When Depression Doesn’t Respond to Standard Treatments, There’s Often a Biochemical Reason

One of the biggest frustrations I see is people who have spent years trying one antidepressant after another, changing doses, adding supplements, or trying different therapies—yet no one has ever stopped to ask a simple question:

“Why isn’t this working?”

That question is what first attracted me to the work of Dr. William J. Walsh.

After studying more than 30,000 people with clinical depression and analysing over 250,000 laboratory tests, Dr. Walsh and his team discovered something remarkable: depression isn’t a single biochemical condition. Instead, many people fit into one of several distinct biochemical patterns—or biotypes—each with its own characteristic symptoms, laboratory findings, and nutritional treatment approach.

As a practitioner personally trained by Dr. Walsh, I use this model because it provides an exceptionally valuable starting point for understanding what’s happening beneath the surface.

But here’s something that’s equally important to understand.

The Walsh Protocol is the beginning of the investigation—not the end of it.

Two people may both be diagnosed with depression.

One may respond extremely well to folate.

Another may actually become worse.

One person’s symptoms may be driven by undermethylation.

Another’s may be caused by copper overload, pyrrole disorder, chronic inflammation, or an entirely different biochemical process.

From the outside, they appear to have the same condition.

Underneath, they may be following completely different biochemical pathways.

That’s why I don’t believe in treating a diagnosis.

I believe in understanding the person behind the diagnosis.

Once we’ve identified your likely biotype, we don’t simply match it to a supplement list and hope for the best. Instead, we build a personalised treatment plan around your entire health picture.

That may include investigating gut function, inflammation, thyroid health, hormonal balance, nutritional deficiencies, amino acid status, organic acid markers, lifestyle factors, sleep quality, stress physiology, previous trauma, and other functional pathology findings that may be contributing to your symptoms.

Sometimes the Walsh biotype explains most of the picture.

Sometimes it explains only part of it.

Our job is to uncover the remaining pieces.

Rather than relying on trial and error, we work systematically—asking better questions, performing targeted investigations where appropriate, and continually refining your treatment plan as new information emerges.

Most people never require extensive genetic testing.

However, if we’ve been working together for several months and your progress has plateaued—or we’re simply not seeing the improvements we’d reasonably expect—then broader genetic testing can sometimes provide the missing piece of the puzzle.

Rather than seeing that as a dead end, I see it as another opportunity to understand your biology more deeply and further personalise your care.

This staged approach allows us to investigate intelligently, rather than ordering every possible test at the beginning. If you’d like to learn more about how we decide which investigations to perform, and when, you can also explore our Pathology Testing Packages & Pathways, where I explain the different testing options and how they fit into your individual recovery journey. (Link to Pathology Testing Packages & Pathways.)

💡 Same diagnosis. Different biochemistry. Different treatment. That’s why we test—not guess.