Memantine

Article Highlights:

• Overview
• Mechanism of Action of Memantine and Namenda
• Research into memantine
• Considering Namenda and memantine for patient treatments
• Side Effects of Memantine and Namenda
• Memantine Dosage
• Drug interactions with Memantine and Namenda
• Alternatives to Memantine and Namenda
• Memantine and Donepezil Prescribed together
• Stopping treatment with Namenda and memantine

Overview: Memantine for Dementia Patients

Memantine, or memantine hydrochloride, is also known by the brand name Namenda. It is an FDA-approved medication to treat Alzheimer’s Disease in the moderate to severe stages. It is often prescribed in combination with a cholinesterase inhibitor, more specifically with donepezil (brand name Aricept).

There is an FDA-approved formulation of donepezil combined with memantine called Namzaric. It is called Namenda when prescribed on its own, without donepezil. Memantine has also been prescribed off-label to treat Vascular dementia, Lewy Body dementia, and Parkinson’s Disease. Memantine is part of a class of drugs known as N-methyl D-aspartate (NMDA) receptor antagonists, meaning they block the activity of the receptors of glutamate. Namenda can delay the worsening of cognitive symptoms for around 6 months on average. This short time of effective postponement highlights the fact that drug treatment is a solution for delaying symptoms, but it ultimately does not stop the progression of the disease.

Mechanism of Action of Memantine and Namenda

Memantine’s action in the brain is different from that of the cholinesterase inhibitors. Namenda, brand name of memantine, works to block the reception of the neurotransmitter or brain chemical glutamate, preventing glutamate from building up in the brain. When levels of glutamate increase in the brain, they can lead to cell death, and they may contribute to the development of the plaques and tangles found in Alzheimer’s Disease. Being a neurotransmitter, glutamate is an important communicating chemical to the brain, sending and receiving signals. It thus plays an important role in connection with memory and learning, although the accumulation of glutamate leads to problems.

Research into Memantine

Although there is increasing need for further research into the long-term effects of memantine, research has already shown that in the short-term, it can delay the worsening of cognitive symptoms that affect the performance of activities of daily living (ADLs). Research has shown that Namenda can delay the worsening of symptoms for up to 6 months on average.

Two randomized, double-blind studies with placebos were conducted in the United States to determine the cognitive enhancing effects of memantine, and to gain approval from the FDA. In addition, a third study was conducted in Latvia that supported the positive effects of Namenda in the treatment of cognitive symptoms of patients suffering with Alzheimer’s Disease. While the use of this drug may offer short-term delay of cognitive symptoms, memantine does not offer a cure nor ultimately delay the progression of Alzheimer’s Disease and other types of dementia.

Memantine has been FDA-approved for the treatment of moderate to severe Alzheimer’s disease although in many studies, it has also been successfully used in the treatment of Vascular Dementia and Mixed Dementia, i.e. the combination of Alzheimer’s disease and Vascular Dementia. When Namenda is used to treat other dementias besides Alzheimer’s Disease, it is prescribed “off label”, meaning that it is used to treat a condition other than the one it is commonly prescribed for. There is evidence of the effective use of memantine in treating Lewy Body Dementia (LBD), while it has not shown to have much efficacy with Parkinson’s Disease Dementia (PPD).

Quick Fact:

Activities of Daily Living (ADLs) is a term used by medical care workers and physicians to describe everyday basic care activities that a person performs. ADLS includes tasks such as grooming and bathing, using the bathroom, being able to dress one’s self, the ability to get around, and eating. The effects that a new medication has on the ADLs of a patient are assessed when considering its effectiveness. For example, memantine helps delay the worsening of cognitive effects that Alzheimer’s and dementia has upon ADLs, enabling a patient taking memantine to better perform ADLs independently for a little longer. For some families and caregivers, this offers time in which the loved one can remain at home rather than in a clinical care setting.

Considering Namenda and Memantine for Patient Treatments

Namenda may be prescribed on its own, or with a cholinesterase inhibitor such as Aricept (Donepezil), in adults suffering cognitive symptoms of moderate to severe stage Alzheimer’s Disease. Memantine should not be used for patients with liver or kidney problems, or for patients known to be allergic to memantine or any other ingredients in the drug.

Side Effects of Memantine and Namenda

Memantine is considered an easy to tolerate drug, meaning that patients seem to adjust promptly to its known side effects. The most common sides effects of Namenda include:

• Constipation
• Dizziness
• And headaches

Research supports an added benefit of combining memantine and the cholinesterase inhibitor, Donepezil. Yet it is important to note that side effects may be experienced when starting two drugs simultaneously. Combining these two drugs may offer the benefit of the GI side effects “cancelling” each other out. In other words, the constipating effects of Namenda may help alleviate the issue of diarrhea from Donepezil or other Cholinesterase inhibitors.

Memantine Dosage

Memantine is available in 5mg and 10mg tablets as well as a 2mg/mL oral solution. Namenda tablets are often started at a lower dose and then slowly titrated to an effective dose, starting at 5mg once daily, then progressively moving toward 10mg twice daily for a max dosage of 20mg daily. This process is often spread across 4 weeks to let the body adjust and to be able to ascertain side effects. There is also a once daily extended release 20mg dose of memantine available which, generically, is known as memantine hydrochloride extended release, (brand name Namenda XR). The oral solution form of Namenda is free of alcohol, dyes, and sugar, and it provides a good option for patients with dysphagia (swallowing difficulty).

Memantine can be taken before or after meals, but it must be taken at the same time each day. If a dose is missed, then the next scheduled dose should be taken, never doubling doses. It is important to consult your loved one’s physician if several doses have been missed because the titration process may need to be resumed to work back up to an effective dose. Never stop medications without first consulting your loved one’s physician if you have concerns about their medications.

Case story – David’s Grandfather’s Dysphagia

David’s 68-year-old grandfather recently seemed to be progressing quickly towards a worsening of his Alzheimer’s Disease. When his grandfather’s physician prescribed cholinesterase inhibitors, David’s grandfather seemed to react badly, and he had chronic diarrhea and vomiting with the medication. With the passage of time, David’s grandfather also began to suffer swallowing issues that led to some near-choking incidents. When David brought his grandfather to the doctor for their latest visit, he brought up the issues of his worsening cognitive symptoms as well as his difficulty swallowing. The physician recommended memantine for the treatment of his Alzheimer’s symptoms; he prescribed it in the form of an oral solution. He also recommended that David’s grandfather see a speech pathologist to address his swallowing issues. The speech pathologist diagnosed David’s grandfather as suffering dysphagia due to the worsening of his Alzheimer’s Disease, and he recommended he go through occupational therapy sessions.

A few months of treatment with memantine later, David’s grandfather seemed to be responding well, and his cognitive symptoms improved. His dysphagia did not totally reverse, but occupational therapy seemed to help him learn to better swallow, and in the sessions, David also learned how his grandfather could avoid choking.

Drug Interactions with Memantine and Namenda

Namenda may cause serious interactions if taken with other NMDA antagonist drugs. Moderate interactions may occur with urinary alkalizing drugs, such as metformin, cimetidine, ranitidine, hydrochlorothiazide (HCTZ), triamterene (TA), and quinidine; these can result in reducing the efficacy of memantine and the interacting drug.

Alternatives to Memantine and Namenda

There are currently no other FDA-approved NMDA antagonists for the treatment of Alzheimer’s Disease. An alternative to memantine may be to take the cholinesterase inhibitor donepezil on its own. Other NMDA antagonists may be used for the treatment of other conditions such as Parkinson’s Disease, but for Alzheimer’s disease specifically, memantine is the only drug FDA-approved medication for treatment. Consult with your loved one’s physician if you feel memantine may not seem to be appropriate for your loved one’s current condition. Since every patient has a unique medical history, consulting with your physician is vital to proper treatment. Never stop a medication suddenly without consulting with the patient’s physician.

Memantine and Donepezil Prescribed Together

It is common for memantine and Aricept (donepezil) to be prescribed together in patients with moderate to severe Alzheimer’s Disease, although they are not commonly started together. While both drugs work upon the brain in different ways, affecting different chemicals, there seems to be an additive effect of cognitive enhancement when both drugs are combined.

Donepezil is a cholinesterase inhibitor, meaning that it acts to increase the levels of acetylcholine in the brain, thus increasing communication between brain cells. Memantine lowers the level of glutamate, which at high levels damages and can kill brain cells. Neither of these drugs interact or interfere with one another, and they can therefore be safely used together. There is a combined drug, known as the brand name Namzaric, which is available and contains both drugs in combination.

Some studies show that moderate to severe Alzheimer’s patients benefit greatly from the combination therapy of these two drugs, while one recent study showed that donepezil alone was more effective than the combination therapy of donepezil and memantine. These types of mixed results demonstrate another difficulty of Alzheimer’s drugs in that some patients are more responsive than others; there is no one size fits all drug therapy with Alzheimer’s and other types of dementia. In addition, the fact to remember with these drugs is that they do not offer a cure, but rather a possible temporary relief from cognitive symptoms. Nevertheless, while patients in some of these studies did not benefit from combination therapy, there are others who did.

Rebecca’s Grandfather

Rebecca’s 75-year-old grandfather Robert was diagnosed with dementia over 5 years ago. As the disease progressed, Rebecca has notice changes in her grandfather’s ability to participate in simple daily activities. Rebecca’s grandfather loved and raised her, so that she would hate to not be able to care for him, but she worries that in the coming few months, she may have no other choice but to move him into a memory care ward at a facility. She wants him to be able to remain in her home as long as possible before having to seek out a memory care facility, and she decides to bring up her concerns at her grandfather’s next doctor appointment. Robert’s physician asks about the different tasks he performed when he began to have problems. Rebecca mentions he has begun to have more difficulty tying his shoes as well as finding his way around at the library, the one place he loves most and has visited every Friday since Rebecca was a young girl. The physician mentions that adding the drug memantine may help since Robert is already taking Donepezil. He tells Rebecca it may help delay the progression of these types of symptoms for about 6 months or more. He prescribes the combination med Namzaric to Robert and tells Rebecca to follow up in two months or sooner if her grandfather seems to get worse or has a reaction to the new medication.

Two months later, Rebecca takes her grandfather back to the doctor and mentions she has noticed a difference. Robert seems to be functioning well in his daily activities with the combination med, and she tells the doctor that he has been able to dress himself daily as well as groom himself. Rebecca tells the doctor she feels the medication is being well tolerated as well. The physician thus refilled the prescription, and Robert was able to remain in his granddaughter’s home for a little over a year before his symptoms worsened.

Stopping Treatment with Namenda and Memantine

No medication should be discontinued without the knowledge and supervision of the patient’s physician. Whatever the drug you are thinking of, you should always take it up with your physician and learn about its benefits and possible side effects. With the progression of Alzheimer’s Disease, the drugs used to treat it, such as memantine may, no longer offer any cognitive benefits as the patient begins to decline. There may therefore be a time when the issue of efficacy and necessity must be discussed.

Since, Namenda only offers temporary delay of the worsening of cognitive symptoms, there will be a good time to address the question of whether or not to continue the medication. The stopping of any dementia medications should be done slowly and with the physician’s consent, if only to track the medication’s effectiveness and other reactions while the medication dose is lowered. That way the physician can easily assess if memantine needs to be started again or can be discontinued altogether.

There are times, as the medications are being gradually reduced, when the progression of the disease can be perceived as having caused a considerable decline in cognitive function. Alternatively, there are times when it is demonstrated that the medication may have been helpful in alleviating or delaying cognitive symptoms. If done properly, with tapering down, the physician can then easily titrate the medication back up if stopping treatment may have had negative results. In the later stages of Alzheimer’s Disease, the decision may be made to discontinue medication once the patient has reached a level of total dependence and care due to the exacerbation of the symptoms of the disease.

Ruth’s Mother’s Treatment Predicament

Ruth’s 78-year-old mother was about a year ago assessed as being in the moderate stages of Alzheimer’s Disease, and her mother’s physician had prescribed memantine to control behavioral and cognitive symptoms. The medication worked dramatically well in the beginning, although Ruth recently felt she had seen no change of late, meaning no observed progress or regression. Concerned about all the other prescription drugs her mother was taking, Ruth decided to discuss stopping the memantine since she saw no recent change or progress with the drug. Her mother’s physician agreed to begin a slow process of stopping the drug under her supervision. She explained to Ruth that she would taper down her mother’s dose of Namenda over the course of 4 weeks. She instructed Ruth to carefully observe her mother’s behavior and to report any drastic changes or reactions immediately if they occurred. Two weeks later, having started the gradual stopping of memantine, Ruth’s mom began to drastically decline cognitively. Her behavior seemed erratic with increased confusion and suspiciousness. She was also more withdrawn, and she began wandering and getting lost both at home and in the back yard. Ruth immediately reported these changes to her mother’s physician, and they made an appointment for that same week. Ruth and her mother’s physician decided it may be best to continue the memantine, and the physician gave Ruth instructions on how to slowly increase back up to an effective dose.

About a few weeks after increasing her mother’s Namenda back up to its effective dose, Ruth noticed a significant improvement in her mother’s behavior. Ruth’s mother continued on memantine for another 8 months before she began to decline, at which point Ruth began the process of discontinuing the medication successfully.

Final Thoughts

Memantine can offer relief for Alzheimer’s patients and other dementia patients. It acts either by delaying the onset of cognitive issues such as memory, confusion, and inability to perform ADLs, or by stabilizing the patient’s current condition. Clinical studies demonstrated it to be a well-tolerated drug as well as an effective drug for many patients. In combination with donepezil, memantine may offer a compound effect that helps slow down the decline in cognitive function. While Namenda is a good option for some patients, not all patients respond well to it. It is therefore all the more important to discuss with your loved one’s doctor if memantine may be an appropriate part of their treatment regimen.