Drugs & Aging

, Volume 3, Issue 5, pp 460–478 | Cite as


A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in Geriatric Agitation
  • John W. Steele
  • Diana Faulds
  • Eugene M. Sorkin
Drug Evaluation



Tiapride is a substituted benzamide derivative with selective dopamine D2-receptor antagonist properties which appears to have preferential affinity for extrastriatal dopamine receptors. Animal and clinical studies show that tiapride has anxiolytic properties but the mechanism of action is uncertain. Results from limited studies indicate that the clinical efficacy of tiapride in the treatment of agitation, aggressiveness, anxiety and sleep disorders in the elderly appears superior to that of placebo, chlorpromazine, lorazepam and meprobamate. Tiapride also exerts a beneficial effect on vigilance and alertness in elderly patients and causes less sedation than chlorpromazine. Tiapride is well tolerated at the dosages recommended for elderly patients.

Further well designed comparative studies with newer drugs are needed to determine the relative place of tiapride in the treatment of geriatric agitation, and such studies should also address the quality-of life benefits for the patient. Additional clinical experience to determine the efficacy of tiapride in elderly patients with more than one disease condition, receiving concomitant medications, and/or with renal impairment is also required. However, despite these current limitations, tiapride may have potentially important applications in this difficult area of clinical medicine.

Pharmacodynamic Properties

Tiapride, an atypical neuroleptic drug, is a selective dopamine D2-receptor antagonist, and is particularly active at receptors which have been sensitised to dopamine. In vivo studies show that it binds preferentially to dopamine receptors in extrastriatal rat brain tissue, particularly in the hippocampus. Affinity for D1-receptors is very weak and the exact nature and clinical significance of the reported affinity for dopamine receptor subtypes remains to be determined. Tiapride has not been shown to have clinically significant effects on other receptors, although the mechanism of its anxiolytic activity remains uncertain.

In stress model tests in rodents, tiapride ⩾0.5 mg/kg displayed anxiolytic properties equipotent with diazepam 0.125 mg/kg and triazolam 0.1 mg/kg, and intraperitoneal tiapride 10 mg/kg twice daily did not cause withdrawal effects, unlike intraperitoneal diazepam at the same dosage. There was no marked sedative effect in rats receiving tiapride 40 mg/kg but the catalepsy-inducing effects of haloperidol or chlorpromazine were potentiated. High doses also potentiated the muscle relaxant properties of diazepam in mice.

In common with other dopaminergic antagonists, tiapride caused an increase in prolactin; however, the effects of prolonged elevation of prolactin in the elderly are unknown. Tiapride also has a beneficial effect on vigilance and alertness in elderly patients, which are useful adjunctive properties in the therapy of anxiety, agitation or aggressiveness.

Pharmacokinetic Properties

Tiapride is about 75% absorbed following oral or intramuscular administration in healthy volunteers. Distribution is rapid and peak plasma concentrations are reached in about 0.5 to 1.0h after oral or intramuscular administration. There is no evidence of protein binding or clinically significant accumulation of tiapride. The elimination half-life of tiapride in healthy young volunteers and patients is between 3 and 5 hours. Most of the dose is eliminated unchanged in the urine, with a small percentage as de-ethylated and N-oxide metabolites. Dosage reduction is required in patients with renal impairment.

Therapeutic Use in Geriatric Agitation

Tiapride 200 to 300 mg/day is recommended as an anxiolytic drug in elderly patients, with onset of action from a few to 14 days. Comparative studies have shown that tiapride at dosages of 75 to 150 mg/day, 150 mg/day, or 75 to 300 mg/day orally, and 400 mg/day intramuscularly, is significantly better in controlling senile agitation, behavioural problems and related conditions than placebo, lorazepam (3 mg/day), chlorpromazine (18.75 to 75 mg/day) or meprobamate (800 mg/day intramuscularly) respectively.

Although a substantial number of noncomparative studies had design and assessment deficiencies, they indicate that tiapride 50 to 1200 mg/day in elderly patients has some effect in relieving agitation, aggressiveness and anxiety. In addition, there is evidence to suggest that tiapride also improves alertness and vigilance in the elderly.


Tiapride was well tolerated in elderly patients in noncomparative and comparative clinical trials over periods ranging from 3 days to several years. The reported adverse effects most likely to occur in the elderly are drowsiness, agitation, dyskinesia, digestive problems, dizziness and weakness. Only extrapyramidal reactions (4%) and drowsiness (6.7%) occur more frequently in the elderly than in the general population (2.5 and 5%, respectively). At therapeutic dosages, tiapride caused less sedation than chlorpromazine. Other adverse events are regarded as mild, and reversible on tiapride withdrawal. In a double-blind comparative study in 134 elderly patients after cerebrovascular accidents, the effect of tiapride 75 to 150 mg/day on daily activities and tolerability was not significantly different from placebo.

Dosage and Administration

The recommended dosage of tiapride in elderly patients is 200 to 300 mg/day in divided doses for up to 2 months. Therapy may be continued for longer periods following medical reassessment. Patients with renal impairment may require dosage reduction.


Dopamine Receptor Metoclopramide Chlorpromazine Tardive Dyskinesia Sulpiride 
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© Adis International Limited 1993

Authors and Affiliations

  • John W. Steele
    • 1
  • Diana Faulds
    • 1
  • Eugene M. Sorkin
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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