11 Reasons Your Antidepressant Isn’t Working — And How Holistic Mental Health Can Help

Depression / Integrative Medicine / Mental Health

11 Reasons Your Antidepressant Isn’t Working — And How Holistic Mental Health Can Help

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This article was medically reviewed by Taylor M. Hall, M.S., CMFC, LPC

Did you know that approximately 30% of people with depression do not respond to their first antidepressant medication?

There can be many different reasons for this, as antidepressant medication is not a one-size-fits-all solution. It’s a complex mix of chemistry, physiology, and psychology. Just as our bodies and brains are unique, so too is the way we respond to medication.

In this article, we’ll cover 11 hidden reasons why your antidepressant might not be working, including some of the primary integrative and holistic treatment options that can help you find relief.

A lot of this article will be addressing what’s known as treatment-resistant depression, so let’s start with a quick look at what exactly this means.

What is treatment-resistant depression?

Assuming that you’ve given one or more antidepressants a chance to work, you might have what’s known as treatment-resistant depression. This refers to a type of depression that does not improve with the typical courses of antidepressant medications.

It can be hard enough to seek help for depression, so when that help fails, it’s easy to feel stuck in a cycle of depression without an apparent way out. The result can be an additional layer of hopelessness on top of the difficulties you’re already facing.

If this describes what you’re experiencing, please know that you’re not alone. After all, antidepressant medications are typically only effective for about 60-70% of individuals with depression.

The good news is there’s a whole world of integrative and holistic treatment options that can not only reduce your symptoms, but work to heal your depression at the deepest root level.

What is an integrative or holistic mental health approach?

An integrative or holistic approach to mental health involves addressing all aspects of your well-being in order to enhance your overall health and wellness. This includes your mental, physical, emotional, and even spiritual well-being.

For example, your depressive symptoms could have a physical root cause like a nutritional deficiency. Or your depression could be caused by something psychological or emotional, such as a highly stressful workplace or a traumatic relationship.

Addressing the different dimensions of your well-being can have profound results for your health, and integrative mental health treatment often works when standard care doesn’t.

Integrative Depression Plans

If you see an integrative depression specialist, your depression treatment plan could include combining antidepressant medication with psychotherapy. This combination can increase the likelihood of treatment success.

Your plan might also include holistic lifestyle changes, like exercise and mindfulness-based practices such as meditation and yoga.

Another option in integrative depression treatment is ketamine, a breakthrough treatment for conditions like depression, anxiety, and PTSD.

At our center, we sometimes use ketamine infusions as well as ketamine-assisted psychotherapy to provide fast-acting relief while psychiatric medications like antidepressants begin to take effect.

In other cases, we work with ketamine patients to reduce or eliminate their need for antidepressants altogether.

Everyone has different preferences when it comes to their mental health, which is why you’ll find multiple treatment options accompanying each of the 11 reasons below.

Our hope is that by properly identifying the right cause of your depression, you can finally find the relief you deserve and get back to feeling like yourself again.

11 Reasons Why Your Antidepressants Might Not Be Working

1. Nutritional Deficiencies

Deficiencies in nutrients like vitamin D, B vitamins, zinc, magnesium, and omega-3 can all cause depressive symptoms. They can also reduce the effectiveness of antidepressant medications.

These nutrients help support vital functions like neurotransmitter synthesis, nerve signaling, neuroplasticity, and inflammation regulation. Without adequate levels of these nutrients, antidepressants can have trouble working at their full potential.

Ready to help your depression with nutritional support?

Recommended treatments include:

  • Testing for nutritional deficiencies
  • Diet changes to correct deficiencies
  • Oral or IV vitamin supplementation
  • Amino acid therapies to support neurotransmitters

2. Chronic Inflammation

It’s been said that inflammation is at the root of all disease, so it’s not surprising chronic inflammation isn’t helpful here.

We’re not talking about short-term inflammation here, like the kind you get when you’re combatting a cold, which signals something helpful taking place. We’re talking about on-going chronic inflammation, which doesn’t signal anything positive.

Sources of on-going inflammation include autoimmune diseases, food sensitivities, leaky gut, infections, and chronic stress (like the kind you get from toxic relationships or work environments). This type of inflammation can create a wide host of problems for your health, including issues with mood regulation in the brain. This in turn leads to depressive symptoms.

Ready to reduce your inflammation and boost your immune function?

Recommended treatments include:

  • Immune labs to identify inflammation
  • Elimination diets
  • Anti-inflammatory nutrients and botanicals
  • Low dose immunotherapy for autoimmunity
  • IV vitamin C for immune support
  • Ketamine infusion therapy to reduce inflammation


3. Hormonal Imbalances

When hormones like estrogen, progesterone, cortisol and thyroid hormones are too high or low, it impacts the balance of chemicals in your brain. The result can be a number of mood-related issues, including clinical depression. Hormonal imbalances can also impact your ability to metabolize antidepressant medication.

Causes of hormonal imbalance might include thyroid disorders, peri/menopause, PCOS, or high cortisol levels from stress.

Ready to balance your hormones for better mental health?

If hormonal havoc is wrecking your mood, lab testing and integrative protocols can get your biochemistry back on track and restore optimal hormone levels.

Recommended treatments include:

  • Testing key hormones like thyroid, cortisol, estrogen, progesterone
  • Bioidentical hormone replacement therapy
  • Adaptogens and nutraceuticals for hormonal balance
  • Stress management techniques
  • IV nutrient therapies to support hormone metabolism


4. Untreated Trauma

Unresolved trauma from experiences like abuse, neglect, disaster, accidents, violence, or loss can significantly contribute to treatment-resistant depression.

Trauma can also be relational and complex. Regarding relational trauma, therapist Taylor M. Hall states “Trauma is personal to everyone. What may be a traumatic incident to someone may not be to someone else. Additionally, it should be noted that smaller, repeated traumas can do just as much damage to one’s sense of self (sometimes even more so) than ‘bigger’ events.”

As an example, Taylor advises us to think about the idea that we’re not good enough. “This is a learned thought pattern based off repeated criticisms and negative feedback loops. No one comes into this world thinking they’re not good enough — this is a message we learn through pain. This is an example of how relational or complex trauma can affect the individual.”

Trauma fundamentally alters brain structure and function in ways that disrupt emotion regulation, cognitive processing, reward response, impulse control, and sense of self. Unfortunately, antidepressants alone can’t fully address the complex neurological and psychological impacts from trauma.

Is untreated trauma helping to drive your depression?

If so, here are some of the recommended treatments:

  • Screening assessments for trauma history and PTSD
  • Psychotherapy to process how trauma has affected your life and promote healing
  • IFS (Internal Family Systems) work, including inner child therapy and parts work
  • EMDR (Eye Movement Desensitization and Processing)  to process traumatic memories
  • Somatic therapies to release trapped trauma
  • Mindfulness practices to manage trauma triggers
  • Support groups to reduce isolation
  • Ketamine-assisted psychotherapy


Heal your depression from the roots out with integrative care

Is your depression hard to treat? Call to schedule your free 15-minute consultation at (720)222-0550or fill out the form at the bottom of this page to contact us.

5. Lifestyle Factors

Unhealthy lifestyle habits like poor sleep, inactivity, and stress can both drive depression and reduce antidepressant effectiveness. Social isolation and poor exposure to sunlight and nature can be similarly damaging to your mood and mental health.

Lifestyle improvements like sunlight exposure, better sleep hygiene, and more social connection can naturally boost production of serotonin, dopamine, and norepinephrine — the same neurotransmitters targeted by antidepressants. This can make it easier for medication to do its job, and reduce the need for medication in the first place.

Ready to support your depression treatment with lifestyle changes?

Recommended treatments include:

  • Sleep interventions such as CBT-I, light therapy, and meditation
  • More exercise, yoga, and time outdoors
  • Dietary changes to balance blood sugar and reduce inflammation
  • Stress management techniques, including psychotherapy and CBT
  • Ketamine infusion therapy to rapidly improve mood as lifestyle changes take effect


6. Gut Microbiome Imbalances

Your gut microbiome heavily influences your mental health.

Trillions of bacteria and microbes live in your digestive tract, producing neurotransmitters like serotonin. And when your gut becomes imbalanced from things like poor diet, antibiotics, and stress, it can reduce serotonin and bring on the symptoms of depression.

The condition know as “leaky gut” can also be a factor. Also known as intestinal permeability, leaky gut refers to a condition in which the lining of the small intestine becomes damaged or abnormal. This allows toxins, microbes, and undigested food particles to leak through the intestinal wall into the bloodstream where they can wreak havoc on your mood.

Last but not least, poor nutrient absorption can also stem from gut issues. And when you’re not absorbing enough nutrients, this can decrease the effectiveness of your antidepressants and exacerbate your depressive symptoms.

Ready to heal your gut for depression relief?

If you think gut issues could be worsening your depression, helpful solutions include:

  • Probiotic supplements to support your gut microbiome
  • Elimination diets to identity any food sensitivities
  • Digestive enzymes and gut-healing nutrients
  • A gut-healthy nutrition plan
  • IV vitamin therapies to deliver nutrients and enhance nutrient absorption


7. Accompanying Anxiety Disorders

It’s estimated that 50-60% of those with depression also have an anxiety disorder such as generalized anxiety, OCD, PTSD, panic disorder, or phobias. 

The cognitive distortions and ruminations present in anxiety can contribute to pessimism and loss of interest. These, along with other depressive symptoms, make it harder for antidepressants to be effective. Untreated anxiety can also negate the help of antidepressants more directly, disrupting the same neurotransmitters that antidepressants work on. 

Thankfully, concurrent evidence-based treatment of both depression and anxiety-related disorders can greatly improve outcomes for both conditions. 

Ready to address your co-occurring anxiety and depression?

At our center, we use a multi-modal integrative approach to alleviate anxiety’s grip, allowing antidepressants and other interventions to properly control remaining depressive symptoms.

Recommended treatments can include:

  • Assessments to identify anxiety disorders
  • Anti-anxiety medications as needed
  • CBT, DBT, and mindfulness-based therapies
  • Breathwork, meditation, yoga for anxiety
  • Ketamine infusion therapy for rapid anxiety relief

8. Interactions from Other Medications

Antidepressants rely on specific metabolic pathways and enzyme systems in order to be successfully processed in your body. Other medications like blood pressure drugs, pain meds, stomach acid reducers, and sleep aids can all impact these metabolizing enzymes and lead to too much or too little antidepressant activity.

Additionally, some medications have direct effects on neurotransmitter activity and can dampen or even fully negate the benefits you’re seeking from antidepressant therapy.

If you’re unable to discontinue medications that interfere with your antidepressants, consider options like ketamine treatment or ketamine-assisted psychotherapy. Ketamine works differently than antidepressants, so it doesn’t have the same interactions.

Ready to look at the medication interactions that could be interfering with your depression treatment?

Recommended treatments include:

  • Screening for medication interactions
  • Pharmacogenomic testing to guide medication selection
  • Medication management adjustments to resolve interactions
  • Nutraceuticals to support detoxification
  • Ketamine infusion therapy or ketamine-assisted psychotherapy


9. Genetic Considerations

Your unique genetic makeup can influence how you respond to different antidepressant medications. For instance, genetic variability in your liver enzymes determines how fast or slow you can metabolize certain drugs. This can result in medication levels that are either too high or too low if your dosage doesn’t align with your genetics.

Additionally, there are over 1,000 genes that may impact depression development and treatment response. Genetic testing can provide insight into which medications are more likely to be effective and well-tolerated based on your individual DNA.

Ready to examine the genetic influences in your antidepressant response?

Recommended treatments:

  • Pharmacogenomic testing to match medications to genotype
  • Gene-guided prescription of optimal antidepressant drug(s)
  • Nutritional support customized to genetic needs


10. Untreated Mold Exposure

Many people aren’t even aware they’ve been exposed to toxic mold, making this a very easy cause of depression to overlook.

Toxic molds, such as black mold, penicillium, and aspergillus release mycotoxins. When inhaled or ingested, these can can lead to brain inflammation. This inflammation can disrupt neurotransmitter signaling and directly cause symptoms of clinical depression, including depressed mood, loss of interest, changes in sleep and appetite, fatigue, and trouble concentrating.

Ready to treat your mold illness and improve your depressive symptoms?

Recommended help includes:

  • Mold testing and inspection of home/work environments
  • Avoidance of environments where mold is known or likely
  • IV glutathione to support liver detoxification
  • Ozone therapy to reduce oxidative stress
  • Binders and detox supplements to eliminate mycotoxins
  • Antifungal medications or herbals if needed


11. Co-Occurring ADHD

It’s estimated that as many as 20-30% of those with ADHD also have clinical depression. While ADHD doesn’t directly reduce the effectiveness of antidepressants, ADHD symptoms like trouble focusing and low motivation overlap with symptoms of untreated depression. This overlap can make it difficult to tell when antidepressants are being effective, as you might still have some of the same unwanted symptoms.

Untreated ADHD symptoms can also make it difficult to adhere to a depression treatment plan, from procrastination making appointments and picking up refills to missed doses from disorganization and lack of follow through.

Fortunately, treating ADHD and depression simultaneously can target the overlapping symptoms for more complete relief.

Ready to manage your ADHD and depression together?

Recommended treatments include:

  • Screening assessments for ADHD
  • Stimulant and non-stimulant medications for ADHD symptoms
  • CBT for ADHD management
  • Skills training for organization, focus, time management
  • Ketamine infusion therapy to treat both ADHD and depression


Need help for treatment-resistant depression in the South Denver area?

Get complete integrative and holistic mental health care under one roof at our Englewood Depression Treatment Clinic (by the Denver Tech Center)

As you’ve seen, treatment-resistant depression often stems from biological or lifestyle root causes. These factors can prevent antidepressants from providing the relief you seek.  In other cases, untreated trauma or co-occurring disorders like ADHD and anxiety are to blame.

If you’re in South Denver, Englewood, Centennial, or near The Denver Tech Center and need help getting to the root causes of your treatment-resistant depression, reach out for a free consultation with our team. We’d be happy to answer any questions you have, and get you started on a path to longterm healing and thriving.

Call for your free consultation today at (720)222-0550 or fill out the contact form below.

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