Memantine is a drug approved for the treatment of moderate-to-severe Alzheimer’s disease. It is also used “off-label” to treat dementia, ADHD, PTSD, and other psychiatric conditions. What does the science have to say about how it works and what it does? Read on to learn more about this drug, its mechanisms, side-effects, and more!
Disclaimer: This post is not a recommendation or endorsement for memantine. This medication is only FDA-approved for the treatment of certain specific medical disorders, and can only be taken by prescription and with oversight from a licensed medical professional. We have written this post for informational purposes only, and our goal is solely to inform people about the science behind memantine’s effects, mechanisms, and current medical uses.
What Is Memantine?
Originally developed in the 1960s to treat diabetes, memantine was approved by the FDA in the US in 2003 for the treatment of moderate-to-severe Alzheimer’s disease [1]. Memantine is commonly sold under the trade name Namenda.
Currently there are just five medications – including memantine – which have been approved for the treatment of cognitive decline in Alzheimer’s. The other four are all acetylcholinesterase inhibitors, which means that they work primarily by preventing the breakdown of the neurotransmitter acetylcholine. However, memantine works differently, by blocking NMDA receptors, making it the only drug in its class [2].
It is important to note that memantine and other Alzheimer’s drugs do not cure Alzheimer’s – they only slow some of the cognitive decline commonly seen in this disease. Therefore, these drugs are useful for improving the daily functioning and quality-of-life of Alzheimer’s patients; but they nevertheless do not reverse the course of the disease once it has started, nor do they fully prevent the disease from progressing over time.
Mechanism of Action
Memantine is believed to slow the neurotoxicity associated with Alzheimer’s disease and other neurodegenerative diseases [3].
Memantine’s main mechanism is through glutamate NMDA receptor inhibition in the brain. Too little or too much glutamate can lead to cell death. Memantine quickly binds to and blocks NMDA receptors, which can counteract toxicity caused by too much excitation (excitotoxicity), and thereby prevents programmed cell death (apoptosis) [4].
Memantine also blocks 5-HT3 (serotonin subtype 3) receptors. This receptor is found in several areas of the limbic system including the amygdala and hippocampus [5].
Memantine also blocks nicotinic receptors [6].
Finally, 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. This also suggests that this mechanism may not be central to the drug’s main therapeutic effects [7].
Approved Medical Uses
1) Slows the Progression of Moderate-to-Severe Alzheimer’s Disease
The FDA has officially approved memantine for the treatment of certain cases of Alzheimer’s disease, and this is the most typical medical use of memantine.
Consequently, there is a large pool of high-quality evidence that supports memantine’s use in moderate-to-severe cases of Alzheimer’s disease (AD).
Most studies support 20mg a day (or 10mg twice daily) to be the most effective dose [1].
In a randomized controlled trial in 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, all of which are used by clinicians to measure diverse aspects of cognitive function and behavior in Alzheimer’s patients [1].
However, this same study also reported that there were no apparent benefits of the use in memantine in patients with only mild Alzheimer’s disease [1].
Donepezil is another medication commonly used to treat AD. In a recent meta-analysis of 28 studies, the combination of donepezil and memantine was reported to significantly improve cognitive function, behavioral and psychological symptoms, and global functions more than donepezil alone, with the same side effects [8].
Off-Label Medical Uses
Occasionally, doctors will prescribe drugs like memantine to help treat conditions that fall outside of the official uses approved by the FDA – also known as “off-label” drug use [9, 10, 11]. Usually, this is done because there is actually decent evidence that the drug may help, although this evidence might not be quite strong enough to get full FDA approval (which generally has very strict requirements).
As always, however, always remember that the decision to use medications in this way can only be made by a licensed medical professional.
1) Treating Dementia
One of the most common “off-label” uses of memantine is to treat other (i.e. non-Alzheimer’s-related) forms of dementia – a use that actually has quite a bit of solid scientific evidence to back it up, in spite of it not being officially approved by the FDA.
In the context of dementia treatment, the specific form of dementia that has the most evidence to support it is vascular dementia. However, there are also several other types of dementia that have evidence to support the use of memantine in treatment, and it’s not uncommon for doctors to prescribe memantine as a part of the treatment for patients with these conditions.
Vascular Dementia
In a study (double-blind randomized controlled trial) of 548 patients with vascular dementia, those treated with memantine for 28 weeks were reported to score significantly higher on their mini-mental status exam (a clinical test that is used to assess the progression of cognitive decline, especially in dementia) compared patients on placebo [12].
Severe Dementia
In a study (randomized controlled trial) of 166 patients with severe dementia in either Alzheimer’s or vascular dementia, the group treated with memantine were reported to show better functional outcomes, and were less dependent on their caregivers, after 12 weeks of treatment with memantine [13].
Dementia of Wernicke-Korsakoff Syndrome
Dementia of Wernicke-Korsakoff syndrome (WKS) is dementia caused by vitamin B1 deficiency. This is most commonly (though not necessarily always) caused by long-term alcohol abuse, and is often difficult to treat.
After 28 weeks of memantine treatment, 16 WKS patients were reported to show improvements in both thinking and overall functioning when compared to the placebo group (randomized controlled trial) [14].
2) May Decrease Symptoms of ADHD
Doctors will also sometimes prescribe memantine to help reduce or better manage some of the symptoms commonly seen in ADHD.
Forty children with ADHD (double-blind randomized controlled trial) were treated with either methylphenidate, a drug used to treat ADHD, or memantine, for 6 weeks. Memantine was reported to be similar to methylphenidate in its ability to decrease symptoms of ADHD. There was no difference in the frequency of side effects between the two treatments [15].
In another study (double-blind randomized controlled trial) 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 [16].
3) May Decrease Symptoms of PTSD
Some evidence supports the use of memantine in the treatment of PTSD.
Taking 20mg per day of memantine for 12 weeks reportedly decreased symptoms of inappropriately increased awareness and avoidance in a case series of 4 veterans. The patients also reported experiencing a subjective improvement in their mood, memory, and concentration [17].
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 [18].
4) May Help Improve Bipolar Disorder
Bipolar disorder is a mental disorder characterized by periods of both elevated mood (mania) and depression, and some evidence exists that suggests that memantine may be helpful in treating some of its associated symptoms.
For example, an open-label pilot study in 33 bipolar disorder patients hospitalized for mania reported that 21 days of memantine reduced symptoms of mania [19].
One case study of a bipolar patient resistant to conventional treatment reported that 10 mg/day of memantine for 4 weeks resulted in a complete disappearance of manic symptoms [20].
Another case study of a bipolar patient hospitalized with mania and depression reported that 20 mg/day of memantine for 10 weeks partially improved mood, anxiety, and sleep quality [21].
5) 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 was reported to slightly decrease anxiety in 7 patients with GAD [22, 23].
6) May Decrease Symptoms of Obsessive-Compulsive Disorder (OCD)
According to some studies, memantine has shown some potential when used in addition to first-line treatments for OCD. Some studies reported benefit, one case documenting a 100% response [24].
Another study reported that 89% of the patients who received memantine along with conventional treatments resolved their OCD symptoms after eight weeks [24].
7) May Reduce the Negative Symptoms of Schizophrenia
The so-called “negative symptoms” of schizophrenia (such as decreased speech and socialization; reduced emotional response) were reduced when memantine was added to antipsychotics [25].
Other Potential Uses
In addition to some of the relatively well-accepted (but still technically unofficial) “off-label” uses described in the previous section, memantine has also been studied for its potential to treat a variety of other health conditions or other noteworthy effects.
However, keep in mind that the evidence supporting these potential applications is still only preliminary, and a lot more additional research will be needed before any of these applications are ever officially approved for medical use. Therefore, it is important to take all of the information below with a healthy grain of salt!
1) May Help Treat Nystagmus
Acquired fixational pendular nystagmus (APN) is a type of eye condition where eyes make repetitive uncontrolled movements that appear as excessive motion, and which blurs the patient’s 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 [26].
Infantile nystagmus (IN) often occurs in the first 3 to 6 months of life. Memantine has been reported to reduce the symptoms of IN, as well as improve vision and the ability to angle the eyes in order to focus on objects (foveation) [27].
2) May Help Treat Migraines and Headaches
According to one study, 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 [28].
Memantine, taken daily, was also reported to help reduce the frequency of chronic cluster headaches in individuals who did not respond to other preventative treatments [29].
In 28 patients with refractory migraines, memantine taken daily reportedly helped to decrease the number of days with a headache from 22 per month to 16 days per month [30].
3) May Help with Short-Term Treatment of Substance Use Disorders
Some evidence suggests that memantine may have potential as a complementary medication to help treat addiction and other substance use disorders (meaning that it is used together with other, more “conventional” drugs – and not used just on its own).
For example, a double-blind randomized controlled trial in 80 young adults with opioid dependence treated with buprenorphine and/or naloxone were also given either memantine or a placebo. The memantine group was reported to be significantly less likely to relapse compared to the placebo group, as observed over the course of eight weeks [31].
Methadone is another medication used to help individuals with opioid use disorder. When memantine was combined with methadone, the two medications reportedly decreased the total amount of methadone needed to curb individuals’ craving for opioids over the course of 12 weeks of treatment [32].
According to one animal study, memantine disrupted conditioned alcohol-seeking behaviors in mice. This suggests that it may be an option to treat alcoholism, although additional studies in human patients will be needed to know for sure how much clinical potential it might have in such cases [33].
4) May Protect Against Mild Traumatic Brain Injury
Although this effect has not been studied directly in humans, at least one animal study has reported that treating mice with memantine after they experienced repetitive mild traumatic brain injury showed less extensive damage to their brains compared to controls [34].
However, this effect would need to be studied in human patients to find out for sure whether a similar effect would be seen in humans, and not just mice.
5) May Delay Amyotrophic Lateral Sclerosis (ALS)
According to one animal study, when memantine was administered to mice with ALS, the disease progression was significantly delayed, and lifespan was increased [35].
Once again, however, this effect has not yet been directly observed in any human populations, so it’s too early to know how much potential memantine might have in the medical treatment of ALS.
Memantine Side–Effects
Given that memantine has met FDA approval for medical use, the majority of scientific evidence supports the overall safety and effectiveness of memantine. It is generally well-tolerated, and does not appear to cause an unusually high rate of negative side-effects [36].
Nonetheless, like any drug, there is always at least some potential of experiencing adverse side-effects, and so it’s important to be aware of these.
The most commonly reported side effects of memantine include constipation, nausea, and headache. Other reported side effects include [37]:
- 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
For patients with severe liver or kidney impairments, clinicians have been advised to prescribe a lower dosage of memantine accordingly. In patients with especially severe kidney impairments, it is recommended that dosages not exceed more than 5mg twice daily (10mg/day) [37].
Contraindications
Although memantine has a number of relatively well-supported medical uses when administered by qualified medical professionals, there are a number of factors that doctors may look for that might disqualify someone from receiving memantine treatment (due to elevated risk of negative side-effects or other adverse reactions).
As always, the best way to minimize the risk of experiencing adverse reactions from memantine (or any other medication) is to make sure that your doctor is fully aware of any other medications or supplements you are taking, other pre-existing health conditions you have, and any other information that could be relevant to your treatment.
May Exacerbate Symptoms of Lewy-Body Dementia (DLB)
According to 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 reportedly developed severe changes in awareness, visual hallucinations, agitation, and worsening parkinsonism. After being properly diagnosed with DLB his memantine treatment was stopped, his overall treatment plan was adjusted, and there was a dramatic improvement in his symptoms [38].
Another study reported a slight improvement or no benefit of memantine in DLB [39].
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 [40].
Furthermore, memantine caused short-term worsening of neurologic symptoms in MS, thereby exacerbating the cognitive deficits [41].
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 [42].
Warnings
Memantine has warnings in those with kidney and liver dysfunction or impairment [3].
The efficacy and safety of memantine in children has not been studied extensively enough for it to be approved for use in younger patients [3].
Use During Pregnancy and Breastfeeding
Memantine was listed as a category B in the old FDA pregnancy risk ratings for drugs. Animal reproduction studies have shown adverse events, and patients are advised to use memantine with caution before- or during pregnancy [3].
It is unknown if memantine is secreted and transmitted to nursing infants through breast milk – and it should, therefore, be used with caution in mothers who are breastfeeding [3].
Drug Interactions
Memantine has been reported to increase the concentration of sertraline (an antidepressant) in the brains of mice. Some researchers have therefore hypothesized that combining memantine with antidepressants could enhance their potency and effects, although much more clinical research would be needed in order for this to become a part of standard medical practice [43].
Forms and Dosage
Note: The information in this section describes typical dose information for medical applications of memantine. Only a medical professional is properly qualified to determine the specific dosage that will be ideal for any individual case – and it is important to always discuss treatment plans with your doctor, and to follow their directions as carefully and accurately as you can to ensure the best treatment.
Memantine is available as [3]:
- Immediate-release 5 mg and 10 mg tablets
- Extended-release (24 hours) 7 mg, 14 mg, 21 mg, and 28 mg capsules
- A 2 mg/mL (360 mL) oral solution
Clinical trials typically use somewhere between 5-40mg per day, often administered in two equal doses spread over the course of the day. Some guidelines recommended to start patients off at 5mg once daily, and increase (“titrate”) the dose in increments of 5mg every week until reaching a dose of 20mg per day [13, 1, 44].
Limitations and Caveats
Memantine is a prescription medication that needs to be approved and prescribed by your doctor.
There is the possibility of experiencing adverse side-effects or interactions: therefore it is important that you are continually monitored by your doctor while taking memantine.
It is important to evaluate the relative benefits and risks of memantine treatment with your primary care provider prior to starting this medication, and to ensure that you have a good understanding of the medication and its effects.
