Synopsis: It is important to know that medical conditions can cause depression or mimic the symptoms of depression. While dozens of medical conditions can contribute to depression, this article covers 10 of the most common. Knowing what these conditions are and screening for them can ensure better treatment and a speedier recovery.

BY LEN LANTZ, MD / 6.23.20; No. 28 / 13 min read

Disclaimer: Yes, I am a physician, but I’m not your doctor, and this article does not create a doctor-patient relationship. This article is for educational purposes and should not be seen as medical advice. You should consult with your physician before you rely on this information. This post might also contain affiliate links. Please click this LINK for the full disclaimer.

The crossover symptoms of depression and medical diseases

Some of the symptoms of depression include sad/irritable moods, loss of joy and decreased motivation and energy. As you can imagine, some of these same symptoms occur when a person has a medical illness. While some of these illnesses are simple to screen for, they can also start small and build slowly, so that a person is left wondering “What’s wrong with me? I’ve just been feeling so tired and down lately. Maybe it’s my diet?”

While some people know with certainty the medical cause of their depression, such as cancer, stroke or heart attack, others have to search for clues with their primary care provider. Not all yearly laboratory screening catches these seemingly milder but debilitating medical illnesses. Also, it is important to acknowledge that many forms of substance abuse, such as alcohol, cannabis and cocaine abuse, are commonly associated with depressive symptoms.

Who can help?

It can be hard to know who can help screen for some of these conditions. If a person meets clear criteria for major depressive disorder, primary care physicians might be slow to order comprehensive medical testing to save on insurance medical costs, especially in highly restrictive HMOs. For example, obtaining a sleep study to assess for sleep disorders is not cheap. Alternately, a person’s psychiatrist might be hesitant to order the testing as, in most cases, they would not be the medical specialist who would start treatment if a nonpsychiatric condition were found. Lastly, some medical conditions are very challenging to diagnose, especially if similar medical conditions must be ruled out first.

Often, it is best to work with your primary care provider and start with some of the less expensive screenings mentioned below. You should move on to more expensive/extensive testing or a medical specialist if the initial testing is negative and if there is a high index of suspicion for the remaining conditions.

Clinical vs. subclinical disease

Most people understand clinical disease, which is being sick from an illness. Clinical disease involves symptoms noticed by the person and findings on examination by your doctor. However, other people can have a subclinical disease, which essentially means that the disease was caught early or is not yet showing symptoms or appearing on a screening. Sometimes subclinical disease is only found because you go searching for it, such as getting bloodwork or diagnostic imaging to look for it. For example, some people with depression say that their depression is better but they still feel tired (without having extreme fatigue). In these cases, a doctor might screen for a thyroid abnormality or low Vitamin D through bloodwork.

Some of the conditions below have both clinical and subclinical presentations. The first six conditions can be screened through laboratory testing. The remaining conditions are a bit more challenging and/or costly to diagnose.

Thyroid abnormality

The US lifetime prevalence of diagnosed thyroid disease is around 4% in men and 15% in women (Dzierlenga et al, 2019). These numbers do not capture all thyroid disease or subclinical thyroid disease. Both elevated and depressed thyroid levels can be associated with major depression, but the prevalence of depression in people with hypothyroidism is higher at 18% (Mohammad et al, 2019) compared to hyperthyroidism at 10% (Bang Bové et al, 2014). Screening bloodwork to assess thyroid function includes:

• TSH

• Free T4

• Free T3

Some common symptoms of low thyroid function (hypothyroidism) include:

• Depression

• Fatigue

• Weight gain

• Intolerance to cold

• Constipation

• Dry, thinning hair

• Dry skin

• Heavy or irregular menses

• Goiter (an enlarged thyroid that might cause your neck to look swollen)

Some common symptoms of elevated thyroid function (hyperthyroidism) include:

• Insomnia

• Weight loss

• Nervousness, irritability or mood instability

• Trouble tolerating heat

• Hand tremors

• Muscle weakness

• Fatigue

• Racing heartbeat

• Frequent bowel movements or diarrhea

• Goiter

The interactions among thyroid hormones are not fully understood. For example, a normal thyroid lab result does not always mean your thyroid function is normal, so it comes as no surprise that there are many different opinions amongst doctors about how to treat thyroid disorders. Some doctors appear very comfortable prescribing the form of thyroid hormone known as T4 but not T3 for low thyroid, despite the finding that a significant percentage of people with low thyroid have low T3.

Some patients have a lack of confidence in their treatment due to inconsistent treatment approaches and/or a lack of success in their treatment. For example, up to 10% of people with low thyroid (hypothyroidism) who are treated with T4 alone do not feel completely better (Wiersinga, 2014). Research on patients who are on T4 shows that about 16% of patients have genetic variations that indicate that they will feel and function better on a combination of T4 and T3 (Panicker et al, 2009).

Another interesting thing to consider is that there is a strategy stretching back decades that shows that adding in thyroid hormone can be effective in helping treatment-resistant depression. Most of the doctors who try this strategy nowadays prescribe T4, but the majority of the research showing that this strategy can be effective involves prescribing T3 (Joffe, 2011). When the efficacy of T3 was compared to T4 in helping treatment-resistant depression, T3 was clearly more effective (Joffe et al, 1990).

Low Vitamin D

The prevalence of low Vitamin D in the US is 46% (Forrest et al, 2011), with higher rates found in northern states and among black people (82%) and Hispanic people (69%). The correlation between low vitamin D levels and depression has been clearly established in the medical literature (Cuomo et al, 2017). Vitamin D helps with calcium absorption, so you can imagine that low Vitamin D levels can be associated with problems related to low calcium. The bloodwork regarding low Vitamin D involves getting a Vitamin D level (Serum 25-Hydroxyvitamin D [25(OH)D]). If you know you have low Vitamin D, you may also want to have your calcium level checked. Common symptoms (which may be subtle) of low Vitamin D include:

• Depression

• Fatigue

• Muscle weakness, aches or cramps

• Bone pain

Most people who have low Vitamin D take over-the-counter (OTC) supplements to bring up their blood level to the normal range, a process that can take months. Prescription-strength Vitamin D is available for people who struggle to absorb OTC Vitamin D. Also, for people who have extremely low Vitamin D levels, their doctors may start them on prescription-strength Vitamin D for a few months and then switch them to OTC Vitamin D to maintain a normal blood level.

Iron deficiency anemia

The likelihood of iron deficiency anemia differs depending on your age and gender. For example, 2% of adult men have iron deficiency while up to 12% of Caucasian women and 20% of black and Hispanic women have it (Killip et al, 2007). Some of the symptoms of the condition include:

• Fatigue, weakness or shortness of breath

• Dizziness

• Headaches

• Chest pain

• Coldness in the hands and feet

• Difficulty concentrating

• Restless legs syndrome

Common bloodwork to screen for iron deficiency anemia includes:

• Complete Blood Count (which looks at RBC, HGB, HCT and MCV as markers of anemia)

• Ferritin level (looks at iron stores in the body)

• Follow-up testing depending on the above tests includes:

  • TIBC (total iron-binding capacity)

  • Fe (serum iron)

  • TfR (serum transferrin receptor)

If you have iron deficiency anemia, it is important to find out why. You may have low iron in your diet, a problem absorbing iron in your digestive tract or some other condition, such as a gastrointestinal bleed. In people over age 65, iron deficiency anemia is due to gastrointestinal cancer in 9% of the cases.

It is best to follow your doctor’s advice when taking OTC iron supplements. In rare cases, you might require an IV infusion of iron. Keep in mind that iron is absorbed better when taken on an empty stomach with vitamin C. Not only will taking iron with Vitamin C help with absorption, it will also help reduce gastrointestinal side effects (such as constipation or black stool) from the iron. Some people have nausea when taking OTC iron and benefit from a slow-release formulation (Slow Fe). A typical supplementation dose for an adult is 325 mg of ferrous sulfate (65 mg of elemental iron) along with 100mg-200 mg of Vitamin C. On a side note, for people with restless legs syndrome, getting their ferritin levels above 75 typically results in an improvement in their symptoms.

Low Vitamin B12

The US prevalence of Vitamin B12 deficiency is 6% in people under age 60 and 20% in people age 60 and above (Langan et al, 2017). There is some disagreement by researchers as to what the cutoff for deficiency should be, which has led some to speculate that the rates of B12 deficiency in the US are greater than most suspect. Symptoms of low Vitamin B12 include:

• Depression or irritability

• Weakness or fatigue

• Vision worsening

• Worsened memory

• Mouth ulcers

• A feeling of “pins and needles” (paraesthesias) of your hands or feet

• Pale yellowing of skin color

• Sore and red tongue (glossitis)

• Staggering or difficulty walking

• Paranoia and delusions (severe cases)

The bloodwork regarding low Vitamin B12 involves getting a serum Vitamin B12 level. In some cases, follow up testing includes obtaining a serum methylmalonic acid level (if looking for pernicious anemia). It is important to work with your doctor in addressing low Vitamin B12 both in getting your oral Vitamin B12 dose correct and starting Vitamin B12 (cyanocobalamin) shots for more rapid recovery.

Autoimmune disorders

According to the National Institutes of Health (NIH), there are more than 80 specific diseases that are categorized as autoimmune disorders, which have a prevalence of over 7% in the US population. Some of the specific diseases are rare, while others are more common, such as type 1 diabetes, multiple sclerosis, lupus and rheumatoid arthritis. The lifetime prevalence of major depression in these more common illnesses is:

• Type 1 diabetes: 28%

• Multiple sclerosis: 19% to 54%

• Lupus: 11% to 47%

• Rheumatoid arthritis: 17% to 39%

You might wonder whether depression is a symptom of autoimmune disorders or if it is instead caused by the stress of having to deal with a disease. That is a worthwhile concern, but it’s more important to know if you have a disease in the first place. There is some basic screening bloodwork that can assess in a nonspecific manner whether or not an autoimmune disorder is likely. If the screening tests are abnormal, more specific testing can be obtained. The antinuclear antibody (ANA) immunofluorescence assay (IFA) is a first-line screening test and considered to be the gold standard because of its high sensitivity. Additional testing might be appropriate to order depending on your other symptoms and the results of the ANA. A positive ANA screen often triggers automatic additional testing, which is more specific for the most common autoimmune diseases.

Infectious disease – HIV and Lyme disease

In the US, about one out of 300 people is positive for HIV (human immunodeficiency virus). Among people with HIV, the lifetime prevalence of depression is 22% to 61%. Late stages of HIV infection, called AIDS (acquired immunodeficiency syndrome), is associated with many other illnesses, including memory loss, depression and other neurologic disorders.

Lyme disease is rare and occurs in one out of 1000 people. The disease can become chronic when people do not get treatment for their initial infection. In one study, 32% of people with chronic Lyme disease were suicidal (Bransfield, 2017). Symptoms of chronic Lyme disease include rash, joint swelling and numerous neurological symptoms, such as fatigue, muscle aches and brain fog. If you believe you have chronic Lyme disease, it is reasonable to meet with your primary care provider but they likely will refer you to an infectious disease specialist for further workup and treatment.

Medication side effects

Some medications are known to cause drug-induced depression (DID). The list of possible medications is long. Rates of depression and the strength of the evidence vary from medication to medication. Medications that have been implicated – even at a low rate – in the emergence of depression or suicidality are:

• Beta blockers (for treating high blood pressure)

• Calcium channel blockers (for treating high blood pressure)

• ACE inhibitors (for treating high blood pressure)

• ARBs (for treating high blood pressure)

• Rimonabant and Taranabant (for treating obesity)

• Finasteride (for treating hair loss or enlarged prostate)

• Isotretinoin (for treating cystic acne)

• Progesterone inserts (for birth control)

• Alpha interferons (for treating various cancers)

• Beta interferons (for treating autoimmune disorders)

• Corticosteroids (for treating many conditions, especially those with inflammation)

• Leukotriene antagonists (for treating allergies and preventing asthma attacks)

• Varenicline (for smoking cessation)

• Anticonvulsants (for treating seizures)

• Antidepressants (for treating depression and anxiety

If you suspect that a medication you are taking is causing depression or suicidal ideation, contact your doctor immediately to address your concern.

Chronic pain

The CDC (Centers for Disease Control and Prevention) reports that studies of the prevalence of chronic pain in the US have a wide range, but most recent reports indicate a prevalence of 20%. It’s no surprise that among people with chronic pain, up to 46% also have major depression (Bair et al, 2003). That’s because chronic pain steals so much from people. Individuals with chronic pain can experience substantial fatigue, frustration, hopelessness and sadness related to their condition. Chronic pain interferes with their relationships, work and life activities. Individuals with inadequately controlled chronic pain are strongly encouraged to work with a pain specialist to gain greater control of their symptoms.

Obstructive sleep apnea

The prevalence of obstructive sleep apnea (OSA) in the US is 22% for men and 17% for women (Franklin et al, 2015). OSA can mimic major depressive disorder as it is associated with extreme fatigue, cognitive dysfunction and low motivation. Its association with depression is likely due both to the lack of restful sleep and the effects of low oxygenation to the brain at night. For people with sleep apnea, the prevalence of major depressive disorder is nearly 18% (Jehan et al, 2017). Common symptoms/signs of obstructive sleep apnea include:

• Depression or irritability

• Excessive daytime sleepiness

• Loud snoring

• Pauses in breathing (waking up suddenly with jerking body movements, often gasping and choking)

• Waking in the morning with a dry mouth or sore throat

• Morning headaches

• Difficulties with memory or poor concentration during the day

• Decreased libido

Obstructive sleep apnea can be diagnosed accurately and treated effectively. It is critical to get treatment for OSA, not only because depression can be related to the condition but also due to other medical risks of untreated OSA, the worst being heart failure and stroke.

Fibromyalgia and chronic fatigue syndrome

Fibromyalgia and chronic fatigue syndrome are difficult to diagnose because they are diagnoses of exclusion, meaning that all other medical illnesses must be ruled out before the diagnosis is made. There can be a strong overlap between the symptoms found in fibromyalgia, chronic fatigue syndrome and other chronic medical illnesses. If a person has a medical condition other than fibromyalgia or chronic fatigue syndrome, is it is imperative to accurately diagnose and treat the other medical condition to change the trajectory of that illness and prevent further decline or premature death. Some people find it very hard to get their primary care provider to take seriously their condition of fibromyalgia or chronic fatigue syndrome, as these can be complicated illnesses to accurately diagnose. Also, limited treatment efficacy has been found for fibromyalgia and chronic fatigue syndrome.

Fibromyalgia

Fibromyalgia is a complex condition with diagnostic criteria that have changed over time. In the past, doctors would screen for tender points or trigger points in specific areas of a person’s body, but newer guidelines do not require the presence of tender points. A diagnosis of fibromyalgia now can be made if a person has more than 3 months of widespread bodily pain with no other medical explanation for the pain. The lifetime prevalence of fibromyalgia in the US is around 2% (Wallit et al, 2015). Fibromyalgia sufferers have a lifetime prevalence of major depression of 65% (Løge-Hagen et al, 2019). Symptoms of fibromyalgia can include:

• Depression or anxiety

• Pain and stiffness all over the body

• Tender points

• Sleep problems

• Fatigue and tiredness

• Brain fog or “Fibro fog” (problems with memory and concentration)

• Headaches (including migraines)

• Digestive problems (bloating, constipation or irritable bowel syndrome)

• Numbness or tingling in hands, arms, legs and feet

• Painful menstrual cramps

Chronic Fatigue Syndrome

Chronic fatigue syndrome is also called myalgic encephalomyelitis. It is not a well-understood disorder. For some sufferers, the condition develops gradually. For others, the disorder begins suddenly, often following a loss (death of a loved one), physical or psychological trauma or flu-like infection. Chronic fatigue syndrome affects women more often than men and its estimated prevalence in the US is 1% (Valdez et al, 2019). People with CFS have a lifetime prevalence of major depression between 46% and 75% (Bram et al, 2018).

The main symptoms of chronic fatigue syndrome are extreme mental and physical tiredness that can't be explained by any underlying medical condition. Chronic fatigue syndrome is a complicated disorder with symptoms including:

• Extreme exhaustion lasting more than 24 hours after physical or mental exercise

• Non-restful or non-refreshing sleep

• Chronic flu-like symptoms

  • Headaches

  • Sore throat or glands

  • Feeling sick or dizzy

  • Muscle and joint pain

• Problems with memory and concentration

Jolynn’s story

“Jolynn” was a 39-year-old woman who had been on the same antidepressant for five years. For the last six months, she felt that her medication was not working as well. Also, even though she been on the medication for years, she was starting to gain weight and feel increasingly bloated. She noticed some other physical symptoms like constipation and feeling cold, but she figured that maybe she was having these symptoms due to getting older.

She met with her primary care physician, who switched her anti-depressant medication, but nothing seemed to improve. She was referred to a psychiatrist, who performed a comprehensive assessment, which included asking about physical symptoms. When she was asked when her last thyroid test was completed, she assumed that it had been done three months ago when she had her annual wellness screening through her workplace. Her psychiatrist obtained a copy of the results and noticed that there was no screening test for her thyroid. Her psychiatrist decided to go ahead and order laboratory testing for her thyroid and found that she had hypothyroidism.

When her psychiatrist asked about other symptoms of hypothyroidism such as hair loss, skin changes, and changes in her menses, she was surprised to realize that she had those symptoms as well. Her psychiatrist spoke with her primary care physician, who decided to start replacement thyroid hormone medication. She was very encouraged when she noticed a gradual improvement in her motivation and energy on a starting dose of thyroid hormone. When her doctor increased the medication a month later, she felt her energy and motivation returning to normal and she was excited that she was finally able to start losing some of the weight that she had gained!

Knowing for certain

Most people want to know if they might have a medical condition causing depressive symptoms but they don’t know where to start. A good starting point is to write down all of the physical symptoms you are noticing and schedule an appointment with your primary care physician. You can bring the above list of possible medical causes of depression with you as you work to determine cost-effective screening approaches. You might find that the depressive symptoms are caused by a medical condition and start treatment for the medical condition. Or, you might rule out medical causes of depression and have the peace of mind to start other treatments for your depression.

For further reading, check out:

• My article “Finding a Good Psychiatrist”

• My article “Your Safety Plan for Suicide Prevention“

• A Guide to Rational Living by Drs. Ellis and Harper (See Len’s Book Review)

• Mind Over Mood, Second Edition: Change How You Feel by Changing the Way You Think by Drs. Dennis, Greenberger and Padesky (See Len’s Book Review)

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