Dexamethasone-suppression test: Neurochemical Tests for Depression

"Dexamethasone-suppression test" (DST) helps to illuminate neuroendocrine abnormalities. Many depressive patients (about 50%) produce abnormally large amount of cortisol, although it is not clear whether this is a cause or an effect of the illness. These patients fail to suppress the hypothalamic-pituitary-adrenal axis when taking dexamethasone, and DST test is abnormal. This test can be useful in clarifying the diagnosis between schizophrenia and a depression with many psychotic features. This test does seem to suggest that part of the cause of the illness may reside in the hypothalamus or the higher brain centers that govern it.

The DST was the first, and is to date the most studied, putative biological marker in research on depressive disorders. In 1968 Carroll showed that while depressed, patients fail to suppress plasma cortisol. This led Carroll to claim that a positive DST is a specific laboratory test for melancholia or severe forms of depression.

The sensitivity of the DST (rate of a positive outcome, or nonsuppression of cortisol) in major depression is modest (about 40%-50%) but is higher (about 60%-70%) in very severe, especially psychotic, affective disorders, including major depression with psychotic as well as melancholic features, mania, and schizoaffective disorder. The specificity (true negative outcome) of the DST in normal control subjects is above 90%, but it varies from less than 70% to more than 90% in psychiatric conditions that often need to be separated from major affective disorders. In dementia the specificity is even lower.

In addition, a number of medical conditions, including severe weight loss and use of alcohol and certain other drugs (barbiturates, anticonvulsants, and others), can produce false positive results. Positive initial DST status in major depression does not add significantly to the likelihood of antidepressant response, and a negative test is not an indication for withholding antidepressant treatment. Some recent data suggest that DST-positive depressions (cortisol nonsuppression) are less likely than DST-negative cases (cortisol suppression) to respond to a placebo. If this is confirmed, it would increase the real magnitude of the difference in treatment response between DST-positive and DST-negative depressed patients. Failure to convert to normal suppression of cortisol with apparent recovery from depression suggests an increased risk for relapse into depression or suicidal behavior. Although the clinical utility of the DST as currently understood is limited, in certain specific situations its thoughtful use may aid clinical decision making. The association of an abnormal test result with major affective disorders encourages continued research on the DST.


The test is done by giving the patient with suspected depressive illness a once-off low dose (1 mg) of dexamethasone (a steroid medication) about 11 pm one night, and taking the blood for testing late the next afternoon or evening. It is recommended to take the pill with milk or an antacid to help prevent an upset stomach or heartburn. Remember that you will not be able to eat or drink anything for 10 to 12 hours before the morning blood test.

Note that some medicines may change the results of this test. Be sure to tell your doctor about all the nonprescription and prescription medicines you take. You may be asked to stop taking some medicines (such as birth control pills, aspirin, morphine, methadone, lithium, monoamine oxidase inhibitors [MAOIs], and diuretics) for 24 to 48 hours before your blood is drawn. Talk to your doctor about any concerns you have about the need for the test, its risks, how it will be done, or what the results will mean.

The level of cortisol (cortisone) in the blood is measured. The person without depression responds to the presence of dexamethasone in their body by drastically reducing (suppressing) the amount of cortisol in their blood automatically, so their blood test shows low levels of cortisol. However, in about 50 - 60% of people with depressive illness, their body ignores the presence of dexamethasone, and this blood test shows HIGH levels of cortisol the next day. The failure to suppress cortisol production despite dexamethasone confirms the diagnosis of depressive illness. Normal suppression gives levels about 30-40 nmol/l. Levels above 140 after dexamethasone are normally regarded as a positive test indicative of depressive illness, in the absence of severe physical illness, enzyme inducing medications, high alcohol intake or hormonal illnesses.

That is still not clear why there are two different types of depressive illness, namely one type which can be measured by this test, and another type (with identical clinical symptoms) which cannot be measured in the laboratory. Nor that is not clear why the DST is abnormal in some depressed patients while they are ill, returning to normal when they recover.

Your own physician or psychiatrist can discuss the benefits and limitations of this test in your particular case.  An abnormal DST is not enough evidence alone to diagnose depressive illness (physically ill, malnourished and elderly people have abnormal DST’s in about 20% of cases).  However, in people who are told their symptoms are due to unhappiness or due to unresolved emotional hang-ups, an abnormal DST is very good reason to suggest they have gone on to develop depressive illness, as a result of the stresses involved.

It must also be remembered that 50% of people with depressive illness still DO have the illness, although they respond normally on this test, just as some people have back pain without any abnormality showing on their X-rays.

What Affects the Test?

Reasons you may not be able to have the test or why the results may not be helpful include:
  • Pregnancy or extreme obesity.
  • Severe weight loss, dehydration, or acute alcohol withdrawal.
  • Severe injury.
  • Diabetes.
  • You take medicines, such as barbiturates, phenytoin (Dilantin), birth control pills, aspirin, morphine, methadone, lithium, monoamine oxidase inhibitors (MAOIs), spironolactone (Aldactone), and diuretics.

Some people may quickly process (metabolize) the dose of dexamethasone. In these people, cortisol levels will not drop unless a higher dose of the medicine is given.

Sources and Additional Information:


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