Memantine for Agitation in Dementia

Agitation is a cause of morbidity and mortality in Alzheimer's due to distress and use of medication with side effects. Memantine has beed shown to be associated with less agitation and a recent study by forrest pharmaceuticals failed to recruit. We will perform a 12 week rct in 164 patients to test this hypothesis in a locality with no competing studies and in a clinical setting where the drug is not often used. We will compare with placebo and also use a rescue protocol derived from international best practice.

Inclusion criteria

• Residential/Inpatients at recruitment to the study with a history of at least 2 weeks behavioural disturbance.
• Alzheimer's Disease only as per McKhann Criteria + Hachinski Score<=4.
• Moderately severe to severe Alzheimer's Disease (baseline MMSE </=19).
• Clinically significant agitation that requires treatment.
• Severity of agitation defined by Cohen Mansfield agitation inventory (CMAI) > /=45.
• Age >/= 55.

Exclusion criteria

• Memantine usage in the 4 weeks prior to the start of the study.
• On Cholinesterase inhibitor for less than 3 months and not on a stable dose.
• Anti-psychotic, anti-epileptic, antidepressant, benzodiazepine, lithium or hypnotic dosage alteration in the 2 weeks prior to the start of the study.
• Antiparkinsonian medication.
• Hypersensitivity to memantine or any of the excipients in the formulation.
• Severe renal impairment.
• Epilepsy, history of convulsions or seizure, or receiving any anti-epileptic treatment.
• Concomitant usage of N-methyl-D-aspartate (NMDA) antagonists such as amantadine, ketamine or dextromethorphan.
• Recent myocardial infarction, uncompensated congestive heart failure and uncontrolled hypertension.
• Severe, unstable or poorly controlled medical illness.
• Any disability that may interfere with the patient completing the study procedure.
• Active malignancy.
• Delirium, pain or any medical illness as a clear cause of agitation.
• Any important drug interactions: Prohibited during study and in the 14 days preceding enrollment/inclusion are: Analgesic dextromethorphan, Dopaminergics- amantadine, Warfarin due to theoretical INR prolongation.