Amitriptyline and bromazepam in the treatment of vibratory angioedema: which role for neuroinflammation?

Vibratory angioedema is a rare form of physical urticaria, hereditary or acquired, which occurs at body sites exposed to vibrations. Pathogenic mechanisms of disease are not completely clear and, consequently, current pharmacological treatment is sometimes unsatisfactory. We report the case of a horn player affected by acquired vibratory angioedema, relapsing after prolonged use of the instrument and resistant to systemic antihistamines and corticosteroids, which successfully responded to therapy with low doses of amitriptyline and bromazepam. A neuroinflammatory mechanism can be likely implicated in the pathogenesis of vibratory angioedema, in line with many different cutaneous/mucosal diseases involving a complex interplay of homeostatic/allostatic systems. Furthermore, in mucosal diseases, such as vibratory angioedema, physical/psychological stressors have a relevant role. In such cases, because of the complex interplay between nervous and immune system, the pharmacological activity of benzodiazepines and typical antidepressants may downregulate neuroinflammation.

Concurrent Presentation of Burning Mouth Syndrome and Globus Pharyngis in Enugu, Nigeria: A Ten-year Clinical Evaluation.

PURPOSE: To review 22 patients with globus pharyngis among a group of 39 patients who presented with burning mouth syndrome and to highlight the clinical presentation and treatment outcome of these oropharyngeal symptoms, often ignored by practicing oral surgeons. PATIENTS AND METHODS: We carried out a retrospective review of 39 patients with burning mouth syndrome seen at oral surgery units of three specialist hospitals in Enugu, Nigeria between 2001 and 2010. The focus was on the 22 of these patients with burning mouth syndrome and globus pharyngis (the persistent sensation of having phlegm, a pill or some other sort of obstruction in the throat when there is none). Relevant information included patients' oral habits and dental status, past medical history, sociodemographic data, onset of symptoms and treatment outcome. RESULTS: Amongst the 22 patients, 8 (36.4%) were males while 14 (63.6%) were females, giving a male to female ratio of 1:1.8. Of the 8 male patients, 3 (37.5%) were retrenched workers, 2 (25%) were drug addicts, 2 (25%) had a history of psychiatric problems and 1 (12.5%) had post-radiation therapy due to diagnosis of adenocystic carcinoma. Amongst the 14 female patients, 6 (42.8%) were divorcees, 3 (21.4%) were unemployed and unmarried, 2 (14.3%) had menopausal problems, 2 (14.3%) had dental prostheses and 1 (7.2%) had a history of mental disorder. CONCLUSION: Globus pharyngis can present at the same time in some individuals with burning mouth syndrome. The emotional aetiological factor in this unusual ailment calls for proper examinations and a multidisciplinary approach in the management of patients who presented with burning mouth syndrome, especially with a history of depression.

[Six-month follow-up study of drug treatment for cannabis addiction: comparison study of four drugs].

OBJECTIVES: Marijuana addiction is one of the most common forms of addiction worldwide. A variety of reasons for use exist, however, there are only a few tested treatments with frequent relapses. In this study, we examined the efficacy of four pharmacotherapy agents for the treatment of marijuana addiction: naltrexone, bupropion, escitalopram and bromazepam. MATERIALS AND METHODS: A total of 59 patients were randomly assigned into four groups. Each group received one of the pharmacological agents for 120 days. Four types of questionnaires were employed: The Hamilton Rating Scale for Depression--21 items, the Hamilton Rating Scale for Anxiety, the Global Assessment of Functioning and a Visual Analogue Scale for perceived need of the drug. In addition, random urine tests were performed to detect tetrahydrocannabinol [THC). RESULTS: Naltrexone proved to be the most efficacious of the four agents, with only four dropouts. Other agents proved less efficacious with six, seven and eights dropouts for bupropion, bromazepam and escitalopram, respectively. In addition, naltrexone was most efficacious in reducing anxiety and depression rates, and increasing functioning and perceived need for drug use. CONCLUSION: Out of four pharmacological agents, naltrexone proved to be most efficacious in treating marijuana addiction and related disorders. Further studies are needed to confirm our results.

Chemical gastritis after chronic bromazepam intake: a case report.

BACKGROUND: We describe a rare case of diffuse macroscopic discoloration and chemical gastritis due to chronic bromazepam intake. The chemical composition of pharmaceuticals has to be considered at endoscopy and it is evident that some chemical substances damage the epithelial tissue and lead to clinical symptoms. CASE PRESENTATION: Endoscopy was performed in an 82-year-old patient due to gastroesophageal reflux symptoms and epigastric pain. Gastroscopy showed a hiatal hernia and a scarred duodenal bulb. More striking was the yellow-brownish discoloration of the gastric and the duodenal mucosa. The gastric antrum and the duodenal bulb showed local discoloration that could not be rinsed off. The medical history indicated that bromazepam (6 mg) had been used daily as a sleeping aid in the previous two years. The histopathological findings showed appearances of chemical gastritis. Within the lamina propria and on the epithelial surface there were granules. There was no foreign body reaction to these granules. Corpus mucosa showed a mild chronic gastritis. CONCLUSIONS: If discoloration of the mucosa at endoscopy is seen, a careful drug history must be sought. This is the first case in literature that shows a chemical gastritis after bromazepam intake.

Kinking of Bilateral Internal Carotid Arteries as Cause of Cognitive Dysfunction.

INTRODUCTION: Dolichoarteriopathies of the internal carotid artery (DICAs) is divided into three forms: tortuous, coiling and kinking. In case of kinking, internal carotid artery forms a sharp angle of <90 degrees, while in the background there is metaplasia of a tunica media with unknown etiology. The association with stroke is still questionable, but it is believed that it can be associated with cerebral ischemia and with clinical symptomatology that accompanies cerebral ischemia. AIM: Aim of article was to present diagnostic and therapeutic modality of patient with verified internal carotid artery kinking. CASE REPORT: The 55-year-old male patient was admitted to the Department of Neurology, General Hospital «Prim.dr. Abdulah Nakas¼, due to dizziness and instability while walking, forgetfulness, memory loss and low mood. He has previously been reported to be hypertensive and with diagnosis of diabetes mellitus and dyslipidemia. Doppler sonography also suspects on distal subocclusion of the internal carotid artery (low flow rates were observed). Diagnostic transcranial Doppler (TCD) of vertebrobasilar artery showed decreased blood flow velocities in both vertebral and basilar artery and indicated atherosclerotic altered blood vessels of the brain. CTA findings indicate bilateral kinking of internal carotid artery with right duplex Kinking. SPECT with 15 mCi 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) verified global cortex hypoperfusion, indicating chronic vascular failure. The patient was treated with acetylsalic acid, clopidogrel, atorvastatin, donepezil, memantine, escitalopram, bromazepam, along with antihypertensive and antidiabetic therapy (per os). CONCLUSION: A severe degree of kinking can cause neurological symptomatology, especially if it is bilateral. Symptoms of cerebrovascular disease are more pronounced when autoregulation of cerebral hemodynamics is impaired. Bilateral severe degree of kinking possibly can cause cognitive impairment. Diagnosis, analysis of the existence of possible risk factors for the onset, and the existence of genetic predisposition are a prerequisite for better understanding of the disease and optimal treatment.

Hyponatremia-induced seizure during carbamazepine treatment.

We report the case of a 54-year-old woman who was admitted for benzodiazepine withdrawal. After 6 weeks of carbamazepine treatment (600, then 200 mg) the patient suddenly suffered from a grand mal seizure. Laboratory findings revealed a clinical significant hyponatremia of Na 125 mmol/l (baseline: 143 mmol/l). CCT and ECG were normal. To our knowledge, this is the first description of a seizure related to hyponatremia in an adult carbamazepine-treated patient.

Double-blind, comparative study of cyamemazine vs. bromazepam in the benzodiazepine withdrawal syndrome.

Cyamemazine is an anxiolytic antipsychotic, which reduces ethanol withdrawal symptoms. Here, we investigated if cyamemazine can be also effective as substitute drug to facilitate benzodiazepine withdrawal. A total of 168 patients treated with benzodiazepines for at least 3 months and with a <18 score in the Hamilton Anxiety Rating Scale (HARS) were included in the study. Previous benzodiazepine treatment was withdrawn, and patients were randomized to a 4-week treatment with cyamemazine (25-50 mg q.d.) or bromazepam (3-6 mg q.d.), followed by 2 weeks of placebo. The primary efficacy variable was the maximal anxiety rebound as measured with the HARS during the 42 days of treatment. No statistically significant differences between treatment groups were found for the extent or incidence of rebound anxiety. Considering all dropout patients as withdrawal failures, after 6 months of follow-up, 56/84 patients in the cyamemazine group (66.7%) and 55/84 patients in the bromazepam group (65.5%) were successfully withdrawn. 28 patients in the cyamemazine group and 18 in the bromazepam group had an adverse event, including anxiety, insomnia, dry mouth and somnolence. No extra-pyramidal symptoms were reported. In conclusion, cyamemazine was comparable to bromazepam in ensuring successful benzodiazepine withdrawal and in controlling the acute benzodiazepine withdrawal syndrome. Cyamemazine may be useful to facilitate benzodiazepine withdrawal in those patients where bromazepam substitution is not appropriate.

Benzodiazepines prescription in Dakar: a study about prescribing habits and knowledge in general practitioners, neurologists and psychiatrists.

Benzodiazepines are relatively well-tolerated medicines but can induce serious problems of addiction and that is why their use is regulated. However, in developing countries like Senegal, these products are used without clear indications on their prescription, their dispensation or their use. This work focuses on the prescription of these medicines with a view to make recommendations for their rational use. Benzodiazepine prescription was studied with psychiatrists or neurologists and generalists in 2003. Specialist doctors work in two Dakar university hospitals and generalists in the 11 health centres in Dakar. We did a survey by direct interview with 29 of 35 specialists and 23 of 25 generalists. All doctors were interviewed in their office. The questionnaire focused on benzodiazepine indications, their pharmacological properties, benzodiazepines prescribed in first intention against a given disease and the level of training in benzodiazepines by doctors. Comparisons between specialists and generalists were made by chi-square test. Benzodiazepines were essentially used for anxiety, insomnia and epilepsy. With these diseases, the most benzodiazepines prescribed are prazepam against anxiety and insomnia and diazepam against epilepsy. About 10% of doctors do not know that there is a limitation for the period of benzodiazepine use. The principal reasons of drugs choice are knowledge of the drugs, habit and low side effects of drugs. All generalists (100%) said that their training on benzodiazepines is poor vs. 62.1% of specialists, and doctors suggest seminars, journals adhesions and conferences to complete their training in this field. There are not many differences between specialists and generalists except the fact that specialists prefer prazepam in first intention in the insomnia treatment where generalists choose bromazepam. In addition, our survey showed that specialists' training in benzodiazepines is better than that of generalists. Overall, benzodiazepine prescription poses problems particularly in training, and national authorities must take urgent measures for rational use of these drugs.

Pharmacological and psychosomatic treatments for an elderly patient with severe nausea and vomiting in reaction to postoperative stress.

Here we present a case of successful treatment employing a mixed approach including pharmacological and psychosomatic treatments for a 72-year-old woman who experienced severe nausea and vomiting in reaction to postoperative stress from gastric cancer surgery. This case demonstrates that appropriate provision of psychosomatic treatments, including a psychotherapeutic session and autogenic training, enhances the efficacy of pharmacotherapy.

Comparison of tenoxicam and bromazepan in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled trial.

Fibromyalgia is a painful syndrome of non-articular origin, predominantly involving muscles, and the commonest cause of chronic widespread musculoskeletal pain. The diversity of therapeutic programs for patients with fibromyalgia reflects both the lack of a known pathophysiology for this disorder and the low efficacy of the current therapies. We studied the efficacy of tenoxicam and bromazepan in the treatment of patients with fibromyalgia. One hundred and sixty-four patients from our Rheumatology Outpatient Clinic fulfilling the American College of Rheumatology criteria for the classification of fibromyalgia, with widespread pain at study entry. Each of the 164 patients was randomly assigned to 1 of 4 treatment groups: double placebo (P), tenoxicam (20 mg) + placebo (T), bromazepan (3 mg) + placebo (B)m or tenoxicam (20 mg) + bromazepan 3 mg (TB). Patient global assessment of disease, pain, sleep quality, morning stiffness, and number of tender points were evaluated at baseline and 8 weeks afterwards. At the end of the trial, 17%, 10%, 12%, and 29% of the P, T, B, and TB patients, respectively, had clinical improvement. A statistically significant difference was found only between the T and TB groups. Our data indicate that treatment with tenoxicam + bromazepan can be effective for some patients with fibromyalgia, but the differences with the placebo group were neither clinically nor statistically significant.

Impaired hypothalamic-pituitary-adrenocortical (HPA) system is related to severity of benzodiazepine withdrawal in patients with depression.

A concatenation of data indicates that the pathogenesis of depression is related to an increased production and secretion of corticotropin-releasing hormone (CRH). Benzodiazepines profoundly suppress the basal and stress-related activation of the hypothalamic-pituitary-adrenocortical (HPA) system and discontinuation of these drugs results in rebound activation. We therefore investigated whether the extent of HPA system dysregulation is related to the severity of benzodiazepine withdrawal in patients with depression. We performed the combined dexamethasone/CRH test before benzodiazepine discontinuation (taper-off max. 5 mg diazepam-equivalents/week) in 14 depressed patients (13 f, 1 m, mean age 54.6 +/- 14.6) who responded to the antidepressant treatment. The severity of withdrawal symptoms was measured using the Clinical Institute Withdrawal Assessment-Benzodiazepines (CIWA-B) questionnaire. The depressive psychopathology was monitored using the Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale and Beck Depression Inventory. Patients with more severe benzodiazepine withdrawal (CIWA-B-increase > 14 pts; n = 7) showed a significant higher cortisol and ACTH response in the dexamethasone/CRH test preceding the discontinuation of benzodiazepines than patients displaying less severe withdrawal symptoms (CIWA-B-increase <14 pts.; n = 7) (ANCOVA, p < 0.05). Both groups did not differ in the pre-taper psychopathology ratings and their basal neuroendocrine activity. In view of the GABAergic inhibition of HPA system activity and the anxiogenic effect of CRH, benzodiazepine withdrawal symptoms may be partly due to a disinhibition of the HPA system during discontinuation of benzodiazepines.

Bromazepam in generalized anxiety. Randomized, multi-practice comparisons with both chlorprothixene and placebo.

Bromazepam was compared with placebo and with chlorprothixene in a randomized, double-blind group-comparative multicenter trial in general practice. Two hundred and forty-five patients with generalized anxiety disorder (DSM-III 1980) were treated for 2 weeks with two daily doses of bromazepam, 3 mg or chlorprothixene, 15 mg or placebo. Median reductions in Hamilton Anxiety rating were 12 (bromazepam), 10.3 (chlorprothixene) and 7.3 (placebo). The study revealed significant superiority of bromazepam over placebo (median differences 3.3, 95% confidence limits: 0.3 and 6.1) but not over chlorprothixene (median difference 1.4, 95% confidence limits -0.8 and +3.5). Significantly higher rates of tiredness, sedation and hypersomnia were found on bromazepam and chlorprothixene compared to placebo. Tolerance was rated as "at least good" in 85.6% on bromazepam, in 86% on chlorprothixene and in 87.8% on placebo. Neither previous psychopharmacological treatment nor presence of psychosocial stress were of perceptible influence. Bromazepam and chlorprothixene are both superior to placebo in generalized anxiety states treated in general practice, but spontaneous improvements/placebo effects are substantial.

Low dose neuroleptanxiolysis in anxiety states.

1. In order to prove that neuroleptanxiolysis represents a therapeutical alternative in the treatment of patients suffering from anxiety we conducted four investigations. 2. In the first study it was experimentally proved with 45 outpatients suffering from anxiety that fluspirilene (1.5 mg per week) is superior to bromazepam (6 mg/day), especially in patients with a high degree of somatic anxiety. 3. In the second study the tolerance of fluspirilene (1.5 mg per week) was investigated in 1261 patients with anxiety states and psychoreactive disorders under controlled and open conditions for a period of six weeks. Side effects were found in 11.5% of the patients. All side effects had in common that they occurred already within the first few weeks of treatment. 4. In the third study investigating the dose-effect relationship 106 patients received either 0.5, 1.0, or 1.5 mg fluspirilene per week for a period of 6 weeks. The main result of this study was the verification of a clear dose-effect relationship. 5. The fourth study compared 155 patients who had received long-term treatment with fluspirilene (max 1.5 mg/week) and 121 patients with long-term benzodiazepine treatment. No differences were found with regard to the frequency and intensity of extra-pyramidal disturbances. 6. The therapeutical relevance of the findings was emphasized in the general discussion.

Insomnia and psychotropic drug consumption.

1. During an epidemiological study conducted by telephone on sleep disorders in the metropolitan area of Montreal (Quebec, Canada), the authors found that 5% of subjects used psychotropic drugs. These drugs were usually prescribed by a general practitioner (72.9%). 2. From this population, the authors drew three groups of subjects: users with sleeping difficulties (USD); non users with sleeping difficulties (NUSD) and, non users without sleeping difficulties (NUWSD). 3. Results showed that the utilization of psychotropics was usually chronic and more frequent among the elderly and women. 4. In multivariate models, when users were compared to NUWSD, the authors found eight variables significantly associated with psychotropic consumption: age (> or = 55), sex (female), presence of physical illness, medical consultation, dissatisfaction with sleep onset period and sleep quantity, sleep onset period greater than 15 minutes, and to never or rarely dream. 5. When users were compared to NUSD, three variables were found to be associated with psychotropic consumption: age, to be formerly married, and to experience regular nighttime awakenings. 6. It appears that the utilization of psychotropic drugs does not increase the quality of sleep when consumers are compared to non treated insomniacs (NUSD) on parameters of sleep satisfaction.

New concepts in benzodiazepine therapy: rebound anxiety and new indications for the more potent benzodiazepines.

Abrupt withdrawal of benzodiazepine treatment in generalized anxiety patients was found to induce a rebound anxiety state in addition to minor physical symptoms. Controlled clinical trials suggest that the newer high potency benzodiazepines (alprazolam, clonazepam and bromazepam) have novel psychiatric indications and greater anxiolytic effect than the classical benzodiazepines. Alprazolam, a triazolobenzodiazepine, was superior to placebo in the treatment of panic disorder, for which medium or low potency benzodiazepines are generally inefficacious. Clonazepam, an anticonvulsant which increases 5HT synthesis, was more efficacious than lithium in reducing manic symptoms. Bromazepam, a new potent benzodiazepine, was superior to diazepam in the treatment of generalized anxiety disorder.

Controlled study on the anxiolytic activity of a newly-developed benzodiazepine, metaclazepam.

A double-blind, parallel group study was carried out in 50 patients with an anxiety disorder to compare the anxiolytic efficacy and tolerability of a recently developed benzodiazepine, metaclazepam, with that of bromazepam. Patients were allocated at random to receive treatment for 2 weeks with either 15 mg metaclazepam or 4 mg bromazepam per day in two divided doses. Assessments were made using the Hamilton anxiety rating scale (physician) on entry and after 7 and 13-days' treatment, and a visual analogue scale (patients) on entry and at the end of the study. The results showed that there was a significant, marked reduction in anxiety rating scores after 1 and 2 weeks in both groups and a significant improvement in the patients' subjective assessment of their condition after treatment. Few side-effects were reported in either group.

A double-blind comparison of the anxiolytic activity of two benzodiazepines, metaclazepam and bromazepam, in anxiety neurosis.

A double-blind controlled trial was carried out in 50 patients with anxiety neuroses to compare the effectiveness of metaclazepam, a recently developed benzodiazepine with anxiolytic activity, and bromazepam. Patients were allocated at random to receive treatment for 13 days with either 15 mg metaclazepam or 4 mg bromazepam per day, in 2 divided doses. The patients' anxiety status was assessed on entry and after 7 and 13 days of treatment by the physician, using the Hamilton multi-factorial rating scale, and by the patients, using a self-assessment rating scale. Both drugs produced a highly significant reduction in mean total scores, improvement being evident by the Day 7 assessment. Correlation between scores on the two scales was significant at all time points. Metaclazepam, however, was rated as producing a significantly greater improvement from baseline than with bromazepam on the self-rating scale.

Bromazepam: acute benefit-risk assessment in general practice.

A study was carried out in general practice to assess the benefit-risk ratio of a single new drug, bromazepam, prior to marketing. Analysis of data supplied by 393 participating doctors on 3101 patients showed that bromazepam, in a dose range of 3 mg to 9 mg daily in divided doses, was effective as an anxiolytic in 79% of the patients and that the acute risk of treatment was predictable and low. It is concluded that the acute benefit-risk ratio is acceptable with respect to the class of drug and indication for which bromazepam is prescribed.