Sodium valproate in aggressive behaviour in dementia: a twelve-week open label follow-up study

Abstract

Introduction: Short-term randomised clinical trials on valproate in distinct types of disturbed behaviour in dementia showed no effects on aggressive behaviour.

Objectives: To assess the course of disturbed behaviour during medium term treatment with sodium valproate for aggressive behaviour.

Design: An open label observational 12-week follow-up study consecutive to a preceding randomised control trial; assessments at 4-week interval.

Setting: A psychogeriatric medium-stay ward at a psychiatric teaching hospital and psychogeriatric nursing home wards.

Participants: Patients who completed a preceding randomised placebo controlled clinical trial on sodium valproate in aggressive behaviour in dementia were included.

Intervention: The starting dose of sodium valproate was 2 x 6 ml of a 40 mg/ml suspension (daily defined dose of 480 mg). The patient's regular physicians managed all treatment decisions, including decisions on dosage and plasma level measurements of sodium valproate and decisions regarding discontinuation. Co-medication was allowed and any change in prescription was recorded.

Measurements: The Social Dysfunction and Aggression Scale-9 (SDAS-9), the Behaviour Observation scales for Intramural Psychogeriatrics (in Dutch: Gedragsobservatieschaal voor Intramurale Psychogeriatrie (GIP) and the Clinical Global Impression of aggressive behaviour (CGI) were performed at the last week of each 4-week interval.

Results: Data of 39 patients (F=24 and M=15) were analysed. At week 12 compared to week 0 mean sodium valproate prescriptions were higher; aggressive behaviour as measured by the SDAS-9 improved. Non-social behaviour, apathetic behaviour, disoriented behaviour and distorted memory improved, but rebellious behaviour increased as measured by the GIP. Seven patients died during this study.

Limitations of the study: Open label observational design; absence of placebo/reference prescription; no systematic measurements of sodium valproate plasma levels and the allowance of psychotropic co-medication.

Conclusion: Low dose sodium valproate may be effective reducing a broad range of types of disturbed behaviours in aggressive demented patients. The high death rate underlines the fragility of demented patients with aggressive behaviour.