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Depressed But Antidepressants Don’t Work? Adrenal Fatigue or Neurotransmitter Imbalances May Be Responsible.

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Determining the root cause or causes of depression is not an easy matter. Symptoms of depression include persistant feelings of sadness or even despair, difficulty concentrating, impair memory, sleep problems, weight gain or loss, loss of interest or pleasure in previously enjoyable activities, lack of energy, fatigue, being unable to feel adequately rested, anxiety, irritability, suicidal thoughts, slow speech and slow movements, digestive pain, head aches, and other pains.

Many of the psychosocial situations that create depression can also cause neurotransmitter imbalances and adrenal fatigue. Job problems, the illness or death of a loved one, divorce, an abusive spouse, child custody battles, and many other common problems can create the symptoms of depression. But knowing that some or all of that list of symptoms of depression are present does not tell you the underlying cause with any certainty. Yet doctors often simply assume they “know” that since you have a stressful situation that your depressive symptoms must be treatable with an SSRI antidepressant. If only it were that simple!

Why SSRI Antidepressants May Not Work

Having low serotonin levels is often spoken of as being “the cause” of depression, almost as if there is no other possible reason. But that is far from the case. Most of these symptoms of depression listed above also apply to a variety of neurotransmitter imbalances apart serotonin.

If you have been diagnosed with depression and have tried antidepressants and find they are not effective, it is very possible that your symptoms may have nothing to do with low serotonin. But low or high levels of many neurotransmitters can also cause a variety of symptoms similar to low serotonin. Without testing, it is difficult to know the real cause.

High levels of epinepherine (adrenalin) can cause sleep difficulties, anxiety, and problems with attention and concentration. Low levels of epinepherine can cause fatigue, lack of attention and concentration, and weight gain or difficulty losing weight. High and low levels of norephinepherine can have similar effects as high and low levels of epinepherine, but high norepinepherine might also raise blood pressue. The same problems can occur from other out-of-range neurotransmitters including glycine, taurine, GABA, glutamate, PEA, and histamine.

Yet low serotonin is the first thing that comes to mind for most doctors when they hear of somebody with symptoms of depression who has psychosocial reasons for it. And when they think of serotonin, it is like their minds fixate on the big pharma literature message of “SSRIs are the answer to all depression — just keeping trying them until you find one that works for this patient”. Out comes the prescription pad, and probably the first drug that will pop into mind is whatever the latest and greatest SSRI being touted by the big pharma rep who just took the doctor to dinner or golf or the one at the top of the “cost effective” list published by the HMO. It’s a very common mistake to jump the gun like this.

The most common antidepressants today are SSRI (Selective Serotonin Reuptake Inhibitors) that work by modifying the availability and action of the important neurotransmitter serotonin in the brain. But people who are suffering from other neurotransmitters imbalances and/or adrenal fatigue could have all the above symptoms and yet have normal or even high levels of serotonin. That means that many of the most common SSRI antidepressants like Zoloft, Celexa, Lexapro, Paxil, and many other variants are probably not going to do a thing to help you. They could instead just make matters worse, causing troublesome side effects while draining your wallet and misleading you from getting a real cure.

So if you’ve tried various antidepressants and are having no luck, consider getting your adrenal function checked. You should get tested for your cortisol levels four times during the day, at waking or 8am, noon, 4pm, and bedtime or midnight. You should also get your DHEA level tested. Low DHEA can present some of the same symptoms as the low cortisol levels that often come from adrenal fatigue. In fact, the adrenal glands are involved in making both the DHEA and cortisol hormones.


Adrenal Insufficiency

Every one of the above-listed symptoms of depression can also be caused by a condition known as adrenal insufficiency or adrenal fatigue.

Very severe adrenal gland failure can be caused by Addison’s Disease. Most of the time that is caused by an autoimmune reaction that severely injures or destroys the adrenal glands. Adrenal fatigue is generally not as severe in its impact to hormones, but can come close.

Often adrenal fatigue is caused by long-term chronic stress and environmental factors that are similar to those that are traditionally thought to be connected with low serotonin related depression. Damaged adrenal glands often fail to produce enough hormones, particularly cortisol and DHEA (dehydroepiandrosterone). This often causes the same set of symptoms typically associated with low serotonin related depression although the physiological cause is entirely different. Adrenal gland damage can be insidious, taking months or years before the damage is severe enough that the symptoms because intolerable.

Adrenal problems can generally can be detected by testing for cortisol and DHEA levels as those are two of the major hormones produced by the adrenal glands. The adrenal glands sit on top of the kidneys and they pump out a variety of important hormones besides cortisol and DHEA including pregnenolone, progesterone, testosterone, androstenedione, dihydrotestosterone, corticosterone, and aldosterone. If this hormone factory isn’t working well, the impact to the body can be staggering and pervasive and can cause a range of symptoms including every one of the symptoms of depression listed above.

You may have noticed the list of hormones above didn’t include forms of estrogen such as estradiol, estrone, and estriol. Those are derived from androstenedione and testosterone, so a shortage of the hormones produced by the adrenal glands may also impact the various estrogen levels, too.

Also of note is that if you have noticed very rapid weight gain, it is possible that your cortisol levels are too high and you might be suffering from something called Cushing’s syndrome. Many of the symptoms of high cortisol are like those of low cortisol. This make it all the more important to run tests before trying a treatment for an illness that may be related to imbalanced cortisol.

Differentiating Between Conditions With Depression Symptoms

Sadness, anxiety, insomnia, low energy, extreme fatigue, chronic pain, and painful intestinal problems are also among the more common symptoms of the health conditions fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, Lyme disease, multiple sclerosis, sleep apnea, hypothyroidism, and probably many others. There is research that shows unbalanced hormones, particularly the adrenals cortisol and DHEA and the thyroid hormones, are often found in people diagnosed with any of these conditions.

One person can have multiple interrelated health conditions with overlapping symptoms. This makes it particularly difficult to figure out what is wrong. If you are suffering from symptoms that match multiple conditions then you are going to need to do some testing to narrow down the most likely root cause or causes and then start working on correcting them one or two at a time.

A common thread to the findings of people with any of these types of disorders is that they often see their test results look OK when they feel OK and look bad when they feel bad. So you may need to test on different days, with lab slips or test kits ready to go based upon how you are feeling. Often times, if you can see a pattern that affects how you feel then that is a hint to the underlying conditions. For instance, if you feel far worse at night and morning and better in the afternoon or evening, it may have something to do with a hormone that varies by the time of day. Cortisol is particularly likely to vary by time of day, but other hormones may also vary in this fashion.

Why is there so many commonality of symptoms across so many differently named conditions? One obvious reason is that the body’s symptoms are heavily interconnected, thus making problems in one area likely to cause problems in another particularly when it involves something with actions throughout the body like hormones. Another obvious reason is that many of these conditions worsen inflammatory reactions and those reactions when chronic tend to produce lasting pain and cause the body’s repair mechanisms to go haywire.

Distinguishing Between Adrenal Fatigue and Hypothyroidism

It is often very difficult to distinguish between low thyroid function and adrenal fatigue, especially when both are present at once. Dr. Lam’s website contains a chart comparing the characteristics of adrenal fatigue and hypothyroidism [3] which is very helpful. You’ll notice there is a lot of commonality of symptoms.

It is entirely possible to suffer adrenal fatigue and hypothyroid problems simultaneously. Doctors with expertise in treating both have found that trying to fix the hypothyroid problem without fixing the adrenal fatigue problem is possibly going to worsen the overall health condition. The general rule is that poorly functioning adrenals are likely to cause the thyroid to function poorly, also.

As a result, doctors who have expertise on treating both conditions tend to treat the adrenal fatigue problem first and foremost and then monitor the thyroid problems to see how they change. They may wait to directly treat any remaining hypothyroid condition until after determining that adrenal function has improved measurably.

On the web page with the chart I mentioned earlier, Dr. Lam offers a good explanation for why treating hypothyroidism without treating adrenal fatigue can cause worse health problems. The essence of the explanation hinges on the observation that reduced thyroid hormone levels are often the body’s way of protecting itself from excessive energy demands by ramping down metabolic rates. If you force the thyroid function to increase by adding more thyroid hormones but the adrenal glands are damaged, it can put much more stress on the adrenals and cause them to fail even further.

Two really easy measurements that can help distinguish between the conditions are body temperature and blood pressure. Low body temperature is often present in both conditions, but with adrenal fatigue it is more variable. You’ll need to measure it a few times per day, try to base it upon consistent times after waking and measure it apart from meals or physical activity. Measure it a couple of hours after waking, then four hours after that, then another four hours later, and again just before bedtime. For instance, if you wake at 8am, then try 10am, 2pm, and 6pm (just before dinner), and just before going to sleep at 10pm. If you see a lot of variability in temperature from the average, it is more likely you have an adrenal fatigue problem.

Take your blood pressure lying down or sitting down and then again immediately after standing up. Healthy people or those with early adrenal fatigue are likely to see their systolic blood pressure increase a bit when they stand to help maintain the overall diastolic blood pressure. People who are suffering from high cortisol levels will often have higher blood pressure than before their cortisol levels rose from stress. Those with late stage adrenal fatigue and low cortisol will see their systolic blood pressure drop, sometimes by 5 or even 10 mmHg after standing. This is because the adrenal glands cannot pump out enough hormones to help the body quickly regulate blood pressure. Often these people will experience dizziness from standing, too. There of course could be other reasons for these symptoms, but they are a solid clue suggesting that you need some more definitive testing to better understand your adrenal function.

Ordering Cortisol, DHEA, and Neurotransmitter Tests

It is often difficult to get mainstream doctors to order appropriate tests. Psychiatrists in particular often dole out SSRI prescriptions one after another, trying every variant under the sun, without it working and without running any tests to see what really is wrong. As a result, you may need to see an integrative medical practitioner or take matters into your own hands and order your own tests. Ordering your own tests can often save you a great deal of money. You can take the results to a doctor after reviewing them yourself to get additional help.

Strangely enough, you may actually need to explain some of the test results to many mainstream doctors who are not familiar with using them. Be prepared to do some reading to understand them. If you’re stumped, you can leave a comment on this message and I’ll help you try to make sense of your results. For privacy reasons, please don’t use your real name.

For the best understanding of your cortisol levels, you really need to run tests at four times of the day. Probably the most convenient way to do this is via saliva tests. Unfortunately, some people have a lot of trouble making enough saliva so you may need to pick a day that you can stay at home and relax while you do collect test samples every few hours.

A few good sources for cortisol saliva tests you can order on your own include:

ZRT Labs Diurnal (4 times) Cortisol saliva test kit [4]

ZRT Labs Cortisol and DHEA tests [5]

PrePaidLabs / Labcorp Cortisol Saliva Diurnal (4 times) test set [6]

If you haven’t had any other hormone testing recently, you may want to pick a set of tests that include testosterone and estrogen, also, as imbalances in those hormones are particularly common in aging men. Such tests that can be done at home via saliva collection include:

ZRT Labs Saliva Tests (Estradiol, Testosterone, DHEA-Sulfate, Cortisol 4 times) and Blood Spot (TSH, free T3, free T4, and TPO thyroid tests plus vitamin D, 25-OH test [7]

Adrenal Hormones Saliva Testing Kit from ZRT labs (Dirunal Cortisol and DHEA-S) [8]

If saliva testing or blood spot testing is not going to work for you because you can’t make enough saliva or have difficulty pricking yourself to get a blood drop, you could use blood draw tests instead.

Life Extension / Labcorp Dehydroepiandrosterone Sulfate (DHEA-S) Blood Test [9]

You could use an AM/PM cortisol blood test to get a better idea than you would get from just one cortisol measurement per day. This may be enough for some people, but four tests in a day is better.

Life Extension / Labcorp Cortisol AM/PM Blood Test [10]

Life Extension’s Male Weight Loss Panel Blood Test [11] and Female Weight Loss Panel Blood Test [12] cover pretty much everything listed above other than the cortisol and TPO (a thyroid antibody test), plus they also include a number of other measurements that are helpful for evaluating overall health status that are not included in the saliva and blood spot tests listed above. Those include C-Reactive Protein, a marker for inflammatory conditions, and homocysteine which is a marker for cardiovascular and kidney diseases.

For neurotransmitter testing, one option is to order a NeuroRelief NeuroScan urine test kit [13] online. It includes a consultation with a licensed nurse practictioner regarding your results. A more comprehensive test covering the same neurotransmitters plus saliva DHEA and cortisol tests is the NeuroAdrenal Profile test kit [14]. These tests from NeuroScience [15] are also often available from doctors and clinics, but they often cost more.

Please see my previous article 40% of US Population May Have Hypothyroidism [16] for more discussion on thyroid testing as many of the symptoms of hypothyroidism are similar to adrenal fatigue and neurotransmitter imbalances. It is actually very common to have low T3 and T4 thyroid hormones in combination with adrenal gland problems so testing for this is a good step to take.

Related Books

Further Reading

Chronic Stress Kills: High Cortisol Levels Damage the Brain, May Lead to Shorter Life and Neurodegenerative Diseases Such As Alzheimer’s and Parkinson’s [17]

Cortisol Imbalances May Cause Weight Gain, Depression, Anxiety, and Insomnia [18]

Low Cortisol, Low CoQ10, and Mitochondrial Dysfunction Often Found in Adrenal Fatigue, Chronic Fatigue Syndrome, Fibromyalgia, and Myalgic Encephalomyelitis Patients [19]

Melatonin Helps Improve Sleep and Boost Immune System, Little Sign of Toxicity Even At Very High Doses [20]

40% of US Population May Have Hypothyroidism [16]

Meaning and Interpretation of Medical Tests [21]

Adrenal Disease [22]

Adrenal Fatigue: Do You Have It? [23]

Adrenal Fatigue and How to Beat It [24]

Ovarian-Adrenal-Thyroid (OAT) Axis Imbalance [25]


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