Best Antidepressants for MTHFR Mutation
If you have the MTHFR mutation, certain antidepressants may be more effective for you. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are the first-line antidepressants also for people with MTHFR mutations. Often, supplementing folate, including 5-MTHF supplements, may be beneficial alongside conventional antidepressants. However, the best choice always depends on individual genetic makeup and should be discussed with a healthcare professional. Always consult your doctor before starting any new medication.
What is the MTHFR mutation?
The MTHFR mutation refers to a change in the MTHFR gene. This gene provides instructions for making methylenetetrahydrofolate reductase, an enzyme crucial for processing amino acids. The MTHFR gene is essential for a chemical reaction involving forms of the vitamin folate (commonly referred to as folic acid or the generic name vitamin B9). The MTHFR-coded enzyme converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a reaction required for the multistep process that converts the amino acid homocysteine to another amino acid, methionine. Methionine, in turn, is necessary for making methylfolate, a bioactive form of folic acid [1, 2, 3].
The MTHFR gene mutation leads to elevated levels of homocysteine in the blood and low levels of folate and other vitamins. This mutation can be relatively common and may increase the risk for a variety of health conditions, including thrombosis, hypertension, neural tube defects, and others [1]. However, many people do not realize they have a mutation in the MTHFR gene and only discover this if they get genetically tested or have another health condition [4].
What mutations in the MTHFR gene can you have?
There are three primary clinically significant mutations of the MTHFR gene. These include C677T, A1298C (also known as the A-C haplotype), and T1317C, all of which are linked to a higher risk of cardiovascular complications such as thrombosis, stroke, hypertension, or myocardial infarction, as well as prenatal defects such as neural tube defects or recurring pregnancy loss [1].
Severe MTHFR deficiency is an infrequent inborn error of folate metabolism. It is characterized by homocystinuria and hypomethioninemia (medical terms for high homocysteine and low methionine). It may lead to neurological abnormalities, pathologically slow mental development resulting in retardation, and premature vascular disease [2].
What are Antidepressants?
Antidepressants are a type of medication primarily used to treat depression, a serious medical illness that affects mood and overall mental health. These medications balance neurotransmitters throughout the brain, particularly relating to stress and mood [5].
Antidepressants are also used for conditions outside of major depression. They can be prescribed off-label (meaning that this use is outside of FDA regulation) for chronic pain, chronic fatigue, or even menstrual symptoms [6]. In psychiatry, specific antidepressants are also used for anxiety disorders, including social anxiety disorder, OCD, bipolar disorder or eating disorders [8.
There are many types of antidepressants available, and different people respond differently to these medications. It may take a few weeks for the effects of antidepressants to be felt, and in some cases, a person might need to try several different types before finding one that effectively manages their symptoms without causing side effects [7, 8]. Treatment-resistant depression is when an individual does not respond to two or more types of antidepressants, which means they may need to try more experimental strategies.
Types of antidepressants
The most common types of antidepressants are selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, dopamine reuptake blockers, and monoamine oxidase inhibitors (MAOIs) [9, 8]. SSRIs are the most widely used, with lower side effects and risks. One also cannot develop a tolerance to SSRIs, unlike tricyclic antidepressants and dopamine reuptake inhibitors. MAOIs are the oldest type of antidepressant and have a higher risk of adverse drug interaction or overdose.
It's important to note that although antidepressants are commonly used and prescribed, they are not always the best option. For mild to moderate severity depression, lifestyle adjustments or psychotherapy can be most helpful in the long term [7].
What are the best antidepressants for the MTHFR mutation?
The MTHFR mutation has been linked to depression and is more common in patients with treatment-resistant depression [10, 11]. This indicates that patients with MTHFR mutations may respond to conventionally prescribed antidepressants differently. Despite this, the best antidepressant treatment for individuals with this mutation is not definitively established. In this section, we will discuss the evidence to date of which antidepressants work better/worse in populations with the MTHFR mutation.
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Another study found that l-methyl folate, a form of B-vitamin folate, may be a safe and effective adjunct to antidepressant treatment for managing treatment-resistant depression in pediatric patients with the MTHFR mutation [13]. This suggests that l-methylfolate could potentially enhance the effectiveness of antidepressants in individuals with this mutation. Indeed, this theory is supported by further empirical evidence, where patients who get better with 5-MTHF supplements adjunct with antidepressants are very likely to have a mutation in the MTHFR gene. This indicates a critical role for genetic testing in selecting an appropriate antidepressant combination for depression.
However, it's important to note that the effectiveness of antidepressants varies significantly among individuals, even without the MTHFR mutation. Therefore, it's essential to consult your healthcare provider regularly when taking antidepressants, and they will be able to advise whether a genetic test or antidepressant change is appropriate.