Combined occlusal and pharmacological therapy in the treatment of temporo-mandibular disorders.

OBJECTIVE: Aim of the present work is to assess the effectiveness of a scientific protocol built up to relieve pain in chronic temporo-mandibular disorders (TMD) using Michigan splint together with a pharmacological therapy compared to the traditional occlusal therapy by Michigan splint alone. PATIENTS: 35 adult patients, with signs and symptoms of TMD lasting more than 6 months, were enrolled into this study and divided into two groups: the first receiving occlusal therapy by Michigan splint and pharmacological therapy with Delorazepam and Thiocolchicoside, while the second receiving occlusal therapy by Michigan splint and "placebo" administration. The comparisons between the two experimental groups were assessed using a 5 steps visual-analogue scale (V.A.S.). RESULTS AND CONCLUSIONS: The outcomes from the experimental groups were statistically compared resulting significantly different with an improvement or disappearance of signs and symptoms in the treated group with respect to the placebo group at 12 and 18 months from the beginning of the experiment (p < 0.001).

Folie à deux: double case-report of shared delusions with a fatal outcome.

BACKGROUND: Treatment of shared delusional disorder (folie à deux) often involves separation and use of antipsychotic medication, with uncertain outcomes and potential risks. METHODS: We report on two highly interdependent and chronically psychotic sisters with shared systematic delusion, followed by psychiatrists over several years. RESULTS: The dominant patient was diagnosed with schizoaffective disorder and her non-dominant sister with paranoid schizophrenia. Both received antipsychotics and supportive therapy as outpatients and allowed to continue conjoint therapy with individual psychiatrists-therapists. They returned for follow-up visits for 20 months, when the dominant decided to continue treatment alone, as her sister gradually improved symptomatically and functionally. After separation, the dominant became increasingly anxious. She impulsively ingested an overdose of the non-dominant sister's medicines and died of cardiac arrest, despite her sister's efforts to seek medical assistance. The surviving non-dominant sister developed anxiety and increasing agitation requiring psychiatric hospitalization and increased pharmacotherapy. She improved gradually, but continued to be dysfunctional and required placement in a psychiatric inpatient unit for several months, eventually doing better in a community-based rehabilitative program with regular psychiatric follow-up. CONCLUSIONS: Combined treatment of patients with folie à deux may encourage continuous pathological interactions, but separation may increase risk of adverse outcomes.

Peripheral benzodiazepine receptor messenger RNA is decreased in lymphocytes of generalized anxiety disorder patients.

BACKGROUND: The aim of this study was to assess whether the decrease of peripheral benzodiazepine receptor (pBR) number in peripheral blood mononuclear cells (PBMC), previously observed in patients with generalized anxiety disorder, is paralleled by changes in the relative content of messenger RNA (mRNA) encoding pBR. METHODS: Eight patients with a DSM-III-R diagnosis of generalized anxiety disorder were examined before, during, and after 2'-chloro-N-desmethyl-diazepam treatment. Eight healthy subjects were analyzed in parallel. The relative content of pBR mRNA was determined by reverse-transcriptase-polymerase chain reaction, using beta-actin as internal standard. Kinetic binding properties of pBR were measured using 3H-PK11195 as a ligand. RESULTS: pBR and pBR mRNA were significantly decreased in untreated generalized anxiety disorder patients as compared to controls (by 45% and 70%, respectively). Both pBR density and mRNA levels returned to control values during treatment or after withdrawal, which also coincided with recovery from anxiety. CONCLUSIONS: These results suggest that the turnover rate of pBR is reduced in PBMC of generalized anxiety disorder patients, and that this change occurs at the transcriptional level.

Paroxetine efficacy in the treatment of generalized anxiety disorder.

Recently, there has been a renewed interest in alternatives to the benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim of the present study was to compare the efficacy of paroxetine vs. imipramine and 2'-chlordesmethyldiazepam in 81 patients with a DSM-IV diagnosis of GAD. Approximately two-thirds of the patients who completed the study improved greatly or moderately on all three active drugs. During the first 2 weeks of treatment, 2'-chlordesmethyldiazepam treatment resulted in the greatest improvement in anxiety ratings. Both paroxetine and imipramine treatment resulted in more improvement than 2'-chlordesmethyldiazepam by the fourth week of treatment. Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2'-chlordesmethyldiazepam affects predominantly somatic symptoms. Our results suggest that paroxetine is effective for the treatment of GAD.

Benzodiazepine misuse by drug addicts.

Using a high-performance liquid chromatography method, we measured seven commonly prescribed benzodiazepines (chlordiazepoxide, nitrazepam, nordiazepam, oxazepam, lorazepam, temazepam and diazepam) in 100 urine samples obtained from patients attending the Leeds Addiction Unit. All of the urines selected for investigation were positive for benzodiazepines using an EMIT (Enzyme Immunoassay) screen. Forty-four of the urines contained a range of benzodiazepines, none of which had been prescribed. Nitrazepam was detected most frequently (61 urine samples), but had not been prescribed to any of the patients in this study. Chlordiazepoxide was detected in 49 urine samples, although it had been prescribed to only five patients. Temazepam was detected in 28 urine samples. Fourteen patients providing 21 urine samples had been prescribed temazepam for treatment. However, temazepam was detected in only 14 of these samples. Multiple benzodiazepine abuse was evident from the high rate of detection of unrelated benzodiazepines.

Effects of liver disease on the pharmacokinetics of intravenous and oral chlordesmethyldiazepam.

We studied the pharmacokinetics of a single 0.5-mg i.v. dose of chlordesmethyldiazepam in 8 patients with liver disease and in 12 age-matched healthy controls. The kinetics were also studied of a single 1-mg oral dose in the patients with liver disease. After i.v. administration the kinetics of total chlordesmethyldiazepam in patients with liver disease differed from those in controls: elimination half-life was almost twice that in controls (395 and 204 h), as a consequence of a marked reduction in total clearance (0.13 and 0.25 ng.ml-1.h-1), whereas the apparent volume of distribution was similar in patients and controls (4.7 and 3.9 l/kg-1). The free fraction of the drug in patients was higher (5.5%) than in controls (2.9%). Correction for differences in protein binding revealed clearance in the patients was one-fifth (1.8 and 10.5 ng ml-1.kg-1) and volume of distribution one-half (65.0 and 118.4 l.kg-1) that in controls. The systemic availability of oral chlordesmethyldiazepam was high (110%) in spite of a relatively slow absorption rate. These results indicate a need for caution in the administration of chlordesmethyldiazepam to patients with liver disease.

[Control of the side effects of ketamine: chlordemethyldiazepam vs diazepam in pre-anesthesia]. / Controllo degli effetti collaterali della ketamina: clordemetildiazepam vs diazepam in preanestesia.

The pre-operative circulatory and psychotomimetic side-effects are studied in one hundred patients undergoing elective plastic-reconstructive surgery and anesthetized by ketamine 5-8 mg/kg i.m. Fifty patients were premedicated by atropine 0.01 mg/kg + CDDz 0.0285 mg/kg i.m. (group C), fifty by atropine 0.01 mg/kg + Dz 0.14 mg/kg i.m. (group D). All patients breathed spontaneously. Statistical analysis was performed with X 2 test. Not statistical difference was observed for the circulatory side-effects, whereas the frequency of emergence phenomena fell significantly from 31% to 14% (p less than 0.05) with CDDZ in greater than 16 years old patients. These finding seem confirm that CDDZ is more effective than DZ in reducing the psychotomimetic side-effects of ketamine, though it may be recommended a its wider experiment in this connection.

Double-blind placebo cross-over study of long-acting (chlordesmethyldiazepam) versus short-acting (lorazepam) benzodiazepines in generalized anxiety disorders.

Chlordesmethyldiazepam a long-acting benzodiazepine was compared with lorazepam a short-acting one in a double-blind placebo cross-over study against generalized anxiety disorders. Chlordesmethyldiazepam therapy was more effective than lorazepam. Clinical efficacy, drowsiness and insomnia seem well correlated with pharmacokinetic properties of these two benzodiazepines. These results further support the use of a long-acting benzodiazepine rather than a short-acting one as an anti-anxiety agent.

[Effects of chlordemethyldiazepam on blood cortisol during surgical stress]. / Effetti del clordemetildiazepam sulla cortisolemia in corso di stress chirurgico.

The pre-operative plasma cortisol levels in 16 male patients undergoing plastic-reconstructive surgery were studied. 8 patients received chlordesmethyldiazepam 0.1 mg/kg-1 i.v. (group C), 8 sodium thiopental 5 mg/kg-1 i.v. (group T) in anaesthesia induction. All patients were premedicated by diazepam 0.15 mg/kg-1 by mouth 90 min before anaesthesia induction and atropine 0.007 mg/kg-1 i.v. just before induction, and received succinylcholine 1 mg/kg-1 i.v. and an endotracheal tube for mechanically controlled ventilation. Anaesthesia maintenance was assured by isoflurane 0.5-2.5% in a N2O/O2 (2/1) gas mixture. Blood samples were collected from each patient at the following times: 24 h before surgery (t0); 30 min after skin incision (t1); 30 min after extubation (t2). Significant variations of blood cortisol levels have not been shown.

[Effects of intravenous administration of chlordesmethyldiazepam on paroxysmal intercritical activity in various electroclinical forms of infantile epilepsy]. / Effetti della somministrazione endovenosa di clordemetildiazepam sull'attività parossistica intercritica in varie forme elettrocliniche di epilessia infantile.

24 patients, ages ranging from 6 months to 14.5 years, affected by epilepsy resistant to common antiepileptic drugs were studied. CDDZ was administered intravenously at doses from 0.5 to 2 mg and EEG was recorded for 45 min (15 min before and 30 after drug administration). In 20 patients the EEGraphic paroxystic activity was modified: in 5 cases a total remission and in 2 cases a partial remission were obtained; in 13 cases the EEG alterations were reduced. Myoclonic petit mal and organic focal seizures were the forms of epilepsy showing the best responses to CDDZ administration. The drug was well tolerated and only in two cases was persistent drowsiness observed for more than six hours, possibly due to concomitant barbiturate therapy.

Diazepam and desmethyldiazepam plasma concentrations in chronic anxious outpatients.

Within the framework of a large-scale clinical study on the effect of diazepam in chronic anxiety, diazepam (D) and desmethyldiazepam (DD) plasma concentrations were determined frequently. Significant relationships were found between the clinical effect and the plasma concentrations of D and DD, respectively; a curvilinear relationship resulted if the dosage was disregarded, but within the individual dosage groups the relationship was found to be linear. For these computations, the daily diazepam dose was treated as a covariable in a factorial analysis of variance approach. It was found, in addition, that the daily diazepam dose was one of the most significant predictors of the plasma concentration of D or DD, respectively. The steady state plasma concentrations were highest in patients experiencing an exacerbation of their conditions of anxiety if they were returned to placebo after 14 to 22 weeks of diazepam medication. The lowest steady state concentrations were found with those patients who showed withdrawal symptoms under these conditions.

[Prevention and therapy of delirium tremens with tiapride and chlordesmethyldiazepam]. / Prevenzione e terapia del delirium tremens con tiapride e clordemetildiazepam.

Forty alcohol abusers (with a history of long-time alcohol addiction and mean daily use over 360 grams of alcohol) were treated with tiapride or chlordesmethyldiazepam when stopped their overdrinking. The aim of such pharmacological treatment was both a valuation of effectiveness towards ten target-symptoms and the attempt to avoid the development of a withdrawal syndrome-or, at least, to shorten its course. Chlordesmethyldiazepam resulted to be on the whole more effective than tiapride in dominating all most dramatic symptoms of Delirium Tremens and in avoiding--in a significantly higher number of patients--the onset of a DT syndrome in all its typical features. Moreover, CDDz appeared as a manageable drug and free from important side-effects, and could control symptoms without need of further therapies.

Does chlordesmethyldiazepam have a specific anti-erotic effect? Report on five observations.

Five observations in adult subjects (4 female, 1 male) in which the administration of chlordesmethyldiazepam (2-4 mg/day) alone, or in association with other psychodrugs has demonstrated a specific anti-erotic action, with a short therapeutic latency period, reversible, and not found in other benzodiazepines (chlordiazepoxide, diazepam, lorazepam, flunitrazepam, prazepam) which the patients had previously taken, are presented in detail. One of the cases was diagnosed with Clérambault Syndrome of seven years' duration [Acta psychiat. belg., 82, 555-564 (1982)].

[Anxiolytics in man: studies on sleep and performance (author's transl)]. / Les anxiolytiques chez l'homme: études sur le sommeil et sur les capacités de rendement.

The development of the benzodiazepin molecule has led to drugs which are specially indicated in the management of anxiety. Such drugs may be ingested overnight in which a beneficial effect on sleep is followed by an anxiolytic effect the next day, or during the day. In each case it is desirable that their day time effect is without or with only minimal impairment of performance. In the present paper studies on the effects of two anxiolytic (potassium chlorazepate and clobazam) on sleep and on performance will be reviewed. Potassium chlorazepate is usually given as a single dose (15 mg) overnight. It has useful hypnotic activity and a sustained anxiolytic effect the next day related to the activity of its long-acting metabolite, nordiazepam. Further, unlike most if not all other, 1,4 benzodiazepines it is difficult to unequivocally impairment of performance. On the other hand clobazam is usually given as repeated doses (10-20 mg) during the day, and with this 1,5-benzodiazepine it is also difficult to establish impairments of performance. Anxiolytics without impairment of performance during the day have obvious clinical advantages, and if they also have a useful hypnotic activity they can be particularly appropriate for the management of insomnia secondary to anxiety.

The psychosedative effect of chlordesmethyldiazepam on anxiety states in neurotic and psychotic inpatients.

A new benzodiazepine, chlordesmethyldiazepam, was administered at a dose of 6 mg/day to 27 patients (18 neurotics and 9 psychotics) with the common symptom of anxiety. The study period was limited to eight days for the whole group, although the drug has been given to some patients for 38 days. Changes in global scores in neurotic patients were determined by administering the Wittenborn and Hamilton rating scales. In psychotic patients the same rating scales were used in addition to the BPRS. A multistimulator was used to evaluate the performance recording complex reaction times (CRT). The statistical evaluation of results shows a highly significant amelioration of all the studied parameters except for reaction times in the psychotic group.

Anxiety and sedation during a stressful situation after single dose of diazepam versus N-desmethyldiazepam--a controlled trial.

Twenty milligram diazepam (DZ) was compared with 20 mg of its main metabolite N-desmethyldiazepam (NDDZ) as single dose, oral premedication in a genuine stressful situation. Fifty patients participated in the randomized, double-blind controlled study. Anxiety and sedation were measured the day before an operation and one hour after premedication, just before the operation. NDDZ was significantly less sedative while the degree of anxiety was rated equal in the two groups. The results may support the hypothesis that a competition between DZ and NDDZ can explain the shift in the effect profile of DZ during long term treatment.