1 The acute and subchronic effects of dothiepin

Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, psychomotor performance and driving-related task performance. Twelve healthy recreational ecstasy users participated in an experimental study conducted according to a double-blind, double-dummy, placebo-controlled three-way cross-over design. MDMA improved psychomotor performance, such as movement speed and tracking performance in a single task, as well as in a divided attention task. MDMA impaired the ability to predict object movement under divided attention. However, the inability to accurately predict object movement after MDMA may indicate impairment of particular performance skills relevant to driving. There was no effect of MDMA on visual search, planning or retrieval from semantic memory.

The primary objective of this study was to compare the objective and subjective effects of amisulpride with those of a classic antipsychotic, haloperidol, when both were given to healthy volunteers in representative therapeutic doses over 5 days. The secondary objective was to compare the effects of relatively low and high doses of amisulpride to confirm the suspected duality of its pharmacologic activity. Twenty-one subjects participated in the four-way, randomized, double-blind, crossover study with repeated daily doses of amisulpride 50 mg, amisulpride 400 mg, haloperidol 4 mg, and placebo. Subjects were institutionalized during treatment periods and were under 24-hour medical supervision. They underwent a series of psychomotor and cognitive tests 1 hour before and 3 and 6 hours after dosing on days 1 and 5. Their extrapyramidal disturbances and drug-related feelings were assessed at the end of each replication. Psychiatric interviews and ratings of depression, subjective well-being, and negative symptoms occurred on day 4. Amisulpride 50 mg had no significant effect on any parameter. Amisulpride 400 mg had several adverse effects on psychomotor and, although less severe, on cognitive performance on the fifth day only. Amisulpride 400 mg produced no significant extrapyramidal disturbances in the group as a whole, although it may have in some individual subjects. Also, it produced no signs of mental disturbances on clinical rating scales or during a structured psychiatric interview. Haloperidol ubiquitously impaired psychomotor and cognitive performance in a similar fashion after the first and the final doses. It produced extrapyramidal disturbances in nearly every subject, the most common being akathisia and the most severe, in the case of one individual, being acute dystonia. Unlike amisulpride, haloperidol produced a number of mental disturbances, the most noteworthy being negative symptoms. Amisulpride seems to be a well-tolerated drug. Its side effects should be much less troublesome to patients using the drug on a long-term basis than those of classic antipsychotics, like haloperidol.

Mefloquine did not impair driving performance but rather improved it in the longer test, suggesting that the drug may possess psychostimulating properties.

Eighteen healthy volunteers participated in a randomized, double blind, cross-over trial. They received mirtazapine, mianserin or placebo during separate periods of 15 days. Mirtazapine and mianserin were respectively administered in doses of 15 mg and 30 mg nocte for the ®rst 7 days and doses of 30 mg and 60 mg nocte for the remaining 8 days. Assessments were made at baseline and on days 2, 8, 9 and 16 of each period to compare eects of drugs and placebo on mood, psychomotor (CTT, CRT, CFF and Vigilance) and`actual' driving performance. Sleep quality and duration and side-eects were assessed at baseline and every treatment day. Mirtazapine 15 mg and mianserin 30 mg slightly impaired psychomotor and driving performance on day 2 of treatment. On day 8, the eects were virtually gone, although some driving impairment could still be observed in the mianserin condition. No drug eects on performance were found on day 9 despite the dose escalation. On day 16 of treatment, driving performance and vigilance slightly decreased in, respectively, the mirtazapine and the mianserin conditions. These eects indicate that tolerance to the drugs' adverse eects was not complete. This observation was also supported by subjective data. Similar increments in sleep duration and feelings of lethargy, drowsiness and weakness were observed throughout treatment with both drugs. Alertness and contentedness was always lower during both drug treatments than with placebo. Spontaneously reported adverse events were similar to self-rated side-eects and more of both were recorded during mianserin treatment. It is concluded that the acute and subchronic eects of nocturnal doses of both drugs were similar and equally low in magnitude. Eects on performance were much less than those seen in other studies after administration during the day. Full daily doses of both drugs should be prescribed in nocturnal dosing regimens, and not in divided doses over the day, for avoiding excessive sedation and performance impairment.