Synaptic dopamine (DA) is mainly regulated by the presynaptic DA transporter (DAT). Single-photon emission computerized tomography (SPECT) with the DAT radiotracer [¹²³I]FP-CIT assesses changes in synaptic DA availability when endogenous DA displaces [¹²³I]FP-CIT or competes for DAT. Here, we investigated the effects of haloperidol (HAL) and clozapine (CLZ) on [¹²³I]FP-CIT binding in the rat striatum and midbrain to assess the utility of [¹²³I]FP-CIT SPECT to quantify changes in synaptic DA availability. Rats underwent [¹²³I]FP-CIT SPECT after intraperitoneal administration of normal saline (vehicle), HAL (1 and 7 mg/kg), CLZ (10 and 54 mg/kg) and bupropion (BUP, a DAT blocker, 20 and 100 mg/kg). In the striatum and midbrain, percent differences in the nondisplaceable binding potential (BP(ND)) of [¹²³I]FP-CIT compared to the vehicle were calculated for the various drugs and doses. In another experiment, changes in endogenous striatal DA concentration were measured by in vivo microdialysis under the conditions used in the SPECT study. BUP dose-dependently occupied DAT at considerable levels. Compared to the vehicle, HAL decreased [¹²³I]FP-CIT BP(ND) in the striatum (−25.29% and −2.27% for 1 and 7 mg/kg, respectively) and to a greater degree in the midbrain (−58.74% and −49.64% for 1 and 7 mg/kg, respectively), whereas the CLZ-treated group showed a decrease in the midbrain (−38.60% and −40.38% for 10 and 54 mg/kg, respectively) but an increase in the striatum (18.85% and 38.64% for 10 and 54 mg/kg, respectively). Antipsychotic-induced changes in endogenous striatal DA concentrations varied across drugs and doses. The data demonstrate that [¹²³I]FP-CIT SPECT may be a useful preclinical technique for detecting increases in synaptic DA availability in the midbrain and striatum in response to HAL, with results comparable to those of in vivo microdialysis.
Animals ; Bupropion ; Clozapine ; Dopamine ; Haloperidol ; Mesencephalon ; Microdialysis ; Rats ; Tomography, Emission-Computed, Single-Photon

BACKGROUND: Terminally ill cancer patients suffer from refractory symptoms, and the last option of treatment is to consider sedatives. However, due to concerns that sedation may shorten survival time, some people prefer not to take sedatives. The purpose of this study was to investigate the effects of sedative administration on survival time among terminally ill cancer patients.METHODS: Two hundreds and thirty-seven patients who were hospitalized to the hospice care unit of public hospitals in Seoul from January, 2015 to March, 2016 were analyzed retrospectively. The univariate and multivariate Cox's proportional hazard regression model was used to determine independent factors related to survival time.RESULTS: The usage of sedation was necessary because the incidence of insomnia was 61.4% in the lorazepam only group, and the incidence of delirium was highest in the haloperidol group and the haloperidol with lorazepam group. Interestingly, multivariate analysis showed that male (HR, 1.766; P < 0.001), decreased consciousness (HR, 1.803; P=0.003), anorexia (HR, 1.506; P=0.012), resting dyspnea (HR, 1.757; P < 0.001), elevated serum bilirubin (HR, 1.657; P=0.001), and the haloperidol with lorazepam group (HR, 0.535, P < 0.001) were each significantly associated with survival time. Furthermore, patients in the haloperidol with lorazepam group survived longer than patients with no such medications.CONCLUSION: There is no evidence that treatment with sedative medication shortens the survival time of patients with terminally ill cancer with refractory symptoms.
Anorexia ; Bilirubin ; Consciousness ; Delirium ; Dyspnea ; Haloperidol ; Hospice Care ; Hospices ; Hospitals, Public ; Humans ; Hypnotics and Sedatives ; Incidence ; Lorazepam ; Male ; Multivariate Analysis ; Palliative Care ; Retrospective Studies ; Seoul ; Sleep Initiation and Maintenance Disorders ; Terminally Ill

OBJECTIVE: Exposing a pregnant female to stress during the critical period of embryonic fetal brain development increases the risk of psychiatric disorders in the offspring. The objective of this study was to investigate the effect of antidepressant tianeptine on prenatally stressed (PNS) rats. METHODS: In this study, a repeated variable stress paradigm was applied to pregnant rats during the last week of gestation. To investigate the effects of antidepressant tianeptine on PNS rats, behavioral and protein expression analyses were performed. Forced swim test, open field test, and social interaction test were performed to determine changes in PNS rats compared to non-stressed offspring. Haloperidol was used as a positive control as an antipsychotic drug based on previous studies. RESULTS: Behavioral changes were restored after treatment with tianeptine or haloperidol. Western blot and immunohistochemical analyses of the prefrontal cortex revealed downregulation of several neurodevelopmental proteins in PNS rats. After treatment with tianeptine or haloperidol, their expression levels were increased. CONCLUSION: Downregulation of several proteins in PNS rats might have caused subsequent behavioral changes in PNS rats. After tianeptine or haloperidol treatment, behavioral changes in PNS rats were restored. Therefore, tianeptine might decrease incidence of prenatal stress related-psychiatric disorders such as depression and schizophrenia.
Adult* ; Animals ; Behavior Rating Scale ; Blotting, Western ; Brain ; Critical Period (Psychology) ; Depression ; Down-Regulation ; Female ; Haloperidol ; Humans ; Incidence ; Interpersonal Relations ; Models, Animal ; Prefrontal Cortex ; Pregnancy ; Rats* ; Schizophrenia

BACKGROUND: This prospective randomized double-blinded study was designed to compare the efficacy of a combination of high dose metoclopramide and dexamethasone with that of haloperidol, midazolam and dexamethasone, for the prevention of postoperative nausea and vomiting (PONV) in patients scheduled for laparoscopic gynecologic surgery who are receiving fentanyl intravenous-patient controlled analgesia. METHODS: The subjects were randomly allocated to either group M (20 mg metoclopramide and 10 mg dexamethasone was administered at induction, n = 35) or group H (1 mg haloperidol, 3 mg midazolam and 10 mg dexamethasone were administered at induction, n = 35). The incidence of PONV and the severity (measured by numeric rating scale) of the patients' nausea and pain were evaluated at 6 hours, 24 hours, and 48 hours, postoperatively. RESULTS: The overall incidence of the PONV was not significantly different between the two groups during the 48 hours period (group M: 21% vs. group H: 12%). The severity of the nausea and pain were similar between the two groups. CONCLUSIONS: The prophylactic use of a combination of 1 mg haloperidol, 3 mg midazolam and 10 mg dexamethasone is as effective and inexpensive as 20 mg metoclopramide and 10 mg dexamethasone to prevent PONV.
Analgesia ; Dexamethasone* ; Female ; Fentanyl ; Gynecologic Surgical Procedures* ; Haloperidol* ; Humans ; Incidence ; Metoclopramide* ; Midazolam* ; Nausea ; Postoperative Nausea and Vomiting* ; Prospective Studies

Galactorrhea, as an adverse effect of psychotropic medications, usually develops due to high dose of antipsychotics. Selective serotonin reuptake inhibitors (SSRIs) have also been reported to be related to galactorrhea. To the best of our knowledge, no previous study reported galactorrhea with methylphenidate (MPH) use. Hereby, we report a case of an adolescent girl who developed galactorrhea after increasing his modifed-release oral MPH to 50 mg/day while under treatment of sertraline and very low dose haloperidol.
Adolescent* ; Antipsychotic Agents ; Female ; Galactorrhea* ; Haloperidol ; Humans ; Methylphenidate* ; Pregnancy ; Serotonin Uptake Inhibitors ; Sertraline

OBJECTIVES: Relapse prevention is a major therapeutic goal in the treatment of schizophrenia. However, many patients experience multiple functional impairments and treatment resistance due to recurrence. This study was designed to investigate the follow-up of patients with using antipsychotic drugs and to compare the total treatment failure rate, withdrawal reasons, and duration period of antipsychotic drugs. METHODS: The subjects were 1963 patients who taking antipsychotic drugs under the diagnosis of schizophrenia. We selected 1836 patients using 10 antipsychotic drugs according to frequency of using. The rate of total treatment failure of them was divided into 6-month, 1-year, 2-year, 3-year, and 5-year according to the time of drug withdrawal. We compared the total treatment failure rate at 1 and 3-year between 10 antipsychotic drugs. RESULTS: The total treatment failure rate of clozapine was lowest compared with the other 9 antipsychotic drugs in all the surveyed periods. When evaluating actual number of subjects, olanzapine, sulpiride, risperidone, aripiprazole, amisulpride, and haloperidol were lower significantly compared with ziprasidone at 1-year in the total treatment failure rate, but there was no significant difference between them except clozapine at 3-year. The results of the analysis based on the number of prescriptions showed that the total treatment failure rate of the atypical antipsychotic drug was lower than that of the typical antipsychotic drug at 1-year, but the difference was decreased over time except quetiapine and ziprasidone. CONCLUSION: In conclusion, although there is some controversy about which drug to prescribe to the patient, the clinician needs a proper prescription considering various factors such as efficacy, side effects, price, and formulations of each drug.
Antipsychotic Agents* ; Aripiprazole ; Clozapine ; Diagnosis ; Follow-Up Studies ; Haloperidol ; Humans ; Prescriptions ; Quetiapine Fumarate ; Recurrence ; Risperidone ; Schizophrenia ; Secondary Prevention ; Sulpiride ; Treatment Failure

OBJECTIVES: Relapse prevention is a major therapeutic goal in the treatment of schizophrenia. However, many patients experience multiple functional impairments and treatment resistance due to recurrence. This study was designed to investigate the follow-up of patients with using antipsychotic drugs and to compare the total treatment failure rate, withdrawal reasons, and duration period of antipsychotic drugs. METHODS: The subjects were 1963 patients who taking antipsychotic drugs under the diagnosis of schizophrenia. We selected 1836 patients using 10 antipsychotic drugs according to frequency of using. The rate of total treatment failure of them was divided into 6-month, 1-year, 2-year, 3-year, and 5-year according to the time of drug withdrawal. We compared the total treatment failure rate at 1 and 3-year between 10 antipsychotic drugs. RESULTS: The total treatment failure rate of clozapine was lowest compared with the other 9 antipsychotic drugs in all the surveyed periods. When evaluating actual number of subjects, olanzapine, sulpiride, risperidone, aripiprazole, amisulpride, and haloperidol were lower significantly compared with ziprasidone at 1-year in the total treatment failure rate, but there was no significant difference between them except clozapine at 3-year. The results of the analysis based on the number of prescriptions showed that the total treatment failure rate of the atypical antipsychotic drug was lower than that of the typical antipsychotic drug at 1-year, but the difference was decreased over time except quetiapine and ziprasidone. CONCLUSION: In conclusion, although there is some controversy about which drug to prescribe to the patient, the clinician needs a proper prescription considering various factors such as efficacy, side effects, price, and formulations of each drug.
Antipsychotic Agents* ; Aripiprazole ; Clozapine ; Diagnosis ; Follow-Up Studies ; Haloperidol ; Humans ; Prescriptions ; Quetiapine Fumarate ; Recurrence ; Risperidone ; Schizophrenia ; Secondary Prevention ; Sulpiride ; Treatment Failure

OBJECTIVE: We designed a nationwide study with limited exclusion criteria to investigate the prevalence of metabolic syndrome (MetS) in Korea and its relationship with antipsychotic medications. METHODS: This multicenter, cross-sectional, and observational study included patients diagnosed with schizophrenia or schizoaffective disorder. Sixteen hospitals enrolled 845 patients aged 18 to 65 years prescribed any antipsychotic medication between August 2011 and August 2013. MetS was diagnosed using the criteria of the modified Adult Treatment Panel III of the National Cholesterol Education Program with the Korean abdominal obesity definition (waist circumference ≥85 cm in women, ≥90 cm in men). RESULTS: The prevalence of MetS in all patients was 36.5% and was significantly higher in men than women (men, 40.8%; women, 32.2%) and was significantly correlated with age [odds ratio (OR) 1.02] and duration of illness (OR 1.03). The prevalence of MetS across antipsychotic drugs in the major monotherapy group was as follows: 18.8% for quetiapine, 22.0% for aripiprazole, 33.3% for both amisulpride and paliperidone, 34.0% for olanzapine, 35% for risperidone, 39.4% for haloperidol, and 44.7% for clozapine. CONCLUSION: The prevalence of MetS is very high in patients with schizophrenia or schizoaffective disorder. Screening and monitoring of MetS is also strongly recommended.
Adult ; Antipsychotic Agents ; Aripiprazole ; Cholesterol ; Clozapine ; Cross-Sectional Studies* ; Education ; Female ; Haloperidol ; Humans ; Korea* ; Male ; Mass Screening ; Obesity, Abdominal ; Observational Study ; Paliperidone Palmitate ; Prevalence* ; Psychotic Disorders ; Quetiapine Fumarate ; Risperidone ; Schizophrenia*

BACKGROUNDThe management of pain, agitation, and delirium (PAD) in Intensive Care Unit (ICU) is beneficial for patients and makes it widely applied in clinical practice. Previous studies showed that the clinical practice of PAD in ICU was improving; yet relatively little information is available in China. This study aimed to investigate the practice of PAD in ICUs in China.

METHODSA multicenter, nationwide survey was conducted using a clinician-directed questionnaire from September 19 to December 18, 2016. The questionnaire focused on the assessment and management of PAD by the clinicians in ICUs. The practice of PAD was compared among the four regions of China (North, Southeast, Northwest, and Southwest). The data were expressed as percentage and frequency. The Chi-square test, Fisher's exact test, and line-row Chi-square test were used.

RESULTSOf the 1011 valid questionnaire forms, the response rate was 80.37%. The clinicians came from 704 hospitals across 158 cities of China. The rate of PAD assessment was 75.77%, 90.21%, and 66.77%, respectively. The rates of PAD scores were 45.8%, 68.94%, and 34.03%, respectively. The visual analog scale, Richmond agitation-sedation scale, and confusion assessment method for the ICU were the first choices of scales for PAD assessment. Fentanyl, midazolam, and dexmedetomidine were the first choices of agents for analgesic, sedation, and delirium treatment. While choosing analgesics and sedatives, the clinicians put the pharmacological characteristics of drugs in the first place (66.07% and 76.36%). Daily interruption for sedation was carried out by 67.26% clinicians. Most of the clinicians (87.24%) used analgesics while using sedatives. Of the 738 (73%) clinicians titrating the sedatives on the basis of the proposed target sedation level, 268 (26.61%) clinicians just depended on their clinical experience. Totally, 519 (51.34%) clinicians never used other nondrug strategies for PAD. The working time of clinicians was an important factor in the management of analgesia and sedation rather than their titles and educational background. The ratios of pain score and sedation score in the Southwest China were the highest and the North China were the lowest. The ratios of delirium assessment and score were the same in the four regions of China. Moreover, the first choices of scales for PAD in the four regions were the same. However, the top three choices of agents in PAD treatment in the four regions were not the same.

CONCLUSIONSThe practice of PAD in China follows the international guidelines; however, the pain assessment should be improved. The PAD practice is a little different across the four regions of China; however, the trend is consistent.

TRIAL REGISTRATIONThe study is registered at http://www.clinicaltrials.gov (No. ChiCTR-OOC-16009014, www.chictr. org.cn/index.aspx.).

Delirium ; drug therapy ; Dexmedetomidine ; therapeutic use ; Fentanyl ; therapeutic use ; Haloperidol ; therapeutic use ; Humans ; Hypnotics and Sedatives ; therapeutic use ; Intensive Care Units ; statistics & numerical data ; Midazolam ; therapeutic use ; Pain ; drug therapy ; Pain Management ; methods ; Pain Measurement ; methods ; Surveys and Questionnaires

OBJECTIVETo investigate the difference in the efficacy between clonidine transdermal patch and haloperidol tablets in the treatment of moderate to severe tic disorders in children.

METHODSA total of 134 children with moderate to severe tic disorders were randomly divided into clonidine group (n=70) and haloperidol group (n=64). The clonidine and haloperidol groups were treated with clonidine transdermal patch and haloperidol tablets respectively, and the treatment lasted for 8 weeks in both groups. The Yale Global Tic Severity Scale (YGTSS) was used to evaluate the conditions of the children before and after treatment, and the adverse events during the treatment were recorded.

RESULTSThe haloperidol group had a significantly better treatment outcome than the clonidine group after one week of treatment (P<0.05); the treatment outcome showed no significant difference between the two groups after 3, 5, and 8 weeks of treatment (P>0.05). The clonidine group had significantly less reductions in the motor tics, vocal tics, and function impairment scores and total score of YGTSS than the haloperidol group after one week of treatment (P<0.05); there were no significant differences in YGTSS score reductions between the two groups after 3, 5, and 8 weeks of treatment (P>0.05). The clonidine group had a significantly lower overall incidence of adverse events than the haloperidol group (8% vs 37%; P<0.01).

CONCLUSIONSClonidine transdermal patch and haloperidol are both effective in the treatment of moderate to severe tic disorders in children. The clonidine transdermal patch, despite slow action, has comparable efficacy and fewer adverse effects compared with haloperidol.

Child ; Child, Preschool ; Clonidine ; administration & dosage ; Female ; Haloperidol ; therapeutic use ; Humans ; Male ; Severity of Illness Index ; Tic Disorders ; drug therapy ; Transdermal Patch