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Oral lichen planus (OLP) is a usually chronic and relapsing mucocutaneous disease with unknown etiology. Immunosuppressive treatment is sometimes unsatisfactory. We describe four cases of reticular OLP localized on the internal side of cheek, in the territory innervated by sensory free endings of the buccinator nerve, poorly responding to immunosuppressive treatment (topical/systemic corticosteroids, topical cyclosporin). Addition of prazepam 10 mg/day to standard therapy achieved significant improvement and clinical healing in 30-40 days. Because of the complex interplay between the nervous and immune systems, neuroinflammation, acting through conventional axon reflex and/or indirect reflex mechanism involving localized efferent vasodilatory parasympathetic fibers, could have an important pathogenic role in OLP. Such hypothesis could explain, at least partly, the spreading of lesions in OLP primarily triggered (and possibly sustained) by infections, irritants, or autoimmunity. Moreover, neuroinflammation could have a relevant role in OLP related to psychosomatic diseases, where the nervous component is the primary trigger and the main pathogen responsible for the lesions observed. Benzodiazepines modulate neuroinflammation through central, and, possibly, peripheral action. In OLP patients with mild/subclinical psychological conditions, low doses may effectively modulate neuroinflammatory pathways that are not always completely inhibited by immunosuppressive treatment and can contribute to the persistence of inflammation.

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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.

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Naltrexone (NTX) is widely used to prevent relapse of opioid-dependent patients but its association with insomnia and "hyperexcitability" can result in treatment withdrawal. We evaluated whether NTX combined with the benzodiazepine prazepam was more effective than NTX in keeping patients opioid-free. We determined the relapse rate over 6 months in 56 opioid-dependent subjects, divided into 4 equal groups. All groups received psychological support and underwent urine tests for drug metabolites twice weekly. Group 1 did not receive pharmacological treatment (controls). Group 2 received NTX alone (one 50-mg tablet daily); group 3 received NTX (one 50-mg tablet daily) plus placebo (one tablet twice daily); and group 4 received NTX (one 50-mg tablet daily) plus prazepam (one 10-mg tablet twice daily). Ten patients of group 1 relapsed within 3 months, one after 6 months and three remained opioid-free. Six patients of group 2 relapsed within three months, two after 6 months, and six remained opioid-free. Seven patients of group 3 relapsed three months, one after 6 months and six patients remained opioid-free. In group 4, one patient relapsed within 3 months and one patient after 6 months; 12 patients of this group remained opioid-free. At urine tests, a significantly higher percent patients of group 4 remained free of Delta(9)-tetrahydrocannabinol versus patients of groups 2 and 3. In conclusion, many patients remained opioid-free on NTX alone or combined with prazepam, with a significant advantage for the NTX plus prazepam group.

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We report the case of a 61-year old patient with an affective disorder who had been treated with benzodiazepines in low dosages over a 16 year period. This treatment had been prescribed by his physician following several depressive episodes. During this time, the patient remained able to work and exhibited little psychopathological symptomatology. Following discontinuation of medication, however, the depressive phases resumed and were particularly intractable. The clinical implications of this case and the therapeutic strategies for approaching patients with long-term benzodiazepine treatment are discussed.

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UNLABELLED: The efficacy of antidepressants is well established in major depressions, especially those with melancholic features. However, some anxiolytics also appear to have antidepressant properties at least for outpatients. 118 outpatients (25 males, 93 females, age: 18-60) with major depression according to DSM-III criteria, neither melancholic nor suicidal, reaching at least 27 on Montgomery and Asberg depression rating scale (MADRS) and 19 on Hamilton anxiety rating scale (HARS) accepted to participate this double blind study carried out by 15 G.P.s coordinated by 3 psychiatrists. After a one week placebo wash-out-single-blind period, they were randomly, double blind, assigned to one of the two following groups: PR treated with prazepam (30-60 mg), a benzodiazepine anxiolytic or CL treated clomipramine, an imipramine antidepressant (75-150 mg). Patients were evaluated at days 0, 7, 14, and 28, using MADRS, HARS, Clinical Global Impression and Hopkins symptoms check list 58. In addition, G.P.s had to meet monthly for a case discussion group. RESULTS: groups were comparable at day 0. A highly significant improvement of MADRS and HARS scores (p less than 0.001) was observed in the total population. For the completer population evolution was also significantly positive in all the parameters studied but, considering MADRS and HSCL scores, a difference in favor of CL is observed.(ABSTRACT TRUNCATED AT 250 WORDS)

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In order to assess the clinical usefulness of benzodiazepine brief therapy with planned tapering, prazepam as drops was administered to 40 psychiatric outpatients suffering from generalized anxiety disorder. After a one-week placebo period, the patients received prazepam 40 mg daily (i.e., 10 drops in the morning, 10 drops at noon and 20 drops in the evening) during 3 weeks, with the possibility to adjust the doses after one week. The doses were then tapered at 4 mg/d (i.e., 1 drop in the morning, 1 drop at noon and 2 drops in the evening) until complete suppression of the treatment. The assessments, performed before the placebo period, at inclusion, after 1 and 3 weeks of active treatment, and after 1 and 2 weeks of tapering, included the Hamilton anxiety scale, the Lader tranquillizer withdrawal rating scale, and the collection of side effects; moreover, the patients completed daily a visual analogue scale. Results showed a very marked anxiolytic effect of prazepam with an already very significant decrease in the scores on the various scales after 1 week of treatment when the daily dose was significantly reduced. Three quarters of the patients were able to take part in the tapering of prazepam doses without exhibiting any reappearance of anxious symptomatology, rebound anxiety, or withdrawal symptoms. The tolerance of the treatment was rated as good or very good in 91.9% of the patients. This study demonstrates the possibility of a brief anxiolytic treatment followed by tapering in a majority of patients with generalized anxiety disorders. For this strategy, the availability of a drop form represents an obvious advantage.

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A multicentric study has been conducted with a new prazepam formulation (drop) which has been compared with 10 mg tablets. The aim of the study was to check the clinical equivalence of the two formulations. Nine generalists and 9 psychiatrists participated in this double blind study. One hundred fifty four patients with DSM III generalized anxiety criteria were included in this study and received prazepam at an average dosage of 20 mg per day. There were 11 drop outs: 6 in the tablet group and 5 in the drop group. The statistical analysis was done on 143 patients. Before treatment the two groups were equivalent. There was a very significant decrease (p less than 10(-4) in Hamilton anxiety scale scores, physician visual analogic scale and patient visual analogic scale with no difference between both groups. The vigilance, measured by the Mini-Folstein scale, was significantly increased (p less than 10(-4) in both groups. The tolerance was also similar: 14 patients in the tablet group and 10 in the drop one complained of asthenia and somnolence.

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Anxiolytic effects and tolerance of a four weeks treatment with prazepam (single dose of 40 mg in the evening) and with lorazepam (3 daily doses of 1.25 mg) are compared in a double blind study. Patients were treated by psychiatrists and were suffering from neurotic anxiety. Evaluation for therapeutic efficacy used a clinical global improvement scale and the Hamilton Anxiety Scale. Evaluation for side effects used the side effects symptoms check list. Anxiolytic effects of prazepam and lorazepam are not significantly different. Tolerance of the two treatments is comparable. The side effects are essentially an undesirable sedative action.

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The anxiolytic activity and tolerance of two dosage schedules of prazepam, a long plasma half-life benzodiazepine, were compared under double-blind conditions in two groups of 10 inpatients each who met Research Diagnostic Criteria for Generalized Anxiety Disorder and presented chronic and severe symptomatology. Patients received prazepam 40 mg per day on one of two dosage schedules: divided dosage (DD) - 10 mg in the morning and at noon and 20 mg in the evening; or single dosage (SD) - 40 mg in the evening. The 3 weeks of therapy were preceded and followed by 1 week of wash-out for baseline and follow-up assessments, which were performed weekly with the Hamilton Anxiety Scale, Clinical Global Impression, rating of morning drowsiness and evening worsening of symptoms, and patient self-rating of anxiety by means of a visual analogue scale performed both in the morning and in the afternoon. The results showed a clear superiority of the DD over the SD schedule: better anxiolytic efficacy on the Hamilton Anxiety Scale (P less than 0.0005) and on both morning and afternoon visual analogue scales (P less than 0.01 and P less than 0.0002); less morning drowsiness (P less than 0.0001); and steadier anxiolytic effect during the daytime, as globally rated by the investigator (P less than 0.0001) or measured by morning-afternoon differences on the visual analogue scale (P less than 0.005). These results suggest that plasma pharmacokinetics alone may not be sufficient to predict the duration of benzodiazepine anxiolytic activity.

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In a double-blind study the clinical symptomatology and quantitatively analyzed EEG of 42 hospitalized chronic alcoholics (ICD 303) undergoing alcohol withdrawal were investigated before, during and after 3 weeks' treatment with 2 pharmacokinetically different benzodiazepines: the short-acting lopirazepam (a new pyridodiazepine) and the long-acting prazepam. At the end of weeks 1 and 3 the titrated optimal daily doses were 24 and 23 mg lopirazepam and 35 and 32 prazepam, respectively, thus confirming our earlier pharmaco-EEG predictions that on a mg to mg basis the former drug is slightly more CNS potent than the latter. Thereafter, the patient population was divided into 6 subgroups: 2 groups continuing on active medication, 2 groups receiving placebo, and 2 groups with no pharmacotherapy for 1 week. Clinical assessments included the CGI, the Hamilton Anxiety Score, the Zung Self-Rating Scale for Anxiety and Depression, the Zerssen Befindlichkeitsskala and the questionnaire for somatic findings and side effect and were carried out on days 0, 7, 21 and 28 as was a radioreceptor assay for benzodiazepines in plasma. Quantitative EEG investigations were carried out on days 0, 21 and 28 and included recordings before and 2 h after one single dose of 10 mg. Statistical analysis demonstrated a marked and highly significant decrease in psychopathology as well as good drug tolerance at the end of the first week of therapy and thereafter a slight continuation in improvement until the end of the 3rd week. There were, however, no statistically significant differences between the 2 active compounds, nor were there any statistically significant differences between the 6 subgroups in the 4th week. On the other hand, blood level investigations demonstrated that even after a 3-week treatment period, blood levels dropped down to a morning minimum 12 h after the last evening medication of the short-acting lopirazepam, while plasma levels of the long-acting prazepam remained high. This was also reflected in the spectral analyzed EEG, which showed, after one single dosage of both drugs, a typical anxiolytic profile which was more pronounced after lopirazepam than prazepam, while after the chronic administration (12 h after the evening medication) only prazepam showed an anxiolytic profile. The lopirazepam-treated patients exhibited on the one hand a lack of benzodiazepine-specific alterations, but showed on the other hand EEG changes possibly reflecting clinical improvement. The relevance of the findings will be discussed.

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A single-blind, parallel group, multi-centre study was carried out in 2009 patients with an anxiety state to compare the efficacy, tolerance and withdrawal effects of prazepam and diazepam in therapeutically equivalent doses. Patients were allocated at random to receive 30 mg prazepam or 15 mg diazepam per day, either in divided dosage (3 times) during the day or as a single large dose at night. After a 2-week treatment period, drug therapy was withdrawn gradually. Patients were followed-up at weekly intervals over the 4-week study period. Hamilton Anxiety Rating Scale scores and physicians' global assessment of response at each visit indicated that whilst both drugs and dosage regimens were effective patients treated with diazepam responded rather less well and had a greater return of anxiety symptoms after therapy was stopped compared to those on prazepam. Moreover, the prazepam-treated patients, especially those on the divided daytime dosage regimen, had fewer and milder side-effects in the early treatment period. Dizziness was least apparent in the prazepam single night time dosage group and it is suggested that this may be an important practical consideration in the treatment of anxiety in the elderly.

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