Clinical Pearls - Getting the Most Out of Your Neurotransmitter Test

Posted by Ben White on March 26, 2019

By Dr. Kate Placzek, ZRT Laboratory

As with any functional test that measures physiological function, the challenge lies in the interpretation of subclinical levels of measured parameters. However, it is within those subclinical levels that the neurotransmitter test becomes a powerful tool to identify what is contributing to a specific patient’s health issues and how to map toward a successful outcome based on an individual treatment plan.

Learning how to use a new test can be overwhelming, especially when it goes back to neurology which you might not have thought of since medical school. To assist health care providers in approaching neurotransmitter testing as a functional assessment, ZRT has outlined a series of key concepts below.

Our Neurotransmitter & Dried Urine Hormone Test measures dopamine, serotonin, norepinephrine, epinephrine, GABA, glutamate and PEA alongside urine hormones from a simple at-home 4-time-point dried urine collection — with specialist interpretation included.

Fundamentals of Neurotransmitter Interpretation

1. Patterns Are Just as Important as Numbers

It is important to look at the relative levels of neurotransmitters and their relationships with one another. Patterns are just as important, if not more important, than the numbers themselves. For example, a low serotonin with a high 5-HIAA can suggest sluggish MAO-A activity; GABA and glutamate should balance each other; and serotonin and dopamine should both increase or decrease together.

2. Treatment Considerations for Generally Low Neurotransmitter Levels

With generally low-normal or low neurotransmitter results, treatment considerations include precursor amino acid supplementation and cofactor support such as B vitamins, magnesium, zinc, vitamin C and folate.

3. Treatment Considerations for Generally Elevated Neurotransmitter Levels

Treatment strategies should focus on reducing potentially neurotoxic excitatory damage with antioxidants, anti-inflammatory support and neuroprotective therapies — including omega-3 fatty acids, glutathione and N-acetyl cysteine.

4. Devising the Treatment Plan: Inhibitory Before Excitatory

Address inhibitory neurotransmitter support first (for example — 5-HTP, GABA) and then excitatory support (for example — tyrosine, glutamine), otherwise undesirable side effects such as anxiety and agitation may arise. It is typically safe to introduce excitatory support after approximately a week of inhibitory support.

7 Clinical Pearls for Neurotransmitter Testing

1. Low Serotonin with SSRI Therapy

Low urinary serotonin levels are not uncommon in patients on prolonged SSRI use. Over time, SSRIs deplete serotonin from platelets, which could be reflected in the low urinary serotonin result. This is commonly why SSRI treatments will require increasing dosages or stop working over time.

2. Unexpectedly High Serotonin Levels

High serotonin in urine could result from many conditions including food allergies, post-infectious IBS, low vitamin D levels, and use of medications or supplements geared to boost serotonin, such as 5-HTP. The GI tract makes a lot of serotonin when GI inflammation is triggered.

3. PEA Is the Only Neurotransmitter That Crosses the Blood-Brain Barrier Freely and Bidirectionally

Low PEA in urine serves as a recognised biomarker in ADHD. ADHD patients that respond well to treatment typically show marked increases in urinary PEA levels. On the flip side, high PEA is associated with anxiety. High PEA can be addressed by supplementing with SAMe, vitamin B2, copper with zinc, or nutritional lithium.

4. GABA Does Not Need to Cross the Blood-Brain Barrier to Exert Calming Effects

The literature has been inconsistent regarding whether GABA crosses the blood-brain barrier when taken as a supplement. However, since GABA taken as a supplement can be very effective in relieving symptoms of anxiety, this begs the question of its mechanism of action. Recent animal studies shed light on peripheral mechanisms of GABA action — specifically, within the adrenal glands, GABA regulates epinephrine release to make sure the anxiety-provoking “fight or flight” response is not overdone. Therefore, when interpreting a neurotransmitter report, determining the relationship between GABA levels and norepinephrine/epinephrine levels is important. With low GABA, it may be that much more challenging to bring down the sympathetic/adrenal overdrive.

5. Urinary Norepinephrine Is a Product of the Sympathetic Nervous System

Most urinary norepinephrine originates from the sympathetic nerve endings, giving us an idea of how the peripheral nerves are firing. Abnormal norepinephrine results could be addressed by introducing herbal nervines (e.g., Melissa officinalis, Passiflora incarnata) and biofeedback in the treatment protocol.

6. Epinephrine Is Adrenal in Origin

Urinary epinephrine measured by the test is mostly adrenal in origin. Treatment typically involves adrenal adaptogens and lifestyle interventions to reduce stress. Our Adrenal Function Saliva Test Kit (LCMS) measures cortisol at four time points across the day alongside DHEA-S — providing a clear picture of HPA axis function that complements neurotransmitter results when adrenal overdrive is suspected.

7. The Utility of a Diurnal Norepinephrine and Epinephrine Assessment

Sometimes when patients report being under a lot of stress and self-report moderate to severe anxiety, sleep disturbances and irritability, their average urinary norepinephrine and epinephrine levels fall within the normal range. This seeming discrepancy in symptoms and test results could be addressed by running a distribution pattern at 4 time points during the day to see if these catecholamines are following a normal diurnal rhythm.

Our All Day Cortisol Test (4-Point LCMS) captures the full diurnal cortisol and DHEA-S rhythm across the day — helping to identify alterations from a normal predictable circadian pattern and establish a better-tailored treatment plan, supporting when levels are low and suppressing when levels are high.

Conclusion

It takes experience and really knowing and integrating the subjective and objective aspects of a case to achieve a successful interpretation of neurotransmitter results. Learning to “speak the language” is the first step in incorporating the neurotransmitter test into everyday practice. As with any language, the initial building blocks are key to becoming fluent.

Originally by Dr. Kate Placzek, ZRT Laboratory. Reproduced with permission. Last reviewed: May 2026.

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