Structural identification of the related substances of lorazepam tablets by LC-MS / 中国药科大学学报

@#This study aimed to identify the related substances of lorazepam tablets by liquid chromatography mass spectrometry (LC-MS). To separate the related substances of lorazepam tablets, gradient elution was performed using acetonitrile and 0.1% acetic acid -20 mmol/L of ammonium acetate as mobile phase on Inert Sustain C18 (250 mm × 4.6 mm, 5 μm).The accurate mass and elemental composition of the parent ions and their product ions of related substances were determined by electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry (ESI-Q-TOF/MS).The structures of the related substances were identified by spectral analysis. Under the established analytical condition, lorazepam and its related substances were adequately separated, and 22 major related substances with content greater than 0.1% were detected and identified by hyphenated techniques in lorazepam tablets and their stressed samples.Among them, 5 were the impurities listed in the USP or EP, and the others were unknown related substances identified for the first time in this paper.The LC-MS technique can effectively separate and identify the related substances of lorazepam tablets, which provides some reference for quality control.

Diagnostic Variations and Treatment Responses of Catatonic Patients in the Psychiatric In-Patient Department of a Rural Tertiary Care Centre - A Clinical Study from Eastern India.

This is a cross-sectional descriptive study done in the Psychiatric indoor of North Bengal Medical College between December 2018 to December 2019. Catatonia was diagnosed using DSM-5 criteria in the patients admitted. A total 30 patients were included in the study. The patients were assessed by Bush-Francis Catatonia Rating Scale, were given oral or parenteral lorazepam as needed and observed for 2-3 weeks. Non-responders were given modified ECT as per convention. Background diagnoses were checked by thorough history taking and investigations.RESULTSMajority of the patients were Hindu males in their twenties from rural lower-middle socio-economic families, around 20% of them having family history of affective and psychotic illnesses. They were diagnosed mostly with schizophrenia and other psychotic illnesses (53%) and mood disorders (30%). The mean BFCRS score at the time admission was 20.93 ± 6.16. The commonly found symptoms were mutism, staring, negativism, rigidity, posturing/catalepsy, mannerism, and withdrawal. It was seen that 83.33% of cases responded well to lorazepam only, whereas the rest 13.33% required ECT after non-response or partial response to lorazepam. Only one case after diagnosis with catatonia following organic condition was referred to the Medicine Department. The duration of hospital stay was found to be significantly different [F= 3.58 (>3.35)] among different diagnoses groups (mood disorders, psychotic disorders and others) when the catatonic severity, lorazepam dosage and the duration of treatment response were assessed among those groups using multiple one-way ANOVA.CONCLUSIONSThis study has yielded important findings regarding the age and socio-demographic profiles of the patients, family history of psychiatric disorders, clinical features, and significance of diagnostic variations in relation to the treatment with lorazepam and ECT in catatonic patients in the psychiatric indoor in a tertiary care rural hospital of Eastern India.

Assessment of efficacy of promethazine on seizure activity and its interactions with antiepileptic drugs lorazepam and sodium valproate in rats

Background: Presently available antiepileptic drugs are effective in controlling seizures in more than half of patients of all epilepsy but use is often limited by adverse effects. H1 receptor antagonists, have a controversial status in patients of epilepsy. Both pro and antiepileptic effect has been documented in various animal studies. Hence, this study was designed to see the effect of promethazine, an H1 antihistaminic drug and its interactions with antiepileptic drugs lorazepam and sodium valproate in rats.Methods: The effect of promethazine (10 mg/kg) and its interactions with antiepileptic drugs lorazepam and sodium valproate was assessed by using maximal electroshock seizures (MES) and chemoshock pentylenetetrazol (PTZ) method.Results: Promethazine along with lorazepam and sodium valproate in subtherapeutic doses exerted significant protection against MES induced seizures whereas no such protection was observed with PTZ method rather the seizure threshold was reduced.Conclusions: Subtherapeutic doses of promethazine alone and in combination with lorazepam and sodium valproate showed protection against seizures in MES method. However, proconvulsant effect was seen with PTZ method. This shows dual behavior of promethazine on MES and PTZ induced seizures.

Prescripción de lorazepam dentro de la caja Costarricense del seguro social / Prescription of lorazepam within the Costa Rican social insurance Prescrição de lorazepam no fundo de seguro social da Costa Rica / Prescrição de lorazepam no fundo de seguro social da Costa Rica

Objetivo: describir la prescripción de lorazepam dentro de la caja Costarricense del seguro social. Método: el estudio es descriptivo y retrospectivo, de enero de 2011 a diciembre de 2015. La investigación consistió en 339,484 prescripciones de lorazepam. El tratamiento estadístico de los datos se centró en las estadísticas descriptivas de las cinco unidades generadas a partir de las variables, que fueron analizadas por el programa R. Resultados: se observó un aumento exponencial en la prescripción de lorazepam durante el período investigado. El lorazepam ha sido indicado principalmente para adultos mayores de 60 años. Para todos los grupos de población se encontraron recetas por encima de la dosis diaria definida. Las prescripciones fueron realizadas principalmente por médicos generales y en áreas rurales. Conclusión: en vista de este escenario, es necesario revisar las estrategias de prescripción, dispensación y seguimiento para los usuarios de este medicamento, a fin de evitar efectos adversos y daños a la salud de la clientela.

Objective: to describe the prescription of lorazepam in the social insurance fund of Costa Rica. Method: the study is descriptive and retrospective, from January 2011 to December 2015. The investigation consisted of 339,484 lorazepam prescriptions. The statistical treatment of the data was focused on the descriptive statistics of the five units generated from the variables, which were analyzed by the R program. Results: exponential increase in lorazepam prescription was observed during the investigated period. Lorazepam has been mainly indicated for adults over 60 years old. For all population groups prescriptions above the defined daily dose were found. The prescriptions were performed mainly by general practitioners and in rural areas. Conclusion: In view of this scenario, there is a need to review the prescription, dispensing and follow-up strategies for users of this medication, in order to avoid adverse effects and harm to clientele's health.

Objetivo: descrever a prescrição de lorazepam no fundo de seguro social da Costa Rica. Método: o estudo é descritivo e retrospectivo. A investigação foi constituída por 339.484 prescrições de lorazepam. O tratamento estatístico dos dados foi focado na estatística descritiva das cinco unidades geradas, a partir das variáveis, que foram analisadas pelo programa R. Resultados: foi verificado aumento exponencial na prescrição de lorazepam durante o periodo investigado. O lorazepam foi indicado principalmente para idosos de 60 anos. Para todos os grupos populacionais foram encontradas prescrições acima da dose diária definida. As prescrições foram realizadas principalmente por médicos generalistas e em áreas rurais. Conclusão: frente a este cenário, há necessidade de rever as estratégias de prescrição, dispensação e acompanhamento aos usuários dessa medicação, a fim de evitar efeitos adversos e prejuízos para a saúde da clientela.

The dilemma of using physical restraint in delirium tremens: a case report

Delirium tremens (DT) is a common presentation in tertiary care hospitals. Refractory DT, though not very common, is a dreaded presentation in any clinical setting. Usually, patients with DT respond to standard doses of benzodiazepines, but sometimes we encounter patients requiring higher than the usual dose. Also, due to the high level of agitation, confusion and hallucinatory behaviour, physical restraint is frequently used in these patients. We hereby report a case of refractory DT in whom the dilemma of using physical restraint and need for higher doses of Benzodiazepine has been highlighted.

Effects Of Oral Lorazepam Versus Oral Alprazolam On The Postoperative Cognitive Function

Objectives: To compare the effect of oral Lorazepam 1 mg or oral alprazolam 0.5 mg given at night before surgery on cognitive function in patients undergoing elective general surgery receiving general anaesthesia. Methodology: In a prospective double-blind manner 128 patients aged 30 to 50 years belonging to ASA I and II scheduled for elective surgery under general anaesthesia were randomly divided into two equal groups. Group A (n=64) received oral lorazepam 1 mg and Group B (n=64) received oral alprazolam 0.5 mg). Cognitive function were assessed by 1. Rey’s Auditory Verbal Learning test, (RAVLT) test to assess the ability to form new verbal memory, 2. Trail Making Test (TMT) part A to assess psychomotor ability and 3. Digit Span Test to assess short term verbal memory. These were assessed thrice: 1) during preoperative assessment, 2) 30 minutes before induction and 3) 30 minutes after reversal of general anaesthesia, Results: Oral alprazolam affected cognitive processing speed more than oral lorazepam and the association was statistically significant (P-value <0.05) in one of the three tests performed. Other two tests showed statistically insignificant results. Conclusion: Lorazepam might be a better anxiolytic premedicant than alprazolam.

Benzodiazepine premedication in general anaesthesia: a clinical comparative study

Background:The main aims of pre-anaesthetic medication are anxiolysis, analgesia, anti-emesis and reducing perioperative patient risk. Producing a state of amnesia for pre and post-operative events is desired by all. This study has been undertaken to evaluate the role of three of the benzodiazepines i.e. diazepam, lorazepam and midazolam during general anaesthesia, in providing anxiolysis, sedation and amnesia.Methods:The study included patients with ASA grade I and ASA grade II physical status of both sexes, age ranging between 18-60 years. Patients were divided into three groups of thirty patients each, every group receiving intramuscular injections of diazepam 0.1 mg/kg body weight, lorazepam 0.07 mg/kg body weight and midazolam0.08 mg/kg body weight respectively; 45 minutes prior to induction of general anaesthesia. Anxiety assessment before premedication along with assessment of sedation after premedication was done.Results:Before premedication the mean values of pulse rate, blood pressure and respiratory rate were not significantly different among the three groups (p>0.05). Maximum changes in these parameters were observed with Midazolam followed by lorazepam and diazepam. The dose of thiopentone used as inducing agent was also lowered significantly in case of midazolam (p<0.05). One patient in midazolam group showed respiratory depression whereas four patients receiving lorazepam and diazepam showed delayed recovery and prolonged sedation, but the effects were self-limiting. Conclusions: Midazolam offers the maximum advantage in allaying anxiety and providing excellent sedation and amnesia during general anaesthesia and proves to be the most suitable premedicant before general anaesthesia.

Evaluation of the Process Control Capability of Lorazepam Tablets by Near-Infrared Spectroscopy / 中国药学杂志

OBJECTIVE: To evaluate the process control capability of lorazepam tablets produced in China. METHODS: Near-infrared spectroscopy combined with cluster analysis(CLA) and principal component analysis(PCA) were used to characterize the different processes and process control space of lorazepam tablets produced in China. Universal quantitative model was built to obtain the content predictions of individual units(tablets), on base of which process mean value,intra-batch and inter-batch differences and distribution status were calculated by univariate statistics analysis methods. RESULTS: Three different manufacturing processes of lorazepam tablets were characterized by both CLA and PCA. The process control spaces reconstructed by the second and third principal components indicated that the process of manufacturer B had smaller variation than that of manufacturer A. The universal quantitative model had a principal component number of 5, r2 square value of 93.89% and bias of -0.008 56. The statistic distribution of API contents showed that 9 batches out of the total 27 batches had relative lager intra-batch differences and manufacturer B had better inter-batch differences than manufacturer A. CONCLUSION: The method this study established can reveal the control levels of different processes of lorazepam tablets, which provide an efficient quality consistency evaluation means for generic drug consistency assessment.

Use of Haloperidol and Lorazepam for Intractable Symptoms in the Hospice Palliative Care Unit

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.

Benzodiazepine-Associated Carcinogenesis: Focus on Lorazepam-Associated Cancer Biomarker Changes in Overweight Individuals

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.

Clinical observation of three drug therapies in patients with generalized anxiety disorder and its effect on psychological fluctuation / 中国生化药物杂志

Objective To investigate the clinical efficacy and psychological status of three kinds of drug therapy in patients with generalized anxiety disorder. Methods 90 patients with generalized anxiety disorder in our hospital from January 2015 to December 2016 were selected,and according to the different treatment methods divided into the observation group A, observation group B and observation group C,45 cases in each groups. The observation group A with venlafaxine treatment, observation group B with tandospirone treatment, observation group C treated with Laura Si; comprehensive observation of 3 groups of patients with clinical treatment, improve psychological status and the incidence of adverse reactions, drug compliance, strict record the relevant data and comparative analysis. Results 3 groups of patients with clinical curative effect, no significant difference ; observation group A patients psychological status were better than those observed in B and C group. The incidence of adverse reaction was lower than observed in B and C group, medication compliance was higher than B, C group, the difference was statistically significant (P<0.05). Conclusion The patients with generalized anxiety disorder can choose Vin Rafa Sin, tandospirone, Laura Si treatment, but Vin Rafa Sin on the psychological status of patients with improvement is more significant, less adverse reactions, medication compliance of patients, is worthy of clinical application.

Malignant catatonia responsive to low doses of lorazepam: case report / Catatonia maligna responsiva a baixas doses de lorazepam: relato de caso

Abstract CONTEXT: Catatonia can be divided into non-malignant or malignant. The latter is characterized by autonomic instability, exhibiting high fever, tachycardia and hypertension, and is regarded as a fulminant and rapidly progressive subtype. CASE REPORT: This article reports a case of malignant catatonia in a 43-year-old patient who had been presenting psychiatric disorders for the last three years. The patient was stable, maintaining mutism, immobility and autonomic abnormalities. Oral lorazepam (1 mg every eight hours) was introduced and, in a few hours, the patient became afebrile. Two days later, the patient was already responding to verbal commands. CONCLUSIONS: Early intervention with lorazepam reduced the evolution of this patient to a fatal complication. Therefore, this case report sought to show that early diagnosis and intervention reduced the occurrence of serious and irreversible clinical outcomes.

Resumo CONTEXTO: A catatonia pode ser dividida em não maligna ou maligna. A maligna se caracteriza pela instabilidade autonômica, exibindo febre elevada, taquicardia e hipertensão, além de ser considerada um subtipo fulminante e rapidamente progressivo. RELATO DE CASO: Este artigo relata um caso de catatonia maligna em paciente de 43 anos, com transtornos psiquiátricos há três anos. A paciente estava estável, mantendo o mutismo, a imobilidade e as anormalidades autonômicas. Foi introduzido lorazepam, via oral, 1 mg de oito em oito horas, e em algumas horas, a paciente ficou afebril. Em dois dias, já estava respondendo a comandos verbais. CONCLUSÕES: Intervenção precoce com lorazepam preveniu a evolução desta paciente para um desfecho fatal. Portanto, este relato de caso mostrou que o diagnóstico e a intervenção precoces reduziram a ocorrência de desfechos graves e irreversíveis.

The Efficacy and Safety of Clonazepam in Patients with Anxiety Disorder Taking Newer Antidepressants: A Multicenter Naturalistic Study

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.

Effect of small-dose Lorazepam on residual dizziness in elderly benign paroxysmal positional vertigo after successful particle repositioning maneuver / 中华老年医学杂志

Objective To evaluate the effect of small-dose Lorazepam on residual dizziness in elderly patients with benign paroxysmal positional vertigo (BPPV) after successful particle repositioning maneuver (PRM).Methods A total of 268 patients aged 60 years and over, who were diagnosed as BPPV and underwent successful treatment of PRM, were randomly assigned to medication group and control group.The patients in the medication group were prescribed low-dose lorazepam for 1 week (0.25 mg/time, 3 times/d), whereas the patients in the control group were not prescribed any medication.Hamilton Anxiety Scale (HAMA) was employed to evaluate the anxiety status of patients before and after PRM, and the effect of small-dose lorazepam on residual dizziness was accessed by using the Dizziness Handicap Inventory (DHI) scale and the Activities-specific Balance Confidence (ABC) scale in elderly BPPV patients after PRM.Results No difference in HAMA scores was found between the two groups (t=-0.316, P=0.753) before PRM.The medication group (t=19.931, P=0.000) and the control group (t=26.930, P=0.000) showed a significant improvement in HAMA scores after PRM versus before PRM.However, HAMA scores after PRM was lower in the medication group than in the control group (t=14.967, P=0.000).The medication group had significant improvements after PRM versus before PRM in the following: DHI scores (t=43.661, P=0.000), functional (t=32.326, P=0.000981), emotional (t=31.981, P=0.000), physical (t=14.330, P=0.000) subscale scores, as well as in the ABC scores (t=-23.248, P=0.000).The improvements were also found in the control group in DHI scores (t=46.282, P=0.000), functional (t=32.117, P=0.000), emotional (t=34.563, P=0.000),physical (t=13.182, P=0.000) subscale scores, as well as in the ABC scores(t=-24.536, P=0.000)after PRM versus before PRM.However, after PRM the total DHI score, functional,emotional and physical subscale scores were lower in medication group than in control group (t=5.994, 3.206, 4.757 and 2.851, respectively, P=0.009, 0.002, 0.000 and 0.005).The ABC scores were higher in medication group than in control group (t=2.678, P=0.008) after PRM.Conclusions The elderly patients with BPPV are often accompanied by symptoms of anxiety.The small-dose Lorazepam can alleviate residual dizziness in elderly BPPV patients after successful PRM.

Anti-Intrusion Effect of Lorazepam: An Experimental Study

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.

Use of Lorazepam in Drug-Assisted Interviews: Two Cases of Dissociative Amnesia

Drug-assisted interviews are useful for psychiatric diagnosis and treatment. However, amobarbital, a typical medication used for this purpose, is associated with elevated risk of respiratory depression. Benzodiazepines are good substitutes for amobarbital, with similar therapeutic effects and fewer complications. Although drug-assisted interviews are not widely used, they may be beneficial for selected patients who do not respond to conventional treatments such as supportive psychotherapy or psychopharmacotherapy. We report two cases of dissociative amnesia that were treated using lorazepam-assisted interviews. The use of lorazepam in drug-assisted interviews is effective and safe for resolving dissociative amnesia.

The Effect of Lorazepam on the Silent Period of the Motor Evoked Potential

OBJECTIVE: The purpose of this study was to find out whether the duration of the silent period evoked by magnetic transcranial stimulation could be modulated by lorazepam. METHOD: Ten healthy volunteers were tested using the transcranial magnetic stimulation. Responses were recorded in the active abductor digiti minimi muscle, and baseline values were compared to the data obtained at 2 and 5 hours after administration of a single oral dose of 2.5 mg lorazepam. RESULTS: The motor threshold and size of the motor evoked potential remained unchanged after administration of lorazepam. The duration of cortical silent period was prolonged from 169.9+/-33.7 msec at baseline study to 248.1+/-50.4 msec at 2 hours and 248.5+/-47.3 msec at 5 hours after administration of the drug (p<0.01), but the peripheral silent period did not show any significant change. CONCLUSION: We have shown that the cortical silent period evoked by magnetic transcranial stimulation can be prolonged by administration of lorazepam. And the lack of effect on the motor threshold and on the size of the motor evoked potential after administration of lorazepam may indicate that these parameters are physiologically distinct from the cortical silent period. Therefore, prolonged cortical silent period may be resulted from the reinforcement of GABA action by lorazepam at the level of the motor cortex.

Treatment Experiences of High Dose Lorazepam Dependence: Two Case Reports / 대한정신약물학회지

Drugs of the benzodiazepine family pharmacologically have superior anti-anxiety, sedative, anti-convulsant, and muscle relaxant effect resulting in its popular use not only in psychiatry but in other field of medicine. However, the long term use of benzodiazepines may cause to question the efficacy and may amount to dependence, tolerance, and withdrawal symptoms thus leading to sociologic problems. The treatment strategies of benzodiazepine dependence consist of gradual dosage reduction, the substitution to a long half-life benzodiazepine, and providing psychological support. We present two treatment experiences of high dose lorazepam dependence along with the review of corresponding literature.

Symptom Aggravation in an Elderly Schizophrenic due to Lorazepam Discontinuation of Long-term Use of Minimal Dosage: A Case Report / 신경정신의학

Withdrawal psychosis following long-term administration of benzodiazepine is relatively unclear and has rarely reported. Especially, there are few reports of lorazepam withdrawal characterized by psychotic aggravation in schizophrenia. We report a 64 years old chronic schizophreinc case who developed symptom aggravation and paroxysmal attack of severe psychotic symptom, following discontinuation of 1mg lorazepam, which has been used in combination with 100mg chlorpromazine for 13 years. It was suggested that long-term combination therapy with benzodiazepines in schizophrenia was strongly discouraged even if its dosage is minimal.

Reverse Effect of Flumazenil on the Cerebral and Circulatory Functions Suppressed by Lorazepam in Dogs / 대한마취과학회지

The effects of lorazepam on cerebral function, metabolism, and hemodynamics were studied in eight dogs receiving a general anesthesia with isoflurane(0.5 vo1%)-50% nitrous oxide-oxy-gen. The effects of benzodiazepine antaronist, flumazenil, were also examined. Lorazepam(0.5 mg/kg) administration did decrease mean arterial pressure(MAP) and herat rate(HR). It did significantly decrease cerebral blood flow(CBF)(measured by posterior sagittal sinus outflow method) by 25% of control value(68+/-l3 vs. 51+/-12ml/100gm/min, meanSD) and cereberal metabolic rate for oxygen(CMRO ) by 17% (3.96+/-1.04 vs. 3.30+/-0.92ml/l00gm/min, mean+/-SD). Electroencephalogram(EEG) converted to high amplitude, predominantly theta and delta activity. Intracranial pressure(ICP) increased markedly. Following flumazenil(0.06 mg/kg) administration, HR recovered completely to control level but MAP increased only at 5 min. compared to pre-flumazenil value and returned to pre-flumazenil level. CBF recovered to control level for 15 min. and deereased after 30 min. compared to control level but higher than pre-flumazenil level about 9-15%. CMRO recovered completely to control leveL EEG changed to an awake pattern after fluamzenil administration. It is concluded that lorarepam decreased cerebral function and metabolism and depressed hemodynamic fuction. Benzodiazepine antag- onist, flumazenil, was effective in reversing cerebral and hemodynamic effects, may be in dose related manner.