Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the clinical and scientific literature. Please discuss your medications with your doctor.
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 .
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 .
Memantine Mechanism of Action
- Memantine is thought to slow and/or prevent the neurotoxicity associated with Alzheimer’s disease and other neurodegenerative diseases .
- 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 and blocks already activated NMDA receptors, which decreases the toxicity caused by too much excitation (excitotoxicity) and prevents cell death (apoptosis) .
- Memantine blocks 5-HT3 (serotonin subtype 3) receptors. This receptor is found in several areas of the limbic system including the amygdala and hippocampus .
- Memantine also blocks nicotinic receptors .
- 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 .
Uses of Memantine
1) Slows 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 (randomized controlled trial) 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 .
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 .
2) May Help Improve Other Forms of 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 had a better functional outcome and were less dependent on their caregivers after 12 weeks .
In a study (double-blind randomized controlled trial) 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 .
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 (randomized controlled trial) .
3) May Decrease Symptoms of 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 similar in its ability to decrease symptoms of ADHD. There was no difference in the frequency of side effects between the two treatments .
In a 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 .
4) 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 .
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 .
5) 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 study in 33 bipolar disorder patients hospitalized for mania found that 21 days of memantine reduced symptoms of mania .
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 .
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 .
6) May Decrease Symptoms of Generalized Anxiety Disorder (GAD)
7) 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 .
8) 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 .
Memantine, taken daily, helped to reduce the frequency of chronic cluster headaches in individuals who did not respond to other preventative treatments .
9) May Protect 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 .
10) May Delay Amyotrophic Lateral Sclerosis (ALS)
When memantine was administered to mice with ALS, the disease progression was significantly delayed, and lifespan was increased .
Memantine in Combination with Other Drugs
1) Decreases Symptoms of Obsessive Compulsive Disorder (OCD)
Memantine has been used in addition to first-line treatments for OCD. Some studies reported benefit, one case documenting a 100% response .
Another study reported that 89% of the patients who received memantine along with conventional treatments resolved their OCD symptoms after eight weeks .
2) 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 .
3) May Help with Short-Term of Substance Use Disorders
A study (double-blind randomized controlled trial) 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 .
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 .
In mice, memantine disrupted conditioned alcohol-seeking behaviors, suggesting that it may be an option to treat alcoholism .
Side Effects of Memantine
Memantine is generally well-tolerated .
The most common side effects are constipation, nausea, and headache. Other reported side effects include :
- high blood pressure
- back pain
- difficult or labored breathing (dyspnea)
- abnormal gait
- 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 .
Contraindications of 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 .
Another study reported a slight improvement or no benefit of memantine in DLB .
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 .
Furthermore, memantine caused short-term worsening of neurologic symptoms in MS, thereby exacerbating the cognitive deficits .
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 .
Warnings of Memantine
Memantine has warnings in those with kidney and liver dysfunction or impairment and the use of memantine in children has not been studied enough .
Memantine 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 with caution .
It is unknown if memantine is excreted in breast milk and it should be used with caution in nursing mothers .
Drug Interactions of Memantine
In mice, memantine increased the concentration of sertraline (an antidepressant) in the brain, which could lead to greater effectiveness .
Forms and Dosage of Memantine
Memantine is available as :
- 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 have used between 5 mg and 40 mg a day, administered in two equal doses throughout the day. It is recommended to start at 5 mg once daily and increase by 5 mg increments every week (titrated) until reaching a dose of 20 mg a day [9, 1, 41].
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.
Memantine is a drug that affects your neurotransmitters. Want to understand your variants in these genes and how they affect your mood and tendency to respond to such drugs? Check out the Mood DNA Wellness Report here.