Depression Treatment - What to Do If Medication Isn't Working for Your Depression

Start the Admissions Process Online

Fill out your information to receive a free, confidential call from the team at All Points North.


What to Do If Medication Isn’t Working for Your Depression

You’ve been diligently taking your medication for your depression. You’re doing all of the lifestyle management strategies and using the coping skills you’ve learned. You’re doing what seems like “all the right things,” but your depression doesn’t seem to be getting better. Some days, it might even feel like your symptoms are getting worse.

If you’ve tried lots of medications, therapies, and combinations but keep coming back to the same place, you may feel frustrated and left with more questions than answers. The good news is there are options beyond the traditional treatment for depression. Let’s look at depression treatment and what you can do to get relief beyond medication.

Does Medication Always Work for Depression?

Depression treatment is not a straight line: there are degrees of response and sometimes even relapse.

For many people with depression, medication and concurrent psychotherapy typically work quite well to alleviate depressive symptoms. In fact, statistics show that about 40 to 60% of people taking an antidepressant medication reported improvement in their depressive symptoms¹. Antidepressant medication can also reduce the chances of relapse. However, those statistics also tell us that not everyone finds adequate relief.

For a substantial number of people with depression, their symptoms are not relieved or only minimally relieved with antidepressant medications. Research has found that about 30% of people don’t show improvement or experience minimal response². Their symptoms are severe and refractory. This phenomenon is known as treatment-resistant depression.

What is Treatment-Resistant Depression?

Treatment-resistant depression, sometimes referred to as treatment-refractory depression, is more than just depression that hasn’t responded to medication. Treatment-resistant depression is a type of Major Depressive Disorder that is a severe, entrenched depression. People with this type of depression may also experience diminished quality of life, suicidal ideation and attempts, self-injurious behavior, and a higher risk for relapse.

Some of the indicators that your depression might be resistant include²:

  • Symptoms of severe depression, such as thoughts of self-harm, extreme mood swings, isolation, and other medical or psychiatric issues that may be present
  • Minimal or no response to multiple medication trials
  • Depressive symptoms continue to worsen despite taking medication
  • Poor tolerance to antidepressants

What Happens When Antidepressants Don’t Work?

When antidepressant medications fail to offer relief from depression symptoms, it can feel like a hopeless situation. After all, the expectations for relief are high: antidepressants work for a lot of people. When it happens to you, it can be frustrating and a bit scary if you’re currently in crisis.

Why Antidepressants Fail

Medications can fail or lose effectiveness for a variety of reasons:

  • Not every medication is effective for every person — there are lots of different options for everyone
  • You may have medical considerations that impact the efficacy of your chosen medication
  • You may have undergone significant weight gain or loss or hormonal changes that are affecting your current medication’s efficacy
  • Your dosage may need adjustments
  • Your medication timing may need adjusting, or you may need to improve your consistency
  • You are experiencing a true resistant depression

If your depression is not responding to your medications, it’s not your fault; it just means it’s time to look deeper and figure out why. Johns Hopkins Medicine has a helpful guide that explains when to see a doctor, plus the difference between SSRIs, SSNRIs, TCAs, MAOIs, and other common depression medications.

A person sitting on a couch with their head in their hand, elbow resting on their knees, looking frustrated in a dark room.

Finding Support for Treatment-Resistant Depression

If you feel as if your medication isn’t working or your symptoms are worsening, the first thing to do is make an appointment to see your provider. Your provider can help you determine whether it is a medication adjustment issue or if your depression is resistant.

If your provider determines that you are experiencing treatment-resistant depression, don’t despair. All is not lost, and you do not have to “just live with it.”

Is There Hope for Treatment-Resistant Depression?

The answer to this question is a resounding YES! Advances in neurocognitive technology have given us unprecedented insight and understanding into how the brain functions and how to tailor depression treatment. We can “see” the brain and how it responds to various interventions in ways we never could before.

Scientists have explored how the brain functions using noninvasive brain mapping, finding connections for people with severe depression. This improved understanding of the brain’s functioning has led to advances in treatment for depression. These advances are a game-changer for people with treatment-resistant depression.

Medication-Free Options for Severe Depression

For people with treatment-resistant depression, finding what works often means going beyond just medications and therapy. There are now options that use the latest neurocognitive research to understand how the severely depressed brain functions.

Ketamine-Assisted Healing + Therapy

Ketamine serves as a therapy incubator, allowing you and your therapist to gain a deeper level of trust and understanding rapidly, paving the way for future success. When combined with psychotherapy, ketamine can reverse chemical imbalances and help you achieve sustained long-term relief.

Stellate Ganglion Blocks

Doctors first used stellate ganglion blocks almost 100 years ago to treat chronic pain. Since then, treatment has evolved to address PTSD and other stress and trauma effects as physical injuries that can be healed with the right interventions. The SGB protocol is a Dual Sympathetic Reset that brings the fight or flight response back to a pre-trauma state.

Deep Transcranial Magnetic Stimulation (Deep TMS)

Deep TMS is an FDA-approved, non-invasive brain stimulation technique that uses pulsed magnetic fields to activate specific neural circuits associated with depression. Deep TMS has shown to be effective for 3 out of 4 major depression patients, with a 51% remission rate and 75% response rate.³

At All Points North, we incorporate Deep TMS as a therapeutic modality for Major Depressive Disorder, Obsessive-Compulsive Disorder (OCD), anxiety, and smoking cessation.

Hyperbaric Oxygen Therapy (HBOT)

HBOT has been used in the medical community for decades to treat various ailments. It essentially works by using an oxygen chamber to bring oxygen-rich plasma to tissues to promote healing. HBOT can be helpful for people with depression associated with certain medical issues, and, most recently, HBOT has shown promise as an intervention for depression that has been resistant to treatment with medication alone.⁴

HBOT can promote quicker healing, reduced inflammation, formation of new blood vessels, and more. We also use HBOT at the Lodge to help clients find relief from detox symptoms.


Neurofeedback can help retrain the brain by reorganizing and regulating brainwave frequencies. With a computerized feedback program, your brain can learn to function optimally to relieve symptoms and promote long-lasting healing.

Neurofeedback rewrites the way the brain responds to certain stimuli so that you can get to the root of depression, anxiety, PTSD, ADHD, trauma, and stress.


Psychotherapy is a well-established treatment for depression. In fact, psychotherapy can decrease depressive symptoms. Cognitive therapies, in particular, can be especially effective, and psychotherapy combined with medication is significantly more effective in symptom reduction and relapse prevention than medication alone⁵.

Therapy schedules vary from person to person. Sometimes, especially for people with persistent depression, there’s a need for more than a once-a-week meeting. Additional therapy time can give you more support and more opportunity to work on issues.

Complementary Healing Modalities

Beyond traditional psychotherapy, there are many opportunities for complementary healing modalities to help treat depression. Yoga, meditation and breathwork, and other complementary modalities can play an essential role in recovery.

Nature can be incredibly healing, which is why we incorporate various outdoor experiential therapy opportunities for our clients in the beautiful mountains of Colorado.

What to Do When Your Depression Treatment Isn’t Working

When it comes to treating resistant depression, there is no one way — there is only your way. You are a unique individual with your own needs and preferences. There is hope, and there is help available.

If you’ve been diagnosed with major depressive disorder (MDD) that hasn’t responded well to medication, our team of expert clinicians is ready to help you take the next step toward healing and recovery.

At All Points North, we offer a full continuum of care, from detox and assessments to in-person residential and PHP treatment for trauma, mental health, and addiction. Our neurotechnology branch, Plus by APN, exists to address the root causes of mental health issues.

To learn more about what you can expect from your custom treatment plan at All Points North, reach out to one of our Contact Center team members at 855.235.9792 or complete our online contact form. Let us help you reclaim your voice and find your way forward.



  1. “Depression: How Effective Are Antidepressants?” National Center for Biotechnology Information (NCBI), Institute for Quality and Efficiency in Health Care (IQWiG), 18 June 2020,
  2. Al-Harbi, Khalid Saad. “Treatment-Resistant Depression: Therapeutic Trends, Challenges, and Future Directions.” Patient Preference and Adherence, Dove Press, 1 May 2012,
  3. “Deep TMS Treatment for Depression.” BrainsWay, BrainsWay,
  4. Krzystanek, Marek et al. “Whole Body Cryotherapy and Hyperbaric Oxygen Treatment: New Biological Treatment of Depression? A Systematic Review.” Pharmaceuticals 14.6 (2021): 595. Crossref. Web.
  5. Dunlop, Boadie W. “Evidence-Based Applications of Combination Psychotherapy and Pharmacotherapy for Depression.” Focus (American Psychiatric Publishing) vol. 14,2 (2016): 156-173. doi:10.1176/appi.focus.20150042
  • Liberman, J. N., Davis, T., Pesa, J., Chow, W., Verbanac, J., Heverly-Fitt, S., & Ruetsch, C. (2020). Predicting Incident Treatment-Resistant Depression: A Model Designed for Health Systems of Care. Journal of managed care & specialty pharmacy, 26(8), 987–995.
  • Gong, Q., & He, Y. (2015). Depression, neuroimaging and Connectomics: A selective overview. Biological Psychiatry, 77(3), 223-235. doi:10.1016/j.biopsych.2014.08.009
  • American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. American Psychiatric Association. 2010. Available from:
  • Uebelacker, L. A., Kraines, M., Broughton, M. K., Tremont, G., Gillette, L. T., Epstein-Lubow, G., … Miller, I. W. (2017). Perceptions of hatha yoga amongst persistently depressed individuals enrolled in a trial of yoga for depression. Complementary Therapies in Medicine, 34, 149-155. doi:10.1016/j.ctim.2017.06.008

Jess Johnson

Content Marketing Manager

As a fierce proponent of mental health services, Jess believes in the compassionate care and person-centered approach at All Points North. She works to create content that inspires clients and families to advocate for the support they deserve.