Tiapride versus Haloperidol in the Therapy of Aggressiveness and Agitation in Elderly Patients with Cognitive Impairment

Introduction

Agitation and acute restlessness represent a condition characterized by purposeless, disorganized, and excessive psychomotor activity arising due to physical or psychological distress. The behavior is unpredictable and may escalate into aggression. Effective management of acute restlessness requires not only appropriate patient contact and differential diagnosis of the difficulties but also the choice of suitable therapy.

Study Methodology and Patient Population

An international multicenter randomized double-blind study with three parallel groups evaluated the efficacy and safety of a 21-day therapeutic regimen of tiapride at doses of 100–300 mg/day or haloperidol at doses of 2–6 mg/day. The study included 306 patients suffering from mild to moderate dementia and behavioral disorders assessed using the subscore of the Multidimensional Observation Scale for Elderly Subjects (MOSES) for irritability/aggressiveness ranging from 16 to 30 points.

Results

The proportion of respondents who experienced a decrease in MOSES score by at least 25% was higher in the tiapride group (63%; p = 0.04) and haloperidol group (69%; p = 0.004) compared to the placebo group (49%). No significant difference in the number of responders was observed between the active drugs. Similar results were achieved in the reduction of average MOSES scores on days 7 and 21 of therapy.

For tiapride and haloperidol, a significant improvement in the Clinical Global Impression (CGI) score was also achieved compared to placebo (for tiapride p = 0.03; for haloperidol p = 0.02).

No significant difference was observed between the groups in the Mini-Mental State Examination (MMSE) scale throughout the treatment period, indicating that the therapy for restlessness did not worsen the patients' cognitive difficulties.

Adverse events were assessed using the Udvalg Kliniske Undersogelser (UKU) scale, with the number of patients experiencing UKU symptoms being lower in the tiapride-treated group (n = 62; 61%; 212 events) compared to the haloperidol group (n = 77; 76%; 305 events) and similar to patients on placebo (n = 69; 67%; 234 events). The number of patients with at least one extrapyramidal symptom was significantly lower in the tiapride group (n = 16; 16%; p = 0.003) compared to the haloperidol group (n = 34; 34%) and comparable to the placebo group (n = 18; 17%).

Conclusion

The results of the study indicate that tiapride and haloperidol are comparable in efficacy for the treatment of aggressiveness and agitation in elderly patients with cognitive impairment and significantly more effective than placebo. However, tiapride has fewer side effects, with their incidence being comparable to placebo.

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Source: Allain H., Dautzenberg P. H., Maurer K. et al. Double blind study of tiapride versus haloperidol and placebo in agitation and aggressiveness in elderly patients with cognitive impairment. Psychopharmacology (Berl) 2000; 148 (4): 361–366, doi: 10.1007/s002130050064.