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Day # 27: Medical Workup for Depression

Welcome back to our current theme of depressive disorders. Today we will round out some additional clinical pearls to include what medical work-up could be pursued in a patient with new depressive symptoms.

Today's Content Level: Intermediate


•If you remember back to the psychotic disorders theme you may remember that we stressed the importance of medical workup for psychosis before attributing it to a psychiatric diagnosis. We discussed the importance of determining if these symptoms are caused primarily by a medical or neurological condition or induced by medications or other substances.

•Medical workup for depressive disorders is often less revealing as compared to psychotic disorders, and the assessment and diagnosis of depressive disorders are based on clinical interviews and examinations. However, focused tests are indicated in some circumstances and warranted to rule out other medical conditions that can cause or contribute to depressive disorders.

•In previous lessons (day 22, 24, and 25) we discussed the clinical features and symptoms of depression and how to evaluate this in a clinical interview. Today's discussion will focus on the medical workup in specific patient populations.

•Clinical interview -> should address all current and significant past general medical illness, medications, substance use, review of systems, and family medical and psychiatric history in order to identify potential medical contributors of the depressive condition.

•Review the vital signs. If they are normal they don't tell you much, but if abnormal this can be the first clue that something other than purely psychiatric is going on.

•Physical exam -> in most cases a general physical examination is not likely to reveal an underlying cause of depression. It is still recommended for new onset depression, severe depression, treatment resistant depression, and in those who have or are at risk for chronic medical conditions. A more detailed physical exam should be pursued if indicated based on the patient's history and review of systems.

Labs and Imaging

•The utility of screening laboratory tests for patients with depression has not been consistently demonstrated. Similar to the physical exam comments above it is still often recommended in certain scenarios.

Labs are commonly performed in the following scenarios: new onset depression, severe depression, treatment-resistant depression, and in patients who have or are at risk for chronic medical conditions. 1

•It can be particularly important if the patient has no known psychosocial content or precipitant for the new depressive episode or if severely depressed patients have melancholic or psychotic features.

Possible laboratory tests include:

•CBC (complete blood count): screen for underlying anemia and infection which can contribute to low mood and energy.

•CMP (complete metabolic): rule out electrolyte disturbances, glucose, renal failure (creatinine and BUN), and liver function panel (alcohol, fatty liver, hepatitis).

•UA (Urinalysis) and Urine toxicology: screen for alcoholism and drugs of abuse.

•TSH (thyroid stimulating hormone): hypothyroidism can classically present as depressed mood, decreased energy, appetite change, and weight gain.

•Beta hCG (pregnancy test): affects treatment decisions! This will be discussed in later lessons in detail.

•FTA-ABS (fluorescent treponemal antibody absorption) or RPR (rapid plasma reagin): testing for syphilis. If not treated, 30% of patients may develop tertiary syphilis, where neurosyphilis is included. Neurosyphilis can present a variety of psychiatry symptoms, including mania, depression, psychosis and dementia.

•HIV: the classical gold standard used to be ELISA and confirmed with western blot (beyond the scope of this article). Now commonly diagnosed with an HIV viral load. Three technologies measure HIV viral load in the blood: reverse transcription polymerase chain reaction (RT-PCR), branched DNA (bDNA) and nucleic acid sequence-based amplification assay (NASBA). Can present as a variety of psychiatric symptoms.

•Other diagnostic tests that are less commonly included in standard order sets, but should still be considered in certain patients. These additional tests should be pursued as guided by the medical history, review of symptoms, and physical examination. Consider the following:

•Vitamin B12/Folate: Both low folate and low vitamin B12 status have been found in studies of depressed patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. 2

•Vitamin D: Low vitamin D levels have also been associated with depression as well as other psychiatric conditions and some studies suggest modest improvements in mood after supplementation in combination with other standard of care treatments. Also, patients with low vitamin D levels may not respond to treatments until corrected. 3

•Iron: Low iron levels, even if not anemic, is correlated to depressed mood. 4

Endocrine and Autoimmune: In addition to thyroid abnormalities discussed above there are other less common endocrine disorders that can lead to depression and other psychiatric symptoms. Only screen for these if other warnings signs in the patient. Examples include but not limited to adrenal insufficiency, lupus, sjogrens, celiac disease, multiple sclerosis, etc...

•Brain CT or MRI (computed tomography or magnetic resonance imaging): these studies are typically reserved for patients who's presentation and history suggests an increased likelihood of structural brain disease such as those with focal neurologic signs on physical exam or persistent cognitive impairment. It also may be reasonable to obtain in geriatric patients with new onset depression. 5


Good work today. I hope this was a helpful discussion on some of the testing available for the potential medical causes of depression. We are now at the point that we can start discussing the treatment options for depressive disorders. In the coming days we will discuss nonpharm options (TMS, ECT, light therapy, etc.), psychotherapy, and pharmacotherapy. See you then!

Resources today include:

The articles linked in the body of the article

UpToDate article

See our full list of book recommendations

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