OBJECTIVE: The purpose of this study is to evaluate the usefulness of administration of benzodiazepines in patients with major depression being treated with the antidepressant mirtazapine. METHODS: The subjects of this study included 503 patients between 18 and 65 years of age. They were diagnosed with major depression according to the ICD-10 and scored over 18 at baseline on the 17-item HAM-D scale. They were among the 925 patients who have participated in the Remeron (mirtazapine) post-marketing surveillance carried out between September 1999 and December 2000 at 33 institutes in Korea. The patients were initially started on 15 mg/day or 30 mg/day of mirtazapine orally and the dosages could be changed according to clinical judgment during the trial. Benzodiazepines could also be administrated according to clinical judgment. The clinical effects were evaluated before and 1, 2 and 6 weeks after treatment initiation. The therapeutic action of mirtazapine was evaluated using the 17-item HAM-D and CGI. The adverse effects were rated according to patient reports. RESULTS: Their mean age was 45 years old and 61.6% were women. 391 subjects (77.3%) from a total of 503 patients completed the trials. 313 (62.2%) patients were administrated benzodiazepines during the trial. These were alprazolam 37.0%, lorazepam 12.5%, clonazepam 9.1% and diazepam 7.0%. The reasons for prescribing benzodiazepines were: anxiety 43.1%, insomnia 18.3% and somatic symptoms 3.8%. The HAM-D scores of total patients were reduced from 26.1 to 10.9, and CGI scores from 4.5 to 3.0 after 6 weeks with significant changes beginning after 1 week of treatment. No significant differences were found in terms of each interval changes on the HAM-D and CGI scores between the groups with and without benzodiazepines. There were no significant differences of each interval changes of anxiety/agitation factors and sleep disturbance factors between the two groups. The occurrence of side effects was not significantly different between the two groups. CONCLUSION: Administration of benzodiazepines in patients with major depression being treated with mirtazapine may not be useful in reducing depressive symptoms, even for anxiety/agitation and sleep disturbance symptoms.
Academies and Institutes ; Alprazolam ; Anxiety ; Benzodiazepines* ; Clonazepam ; Depression* ; Diazepam ; Female ; Humans ; International Classification of Diseases ; Judgment ; Korea ; Lorazepam ; Middle Aged ; Sleep Initiation and Maintenance Disorders

OBJECTIVE: The purpose of this study is to evaluate the usefulness of administration of benzodiazepines in patients with major depression being treated with the antidepressant mirtazapine. METHODS: The subjects of this study included 503 patients between 18 and 65 years of age. They were diagnosed with major depression according to the ICD-10 and scored over 18 at baseline on the 17-item HAM-D scale. They were among the 925 patients who have participated in the Remeron (mirtazapine) post-marketing surveillance carried out between September 1999 and December 2000 at 33 institutes in Korea. The patients were initially started on 15 mg/day or 30 mg/day of mirtazapine orally and the dosages could be changed according to clinical judgment during the trial. Benzodiazepines could also be administrated according to clinical judgment. The clinical effects were evaluated before and 1, 2 and 6 weeks after treatment initiation. The therapeutic action of mirtazapine was evaluated using the 17-item HAM-D and CGI. The adverse effects were rated according to patient reports. RESULTS: Their mean age was 45 years old and 61.6% were women. 391 subjects (77.3%) from a total of 503 patients completed the trials. 313 (62.2%) patients were administrated benzodiazepines during the trial. These were alprazolam 37.0%, lorazepam 12.5%, clonazepam 9.1% and diazepam 7.0%. The reasons for prescribing benzodiazepines were: anxiety 43.1%, insomnia 18.3% and somatic symptoms 3.8%. The HAM-D scores of total patients were reduced from 26.1 to 10.9, and CGI scores from 4.5 to 3.0 after 6 weeks with significant changes beginning after 1 week of treatment. No significant differences were found in terms of each interval changes on the HAM-D and CGI scores between the groups with and without benzodiazepines. There were no significant differences of each interval changes of anxiety/agitation factors and sleep disturbance factors between the two groups. The occurrence of side effects was not significantly different between the two groups. CONCLUSION: Administration of benzodiazepines in patients with major depression being treated with mirtazapine may not be useful in reducing depressive symptoms, even for anxiety/agitation and sleep disturbance symptoms.
Academies and Institutes ; Alprazolam ; Anxiety ; Benzodiazepines* ; Clonazepam ; Depression* ; Diazepam ; Female ; Humans ; International Classification of Diseases ; Judgment ; Korea ; Lorazepam ; Middle Aged ; Sleep Initiation and Maintenance Disorders

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.
Anesthesia, General ; Animals ; Benzodiazepines ; Dogs* ; Electroencephalography ; Flumazenil* ; Hemodynamics ; Lorazepam* ; Metabolism

Midazolam, a water soluble benzodiazepine, was compared with diazepam as a sedation for spinal anesthesia. Forthy healthy patients were allocated at random to receive midazolam 0.1mg/kg or diazepam 0.2mg/kg at 15 min after tetracaine inction for spinal anesthesia and increments of half of the initial dose every 2 min to induce sleep. Mean dose of midazolam 8.5 mg and diazepam 17.1 mg were injected for sedation throughout surgery. There was no difference concerning sedation level during surgery and speed of recovery. With the same degree of sedation, midazolam produced a higher frequency of anterograde amnesia(70% vs. 30%). Uenous tolerance was better for midazolam. Neither drug caused obstruction of airway nor significant cardiovascular change. Higher degree of amnesia and venous tolerance with midazolam may be advantages of sedation for spinal anesthesia.
Amnesia ; Anesthesia, Spinal* ; Benzodiazepines ; Diazepam* ; Humans ; Hypnotics and Sedatives* ; Midazolam* ; Tetracaine

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

Acute pulmonary thromboembolism (PTE) is a major medical problem in many hospitalized patients with medical and surgical conditions, and venous thromboembolism is responsible for up to 15% of all in-hospital deaths. However, PTE complicating acute intoxication has been reported only rarely, and prophylaxis for venous thromboembolism is not routinely incorporated into the management of acute poisoning in emergency departments or general wards. We describe here a case of pulmonary thromboembolism that developed within 48 h of acute benzodiazepine overdose. A 47-year-old female patient was brought to the emergency department by ambulance. She had been found unconscious, and empty packages of medications prescribed by her psychiatrist and an empty bottle of liquor were found. The estimated drugs and amounts were alprazolam 22.5 mg, diazepam 150 mg, flunitrazepam 7.5 mg, fluoxetine 150 mg, and propranolol 600 mg. Approximately 40 hours after initial presentation, she complained of dyspnea and pulse oxymetry indicated 84%. Her arterial pH was 7.41, pCO2 41.6 mmHg, pO2 46.8 mmHg, and oxyhemoglobin saturation was 83.4%. The serum D-dimer concentration was 2.78 mcg/dL, and computed tomography of the chest showed acute PTE in the right upper lobar and segmental pulmonary arteries and both lower segmental pulmonary arteries. When caring for patients with sedative drug overdose, a high level of suspicion of PTE is required, and appropriate diagnostic and therapeutic measures might be undertaken when PTE is suspected. In addition, appropriate prophylaxis for venous thrombosis should be considered.
Alprazolam ; Ambulances ; Benzodiazepines* ; Diazepam ; Drug Overdose ; Dyspnea ; Emergency Service, Hospital ; Female ; Flunitrazepam ; Fluoxetine ; Humans ; Hydrogen-Ion Concentration ; Middle Aged ; Oxyhemoglobins ; Patients' Rooms ; Poisoning ; Propranolol ; Psychiatry ; Pulmonary Artery ; Pulmonary Embolism* ; Thorax ; Venous Thromboembolism ; Venous Thrombosis

The effects of midazolam and diazepam which were used as an induction agent of general anesthesia were evaluated. And flumazenil which is a potent competitive inhibitor of the specific binding of benzodiazepines at the receptor level was evaluated too. Sixty patients were divided into three groups as follows: Group I (n=20); Midazolam (average 0.24 mgkg-1) was administered as an induction agent and flumazenil (average 0.24 mgkg-1) was administered in recovery room Group II (n=20); Diazepam (average 0.35 mgkg-1) was administered as an induction agent and flumaxenil (average 0.25 mgkg-1) was administered in recovery room Group III (n=20); Midazolam (average 0.24 mgkg-1) was administered as an induction agent and normal saline was administered in recovery room instead of flumaxenil The result were as follows: 1) Systolic and diastolic blood pressure and heart rate were not changed significantly, except diastolic blood pressure decreased significantly (p<0.05) in group II, after intravenous administration of midazolam and diazepam. But these were all increased significantly (p<0.001) after endotracheal intubation in all groups. 2) Systolic and diastolic blood preasure and heart rate were not changed significantly after intravenous administration of flumazenil in group I, II and there were no significant differences between each groups. 3) Tidal volume was increased significantly (p<0.05) in group 1 from 15 min after administration of flumazenil. There were no significant changes in all groups in respiratory rate. SaO2 was increased significantly (p<0.05, p<0.001) in group I, II from 5 min after administration of flumazenil. But it was increased significantly (p<0.05) in group III from 20 min after administration of normal saline too. EtCO2 was decreased insignificantly in all groups. 4) Recovery from anesthesia according to Modified Steward Coma Scale was much improved immediately after administration of flumazenil and was significant (p<0.001) statistically in group I, II from 5 min after administration of flumazenil and reached complete recovery from 20 min after administration of flumaxenil. It was increased gradually and become significant in group III from 10 min after administration of normal saline. These changes of group I, II were significant (p<0.05) compared with group III and reached complete recovery from 60 min after administration of flumazenil.
Administration, Intravenous ; Anesthesia ; Anesthesia, General ; Benzodiazepines ; Blood Pressure ; Coma ; Diazepam ; Flumazenil* ; Heart Rate ; Humans ; Intubation, Intratracheal ; Midazolam* ; Recovery Room ; Respiratory Rate ; Tidal Volume

BACKGROUND: It has been demonstrated that a group of minor tranquilizers, benzodiazepines, are able to relax airway smooth muscle, but the mechanism by which these agents produce muscle relaxation are not fully understood. This study was undertaken to determine the effects and mechanism of diazepam and midazolam on Ca2+ and K+ channel in isolated rat trachea muscles by measuring isometric tension. METHODS: Our experiment was performed to evaluate the effects of midazolam and diazepam by cumulative administration from 10(-6)M to 3 x 10(-5)M to tracheal smooth muscle contraction which was induced by contractile agonists such as ACh 10(-5)M, carbachol 3 x 10(-7)M, and KCl 40 mM. The effects of midazolam and diazepam were evaluated on Ca2+ and K+ channels by inhibition of contraction using a nonspecfic K+ channel blocker such as tetraethyl ammonium (TEA) elicited by a 2 mM Ca2+ space addition to Ca2+ free on high K+ depolarizing rat tracheal muscle. Also, to elucidate any mechanism involved, the effects of flumazenil (a specific central antagonist of benzodiazepines), propranolol (a beta adrenergic antagonist), and atropine (a muscarinic antagonist) and tracheal epithelium removal were examined. RESULTS: In a concentration-dependent way, both midazolam and diazepam relaxed airway smooth muscle directly and had inhibitory effects on voltage-dependent Ca2+ (VDCC) and K+ channels. CONCLUSIONS: These results suggest that benzodiazepines relax airway smooth muscle, not via a neural pathway or benzodiazepine receptor but through a direct action on Ca2+ and K+channels. Benzodiazepine enhanced K+ conductance, leading to a decrease in VDCC opening, thus reducing Ca2+ through the voltage-dependent Ca2+ channel, in addition to inhibiting of intracellular Ca2+ release.
Ammonium Compounds ; Animals ; Atropine ; Benzodiazepines ; Calcium Channels ; Carbachol ; Diazepam* ; Epithelium ; Flumazenil ; Midazolam* ; Muscle Relaxation ; Muscle, Smooth* ; Muscles ; Neural Pathways ; Propranolol ; Rats* ; Receptors, GABA-A ; Trachea*

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

OBJECTIVES: This study investigated the consensus about treatment strategies for the initial treatment of generalized anxiety disorder (GAD). This issue represents one of the subjects addressed by the Korean Medication Algorithm Project for GAD in Korea. METHODS: The executive committee of the Korean Medication Algorithm Project for GAD, supported by The Korean Association of Anxiety Disorders, developed questionnaires about treatment strategies for patients with GAD, based on guidelines or algorithms and clinical trial studies previously published in foreign countries, especially by the International Psychopharmacology Algorithm Project, the National Institute for Clinical Excellence, and the Canadian Psychiatric Association. Fifty-five (64%) of 86 experts on a committee reviewing GAD in Korea responded to the questionnaires. We classified the consensus of expert opinions into three categories (first-line, second-line, and third-line treatment strategies) and identified the treatment of choice according using a Chi-square test and a 95% confidence interval. RESULTS: For the initial treatment of GAD, antidepressant monotherapy and the combination of antidepressants and benzodiazepines as anxiolytics were recommended as the first line strategies. Escitalopram, paroxetine CR and venlafaxine XR were selected as first-line antidepressant treatments, and alprazolam, clonazepam and lorazepam were the preferred benzodiazepines. The mean starting doses and mean maximum doses of the drugs were 7.55+/-3.09 mg and 24.91+/-8.14 mg for escitalopram, 12.57+/-2.83 mg and 44.76+/-15.00 mg for paroxetine CR, and 46.81+/-16.74 mg and 223.32+/-60.64 mg for venlafaxine XR. CONCLUSION: These results, which reflect recent studies and clinical experiences, may provide guidelines for the initial.
Alprazolam ; Anti-Anxiety Agents ; Antidepressive Agents ; Anxiety ; Anxiety Disorders ; Benzodiazepines ; Citalopram ; Clonazepam ; Consensus ; Cyclohexanols ; Expert Testimony ; Humans ; Korea ; Lorazepam ; Paroxetine ; Psychopharmacology ; Surveys and Questionnaires ; Venlafaxine Hydrochloride