Memantine (Ebixa) explained

What Memantine is

Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist. It moderates the action of glutamate, the brain's main excitatory neurotransmitter. In Alzheimer's Disease, excess glutamate activity is thought to contribute to neuronal damage; Memantine reduces this excitotoxic effect without blocking normal glutamate signalling. Memantine is available as Ebixa, Namenda and as generic Memantine.

Memantine has a different mechanism from the Cholinesterase Inhibitors. It can be used alone, or in combination with a Cholinesterase Inhibitor such as Donepezil.

Who Memantine is for

NICE Technology Appraisal TA217 recommends Memantine for:

• Moderate Alzheimer's Disease in people who cannot tolerate or have a contraindication to Cholinesterase Inhibitors;
• Severe Alzheimer's Disease;
• Use in combination with a Cholinesterase Inhibitor in moderate to severe Alzheimer's Disease where this is clinically indicated.

Severity is typically defined by Mini Mental State Examination score: mild Alzheimer's Disease 21 to 26, moderate 10 to 20, severe below 10. Clinicians also use clinical context and Addenbrooke's Cognitive Examination scores.

Memantine is sometimes used in Dementia with Lewy Bodies and in Parkinson's Disease Dementia under specialist guidance, although it is not licensed for these indications.

How Memantine is prescribed

Standard titration

• Week 1: Memantine 5 mg once daily;
• Week 2: 10 mg once daily;
• Week 3: 15 mg once daily;
• Week 4 onwards: 20 mg once daily (target dose).

In people with kidney impairment, doses are reduced and individualised.

Before starting

Kidney function is checked. Unlike the Cholinesterase Inhibitors, a baseline Electrocardiogram is not specifically required, although a baseline Electrocardiogram is often available from the diagnostic work-up.

What benefit to expect

In moderate to severe Alzheimer's Disease, Memantine can produce small to modest improvements in cognition, function and global status, and a reduction in behavioural symptoms (agitation, irritability) in some people. Combination treatment with a Cholinesterase Inhibitor may give incremental benefit. The effect size is similar to or slightly smaller than Cholinesterase Inhibitors. Benefit may be apparent within 4 to 12 weeks.

Side effects

Memantine is generally well tolerated. Reported side effects include:

• Dizziness;
• Headache;
• Constipation;
• Drowsiness, particularly in the first weeks;
• Raised blood pressure (rare);
• Hypersensitivity reactions (rare).

Most side effects are mild and transient. Reducing the rate of titration can help if early dose increases cause symptoms.

Drug interactions

Memantine has fewer drug interactions than many medicines. Specific cautions include:

• Co-prescription with other NMDA antagonists (Amantadine, Ketamine, Dextromethorphan), which should generally be avoided;
• Co-prescription with Levodopa or dopamine agonists, where the dose of Memantine may need adjustment;
• Drugs that alkalinise urine (sodium bicarbonate, carbonic anhydrase inhibitors), which can raise Memantine levels.

Combination with a Cholinesterase Inhibitor

Many people in moderate to severe Alzheimer's Disease are prescribed Memantine together with Donepezil (or another Cholinesterase Inhibitor). The two medicines have different mechanisms and can be combined safely. Combination treatment is associated with better outcomes in trials and is endorsed by NICE TA217.

Monitoring and review

A review at three months after reaching the target dose is standard. Subsequent reviews are typically every six to twelve months. The review assesses tolerability, cognitive and functional response, behavioural symptoms, kidney function, blood pressure and overall care plan.

Stopping Memantine

Most people continue Memantine while there is evidence of benefit and tolerability. Sudden discontinuation occasionally produces a measurable step-down in function. A planned, supervised taper is preferred.

Where to discuss Memantine

Memantine is widely available on the NHS through your GP, often initiated by a memory clinic. If you would like a private review of dementia medication, including a structured plan for combination treatment or switching, The Dementia Service offers virtual consultations and shared-care prescribing with your GP.