Haloperidol decanoate in chronic schizophrenia: a study of 12 months with plasma levels.

1. Clinical activity, extrapyramidal side-effects were evaluated in 22 schizophrenic out patients diagnosed according to DSM III and treated with haloperidol decanoate (50-300 mg i.m. monthly dose) for 12 months. 2. BPRS total scores did not show significant fluctuations showing a clinical stability of the patient population. 3. Patients with a duration of illness greater than 10 yrs (Group 2) showed significant (p less than 0.01) higher EPSE total scores compared to those with a duration of illness less than 10 yrs (Group 1). 4. A positive correlation was found between the administered dose and haloperidol plasma levels. 5. Patients from Group 2 reached the steady-state more slowly and showed a lower total L/D ratio compared to those from Group 1. 6. The pharmacokinetic approach seems desirable in order to adjust the dose and avoid schizophrenic relapses.

[Controlled clinical study on the effect of quazepam versus triazolam in patients with sleep disorders]. / Studio clinico controllato dell'effetto del quazepam vs triazolam in pazienti con disturbi del sonno.

Quazepam (QZP), a new long half-life benzodiazepine, seems to have a more specific hypnotic activity and a "physiological" mechanism of action. This study assessed its clinical efficacy and any withdrawal symptoms occurring after the treatment with QZP and triazolam (TRZ). Sixty-five patients (mean age 41.4 yrs +/- 12.43 SD) with sleep disorders were included in the study. The patients were treated with placebo for 4 days (run-in period) and if no amelioration of insomnia was observed, were then randomly allocated to 15 mg QZP (33 patients) or TRZ (32 patients) for 8 weeks and finally placebo for another week. Sleep quality, efficiency, side-effects and withdrawal effects were assessed by specific rating scales. In comparing data obtained from the two treatments, the following conclusions were drawn: 1) both drugs showed a hypnoinductive efficacy but patients treated with QZP had significantly fewer night awakenings; 2) at the end of treatment only patients treated with TRZ had longer awakenings and rebound symptoms; 3) a lower withdrawal symptom incidence was observed in patients treated with QZP. Therefore, QZP seems to have a good hypnotic effect without inducing withdrawal symptoms. In contrast TRZ turned out to be a merely hypno-inducing drug presenting higher risks of rebound effects after withdrawal.

Ritanserin versus lorazepam: a double-blind, cross-over study of reaction times in healthy volunteers.

Ritanserin, a benzydrilen-piperidine derivative, with a potent, selective and long-lasting antagonist activity on serotonin type 2 receptors, has shown anxyolitic properties and a lesser sedative profile than benzodiazepines. Ritanserin and lorazepam at therapeutical doses, were compared in eight healthy volunteers in a double-blind, cross-over study in order to detect possible different impairments of performances. Before and during the treatment, all subjects were daily submitted to a test of rapidity and regularity of response to acoustic and visual stimuli by means of an electronic device. A visual analogue scale for the self-assessment of the drowsiness degree was also administered. Ritanserin did not modify reaction times, while lorazepam significantly prolonged them. The analysis of data within treatments significantly favoured ritanserin, while between treatments there was only a trend in favour of ritanserin. The analogical scale for concentration showed a significant reduction with lorazepam, whereas for drowsiness no alteration occurred with either drug.

Reduced haloperidol/haloperidol ratio and clinical outcome in schizophrenia: preliminary evidences.

1. The possible influence of haloperidol and its metabolite plasma levels on clinical outcome in schizophrenic patients was evaluated. 2. 18 schizophrenic inpatients diagnosed according to DSM III, were treated with conventional haloperidol p.o. for four weeks. 3. Plasma levels of haloperidol and its reduced metabolite were measured by mass-spectrometry assay. Clinical outcome was evaluated by BPRS. 4. Cluster analysis only considering BPRS improvement and reduced haloperidol/haloperidol ratio was able to discriminate two groups of patients: one of non responders and the other of responders. The former group presented higher ratios than the latter. 5. Reduced haloperidol/haloperidol ratio could be considered as a good marker for prediction of the clinical outcome.

Trazodone in late life depressive states: a double-blind multicenter study versus amitriptyline and mianserin.

Seventy five elderly depressed in-patients, ages ranging from 60 to 83 years, diagnosed as Major Depression according to DSM III were treated, under double-blind conditions, with 75 mg Amitriptyline (AMI) (26 patients), 60 mg Mianserin (MIA) (24 patients) or 150 mg Trazodone (TRZ) (25 patients) p.o. for 5 weeks. There were no differences in the clinical outcome between the three groups of patients at the end of the trial, with a significant amelioration (P less than 0.01) at the Hamilton Rating Scale for Depression and Geriatric Depression Scale. TRZ showed a significantly lower incidence of side effects compared to MIA and AMI. Atypical antidepressants, including TRZ, seem more suitable for treating elderly depression than the first generation antidepressants on the basis of risk/benefit ratio considerations.

Age-related differences in kinetics and side-effects of viloxazine in man and their clinical implications.

Dose kinetics and side effects of viloxazine (VLX) in 16 healthy volunteers (range age 25-90 years) were studied after single oral administration of 200 mg of VLX. Significant differences in peak plasma values (P less than 0.01), t1/2 (P less than 0.01) and Cl/F (P less than 0.05) were found between subjects under 50 and over 60 years. Positive correlations were found between age and peak plasma values (P less than 0.05), age and AUC (P less than 0.01). No correlations were found between age, t1/2 and Cl/F, due to the high interindividual variability in pharmacokinetic profiles. Total reported and observed side effects scores were higher overall in subjects under 50 years than over 60 years and were inversely correlated to AUC (P less than 0.05). Drowsiness was inversely related to the age of subjects (P less than 0.05). Our data support the importance of single dose kinetic studies, particularly for new antidepressants, in relation to age, both to emphasize differences in pharmacokinetic profiles and to predict side effects during chronic treatment.