Lack of effect of amitriptyline on risperidone pharmacokinetics in schizophrenic patients.

The interaction between plasma concentrations of the tricyclic antidepressant amitriptyline and the metabolism of the new antipsychotic risperidone was studied in 12 patients with chronic schizophrenia. Each patient received 3 mg risperidone twice a day for 28 days. Amitriptyline was coadministered at doses of 50 mg/day on day 15 and 100 mg/day on days 16 to 21. Amitriptyline did not significantly affect the mean plasma concentrations or pharmacokinetics of risperidone in schizophrenic patients or influence the antipsychotic fraction (the total concentration of risperidone and 9-hydroxyrisperidone, its primary and biologically active metabolite). These results suggest that risperidone dose need not be adjusted when coadministered with amitriptyline at doses up to 100 mg/day in schizophrenic patients.

A noninvasive evaluation of baroreceptor sensitivity with the Valsalva maneuver and phenylephrine methods.

In a double-blind crossover study, we compared baroreceptor sensitivity (BS) and latency, derived from the phenylephrine method with BS and latency derived from phase IV of the Valsalva maneuver (VM), using the Finapres, a noninvasive blood pressure monitor. Ten healthy volunteers were enrolled in the study and BS was determined with placebo, atropine (0.03 mg/kg) and atenolol (10 mg) and was expressed as the linear relation between the change in RR interval following the blood pressure rise induced by either phenylephrine or phase IV of the VM (i.e., after cessation of straining). Baseline baroreceptor sensitivity (p<0.001) and baroreceptor sensitivity in the presence of atropine (p<0.02) was smaller with the VM but no differences in baroreceptor sensitivity between the two methods were evident after atenolol. Although no linearity existed between the two methods under any of the experimental conditions, baroreceptor sensitivity in the presence of atropine was significantly smaller (p<0.01)(and latency delayed (p<0.08)) compared to atenolol-induced changes with both methods. We found excellent correlation between baroreceptor sensitivity derived from the ECG tracing and Finapres recorded beat-to-beat pulse intervals (p<0.001; r>0.8, under all conditions) although the correlation after atropine was not as close (p<0.01; r=0.7). The smaller baroreceptor sensitivity induced by the Valsalva maneuver with placebo and atropine, but not with atenolol, suggests a parasympathetically influenced vasodilation, and sympathetically medicated tachycardia during phase IV of the VM.

Placebo substitution for methyldopa in geriatric hypertensive patients.

The aim of this study was to obtain an objective evaluation of the possibly inappropriate antihypertensive therapy of elderly patients; this was done by means of placebo substitution for methyldopa, one of the drugs taken by all the participating patients. Forty patients were recruited from a hospital outpatient clinic and randomly allocated to two groups. One group remained on treatment which included methyldopa, while a matching placebo tablet was substituted in the other group. The study was conducted over a period of 6 months in a single-blind manner. Methyldopa was reintroduced in the placebo group when one of the evaluation clauses was recorded. Only 2 patients in the placebo group required reintroduction of methyldopa tablets. In the rest of this group there was no significant difference between systolic and diastolic pressures before and after 6 months of placebo substitution. Withdrawal of unnecessary antihypertensive therapy in the elderly should be considered. Patients must be observed carefully and therapy reintroduced when blood pressures rise.

The comparison of the effects of multi and single doses of buspirone, chlordiazepoxide and hydroxyzine on psychomotor function and EEG.

This study compares the effects of buspirone (5 mg), chlordiazepoxide (5 mg), hydroxyzine (10 mg) and placebo on psychomotor function and EEG, when taken thrice daily for a period of two weeks, with those after a single dose administration. Nine healthy volunteers participated in the study. The battery of psychomotor tests included peak velocity of saccadic eye movements (SEM), a Sternberg memory scanning and choice reaction time test (SMS-CRT) and critical flicker fusion frequency (CFFF). The peak velocity of saccadic eye movements was significantly impaired by the single dose of hydroxyzine (P = 0.03) in comparison to the multidose results. A similar comparison regarding buspirone only approached significance (P = 0.07). The SMS-CRT and CFFF did not reveal any difference between the multi and single dose regimens. Spectral analysis of the EEG did not distinguish between the multi and single dosage schedules regarding the respective drugs in the low doses administered.

The effects of alprazolam, quazepam and diazepam on saccadic eye movements, parameters of psychomotor function and the EEG.

The effects of a single oral dose of alprazolam (1 mg), quazepam (15 mg) and diazepam (10 mg) on the peak saccadic velocity (PSV) of saccadic eye movements (SEM), the Sternberg memory scanning and choice reaction time (SMS-CRT), critical flicker fusion frequency (CFFF), spectral analysis of the EEG and a mood scale were assessed in 9 healthy volunteers in a double-blind, placebo-controlled cross-over study. Alprazolam revealed greater sedative effects than diazepam in the above-mentioned tests. Quazepam had the least sedative effect of the 3 drugs tested, showed a time lag at the onset of its effects and a more prolonged effect on psychomotor impairment than reported previously.