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The St. Hans Rating Scale (SHRS) is a multidimensional rating scale for the evaluation of neuroleptic-induced hyperkinesia, parkinsonism, akathisia and dystonia. This scale and the Abnormal Involuntary Movement Scale (AIMS) were tested by 7 raters (2 experienced, 2 less experienced and 3 totally inexperienced) in 30 psychiatric patients with tardive dyskinesia (TD). The test was performed 3 times in the same patients: 1) live evaluation during a video recording, 2) evaluation 2 weeks later from the videotape, and 3) evaluation after another 2 weeks from the same videotape. The intrarater reliability was high in the experienced group (0.91-0.96 for SHRS hyperkinesia scale, 0.80-0.84 for AIMS, and 0.82-0.97 for SHRS total parkinsonism). No significant changes occurred from live to video evaluation. The interrater reliability coefficient for the experienced group was also high: 0.89-0.95 for the SHRS hyperkinesia scale, 0.76-0.85 for the AIMS scale and 0.95-0.98 for the SHRS parkinsonism scale. The less experienced and the inexperienced raters had coefficients for intra- and interrater reliability that were 0.10 and 0.20 lower, respectively. The SHRS parkinsonism scale had a high construct validity, as determined by the homogeneity coefficients of Cronbach (0.82) and Loevinger (0.43). The corresponding coefficients for the hyperkinesia scales were low, in agreement with the individual distribution of TD (only about 50% present extremity dyskinesia and less than 25% facial, head and trunk dyskinesia, independent of the severity of the syndrome). Finally, convergent validity was found between the SHRS hyperkinesia scale and AIMS and divergent validity between all of the other scales.(ABSTRACT TRUNCATED AT 250 WORDS)

Compared to traditional neuroleptics, most of the new antipsychotics are characterized by a low extrapyramidal side effect (EPS) liability and varying antipsychotic efficacy. This topic is reviewed for four principal classes of new, established, and potential antipsychotics: (1) Antipsychotics such as sulpiride and remoxipride that block a subgroup of dopamine (DA) D2/D3 receptors produce a relatively low level of side effects, including EPS, and have an antipsychotic effect equal to or slightly weaker than traditional neuroleptics. D1 antagonists demonstrate a low level of EPS in primates and may prove to be a valuable new type of antipsychotic drug. (2) Theoretically, partial D2 agonists have the advantage of producing few or no EPS and a specific beneficial effect in negative symptoms, but as yet the expectations have not been fulfilled. (3) Nondopamine drugs such as serotonin (5HT1) agonists, 5HT2 antagonists, 5HT3 antagonists, and gamma-amino-butyric-acid-A (GABA-A) benzodiazepine agonists have anxiolytic, antidepressant, antiaggressive, and maybe antiparkinsonian effects and may play an adjunctive role in the treatment of schizophrenia. 5HT3 antagonists (e.g., ondansetron), partial benzodiazepine agonists, and partial glutamate agonists may prove to be effective antipsychotics. (4) Antipsychotics such as clozapine and risperidone, which affect D2/D3 receptors as well as 5HT, alpha 1, and/or D1 receptors appear to have the most pronounced antipsychotic effect.

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Attitude towards treatment, side-effects, mental state and quality of life was assessed in 53 chronic schizophrenic out-patients on maintenance treatment with depot neuroleptics. It was found that 60% of the patients viewed depot medication positively, while only 8% viewed it negatively. Only 70% of patients complained about side-effects, even though 94% had scored as having them. Hypokinesia and hyperkinesis were the side-effects least noticed by the patients, but most noticed by the treating physician, while the opposite was the case with psychic side-effects. Only 49% of patients thought they had a psychotic illness, and there was no correlation between the patients' own evaluation of the severity of their illness and their score on the Positive and Negative Symptom Scale (PANSS) or the treating physician's evaluation. Quality of life did not correlate with either side-effect score or PANSS score. The schizophrenic patients' assessment of their condition was therefore in general different both from that of the treating physician and from that determined using rating scales.

Tardive dyskinesia (TD) is a syndrome of involuntary movements that develops in predisposed individuals during neuroleptic drug treatment, with an average prevalence of 15%. Neuroleptic (antidopaminergic) drugs are the predominant etiological factor. Although no simple correlation can be established, both dosage and treatment duration seem to be of importance for the development of dyskinesia. It is still uncertain whether some neuroleptics carry a higher risk than others, but it appears that the atypical neuroleptic clozapine, which causes no or minimal dystonia, parkinsonism, or akathisia, also carries no or minimal risk of TD. The pathophysiological mechanisms underlying TD are unclear. The traditional dopamine hypersensitivity theory is no longer viable, whereby new hypotheses have been advanced: TD can be due to the blockade of a subset of striatal dopamine receptors, while parkinsonism is due to the blockade of another such subset, and/or can be due to a reduced GABA turnover in a subgroup of neurons connecting striatum with globus pallidus and substantia nigra. TD is best prevented by a course of neuroleptic medication involving as little antidopamine effect as possible, including minimal doses and shortest possible length of treatment. The main TD treatment principle consists of a gradual dose reduction, possibly over years. It should be added, however, that more recent investigations indicate that traditional antidopaminergic treatment in moderate doses may be safely continued over a long period without an increased risk of TD progression.

Xanomeline is a muscarinic M 1 /M 4 preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects (EPS) at therapeutically relevant doses. In the present study, we examined whether the xanomeline-induced functional dopamine antagonism found in rodent studies could also be observed in nonhuman primates. In addition, we studied whether the lack of EPS observed in rodents also applies to primates. To this end, we investigated the effects of xanomeline on the behavior induced by D-amphetamine and (À)-apomorphine in drug-naive Cebus apella monkeys. Antipsychotic compounds antagonize amphetamine-induced motor unrest and stereotypies in this species. Xanomeline inhibited D-amphetamine-induced motor unrest, stereotypies and arousal as well as apomorphine-induced stereotypies and arousal in drug-naive Cebus apella monkeys. Xanomeline did not induce EPS but vomiting occurred in some monkeys at high doses, in accordance with emetic events observed in Alzheimer patients following xanomeline administration. Even when xanomeline was tested in EPS-sensitized Cebus apella monkeys, EPS were not observed at the dose range of xanomeline used in the D-amphetamine-apomorphine combination study (0.5-3 mg/kg). However, when xanomeline was tested at 4 mg/kg, moderate dystonia was seen in two out of three monkeys. It is concluded that xanomeline inhibits Damphetamine-and (À)-apomorphine-induced behavior in Cebus apella monkeys at doses that do not cause EPS. These data further substantiate that muscarinic receptor agonists may be useful in the pharmacological treatment of psychosis.