1.Use of Haloperidol and Lorazepam for Intractable Symptoms in the Hospice Palliative Care Unit
Wook NAMKOONG ; Jungmin KIM ; Hyunseon EO ; Eunjin CHUNG ; Junga KIM ; Soohyoung LEE ; Kihyon PARK
Korean Journal of Family Practice 2019;9(1):10-16
		                        		
		                        			
		                        			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
		                        			
		                        		
		                        	
2.A Case of Clozapine-induced Corneal and Lenticular Pigmentation
Ji Seon AN ; Young Mi LEE ; Joo Young KWAG ; Joo HYUN ; Jin Seok CHOI ; Kyu Hong PAK ; Sung Kun CHUNG
Journal of the Korean Ophthalmological Society 2019;60(3):276-279
		                        		
		                        			
		                        			PURPOSE: To report a case of corneal and lenticular pigmentation after prolonged clozapine therapy. CASE SUMMARY: A 56-year-old male visited our hospital with a progressive decline in vision that affected both eyes. He had a history of schizophrenia. He was being treated with 200 mg clozapine and 1 mg lorazepam daily, and had been treated with clozapine for 5 years. At the first visit, his best-corrected-visual acuity was 20/32 in both eyes. Slit lamp examination of the corneas showed bright, fine, grayish-brown deposits on the endothelium, and on dilation, bilateral central stellate opacity of the anterior portion of the lens capsule was revealed. CONCLUSIONS: Clozapine may induce corneal and lenticular pigmentation and thus may lead to a decline in vision. Patients on long-term clozapine therapy should be considered for regular ophthalmic review.
		                        		
		                        		
		                        		
		                        			Clozapine
		                        			;
		                        		
		                        			Cornea
		                        			;
		                        		
		                        			Endothelium
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lorazepam
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Pigmentation
		                        			;
		                        		
		                        			Schizophrenia
		                        			;
		                        		
		                        			Slit Lamp
		                        			
		                        		
		                        	
3.Negative myoclonus associated with pregabalin
Kwan Do PARK ; Min Ku KIM ; Se Jin LEE
Yeungnam University Journal of Medicine 2018;35(2):240-243
		                        		
		                        			
		                        			Negative myoclonus (NM) is a jerky, shock-like involuntary movement caused by a sudden, brief interruption of muscle contraction. An 80-year-old man presented with multifocal NM and confusion. Two days before the onset of NM, he commenced the intake of pregabalin at a dose of 150 mg/day for neuropathic pain. His NM resolved completely and mental status improved gradually after the administration of lorazepam intravenously and the discontinuation of pregabalin. Our study suggests that pregabalin can cause NM even in patients without a history of seizures.
		                        		
		                        		
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Dyskinesias
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lorazepam
		                        			;
		                        		
		                        			Muscle Contraction
		                        			;
		                        		
		                        			Myoclonus
		                        			;
		                        		
		                        			Neuralgia
		                        			;
		                        		
		                        			Pregabalin
		                        			;
		                        		
		                        			Seizures
		                        			
		                        		
		                        	
4.Benzodiazepine-Associated Carcinogenesis: Focus on Lorazepam-Associated Cancer Biomarker Changes in Overweight Individuals.
Shih Chieh KU ; Pei Shen HO ; Yu Ting TSENG ; Ta Chuan YEH ; Shu Li CHENG ; Chih Sung LIANG
Psychiatry Investigation 2018;15(9):900-906
		                        		
		                        			
		                        			OBJECTIVE: Cellular, animal, and human epidemiological studies suggested that benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also clearly linked to carcinogenesis. However, no human studies have examined benzodiazepine-associated carcinogenesis as assessed by changes in cancer biomarkers. METHODS: A total of 19 patients were recruited, and received a 6-week treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2 (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen activator inhibitor (PLGF), placental growth factor, transforming growth factor (TGF)-α, tumor necrosis factor (TNF)-α, urokinase-type plasminogen (uPA), vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D. RESULTS: Six cancer biomarkers were significantly increased in all patients as a whole. The subgroup analysis revealed a distinct pattern of change. Overweight patients showed a significant increase in 11 cancer biomarkers, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D. However, normal-weight patients did not show any changes in cancer biomarkers. CONCLUSION: Adiposity may have primed the carcinogenic potential, leading to lorazepam-associated carcinogenesis in overweight patients. Epidemiological studies addressing this issue should consider the potential modulator contributing to benzodiazepine-associated carcinogenesis.
		                        		
		                        		
		                        		
		                        			Adiposity
		                        			;
		                        		
		                        			Angiopoietin-2
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Benzodiazepines
		                        			;
		                        		
		                        			Biomarkers, Tumor
		                        			;
		                        		
		                        			Carcinogenesis*
		                        			;
		                        		
		                        			Carrier Proteins
		                        			;
		                        		
		                        			CD40 Ligand
		                        			;
		                        		
		                        			Epidemiologic Studies
		                        			;
		                        		
		                        			Epidermal Growth Factor
		                        			;
		                        		
		                        			Fas Ligand Protein
		                        			;
		                        		
		                        			Heparin-binding EGF-like Growth Factor
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Interleukin-18
		                        			;
		                        		
		                        			Interleukin-8
		                        			;
		                        		
		                        			Interleukins
		                        			;
		                        		
		                        			Lorazepam
		                        			;
		                        		
		                        			Mortality
		                        			;
		                        		
		                        			Obesity
		                        			;
		                        		
		                        			Overweight*
		                        			;
		                        		
		                        			Plasminogen
		                        			;
		                        		
		                        			Plasminogen Activators
		                        			;
		                        		
		                        			Transforming Growth Factors
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha
		                        			;
		                        		
		                        			Vascular Endothelial Growth Factor A
		                        			;
		                        		
		                        			Vascular Endothelial Growth Factor C
		                        			;
		                        		
		                        			Vascular Endothelial Growth Factor D
		                        			
		                        		
		                        	
5.The Efficacy and Safety of Clonazepam in Patients with Anxiety Disorder Taking Newer Antidepressants: A Multicenter Naturalistic Study.
Sheng Min WANG ; Jung Bum KIM ; Jeong Kyu SAKONG ; Ho Suk SUH ; Kang Seob OH ; Jong Min WOO ; Sang Woo YOO ; Sang Min LEE ; Sang Yeol LEE ; Se Won LIM ; Seong Jin CHO ; Ik Seung CHEE ; Jeong Ho CHAE ; Jin Pyo HONG ; Kyoung Uk LEE
Clinical Psychopharmacology and Neuroscience 2016;14(2):177-183
		                        		
		                        			
		                        			OBJECTIVE: This study compared the efficacy and tolerability of clonazepam with other benzodiazepines in patients with anxiety disorders. METHODS: Inclusion criteria were as follows: age >20 years, diagnosis of anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) criteria, taking only one type of antidepressant, and prescribed one of three oral benzodiazepines (alprazolam, clonazepam, or lorazepam). At baseline and week 6, clinical benefit was evaluated using the Clinical Global Impression-Severity Scale (CGI-S), Clinical Global Impression-Anxiety Scale (CGI-anxiety), and Clinical Global Impression-Sleep Scale (CGI-sleep). RESULTS: Among 180 patients, no differences in demographic characteristics among the three benzodiazepine groups were noted. After six weeks of treatment, all benzodiazepine groups showed significant improvements in CGI-S, CGI-anxiety, and CGI-sleep scores (p<0.001). There were no differences in mean changes in CGI-S, CGI-anxiety and CGI-sleep among the three benzodiazepine groups. The incidence of side effects was significantly lower in the clonazepam group than with the other benzodiazepines. The incidences of adverse events for the clonazepam, alprazolam, and lorazepam groups were 26.7% (n=20), 48.4% (n=31), and 43.9% (n=18), respectively. CONCLUSION: The present study suggests that clonazepam is as efficacious as other benzodiazepines for the treatment of various anxiety disorders. Furthermore, the safety profile of clonazepam was superior to the other benzodiazepines in this study.
		                        		
		                        		
		                        		
		                        			Alprazolam
		                        			;
		                        		
		                        			Anti-Anxiety Agents
		                        			;
		                        		
		                        			Antidepressive Agents*
		                        			;
		                        		
		                        			Anxiety Disorders*
		                        			;
		                        		
		                        			Anxiety*
		                        			;
		                        		
		                        			Benzodiazepines
		                        			;
		                        		
		                        			Clonazepam*
		                        			;
		                        		
		                        			Diagnosis
		                        			;
		                        		
		                        			Diagnostic and Statistical Manual of Mental Disorders
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Incidence
		                        			;
		                        		
		                        			Lorazepam
		                        			
		                        		
		                        	
6.Impact of High Dose Lorazepam on Seizure Threshold in Catatonia: Experience from a Case Study.
Sujita Kumar KAR ; Saurabh KUMAR ; Amit SINGH
Clinical Psychopharmacology and Neuroscience 2016;14(3):321-321
		                        		
		                        			
		                        			No abstract available.
		                        		
		                        		
		                        		
		                        			Catatonia*
		                        			;
		                        		
		                        			Lorazepam*
		                        			;
		                        		
		                        			Seizures*
		                        			
		                        		
		                        	
7.Low Plasma Insulin Level Prolonged Hypoglycemia after High dose Insulin Lispro Injection.
Journal of The Korean Society of Clinical Toxicology 2016;14(2):151-154
		                        		
		                        			
		                        			Increased plasma insulin levels are often observed in exogenous insulin overdose patients. However, plasma insulin level may decrease with time. We report a case of low plasma insulin level hypoglycemia after insulin lispro overdose. The patient was a 37-year-old man with no previous medical history who suspected insulin lispro overdose. Upon arrival, his Glasgow coma scale was 3 points and his blood sugar level (BSL) was 24 mg/dl. We found five humalog-quick-pen (insulin lispro) in his bag. There was no elevation of glucose level, despite an initial 50 ml bolus of 50% glucose and 150 cc/hr of 10% dextrose continuous intravenous infusion. He also suffered from generalized tonic-clonic seizure, which was treated with lorazepam and phenytoin. We conducted endotracheal intubation, after which he was admitted to the intensive care unit (ICU). There were recurrent events of hypoglycemia below BSL<50 mg/dl after admission. We repeatedly infused 50 ml 50% glucose 10 times and administered 1 mg of glucagon two times. The plasma insulin level was 0.2 uU/ml on initial blood sampling and 0.2 uU/ml after 5 hours. After 13 hours, his BSL stabilized but his mental status had not recovered. Diffuse brain injury was observed upon magnetic resonance imaging (MRI) and severe diffuse cerebral dysfunction was found on electroencephalography (EEG). Despite 35 days of ICU care, he died from ventilator associated pneumonia.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Blood Glucose
		                        			;
		                        		
		                        			Brain Injuries
		                        			;
		                        		
		                        			Electroencephalography
		                        			;
		                        		
		                        			Glasgow Coma Scale
		                        			;
		                        		
		                        			Glucagon
		                        			;
		                        		
		                        			Glucose
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypoglycemia*
		                        			;
		                        		
		                        			Infusions, Intravenous
		                        			;
		                        		
		                        			Insulin Lispro*
		                        			;
		                        		
		                        			Insulin*
		                        			;
		                        		
		                        			Intensive Care Units
		                        			;
		                        		
		                        			Intubation, Intratracheal
		                        			;
		                        		
		                        			Lorazepam
		                        			;
		                        		
		                        			Magnetic Resonance Imaging
		                        			;
		                        		
		                        			Phenytoin
		                        			;
		                        		
		                        			Plasma*
		                        			;
		                        		
		                        			Pneumonia, Ventilator-Associated
		                        			;
		                        		
		                        			Seizures
		                        			
		                        		
		                        	
8.Korean Addiction Treatment Guidelines Series (II): Pharmacological Treatment of Alcohol Withdrawal.
Hui Yeon KIM ; Hae Kook LEE ; Kye Seong LEE ; Keun Ho JOE ; Sam Wook CHOI ; Jeong Seok SEO
Journal of Korean Neuropsychiatric Association 2013;52(2):67-75
		                        		
		                        			
		                        			OBJECTIVES: In development of Korean addiction treatment guidelines, the aim of this study was to investigate the experts' consensus regarding current pharmacological practice in treatment of alcohol withdrawal. METHODS: Using recommendations from foreign clinical guidelines, which were either lacking in evidence or could not be directly applied to Korea, the executive committee developed a questionnaire consisting of 17 questions. Using a nine-point scale, members of the Korean Addiction Psychiatry, who were experts (n=150) with sufficient experience in treatment of alcohol use disorder, were asked to evaluate the appropriateness of each item on the questionnaire. We classified the experts' opinion according to three categories, based on the lowest scores of 6.5 or greater as a first-line/preferred treatment, 3.5-6.5 as a second-line/reasonable treatment, and lower than 3.5 as a third-line/inappropriate treatment. The consensus was determined by chi-square test (p<0.05). Response rate was 70.4% (81/115). RESULTS: The results of the survey from the experts were as follows: 1) Symptom triggered therapy (STT) was the most appropriate strategy in treatment of alcohol withdrawal (95% CI 7.41-8.04). 2) Prophylactic benzodiazepine was recommended for management of expecting alcohol withdrawal in out-patient-department patients. 3) Among benzodiazepines, lorazepam was the most preferred. 4) For patients with severe withdrawal, lorazepam 7.4 mg/day (95% CI 6.48-8.25, maximum dose=20 mg) was recommended. 5) Risperidone, quetiapine, and haloperidol were the first-line drugs for patients with alcohol withdrawal and combined psychotic symptoms. 6) 127.5 mg (95% CI 111-145) for 2.8 months of prophylactic thiamine and 213.5 mg (95% CI 190-240) for 6.2 months of thiamine for Wernicke-Korsakoff's syndrome were recommended. CONCLUSION: We hope that these Korean addiction treatment guidelines, added by the Korean experts' consensus, will be helpful in promoting the efficacy of treatment for alcohol withdrawal.
		                        		
		                        		
		                        		
		                        			Benzodiazepines
		                        			;
		                        		
		                        			Consensus
		                        			;
		                        		
		                        			Dibenzothiazepines
		                        			;
		                        		
		                        			Haloperidol
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Korea
		                        			;
		                        		
		                        			Lorazepam
		                        			;
		                        		
		                        			Surveys and Questionnaires
		                        			;
		                        		
		                        			Risperidone
		                        			;
		                        		
		                        			Thiamine
		                        			;
		                        		
		                        			Quetiapine Fumarate
		                        			
		                        		
		                        	
9.Anti-Intrusion Effect of Lorazepam: An Experimental Study.
Hong Seock LEE ; Heung Pyo LEE ; Sang Kyu LEE ; Yong Ku KIM ; Yun Kyeung CHOI
Psychiatry Investigation 2013;10(3):273-280
		                        		
		                        			
		                        			OBJECTIVE: Easy triggering of trauma-related episodic memory fragments caused by perceptual cues is tied to strong perceptual priming in the implicit memory system. And among benzodiazepines, only lorazepam has been consistently reported to have an atypical suppression effect on perceptual priming processes. The aim of this study was to investigate the effects of single doses of lorazepam, diazepam, and a placebo on intrusive memories after exposure to a distressing videotape and to explore whether the anti-intrusive effect of lorazepam is acquired as a result of the suppression of perceptual but not conceptual priming processes. METHODS: Under prospective, randomized, and double-blind conditions, we compared the anti-intrusion effect of a single dose of lorazepam (n=22) with that of diazepam (n=22) and a placebo (n=21) in young healthy Korean college students following exposure to a traumatic videotape. RESULTS: We present the first finding for an anti-intrusion effect of lorazepam. One day after the medication, lorazepam, rather than diazepam or the placebo, significantly reduced the extent of intrusion and data-driven processing of the traumatic information. There were no differences among the three conditions in state anxiety, depression, and an arousal scale throughout the experiment. CONCLUSION: Results from this study suggest the possibility of lorazepam as a candidate anti-intrusion drug, as well as the cautious use of diazepam in the treatment of PTSD patients. The anti-intrusive effect of lorazepam is directly related to its atypical inhibitory effect on implicit perceptual priming processes. The present study provides support for the enhanced perceptual priming hypothesis of PTSD.
		                        		
		                        		
		                        		
		                        			Benzodiazepines
		                        			;
		                        		
		                        			Cues
		                        			;
		                        		
		                        			Diazepam
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lorazepam*
		                        			;
		                        		
		                        			Memory
		                        			;
		                        		
		                        			Memory, Episodic
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Stress Disorders, Post-Traumatic
		                        			;
		                        		
		                        			Videotape Recording
		                        			
		                        		
		                        	
10.Opioids and the Gastrointestinal Tract: A Case of Narcotic Bowel Syndrome and Literature Review.
Adam D FARMER ; Ella FERDINAND ; Qasim AZIZ
Journal of Neurogastroenterology and Motility 2013;19(1):94-98
		                        		
		                        			
		                        			The worldwide use of opiates is increasing yet there is little evidence that in long-term, non-cancer patients, they have an efficacious effect on functional outcomes and quality of life measures. Although it seems paradoxical, chronic opiate use may lead to a pro-nociceptive state. Mechanisms for the development of the hyperalgesic state include activation of the opiate bimodal regulatory systems, dynorphin and spinal cord glia. A potential consequence of chronic opiate usage is the development of narcotic bowel syndrome, which is characterized by chronic or intermittent colicky abdominal pain or discomfort that worsens after the narcotic effects of opiates wear off. It is likely that this is an under-recognized diagnosis. We describe here a case of 26-year old female who had visited our institution multiple times with intractable chronic abdominal pain in the context of normal findings on haematological, biochemical, metabolic, endoscopic and radiological investigations. She had been treated with a multitude of opioid agonists with escalating doses. A diagnosis of narcotic bowel syndrome was made. On elective admission her daily analgesic requirements were 150 microg/hr fentanyl, 100 mg oramorph and 400 mg tramadol (equating to 740 mg oral morphine/24 hr). A detoxification regimen was prescribed which included rapid opiate withdrawal couple with the commencement of methadone, lorazepam, clonidine and duloxetine. She was discharged opiate free, with no abdominal pain, 14 days after admission. Clinicians must be aware of narcotic bowel syndrome, which is often erroneously labelled as a functional gastrointestinal disorder, in patients who have been on long-term opiates.
		                        		
		                        		
		                        		
		                        			Abdominal Pain
		                        			;
		                        		
		                        			Analgesics
		                        			;
		                        		
		                        			Analgesics, Opioid
		                        			;
		                        		
		                        			Clonidine
		                        			;
		                        		
		                        			Dynorphins
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fentanyl
		                        			;
		                        		
		                        			Gastrointestinal Diseases
		                        			;
		                        		
		                        			Gastrointestinal Tract
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lorazepam
		                        			;
		                        		
		                        			Methadone
		                        			;
		                        		
		                        			Narcotics
		                        			;
		                        		
		                        			Neuroglia
		                        			;
		                        		
		                        			Quality of Life
		                        			;
		                        		
		                        			Spinal Cord
		                        			;
		                        		
		                        			Thiophenes
		                        			;
		                        		
		                        			Tramadol
		                        			;
		                        		
		                        			Duloxetine Hydrochloride
		                        			
		                        		
		                        	
            
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