Harvard Mental Health Letter

When depression starts in the neck

Treating an underactive thyroid gland may improve mood.

When someone develops depression, the brain usually becomes the focus of attention. But other organs can be the source of the problem. A common example is when the thyroid gland produces too little hormone — a condition known as hypothyroidism.

Nearly 10 million Americans suffer from hypothyroidism. The condition is much more common in women than in men, and becomes more prevalent with age. As many as one in five women will develop hypothyroidism by age 60.

Although researchers aren't entirely sure why there is a link between hypothyroidism and depression, it is likely that some people are taking antidepressants when they should really be taking thyroid medication. Here is a brief review of when clinicians and patients should consider hypothyroidism as a possible cause of low mood — and what to do next.

Front view: Thyroid gland

illustration of thyroid gland

The mighty thyroid

The thyroid gland is a small butterfly-shaped structure that sits low in the neck, below the Adam's apple (a protrusion made of cartilage that both women and men have). Although it weighs less than an ounce, the thyroid exerts a powerful influence throughout the body. It does so by secreting hormones that affect metabolism, a chemical activity that controls how fast and efficiently cells convert nutrients into energy. By regulating metabolism, the thyroid indirectly affects every cell, tissue, and organ in the body — from muscles, bones, and skin to the digestive tract, heart, and brain.

The thyroid, in turn, is regulated by the pituitary or "master" gland. The pituitary gland (a pea-sized gland that sits beneath the brain) constantly monitors blood levels of hormones, including those produced by the thyroid. When blood levels of thyroid hormones fall, the pituitary gland uses a chemical signal known as thyroid-stimulating hormone (TSH) to prompt the thyroid to pump up production. In response, the thyroid uses iodine from food to produce two hormones. Triiodothyronine, known as T3, contains three iodine atoms, while thyroxine, or T4, contains four. A normally functioning thyroid gland, working in conjunction with the pituitary gland, secretes T3 and T4 into the bloodstream at a steady pace.

In a person with hypothyroidism, however, the thyroid gland does not fully respond to TSH, so blood levels of T3 and T4 remain low. Assuming the pituitary is functioning normally, TSH levels rise; physicians often use the TSH level to help make a diagnosis of hypothyroidism.

When thyroid hormone levels are low, many organs and internal systems slow down, creating a wide range of symptoms — including depression. People over 60 may have only one symptom — such as mood impairment or difficulty concentrating.

Distinguishing depression from hypothyroidism*

Shared symptoms

  • Depressed mood

  • Fatigue

  • Weight gain

  • Reduced sexual desire

  • Trouble concentrating

More typical of depression

More likely hypothyroidism

  • Insomnia

  • Restlessness and inability to sit still

  • Feelings of worthlessness

  • Inappropriate guilt

  • Thoughts of death or suicide

  • Planning or attempting suicide

  • Feeling chilled or overly sensitive to cold temperatures

  • Constipation

  • Muscle cramps or stiffness

  • Dry skin and hair

  • Hair loss

  • Hoarseness

  • Slowed heart rate

*Blood tests measuring thyroid function are necessary to confirm a diagnosis of hypothyroidism.

Causes of hypothyroidism

Hypothyroidism often develops because of some underlying disease or because a medical treatment impairs thyroid function.

Autoimmune disorders. The most common cause of hypothyroidism is Hashimoto's thyroiditis, a chronic autoimmune disorder in which white blood cells make antibodies that attack and gradually disable the thyroid gland. Another autoimmune condition, atrophic thyroiditis, shrinks the thyroid. Either of these conditions significantly reduces thyroid hormone production.

Surgery. Partial or complete removal of the thyroid gland — whether for the treatment of thyroid cancer, an overactive thyroid (hyperthyroidism, the opposite of hypothyroidism), or some other problem — permanently decreases or eliminates thyroid hormone production, depending on how much of the gland is removed.

Radiation. Another treatment for an overactive thyroid, radioactive iodine, may disable the gland, causing permanent hypothyroidism. Likewise, radiation treatment for Hodgkin's disease, lymphoma, or cancers of the head and neck may have the same effect.

Damage to the pituitary gland. A tumor, radiation, or surgery may damage the pituitary gland, thus impairing its ability to produce and release TSH. Without this chemical signal, hormone production in the thyroid may fall.

Medications. Some medications — including the mood stabilizer lithium — can suppress thyroid hormone production.

Other causes. An infection, pregnancy, or other conditions may cause a temporary inflammation of the thyroid gland (thyroiditis). This may trigger a brief period of hyperthyroidism, followed by hypothyroidism. In some cases, the thyroid never fully recovers and hypothyroidism becomes permanent.

Diagnosing and treating hypothyroidism

Unless the pituitary gland is malfunctioning, a simple blood test to measure TSH provides a definitive test for hypothyroidism. Typically a clinician also feels a patient's neck to assess the size of the thyroid gland and checks for other physical signs of hypothyroidism, such as brittle nails and dry skin.

Treatment usually involves taking a medication once a day to restore thyroid hormone levels to normal. Several options exist.

Levothyroxine. The most commonly prescribed drug is a purified form of synthetic T4, levothyroxine (Levothroid, Synthroid, others). Levothyroxine works in the same way natural thyroid hormone does, provides stable levels of hormone, and is well absorbed.

All brands are equally effective, but each brand or generic formulation contains slight variations of ingredients that may affect the amount of drug in the blood. The issue is not one of quality, because generic drugs undergo the same potency tests that brand-name drugs do. Instead, the problem is that pharmacies may substitute one generic for another. Therefore it's important to consult with your doctor if, for any reason, you receive a new brand.

Clinicians determine the initial dose of levothyroxine based on a patient's weight, age, severity of hypothyroidism, and other medical conditions or medications. In older people, for example, raising thyroid hormone levels too quickly may place stress on the heart — so clinicians usually begin with a low dose and increase it gradually. All people metabolize drugs in different ways, making the same dose more effective in one person than another. Certain medications — such as the mood stabilizer carbamazepine (Tegretol) and the antidepressant sertraline (Zoloft) — may reduce the effectiveness of levothyroxine. Given all these factors, clinicians order periodic blood tests to monitor how effective a thyroid medication is for each individual, and make adjustments based on the results.

Other options. Liothyronine (Cytomel), a synthetic version of T3, is eliminated from the system faster than T4, so levels fluctuate more. Another option is liotrix (Thyrolar), which combines both T3 and T4 in one pill. Both of these drugs may require more careful dosing to avoid raising thyroid hormone levels too far. Yet some people respond better to these medications.

Combining antidepressants and thyroid medications

Thyroid medications are sometimes added to antidepressant treatment to improve mood — even when thyroid function is normal. Clinicians usually recommend liothyronine (T3 hormone) to augment antidepressant therapy, but in some cases they recommend levothyroxine (T4). One theory is that thyroid drugs act in concert with antidepressants in the brain. Another idea is that thyroid pills boost chemical activity in the brain, improving mood and concentration.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study evaluated the combination of T3 thyroid hormone and antidepressants in people who had not improved after two previous treatments. About 25% of those taking T3 thyroid hormone saw additional improvement in their symptoms.

Chances of recovery

Most people with hypothyroidism respond positively to treatment and find that depression and other bothersome symptoms subside with time. How long that takes is an individual matter, ranging from weeks to months. Elderly people may take longer to respond, since doses of thyroid medications need to be increased slowly to avoid putting any strain on the heart.

Philip NS, et al. "Pharmacologic Approaches to Treatment Resistant Depression: A Re-examination for the Modern Era," Expert Opinions in Pharmacotherapy (April 2010): Vol. 11, No. 5, pp. 709–22.

For more references, please see www.health.harvard.edu/mentalextra.