Naltrexone plus benzodiazepine aids abstinence in opioid-dependent patients.

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.

[Exacerbation of an affective psychosis after terminating a decade of benzodiazepine treatment. Which therapeutic procedure is sensible?]. / Exazerbation einer affektiven Psychose nach Beendigung einer jahrzehntelangen Benzodiazepinbehandlung. Welches therapeutische Vorgehen ist sinnvoll?

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.

Comparative single-dose kinetics and dynamics of lorazepam, alprazolam, prazepam, and placebo.

Thirty-nine healthy volunteers received single oral doses of either alprazolam (1 mg), lorazepam (2 mg), prazepam (20 mg), or placebo in a randomized, double-blind, parallel group study. Plasma drug concentrations, subjective self-ratings, and the digit symbol substitution test (DSST) were evaluated during 24 hours after dosage. Alprazolam was absorbed rapidly and produced correspondingly rapid sedation and impaired DSST performance. These effects also resolved rapidly, being similar to placebo by 4 to 6 hours after dosage. Sedative and DSST-impairing effects of lorazepam were of slower onset but longer duration than those of alprazolam. After oral prazepam, appearance of desmethyldiazepam in plasma was slow, with minimal sedative and DSST-impairing effects. Twenty-four hours after dosage, both alprazolam and lorazepam significantly impaired recall of a list of 16 words learned previously 3 hours after dosage. Thus benzodiazepines with approximately equivalent clinical anxiolytic properties may have different sedative, performance-impairing, and amnesic profiles after single doses in healthy volunteers; these differences are explained at least in part by pharmacokinetic variations.

[Treatment of anxiety with prazepam, 40 mg. A controlled study versus lorazepam]. / Traitement de l'anxiété par le prazépam 40 mg. Une étude contrôlée contre le lorazépam.

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.

A multi-centre comparison of prazepam and diazepam in the treatment of anxiety.

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.

Prazepam in the treatment of anxiety: a placebo-controlled multicenter evaluation.

A double-blind randomized multicenter parallel group comparison of prazepam in divided doses vs. placebo was conducted by 15 investigators among 847 patients presenting with anxiety alone or concurrent with other medical illnesses. Study groups were well matched for age, sex and level of pre-treatment symptomatology. Efficacy evaluation by a physician questionnaire included serial assessment of global improvement plus 10 target signs/symptoms during the 2 to 4 weeks of treatment. Prazepam was statistically significantly superior to placebo as shown on final on-treatment scores for global improvement ratio and for the target symptoms of anxiety, tension, irritability/hostility, depressive mood, insomnia and somatization.