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Memantine is a drug approved for the treatment of moderate-to-severe Alzheimer’s disease. However, memantine may also be beneficial for ADHD and bipolar disorder. Keep reading to learn more about the uses, side effects, and dosage of memantine.

What Is Memantine?

Originally developed in the 1960s to treat diabetes, memantine was approved in the US in 2003 for the treatment of moderate-to-severe Alzheimer’s disease [R].

Currently, there are just five medications, including memantine, approved for the treatment of cognitive decline in Alzheimer’s. The other four are all acetylcholinesterase inhibitors, which prevent the breakdown of the neurotransmitter acetylcholine. Memantine works differently by blocking NMDA receptors, making it the only drug in its class [R].

Mechanisms of Action

  • Memantine blocks glutamate NMDA receptors in the brain. Too little or too much glutamate can lead to cell death. Memantine quickly binds and blocks already activated NMDA receptors, which decreases the toxicity caused by too much excitation and prevents cell death [R].
  • Memantine blocks the 5-HT3 (serotonin subtype 3) receptor. This receptor is found in several areas of the limbic system including the amygdala and hippocampus [R].
  • Memantine also blocks nicotinic receptors [R].
  • Memantine may activate dopamine D2 receptors. This has only been studied in cell lines where memantine does bind to D2 receptors; however, its action is very short-lived, making it difficult to measure [R].

Uses of Memantine

1) Memantine May Slow the Progression of Moderate-to-Severe Alzheimer’s Disease

There is a large pool of high-quality evidence that supports memantine’s use in moderate to severe Alzheimer’s disease (AD). Most studies support 20 mg a day (10 mg twice daily) to be the most effective dose. In a study (RCT) of 250 patients, memantine for 28 weeks slowed cognitive and functional decline compared to placebo in moderate-to-severe Alzheimer’s. This was assessed using the Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (SDCS-ADLsev), and the Severe Impairment Battery, which measures cognitive function and behavior. There were no benefits of its use in patients with mild Alzheimer’s [R].

Donepezil is another medication used to treat AD. In a recent meta-analysis of 28 studies, the combination of donepezil and memantine improved cognitive function, behavioral and psychological symptoms, and global functions more than donepezil alone, with the same side effects [R].

2) Memantine May Help Improve Other Forms of Dementia

Severe Dementia

In a study (RCT) of 166 patients with severe dementia in either Alzheimer’s or vascular dementia, the group treated with memantine had a better functional outcome and were less dependent on their caregivers after 12 weeks [R].

Vascular Dementia

In a study (DB-RCT) of 548 patients with vascular dementia, those treated with memantine for 28 weeks scored significantly better on their mini-mental status exam (which is used to assess the progression of cognitive decline, specifically in dementia) than patients on placebo [R].

Dementia of Wernicke-Korsakoff Syndrome

Dementia of Wernicke-Korsakoff syndrome (WKS) is dementia caused by vitamin B1 deficiency (usually due to alcohol abuse), which is difficult to treat. After 28 weeks of memantine, 16 WKS patients had improvement in both thinking and functioning when compared to the placebo group (RCT) [R].

3) Memantine May Decrease Symptoms of ADHD

Forty children with ADHD (DB-RCT) were treated with either methylphenidate, a drug used to treat ADHD, or memantine, for 6 weeks. Memantine was similar in its ability to decrease symptoms of ADHD. There was no difference in the frequency of side effects between the two treatments [R].

In a study (DB-RCT) of 26 adults with ADHD, 12 weeks of memantine helped to improve executive functioning when administered with methylphenidate, while the placebo group showed no improvement. These functions included improvement in emotional control, self-monitoring, planning, and organizational skills [R].

4) Memantine May Decrease Symptoms of PTSD

Taking 20 mg per day of memantine for 12 weeks decreased symptoms of inappropriately increased awareness and avoidance in a case series of 4 veterans. There was also a subjective improvement in mood, memory, and concentration [R].

Another case study of a 56-year-old man who suffered from PTSD, depression, suicidal ideation, insomnia, and cognitive impairment reported an improvement in anger control, concentration, memory, and depression [R].

5) Memantine May Help Improve Bipolar Disorder

Bipolar disorder is a mental disorder characterized by periods of both elevated mood (mania) and depression.

An open-label pilot trial in 33 bipolar disorder patients hospitalized for mania found that 21 days of memantine reduced symptoms of mania [R].

One case study of a bipolar patient resistant to conventional treatment found that 10 mg/day of memantine for 4 weeks resulted in a complete disappearance of manic symptoms [R].

Another case study of a bipolar patient hospitalized with mania and depression found that 20 mg/day of memantine for 10 weeks partially improved mood, anxiety, and sleep quality [R].

6) Memantine May Decrease Symptoms of Generalized Anxiety Disorder (GAD)

GAD is characterized by excessive worry or anxiety, which affects a person’s quality of life. Twelve weeks of memantine slightly decreased anxiety in 7 patients with GAD [R, R].

7) Memantine May Reduce and Eliminate Nystagmus

Acquired fixational pendular nystagmus (APN) is a type of eye condition where eyes make repetitive uncontrolled movements that appear as excessive motion and blurs vision. This condition often occurs in patients with multiple sclerosis (MS) and can be distressing.

When memantine was used to treat APN in patients with MS it resulted in complete cessation of the nystagmus [R].

Infantile nystagmus (IN) often occurs in the first 3 to 6 months of life. Memantine reduced the symptoms of IN, improved vision, and the ability to angle eyes to focus on objects (foveation) [R].

8) Memantine May Decrease the Frequency of Migraines and Headaches

Sixty patients who took memantine daily for their migraines had an average of 3.4 fewer migraines per month, whereas the placebo group only had 1 less per month [R].

Memantine taken daily helped to reduce the frequency of chronic cluster headaches in individuals who did not respond to other preventative treatments [R].

In 28 patients with refractory migraines, memantine taken daily helped to decrease the number of days with a headache from 22 per month to 16 days per month [R].

9) Memantine May Protect Against Repetitive Mild Traumatic Brain Injury

Mice that were treated with memantine after experiencing repetitive mild traumatic brain injury had less damage to their brains compared to controls [R].

 

10) Memantine May Delay Progression of Amyotrophic Lateral Sclerosis (ALS)

When memantine was administered to mice with ALS, the disease progression was significantly delayed, and lifespan was increased [R].

Memantine in Combination with Other Treatments

1) Memantine Decreases Symptoms of Obsessive Compulsive Disorder (OCD) when Used in Combination with Other OCD Treatments

Memantine has been used in addition to first-line treatments for OCD. Some studies reported benefit, one case documenting a 100% response [R].

Another study reported that 89% of the patients who received memantine along with conventional treatments resolved their OCD symptoms after eight weeks [R].

2) Memantine In Combination with Antipsychotics Reduces the Negative Symptoms of Schizophrenia

The negative symptoms (decreased speech and socialization; reduced emotional response) of schizophrenia were reduced when memantine was added to antipsychotics [R].

3) Memantine May Help for Short-Term Treatment of Substance Use Disorders

A study of 80 young adults with opioid dependence treated with buprenorphine/naloxone were also given memantine or placebo. The memantine group was significantly less likely to relapse compared to placebo, over the course of eight weeks [R].

Methadone is another medication used to help individuals with opioid use disorder. When memantine was used with methadone, it decreased the amount of methadone needed to curb individuals’ craving for opioids at 12 weeks [R].

In mice, memantine disrupted conditioned alcohol-seeking behaviors, suggesting that it may be an option to treat alcoholism [R].

Dosages

Clinical trials have used between 5 mg and 40 mg a day, administered in two equal doses through the day. It is recommended to start at 5 mg once daily and increase by 5 mg increments every week until reaching a dose of 20 mg a day [R, R, R].

An extended release version has also available that only needs to be taken in one dose daily.

This information is not intended to replace a consultation with your doctor.

Drug Interactions

In mice, memantine increased the concentration of sertraline (an antidepressant) in the brain, which could lead to greater effectiveness [R].

Side Effects and Contraindications

Memantine is generally well-tolerated [R].

The most common side effects are constipation, nausea, and headache. Other reported side effects include [R]:

  • fatigue
  • pain
  • high blood pressure
  • dizziness
  • vomiting
  • back pain
  • coughing
  • difficult or labored breathing (dyspnea)
  • agitation
  • fall
  • insomnia
  • abnormal gait
  • depression
  • anxiety
  • anorexia
  • joint pain

In patients with severe liver or kidney impairment, clinicians should prescribe a lower dosage of memantine accordingly. In patients with severe renal impairment, it is recommended that dosage not exceed 5 mg twice daily [R].

Memantine May Exacerbate Symptoms of Lewy Body Dementia (DLB)

In one case study, a 74-year-old man improperly diagnosed with Alzheimer’s and parkinsonism (tremor, slow movement, impaired speech) was started on memantine and he developed severe changes in awareness, visual hallucinations, agitation, and worsening parkinsonism. After being properly diagnosed with DLB his memantine was removed, his treatment plan was adjusted, and there was a dramatic improvement in his symptoms [R].

Another study reported a slight improvement or no benefit of memantine in DLB [R].

Memantine May Worsen Symptoms of Multiple Sclerosis (MS)

Memory disorders are prevalent in about 40 to 60% of patients with MS. Memantine was not effective at reducing cognitive deficits, and patients who tried memantine had more adverse effects such as fatigue [R].

Furthermore, memantine caused short-term worsening of neurologic symptoms in MS, thereby exacerbating the cognitive deficits [R].

Muscle spasms are another common symptom of MS, causing discomfort and decreasing quality of life. Memantine was not more effective at reducing muscle spasms in MS patients than placebo [R].

Limitations and Caveats

Memantine is a prescription medication that needs to be approved by your doctor. There are adverse effects as mentioned above, therefore it is important that you are monitored regularly by your doctor. It is important to evaluate the risks versus benefits with your primary care provider prior to starting this medication, and ensure you have a good understanding of the medication and its effects.

User Reviews

“I have taken memantine for about 4-5 years. I feel able to cope pretty well considering. I live by myself and manage to do most things. I still have memory issues, but so do most people. I have been fortunate not to have had adverse effects of any consequence” [R].

“My mum who has been diagnosed with vascular dementia and was at the stage of being extremely confused about where she was and who her close relatives were, began taking memantine in January 2015. In short, it has given me my mum back. Mum is now relatively alert, she has markedly improved memory and is back in the present. I had never imagined such an improvement was possible. It’s really strange to be having conversations with mum about what she was like before taking the drug” [R].

“My wife (74) has been taking memantine since the first diagnosis of Alzheimer’s two years ago. She also takes any supplement that promises to help regain or improve memory. Her memory has stayed about the same or gotten a little worse in that time. She has also taken donepezil during the same period” [R].

“My wife began the 4 stage process a couple of months ago, and I stopped it halfway through week 2 because she seemed to be getting more confused. We started again a month ago and are into the 2nd full dose, and I am very concerned that her condition is worse instead of better” [R].

“My mom is 94 we started her on this medication because she was confused to the point of argument mostly in the late afternoon till bedtime. After 5 days of treatment, she seemed to be worse starting when she wakes up. Not sure what to do except to call a doctor on Monday to ask what we should do” [R].

“I began taking this medication on the recommendation of my neurologist for chronic migraines. I am currently taking Topamax and Elavil and I am attempting to get off the Topamax because the neurologist felt it isn’t helping any longer (I agree with her). I totally love the memantine for my migraines!! All I can say is if you are wanting to try something different, please do try this. I have virtually no side effects…maybe the dizziness if I had to pick one, but overall, it is working better than I could have ever hoped” [R].

“As a spousal caregiver, this medication along with Aricept has been very effective. Cognitive skills, writing, alertness, sense of humor have all increased. I am very pleased with the effectiveness of this medication” [R].

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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