Reduced thyroid function and depression: a personalized medicine approach

Low thyroid function, also called hypothyroidism, often develops slowly and can go unnoticed for years. Its early symptoms, such as tiredness, low mood, slowed thinking and weight gain, overlap with depression, so one condition can be mistaken for the other. This article explains how thyroid function and mood are linked, how low thyroid is diagnosed and treated, and how pharmacogenetic testing can help when depression needs treatment.

How are thyroid function and depression linked?

The thyroid is a small gland in the neck that makes hormones controlling the body's energy use. Thyroid hormones also act on the brain and affect mood, energy and concentration. People with thyroid disorders are more likely to have depressive symptoms, and people with depression sometimes have subtle changes in thyroid tests.

• Low thyroid (hypothyroidism) can cause tiredness, low mood, feeling cold, constipation, dry skin, weight gain and slowed thinking.
• Overactive thyroid (hyperthyroidism) can cause anxiety, irritability, a racing heart, poor sleep and weight loss.

Thyroid problems are common, especially in women and older adults, and many people do not know they have one. Because the symptoms overlap, anyone being assessed for depression should have their thyroid checked with a simple blood test.

How is low thyroid function diagnosed?

The main test is TSH (thyroid-stimulating hormone), often with free T4 (thyroxine). TSH comes from the pituitary gland in the brain and tells the thyroid to work harder. When the thyroid is underactive, TSH goes up. In most labs, the normal range for TSH is roughly 0.4 to 4.5 mU/L.

• Overt hypothyroidism: TSH is high and free T4 is low. This is treated with thyroid hormone.
• Subclinical hypothyroidism: TSH is mildly high, usually between about 4.5 and 10 mU/L, while free T4 is normal. Many people have no symptoms, and TSH sometimes returns to normal on its own.

The most common cause of hypothyroidism in Canada is autoimmune thyroid disease (Hashimoto's thyroiditis), in which the immune system attacks the thyroid. It often runs in families.

Does mildly low thyroid function cause depression?

The evidence is mixed. A 2018 meta-analysis found no overall link between subclinical hypothyroidism and depression, although a link was seen in adults younger than 60. In the same analysis, treating subclinical hypothyroidism with levothyroxine did not improve depression. A 2019 international guideline recommends against routine thyroid hormone treatment for most adults with subclinical hypothyroidism, because trials showed no meaningful benefit for symptoms, including low mood and tiredness. Exceptions include women trying to become pregnant, people with a TSH above 20 mU/L and some younger adults with significant symptoms.

Some psychiatrists suggest that people whose depression has not improved with antidepressants and who have subclinical hypothyroidism or a high-normal TSH may benefit from thyroid treatment. This is a decision for you and your doctors to make together.

Can thyroid hormone help antidepressants work better?

Yes, in some people. Liothyronine (T3), the active form of thyroid hormone, is one of the options that can be added to an antidepressant when depression has not improved enough. In the large STAR*D study, adding T3 after two unsuccessful antidepressant trials led to remission in about 1 in 4 people, with fewer side effects than adding lithium. T3 is used at low doses and needs medical monitoring, especially in people with heart disease.

What should you know about taking levothyroxine?

Levothyroxine (brand names include Synthroid and Eltroxin) replaces the hormone T4 and is the standard treatment for hypothyroidism. It raises thyroid hormone levels, which brings TSH back down into the normal range. Tips for taking it:

• Take it the same way every day, on an empty stomach with water, 30 to 60 minutes before breakfast, or at bedtime at least 3 hours after your last meal.
• Keep it apart from calcium, iron and antacids by about 4 hours. Coffee, soy and fibre can also reduce absorption.
• Be patient. Levothyroxine works slowly. TSH is usually rechecked 6 to 8 weeks after starting or changing the dose.
• Your dose is personal. It depends on your weight, age, heart health and TSH results.
• Tell your doctor about other medications. Some medications reduce absorption, such as proton pump inhibitors, and others speed up its breakdown, such as carbamazepine, phenytoin and rifampin, so you may need a higher dose.
• Stop biotin before thyroid blood tests. Biotin (vitamin B7), often taken for hair, skin and nails, does not stop levothyroxine from working, but it can distort thyroid blood tests. It can make TSH look too low and T4 look too high, so your dose may be lowered when it should not be. Stop biotin, including multivitamins that contain it, at least 2 days before a thyroid blood test, and tell your doctor and the lab if you take it.

Taking too much levothyroxine is also a problem. A TSH that is too low can cause anxiety, poor sleep, a racing heart and weight loss. Over time, it raises the risk of atrial fibrillation, an irregular heart rhythm, and of bone loss, especially in older adults. In one study, people aged 60 or older with a very low TSH had three times the risk of atrial fibrillation over 10 years.

There is no genetic test that guides the dose of levothyroxine. The dose is adjusted based on your TSH and symptoms.

Can mood medications affect the thyroid?

Yes. Lithium, a mood stabilizer used for bipolar disorder and sometimes for depression, can reduce thyroid function. People taking lithium are about six times more likely to develop hypothyroidism than people taking a placebo. If you take lithium, your doctor should check your TSH before you start and regularly during treatment. Low thyroid caused by lithium is treated with levothyroxine, and lithium can usually be continued.

Do iodine and vitamin D matter?

Iodine is needed to make thyroid hormone. In Canada, iodized salt prevents deficiency for most people. Too much iodine, for example from high-dose kelp or iodine supplements, can also trigger low thyroid, especially in people with autoimmune thyroid disease. Do not take iodine supplements unless your doctor recommends them.

Vitamin D deficiency is common in people with autoimmune thyroid disease and is also linked to low mood. If you are low, a supplement corrects the deficiency, but the evidence that vitamin D improves depression or thyroid function is mixed. Ask your doctor whether a vitamin D test is right for you.

How can pharmacogenetic testing help?

Many people with low thyroid function and depression need treatment with antidepressants and sometimes other medications, such as pain relievers or stimulants. Your genes, especially CYP2D6 and CYP2C19, affect how your body processes many antidepressants and can explain why one medication causes side effects or does not work.

A Pillcheck test shows how your genes affect antidepressants, anxiety medications, pain relievers and many other medications. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. A Pillcheck pharmacist reviews your results together with all your medications, including thyroid medication, and gives you recommendations to discuss with your doctor.

Summary

• Low thyroid function and depression share symptoms, so a thyroid blood test is part of a depression assessment.
• Overt hypothyroidism (high TSH and low T4) is treated with levothyroxine. Mild (subclinical) hypothyroidism is often monitored rather than treated.
• Treating mild hypothyroidism has not been shown to improve depression in most people, but T3 can be added to an antidepressant when depression does not improve enough.
• Levothyroxine must be taken consistently on an empty stomach, and too high a dose can cause heart rhythm problems and bone loss.
• Lithium can cause hypothyroidism, so TSH should be checked regularly.
• Pharmacogenetic testing can help guide the choice and dose of antidepressants and other medications.

Frequently asked questions

Can low thyroid function cause depression?

Overt hypothyroidism can cause low mood, tiredness and slowed thinking, and these often improve with treatment. The link between mildly low thyroid function and depression is less clear.

Will levothyroxine treat my depression?

If depression is caused by overt hypothyroidism, treating the thyroid often helps. If you have mild hypothyroidism, levothyroxine alone is unlikely to improve depression, and you may need depression treatment as well.

Can I take antidepressants with levothyroxine?

Yes. Most antidepressants can be taken with levothyroxine. Your doctor may check your TSH after you start or change medications.

Can supplements affect my thyroid results?

Yes. Biotin (vitamin B7) can make thyroid blood tests look as if your levothyroxine dose is too high. Stop biotin, including multivitamins that contain it, at least 2 days before a thyroid blood test, and tell your doctor if you take it.

Does Pillcheck test for thyroid disease?

No. Pillcheck does not diagnose thyroid disease. Thyroid function is checked with a blood test. Pillcheck shows how your genes affect your response to medications, including antidepressants.

References

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