【For Those in Treatment】Why Antidepressants May Not Work, 5 Ways Eating Habits Disrupt Brain Chemistry, and the Diet and Fasting That Can Help Restore Balance

“I’m taking antidepressants, but I don’t feel any better.” “I’ve been in treatment for years, and my depression isn’t improving.” Have you been through something like this?

In fact, many people for whom antidepressants don’t work well have “eating habit problems” hiding in the background.

Your everyday diet may be directly disrupting the balance of neurotransmitters in your brain (such as serotonin, dopamine, and GABA) and canceling out the effects of your medication.

This is a field being researched rapidly in a new area of medicine called “Nutritional Psychiatry.”

“What you eat and your mental state are connected.” Learning this fact may be the breakthrough for depression that just won’t lift.

In this article, I’ll explain the science behind how all-day grazing (the habit of eating all day long) disrupts your brain chemistry, and how fasting and better eating can help you regain your mental health.

Please note: never reduce or stop your antidepressants on your own, and always make changes to your diet while consulting your doctor.

Why Aren’t Your Antidepressants Working? Possible Reasons and the Link to Eating Habits

The first thing to know is that antidepressants aren’t the kind of medication that lifts your mood the same day you take them.

Generally, antidepressants are said to take effect gradually over several weeks.

Even if you feel they “aren’t working” one or two weeks after starting, they may still be on their way to taking effect.

On the other hand, if there’s little improvement after using an adequate dose of an antidepressant for 6 to 8 weeks or longer, it may be called “treatment-resistant depression.”

When you feel your antidepressants aren’t working, the main possible reasons are as follows.

A 2023 study reported that young adult patients who don’t respond to antidepressants have a higher rate of later being diagnosed with bipolar disorder.

In other words, the very feeling that “it isn’t working” is an important clue for reviewing the diagnosis and treatment plan.

Physical illnesses, such as an underactive thyroid or anemia, can also cause depression-like “sluggishness” and “low energy.”

If you’re concerned, having your physical condition checked with blood tests and the like is one option.

Depending on your situation, your doctor will consider options such as increasing the dose, adding another medication, switching to a new one, or combining treatment with psychotherapy.

That’s exactly why the most important thing is not to stop your medication on your own because “it isn’t working,” but to tell your doctor honestly that you feel it isn’t working well.

Be careful: stopping antidepressants suddenly can cause withdrawal symptoms such as dizziness, nausea, and anxiety, or bring your symptoms back.

Your Gut and Diet Are the “Soil” That Grows the Crops

With that in mind, the reason this article focuses on is the last one: “eating habits.”

If you compare medication to “fertilizer” spread on a field, your gut and diet are like the “soil” that grows the crops.

No matter how good the fertilizer is, crops won’t grow well if the soil is poor or rough.

Improving the soil while firmly continuing your medical treatment is an important step for anyone who feels their medication isn’t working well.

The Brain’s Neurotransmitters Are Made From “Your Gut and Your Diet”

Much of depression, anxiety, and low energy comes from an imbalance of neurotransmitters in the brain.

Neurotransmitters are the “messengers in the brain” that nerve cells use to exchange information with one another.

If there aren’t enough messengers, or the receiving side has become dull, signals like “this is fun” or “I feel motivated” won’t get through properly.

The four main ones are as follows.

The key point is that the precursors (raw materials) of these neurotransmitters are all nutrients you take in from food.

For example, serotonin is made from an amino acid called tryptophan, found in meat, fish, eggs, soy, and other foods.

If the raw materials don’t arrive, the factory (your brain and gut) can’t make the product (neurotransmitters), no matter how hard it works.

What’s more, the process of assembling the raw materials into the product requires nutrients like iron and vitamin B6 as “tools.”

Even if you get enough protein, the work won’t go smoothly if you’re short on the vitamins and minerals that serve as tools.

Be careful: the more you tend to make do with “just staples” or “just snacks” for your meals, the more likely you are to be short on both materials and tools.

On top of that, over 90% of serotonin is produced in the gut, and it affects mood regulation in the brain through the gut-brain axis.

The gut-brain axis is a system, like a “dedicated phone line,” through which your gut and brain constantly stay in touch via nerves, hormones, and immune substances.

When your gut environment is disrupted, serotonin production in the gut drops, and this is thought to affect your mood as well through the gut-brain axis.

Experiences like getting a stomachache when you’re nervous, or feeling down when your stomach is upset, could be called proof that this line is connected.

Many antidepressants are drugs that help messengers such as serotonin work more easily in the brain.

But if the raw materials for those messengers, and the environment for making them, aren’t in place to begin with, the medication may not be able to work to its full potential.

Think of improving your gut and diet as “laying the foundation” that supports how your medication works.

5 Ways All-Day Grazing Throws Your Brain Chemistry Off Balance

Here I’ll explain how “all-day grazing,” in other words, the habit of always eating something, disrupts the chemical balance of your brain.

① Blood Sugar Spikes Create Dopamine Dependence

Every time you eat refined carbs, dopamine is released in a sudden burst.

As this repeats, your dopamine receptors become less sensitive, and “dopamine dependence” forms, in which you need more and more carbs to get the same satisfaction.

It’s similar to how, if you keep listening to loud sounds, your ears get used to them and you can’t hear anything unless it’s even louder.

② Disrupted Gut Flora Lowers Serotonin Production

The modern diet, high in processed foods, sugar, and refined fats, disrupts your gut flora.

When good bacteria decrease, serotonin production in the gut drops, leading to chronic low mood, anxiety, and sleep problems.

③ Chronic Inflammation Causes Neuroinflammation

The chronic inflammation caused by overeating spreads to the brain as well.

Chronic inflammation refers to a state in which something like a small fire keeps smoldering inside your body.

Recent depression research has confirmed that many people with depression show high levels of inflammatory markers (IL-6, CRP), and the concept of “inflammatory depression” has also been proposed.

④ Nutrient Deficiencies Leave Neurotransmitters Short of Raw Materials

A diet heavy in processed foods and light on vegetables, fish, and fermented foods lacks the nutrients needed to make neurotransmitters.

Nutrients that are especially likely to run short include magnesium, zinc, iron, vitamin D, vitamin B12, and omega-3 fatty acids.

“Hidden malnutrition,” in which your stomach is full but your brain is undernourished, is by no means rare.

⑤ Blood Sugar Swings Cause Excess Cortisol

When blood sugar spikes and crashes repeat, cortisol (the stress hormone) is released frequently.

Chronically high cortisol is known to be strongly linked to depression and anxiety, and to cause shrinkage of the hippocampus (the brain region involved in memory and mood regulation).

A key feature is that these five mechanisms don’t happen separately; they affect one another and create a vicious cycle.

Many people will recognize the pattern: when you feel down, you reach for something sweet, and then blood sugar swings and gut disruption make you feel even lower.

Diet and Fasting Approaches to Balance Your Brain Chemistry

Here are some concrete approaches to balancing your brain chemistry through diet and fasting.

The Positive Effects of Fasting on Brain Chemistry

BDNF is also called “the brain’s fertilizer”; it’s like a plant food that helps the plants called nerve cells grow strong.

When you create time without food through fasting, your gut gets a rest and your blood sugar waves calm down, which makes it easier to create a settled environment for your brain.

Precautions When Fasting During Depression Treatment

However, you need to be especially careful about how you approach fasting while you’re being treated for depression.

If your appetite has dropped and you’re losing weight, if you have a history of eating disorders, or if skipping meals makes your mood or dizziness worse, please don’t fast.

Even if you do start, it’s safer to begin not with 16 hours right away, but by cutting out late-night snacks and leaving a gap of about 12 hours.

Some medications can easily irritate your stomach when taken on an empty stomach, so check with your doctor or pharmacist about the timing of your medication and your meals.

The 7 Best Foods to Heal Your Brain

The key is not to eat large amounts of any one food, but to work small amounts into your everyday meals.

For example, natto and eggs in the morning, a salmon or mackerel set meal at lunch, and walnuts and green tea as a snack: an approach like that is easy to keep up.

If you’d like to learn more about how fasting affects the brain, also see “【What Research Shows】How Does Fasting Affect the Brain? How BDNF and Ketones Work, Memory, Dementia Prevention, and Precautions.”

The Latest Findings From “Nutritional Psychiatry”: How Diet Changes Your Mental State

“Nutritional Psychiatry” is a field of medicine that has developed rapidly since the 2010s.

Diet used to be thought of as something for “physical health,” but it’s become clear that it’s also deeply connected to mental health.

In the “SMILES trial,” published in BMC Medicine in 2017, people with depression followed a Mediterranean-style dietary intervention (centered on fish, vegetables, legumes, and olive oil) for 12 weeks.

As a result, it was reported that 32.3% of the dietary intervention group reached remission (compared with 8.0% of the control group).

Their MADRS scores, a measure of depression symptoms, also improved by an average of 7.1 points more than the control group.

This trial was conducted in Australia, and participants kept up their usual treatment, such as medication and psychotherapy, while adding dietary improvements on top.

In other words, the important point is that the difference came not from “stopping medication and switching to diet,” but from “improving diet while continuing treatment”.

Tips for Bringing the Mediterranean Diet to the Japanese Table

The Mediterranean diet is a way of eating centered on fish, vegetables, fruit, legumes, nuts, whole grains, and olive oil, while cutting back on processed meats and sweets.

In fact, it has a lot in common with traditional Japanese food such as grilled fish, natto, miso soup, ohitashi (blanched greens in a light soy-based broth), and brown rice.

On the flip side, cutting back on sweet pastries, soft drinks, chips and other snacks, and fast food is just as important.

A Word of Caution When Reading Research Results

It’s also true that many studies on diet and depression are still small, or can’t hide what participants are eating from them.

We’re not yet at the stage where anyone can say for certain, “Eat this food and your depression will be cured.”

Even so, reviewing your diet is considered well worth it as part of a combination of medication, psychotherapy, and lifestyle habits.

The paradigm is shifting from an era of “depression is a brain disease, so treat it with medication alone” to “a whole-body approach that includes diet, the gut, and lifestyle habits”.

FAQ: Brain Chemistry and Depression When Antidepressants Aren’t Working

Balance Your Brain Chemistry With Diet and Fasting, and Get Your Brighter Days Back

Start Today! Practical Fasting and Eating Steps to Balance Your Brain Chemistry

For anyone wondering, “Where do I even start?”, here are concrete steps for balancing your brain chemistry.

Don’t rush. Many people find that after keeping it up for a month, their gut environment changes and they notice improvements in mood, energy, and focus.

When you’re feeling down, don’t try to do all five; just choosing one that feels doable is enough.

Keep a Food Diary and Share It With Your Doctor

It’s hard to notice for yourself how your mood changes when you change your diet.

That’s why I recommend a food diary, where you jot down “what you ate and when” along with “your mood, sleep, and physical condition that day.”

Even writing one line at a time in your phone’s notes app can reveal your own patterns, such as tending to feel down the day after eating sweets.

If you show this record at your appointments, it becomes easier for your doctor to tell apart how well the medication is working from the effects of your lifestyle habits.

Especially when you feel “my medication isn’t working,” sharing a record along with how you feel can be a key to moving your treatment forward.

I explain the basics of 16-hour fasting in detail in “【The Complete Beginner’s Guide】What Is Intermittent Fasting? Types, Benefits, How to Do It, and Why You Might Not Be Losing Weight, Explained Simply.”

Key Takeaways

Here’s a summary of the key points.

If you feel your antidepressants aren’t working well, I recommend talking with your doctor about your medication while also reviewing “how you eat”.

However, if you’re being treated by a psychiatrist or a psychosomatic medicine clinic, always talk to your doctor as you work on improving your diet.

And if feelings like “I want to disappear” or “I want to die” become strong, before trying any changes to your diet, contact your doctor, a medical facility, or a local support service right away.

If you want an all-around reset for your gut, brain, and mental health, take a look at ufeelgreat: a science-based fasting program to balance your gut, brain, and mind.

▼ Watch the video version of this article