SSRIs, L-Methylfolate and Pregnancy

Maternal depression is not something that should be taken lightly. The World Health Organization reports that ten percent of all pregnant women are depressed. With depression being so common in today’s society, it is important to understand how it can manifest in women.

Depression can be broken into two categories depending on the severity of symptoms. A major depressive disorder is severe and is categorized by persistent feelings of hopelessness and worthlessness. A persistent depressive disorder is also a chronic form of depression, but it is considered milder.

Studies have looked at the brains of depressed individuals and have noticed lower levels of the neurotransmitters dopamine and serotonin. This observation has led doctors to prescribe depressed patients with different types of SSRIs (Selective Serotonin-Reuptake Inhibitors). The theory behind SSRIs is that the medication “fixes the imbalance” in the brain, bringing serotonin levels back to normal.

Interestingly enough, this theory has been debunked over and over in the field of medical science. Although serotonin is a neurotransmitter that is necessary for the regulation of happiness, anxiety, and well-being, research is showing that it is not low serotonin levels that are causing depression. Clinical-depression.co.uk explains it like this:

“Serotonin is produced in the brain on an ongoing basis and in response to pleasure-giving experiences, in a normally healthy system. But if that system becomes less than healthy, if it is depressed for example, serotonin levels can drop. But low levels didn't cause the depression!”

Despite the evidence, dispensing rates of SSRI drugs have increased. One study, in particular, looked at the increase in dispensing rates over 16 years and noted a steady rise in both depressive cases in addition to SSRI drug use.

Although there are no causal links between SSRI use in pregnancy and fetal harm, we are aware that the medication does pass through to the developing fetus.

One study looked at echocardiographic abnormalities in pregnant women and showed that there is a risk of congenital heart disease in patients who are prenatally exposed to anti-depressant medications. It is important to note that the evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Other studies have shown a handful of adverse outcomes, including gestational hypertension, reduced birth weight, altered neonatal pain responses and persistent pulmonary hypertension of the newborn with exposure to antidepressant medications.

It is essential to note that, as with any drug treatment in pregnancy, the benefits to the mother should be considered versus the possible hazards to the developing embryo/fetus. Maternal mental health is just as important as fetal health.

Low folate levels have not only been found to be associated with depressive symptoms, but they are also correlated with a longer duration of depressive episodes. L-methylfolate is the centrally active derivative of folate that regulates the synthesis of serotonin, dopamine, and norepinephrine, and is a key regulator of the cofactor tetrahydrobiopterin (BH4). BH4 is required by tryptophan, and tryptophan helps to aid in the synthesis of serotonin.

Additionally, low levels of serum and red blood cell folate are linked to severe symptoms of depression. In a study of patients with Major Depressive Disorder who partially responded or did not respond to SSRIs, adjunctive L-methylfolate (15 mg/d) produced greater response rates compared with SSRIs plus placebo (Papkostas, Shelton, & Zajecka, 2011).

Although we are now aware that low levels of serotonin do not cause depression, synthesis of the neurotransmitter is essential for the regulation of happiness, mood, and well-being. It is possible that folate supplementation can help support this synthesis.

Pregnant women should always consult with their doctor before taking any supplements or medications. However, it is worth discussing your options in-depth if you are feeling depressed so you get to the root cause of the depression. L-Methylfolate may be one option worth looking into before starting an SSRI.