

The Horse With Stripes

Antipsychotics for the Prevention and Treatment of Delirium in the Intensive Care Unit: What Is Their Role?

Delirium affects up to 80% of critically ill patients, worsens outcomes, and is frequently treated with antipsychotics despite uncertainty regarding their efficacy and safety. We identified published, English-language, randomized, controlled studies evaluating antipsychotics in ICU patients either with delirium or at risk for developing delirium. In 105 mechanically ventilated patients, the number of days spent alive without delirium or coma was similar between haloperidol (median, 14.0 days; interquartile range [IQR], 6.0-18.0 days) or ziprasidone (median, 15.0 days; IQR, 9.1-18.0 days) prophylaxis, and placebo (median, 12.5 days; IQR, 1.2-17.2 days) groups (p=0.66). Treating delirium with quetiapine, compared to placebo, in 36 ICU patients was associated with a quicker resolution of delirium (median for quetiapine, 1.0 days; IQR, 0.5-3.0 days/median for placebo, 4.5 days; IQR, 2.0-7.0 days [p=0.001]). In a third study, a similar decrease over time in delirium severity was noted between fixed-dose oral olanzapine and oral haloperidol in patients with delirium. None of the studies identified serious safety concerns with administering the antipsychotics that were studied. Published prospective, randomized clinical trials evaluating antipsychotic therapy for preventing or treating delirium in the ICU are few in number. The conclusions that can be drawn from them are limited by their heterogeneity, inconsistency in incorporating non-antipsychotic strategies known to reduce delirium or in maintaining patients in an arousable state, their size, the lack of ICU and non-ICU clinical outcomes evaluated, and the lack of placebo arms. A research framework for future evaluation of the use of antipsychotic therapy in the critically ill is proposed.

The Efficacy of Haloperidol in the Management of Nausea and Vomiting in Patients with Cancer

Haloperidol is used commonly for the control of nausea and vomiting (N/V) in palliative care patients, but there is very little evidence to support its use. To assess the efficacy of haloperidol as an antiemetic in patients with cancer and N/V not related to cancer treatment. Patients with an N/V score of at least 1 on a 4-point scale were prescribed either oral or subcutaneous haloperidol. N/V and toxicity were assessed daily for the duration of the study (maximum five days) by both the patient and an observer (health professional). At Day 2, 33 of 42 (79%) treated patients were assessable for response. Eight (24%; 95% confidence interval [CI]: 10%-39%) patients had complete control of N/V and 12 (36%; 95% CI: 20%-53%) had partial control, giving an overall response rate of 61% (95% CI: 44%-77%). At Day 5, 23 patients were assessable for response. The overall response rate was 17 of 23 (74%; 95% CI: 56%-92%). If all patients are included in the response analysis, the overall response rates at Days 2 and 5 were 47% and 40%, respectively. Haloperidol has some efficacy in the treatment of N/V in this patient group. The results from this uncontrolled study provide pilot data from which to plan future controlled trials of antiemetics in the palliative care population.

The role of RLAI in early schizophrenia treatment: critical aspects regarding efficacy and safety

It is well known that there are high levels of response to treatment topatients with a first episode and early schizophrenia. This outcome is hampered by inadequate treatment adherence, which leads to relapse, and high sensitivity to side-effects. Risperidone Long Acting Injectable (RLAI) treatment has proven to be advantageous compared to oral treatment to these early patients, both clinically and pharmacoeconomically. RLAI has proven to improve treatment adherence, prolong time to relapse vs. more chronically ill patients, to improve patient functioning and also to achieve better symptom control in comparison to oral haloperidol, risperidone and also to patients switched from oral olanzapine. Therefore, treatment with atypicals and especially with RLAI to first episode and early patients can alter favorably the course of the schizophrenic disorder.

Effects of Oral Ziprasidone and Oral Haloperidol on QTc Interval in Patients with Schizophrenia or Schizoaffective Disorder

To characterize the effect of oral ziprasidone and haloperidol on the corrected QT (QTc) interval under steady-state conditions. Design. Prospective, randomized, open-label, parallel-group study. Inpatient clinical research facility. Patients Fifty-nine adults (age range 25-59 yrs) with schizophrenia or schizoaffective disorder who had no clinically significant abnormality on electrocardiogram (ECG) at screening. Intervention. During period 1 (days -10 to -4), antipsychotic and anticholinergic drugs were tapered. On the first day (day -3) of period 2, the drugs were discontinued, and placebo was given for the next 3 days (days -2 to 0). On the last day (day 0) of period 2, serial baseline ECGs were collected. During period 3 (days 1-16), patients received escalating oral doses of ziprasidone and haloperidol to reach steady state. Period 4 (days 17-19) allowed for study drug washout and initiation of outpatient antipsychotic therapy; safety assessments were also performed during this period. At each steady-state dose level, three ECGs and a serum or plasma sample were collected at the predicted time of peak exposure to the administered drug. Point estimates and 95% confidence intervals (CIs) were determined for the mean QTc interval at baseline and for the mean change from baseline in QTc at each steady-state dose level. Mean changes from baseline in the QTc interval (msec) for ziprasidone were 4.5 (95% CI 1.9-7.1), 19.5 (95% CI 15.5-23.4), and 22.5 (95% CI 15.7- 29.4) for steady-state doses of 40, 160, and 320 mg/day, respectively; for haloperidol, -1.2 (95% CI -4.1-1.7), 6.6 (95% CI 1.6-11.7), and 7.2 (95% CI 1.4-13.1) for steady-state doses of 2.5, 15, and 30 mg/day. Although no patient in either treatment group experienced a QTc interval of 450 msec or greater, the QTc interval increased 30 msec or more in 11 and 17 ziprasidone-treated patients at 160 and 320 mg/day, respectively, and in 3 and 5 haloperidol-treated patients at 15 and 30 mg/day, respectively. Most treatment-emergent adverse drug reactions were mild in intensity, and none were severe. The QTc interval in ziprasidone- and haloperidol-treated patients increased with dose. Treatment with high doses of ziprasidone or haloperidol did not result in any patient experiencing a QTc interval of 450 msec or greater.

Prolonged haloperidol induced Parkinsonism in a patient with cirrhosis

A 56 year old lady was admitted to Teaching Hospital Kandy with an acute confusional state which was retrospectively diagnosed as an episode of steroid induced psychosis. On physical examination, patient did not have rigidity, bradykinesia or any other features of Parkinsonism. Haloperidol lactate 10 mg was given intramuscularly to calm the patient and it was followed by oral haloperidol 1.5 mg and benzhexol 2 mg twice a day. Investigations done while she was taking in-ward treatment revealed that she is having cirrhosis (Macronodular cirrhosis in liver biopsy). She was not on any other medication which was likely to give rise to EPS.

VALPROATE-INDUCED DELIRIUM IN A DEMENTED PATIENT

In this study we report a case of valproate-induced delirium in a patient affected with Alzheimer's disease (AD). A 75-year-old woman with AD presented moderate cognitive impairment associated to behavioral disorders, characterized by aggression, agitation, severe insomnia. She was treated with galantamine, promazine, acetylsalicylic acid and pantoprazole. Since behavioral disorders worsened more and more, home neurological consultation was asked. The neurologist prescribed a mood stabilizer, sodium valproate 500 mg daily for the first week and then, twice a day and stopped promazine. After an apparent initial benefit, about 16 days later, patient suddenly developed hyperactive delirium. It was characterized by worsening of insomnia and agitation, severe confusion, delusions, visual hallucinations alternated to sedation. She became progressively unable to walk and completely dependent in daily living activities. An urgent geriatric consultation was performed at patient's home; physical examination showed mild dehydration, normal blood pressure. Oxygen saturation and electrocardiogram were normal. Sodium valproate was immediately stopped and rehydration was performed. The patient was admitted to a Geriatric Unit, where organic and metabolic damages were excluded. During the hospital stay the patient was agitated, aggressive, confused; intramuscular haloperidol 5 mg and saline intravenous infusion 1500 cc daily were performed, they were partly successful. Three days after she was discharged and continued treatment with oral haloperidol 5 mg daily. One week later the patient recovered and she is at present healthy. This is a case report of valproate-induced delirium. The Naranjo scale scored 7, classifying this drug-related event as probable. The present case report suggests the need for minimizing the use of psychoactive drugs in elderly demented patients, whether possible; age-related changes in pharmacokinetics and pharmacodynamics suggest the opportunity of a careful evaluation and a slow titration of treatments in these patients.

Oral versus injectable antipsychotic treatment in early psychosis: Post hoc comparison of two studies

Background: Few studies have compared long-acting injectable second-generation antipsychotics with oral antipsychotics. Long-acting injectable antipsychotics—developed specifically to address the problem of adherence—might have an important role to play in treating early psychosis. Objective: The effects of oral antipsychotics versus risperidone long-acting injection (RLAI) were compared between 2 similar studies lasting 2 years each that were conducted at our site in South Africa. Methods: Results of an open-label study in which patients were treated with flexible doses of RLAI were compared with the results of a randomized controlled trial of flexible doses of oral risperidone or haloperidol. Inclusion criteria for both studies were age 16 to 45 years; confirmed diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder; ≤2 hospitalizations for psychosis; and lifetime exposure to ≤12 weeks of antipsychotic medication. The dose of RLAI was 25 mg every 2 weeks, which could be increased to 50 mg. Doses of oral risperidone or haloperidol began at 1 mg/d and were increased if necessary up to a maximum dose of 4 mg/d (8 mg/d in exceptional cases). Study assessments included the Positive and Negative Syndrome Scale (PANSS), the Extrapyramidal Symptom Rating Scale (ESRS), and body mass index (BMI). Results: The RLAI group included 50 patients (32 men and 18 women; mean [SD] age, 25.4 [7.4] years; BMI, 20.6 [4.6] kg/m 2). The oral risperidone or haloperidol group included 47 patients (27 men and 20 women; mean [SD] age, 25.9 [5.8] years; BMI, 20.1 [3.4] kg/m 2). Compared with patients treated with oral risperidone or haloperidol, RLAI-treated patients had significantly fewer all-cause discontinuations (26.0% [13/50] vs 70.2% [33/47] at 24 months; P < 0.005), greater reduction on the PANSS total score (-39.7 vs -25.7; P = 0.009), higher remission rate (64.0% [32/50] vs 40.4% [19/47]; P = 0.028), and lower relapse rate (9.3% [4/43] vs 42.1% [16/38]; P = 0.001) among the responders. Extrapyramidal symptoms were significantly lower in the RLAI group than in patients treated with oral risperidone or haloperidol, as measured by the maximum change in the mean [SD] ESRS total score (1.40 [2.60] vs 5.61 [5.21] vs 9.04 [6.21], respectively; P ≤ 0.001). The increase in BMI after 6 months was significantly greater in the RLAI group than in oral haloperidol-treated patients (mean [SD], 3.9 [1.9] vs 2.2 [1.3] kg/m 2; P = 0.001) but not significantly different from oral risperidone (3.4 [2.0] kg/m 2; P = NS). Four patients in the RLAI group had adverse events that were possibly related to prolactin, compared with 1 each in the oral risperidone and haloperidol groups. Conclusions: The findings of this post hoc analysis suggest that there were advantages in terms of efficacy, fewer extrapyramidal symptoms, and more weight gain with long-acting injectable second-generation antipsychotics as compared with oral antipsychotic treatment in early-episode psychosis.

Postoperative Delirium

Postoperative Delirium

EFFECT OF OLANZAPINE ON GHRELIN, CHOLECYSTOKININ AND LEPTIN PLASMA LEVELS IN ADULTS WITH FIRST-EPISODE DRUG NAIVE PSYCHOSIS

Neurocognitive deficits in schizophrenia can reach 1 to 2 standard deviations below healthy controls. The comparative effect of typical and atypical antipsychotic medications on neurocognition is controversial, and based primarily on studies with small samples and large doses of typical comparator medications. The present study assessed neurocognitive efficacy. It was hypothesized that olanzapine treatment would improve neurocognitive deficits to a greater degree than either risperidone or haloperidol treatment. This was a double-blind, randomized, controlled, parallel study with neurocognition assessed at baseline, and 8, 24, and 52 weeks. Per protocol, the haloperidol arm was discontinued. Four hundred and fourteen inpatients or outpatients with schizophrenia and schizoaffective disorder were treated with oral olanzapine (n = 159), risperidone (n = 158), or haloperidol (n = 97). Individual domains (executive function, learning and memory, processing speed, attention/vigilance, verbal working memory, verbal fluency, motor function, and visuospatial ability) were transformed into composite scores and compared between treatment groups. At the 52-week endpoint, neurocognition significantly improved in each group (p < 0.01 for olanzapine and risperidone, p = 0.04 for haloperidol), with no significant differences between groups. Olanzapine- and risperidone-treated patients significantly (p < 0.05) improved on domains of executive function, learning/memory, processing speed, attention/vigilance, verbal working memory, and motor functions. Additionally, risperidone-treated patients improved on domains of visuospatial memory. Haloperidol-treated patients improved only on domains of learning/memory. However, patients able to remain in treatment for the entire 52 weeks benefited more from olanzapine or risperidone treatment than haloperidol treatment.

Brief Reports: Psychiatric Opinion and Antipsychotic Selection in the Management of Schizophrenia

561 Objectives: This study examined psychiatrists’ opinions regarding the use of second-generation antipsychotics for treatment-resistant schizophrenia. It then sought to identify factors associated with these opinions. Methods: A national survey was conducted (September 2003–January 2004) of psychiatrists engaged in the management of patients with schizophrenia. Results: Among survey respondents (N=431), most psychiatrists (88%) believed that one or more of the five currently available second-generation antipsychotics could improve treatment-resistant positive symptoms after a failed trial of optimal oral haloperidol treatment. Psychiatrists who reported familiarity with schizophrenia practice guidelines were more likely to have high levels of optimism that these medications improve positive symptoms (odds ratio [OR]=3.6, 95% confidence interval [CI]= 1.4–9.3, p=.009). Psychiatrists who met with a pharmaceutical representative at least once a week were also more likely to have high levels of optimism toward second-generation antipsychotics (OR=2.3, CI=1.4–3.9, p= .001). Conclusions: Reported familiarity with treatment guidelines and frequent contact with pharmaceutical representatives appear to be associated with optimism toward second-generation antipsychotics. (Psychiatric Services 59:561–565, 2008)

Brief Reports: Psychiatric Opinion and Antipsychotic Selection in the Management of Schizophrenia

This study examined psychiatrists' opinions regarding the use of second-generation antipsychotics for treatment-resistant schizophrenia. It then sought to identify factors associated with these opinions. A national survey was conducted (September 2003-January 2004) of psychiatrists engaged in the management of patients with schizophrenia. Among survey respondents (N=431), most psychiatrists (88%) believed that one or more of the five currently available second-generation antipsychotics could improve treatment-resistant positive symptoms after a failed trial of optimal oral haloperidol treatment. Psychiatrists who reported familiarity with schizophrenia practice guidelines were more likely to have high levels of optimism that these medications improve positive symptoms (odds ratio [OR]=3.6, 95% confidence interval [CI]=1.4-9.3, p=.009). Psychiatrists who met with a pharmaceutical representative at least once a week were also more likely to have high levels of optimism toward second-generation antipsychotics (OR=2.3, CI=1.4-3.9, p=.001). Reported familiarity with treatment guidelines and frequent contact with pharmaceutical representatives appear to be associated with optimism toward second-generation antipsychotics.

Adjunctive Haloperidol Prophylaxis Reduces Postoperative Delirium Severity and Duration in At-Risk Elderly Patients

Delirium is a potentially life-threatening syndrome that is particularly common in elderly hospitalized patients, especially those with preexisting neurologic disorders. Nonpharmacological tactics can reduce the incidence and severity of delirium in acute care settings and antipsychotic drugs are widely used to treat established delirium. More effective preventive strategies could notably impact morbidity, mortality, and health care costs. To determine whether antipsychotic drug prophylaxis reduces the incidence and severity of postoperative delirium in at-risk elderly patients. We addressed the objective through development of a structured critically appraised topic that included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of cognitive disorders. One randomized controlled trial addressed the question. In at-risk patients aged >70 years, oral haloperidol 0.5 mg TID, administered from up to 72 hours preoperatively until the third postoperative day, did not alter the incidence of postoperative delirium (15.1%) compared with placebo (16.5%; relative risk 0.91; 95% confidence interval 0.59-1.44). However, the study was underpowered for this primary outcome, possibly because both groups received nonpharmacological delirium prevention strategies. Haloperidol significantly reduced delirium severity ratings, delirium duration (from a mean of 11.8 to 5.4 days), and length of hospital stay in affected participants (from 22.6 to 17.1 day). Adjunctive low-dose haloperidol prophylaxis reduces delirium severity, duration, and subsequent hospitalization length in elderly at-risk patients. Further study is needed to determine the optimal pharmacological approach, combination with nonpharmacological strategies, and generalizability to other settings.

Time to Discontinuation of Depot and Oral First-Generation Antipsychotics in the Usual Care of Schizophrenia

This study compared the time to discontinuation for any reason of first-generation antipsychotics--in oral versus depot formulation--in the usual care of schizophrenia. This study used data from a three-year, prospective, nonrandomized, noninterventional, multisite study of schizophrenia. Participants initiated on oral haloperidol or fluphenazine (N=202) were compared with those initiated on haloperidol or fluphenazine in depot formulation (N=97) on time to all-cause discontinuation for one year after initiation, by using Kaplan-Meier survival analysis, a Cox proportional hazards regression model, and propensity score-adjusted bootstrap resampling methods. Compared with participants treated with the oral formulation, those treated with depot first-generation antipsychotics had a significantly longer mean time to all-cause medication discontinuation and were twice as likely to stay on the medication. In the usual care of schizophrenia, treatment with first-generation antipsychotics in depot formulation appears to be associated with longer time to all-cause medication discontinuation compared with oral formulation of the same medication.

Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Δ-9-tetrahydrocannabinol in humans

Cannabinoids produce a spectrum of effects in humans including euphoria, cognitive impairments, psychotomimetic effects, and perceptual alterations. The extent to which dopaminergic systems contribute to the effects of Delta-9-tetrahydrocannabinol (Delta-9-THC) remains unclear. This study evaluated whether pretreatment with a dopamine receptor antagonist altered the effects of Delta-9-THC in humans. In a 2-test-day double-blind study, 28 subjects including healthy subjects (n = 17) and frequent users of cannabis (n = 11) were administered active (0.057 mg/kg) or placebo oral haloperidol in random order followed 90 and 215 min later by fixed order intravenous administration of placebo (vehicle) and active (0.0286 mg/kg) Delta-9-THC, respectively. Consistent with previous reports, intravenous Delta-9-THC produced psychotomimetic effects, perceptual alterations, and subjective effects including "high." Delta-9-THC also impaired verbal recall and attention. Haloperidol pretreatment did not reduce any of the behavioral effects of Delta-9-THC. Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Delta-9-THC. Haloperidol and Delta-9-THC worsened distractibility and vigilance. Neither drug impaired performance on a motor screening task, the Stockings of Cambridge task, or the delayed match to sample task. Frequent users had lower baseline plasma prolactin levels and blunted Delta-9-THC induced memory impairments. The deleterious effects of haloperidol pretreatment on the cognitive effects of Delta-9-THC are consistent with the preclinical literature in suggesting crosstalk between DAergic and CBergic systems. However, it is unlikely that DA D(2) receptor mechanisms play a major role in mediating the psychotomimetic and perceptual altering effects of Delta-9-THC. Further investigation is warranted to understand the basis of the psychotomimetic effects of Delta-9-THC and to better understand the crosstalk between DAergic and CBergic systems.

Protracted effects of chronic oral haloperidol and risperidone on nerve growth factor, cholinergic neurons, and spatial reference learning in rats

The primary therapeutic agents used for schizophrenia, antipsychotic drugs, ameliorate psychotic symptoms; however, their chronic effects on cognition (or the physiologic processes of the brain that support cognition) are largely unknown. The purpose of this rodent study was to extend our previous work on this subject by investigating persistent effects (i.e. during a 14 day drug-free washout period) of chronic treatment (i.e. ranging from 45 days to 6 months) with a representative first and second generation antipsychotic. Drug effects on learning and memory and important neurobiological substrates of memory, the neurotrophin, nerve growth factor (NGF) and its receptors, and certain components of the basal forebrain cholinergic system were investigated. Behavioral effects of oral haloperidol (2.0 mg/kg/day), or risperidone (2.5 mg/kg/day) were assessed in an open field, a water maze task, and a radial arm maze procedure and neurochemical effects in brain tissue were subsequently measured by enzyme-linked immunosorbent assays (ELISAs). The results indicated that both antipsychotics produced time-dependent and protracted deficits in the performance of a water maze procedure when compared with vehicle-treated controls, while neither drug was associated with significant alterations in radial arm maze performance. Interestingly, haloperidol, but not risperidone, was detectible in the rodent brain in appreciable levels for up to 2 weeks after drug discontinuation. Both antipsychotics were also associated with reduced levels of NGF protein in the basal forebrain and prefrontal cortex and significant (or nearly significant) decreases in phosphorylated tropomyosin-receptor kinase A (TrkA) protein and the vesicular acetylcholine transporter (depending on the brain region analyzed). Neither antipsychotic markedly affected TrkA or p75 neurotrophin receptor levels. These data in rats indicate that chronic treatment with either haloperidol or risperidone may be associated with protracted negative effects on cognitive function as well as important neurotrophin and neurotransmitter pathways that support cognition.

Association of symptomatology and cognitive deficits to functional capacity in schizophrenia

Purpose This study aimed to evaluate the association of positive and negative symptoms, as well as of neurocognition to functional status in patients with schizophrenia. Participants were 309 veterans with DSM-IV-diagnosed schizophrenia or schizoaffective disorder who were enrolled in a 12-month double-blind clinical trial and randomized to receive either 5 to 20 mg/d of oral olanzapine or haloperidol. Patients were assessed at study entry and at 3, 6 and 12-months on the PANSS and measures of verbal memory, verbal fluency, fine motor coordination, visual sequencing/set shifting, and conceptual reasoning. Functional status was evaluated by the Heinrichs–Carpenter Quality of Life Scale (QLS) and by days of employment in the past 30. Hierarchical regression models examined the association of functional status with symptomatology and three neurocognitive factors (motor skills, memory and card sorting), controlling for demographics and visit number. A mixed effects model was used to adjust for repeated observations from the same subjects. Results The PANSS explained 16% additional variance in QLS total score after accounting for demographics and visit number ( p < .001), while the neurocognitive factors explained only 4% additional variance beyond the effect of symptoms. When neurocognition was entered before symptoms, it explained an additional 8% of the variance on the QLS total score, while the PANSS explained an additional 12% over and above neurocognition. Conclusions These findings suggest that symptoms may pose an equal or greater impediment to functional capacity independent of neurocognition, at least in younger non-institutionalized people with schizophrenia.