By Justine Framularo, MA, LMHC, HMIP | Heartfelt Healing Institute

You’ve tried the medication. Maybe two. Maybe more. You’ve waited the six to eight weeks your doctor recommended, adjusted doses, switched prescriptions — and still, the heaviness stays. If this sounds familiar, you’re not alone, and what you’re experiencing has a name: treatment-resistant depression.

But here’s what I want you to hear before we go any further: treatment-resistant does not mean hopeless. It means the path forward looks different — and often, it means your healing requires more than medication alone.

What Is Treatment-Resistant Depression?

Treatment-resistant depression (TRD) is generally defined as major depressive disorder that hasn’t responded adequately to at least two different antidepressant medications, each given at an appropriate dose for an adequate period of time — typically six to eight weeks per trial. Both the FDA and the European Medicines Agency use this two-medication threshold as their standard definition.

And it’s more common than many people realize. Research suggests that roughly 30% of people diagnosed with major depression meet criteria for treatment resistance. The landmark STAR*D trial — the largest real-world depression treatment study ever conducted — found that only about 28–33% of participants achieved remission with their first antidepressant. Even after multiple rounds of medication changes, a significant portion of participants continued to struggle.

These numbers aren’t meant to discourage you. They’re meant to validate what you already know in your bones: this isn’t your fault, and you’re not failing at getting better.

Why Medication Alone Isn’t Always Enough

Depression isn’t only a chemical imbalance — it’s a whole-body experience. Chronic stress can alter the functioning of your hypothalamic-pituitary-adrenal (HPA) axis, the system responsible for how your body adapts to stress. When that system has been

running on overdrive — sometimes for years — a pill that targets serotonin or norepinephrine may only be addressing part of the picture.

This is where I get passionate, both as a clinician and as someone who has lived in a body that needed more than one pathway to healing. Depression often lives in the nervous system — in the tension you carry in your shoulders, the shallow breathing you don’t notice, the fatigue that feels bone-deep. When we only talk about what’s happening in our minds, we can miss what’s happening in our bodies.

The Body Has a Role to Play

Emerging research supports what somatic and body-based practitioners have long understood: the body stores and expresses our emotional experiences. When trauma, chronic pain, or prolonged stress are part of your story, approaches that engage the nervous system directly can open doors that talk therapy and medication alone may not.

Somatic therapy works from the “bottom up” — starting with physical sensations and working toward emotional understanding, rather than the other way around. Techniques like breathwork, body awareness, grounding, and nervous system regulation help your body move out of a chronic state of fight, flight, or freeze and back toward a place of safety and flexibility.

Biofeedback is another powerful tool. A meta-analysis of 14 randomized controlled trials found that heart rate variability (HRV) biofeedback produced a statistically significant reduction in depressive symptoms. HRV biofeedback works by training you to increase the natural rhythm of your heartbeat, which strengthens the communication between your body and brain and supports emotional regulation. The Association for Applied Psychophysiology and Biofeedback has rated HRV biofeedback as “probably efficacious” for treating major depression.

Psychotherapy Works — Even When Medication Hasn’t

One of the most important and underreported findings in depression research is this: psychotherapy can help even when medications have not. A Cochrane review found that patients who received psychotherapy alongside their usual care (including medication) had fewer depressive symptoms and were more likely to be depression-free six months later compared to those who continued with usual care alone.

A more recent meta-analysis found a significant effect of psychotherapy on depressive symptoms in people with TRD, with cognitive behavioral therapy (CBT) and mindfulness-based cognitive therapy (MBCT) showing particularly meaningful results. Dialectical behavior therapy (DBT), which builds skills in emotional regulation, distress

tolerance, and mindfulness, has also shown promise for people whose depression includes chronic suicidal thoughts or self-injury.

The takeaway? If you’ve only been treated with medication, you may not have accessed the treatment that could make the biggest difference for you.

A Different Kind of Healing

In my practice, I work with people whose depression has been called “treatment-resistant” — and what I often find is that their depression hasn’t been resistant to treatment. It’s been resistant to one type of treatment.

When we bring the body into the conversation — through somatic therapy, biofeedback, DBT, and trauma-informed care — something shifts. Healing stops being about “fixing” your brain chemistry and starts being about restoring your whole nervous system’s capacity for regulation, connection, and safety.

I know this not just as a therapist, but as someone who has walked the long road of physical rehabilitation and learned firsthand that the body and mind heal together — or not at all.

If You’re Feeling Stuck

If you’ve been told your depression is treatment-resistant, I want to leave you with this: that label describes where you’ve been, not where you’re going. There are evidence-based approaches beyond medication that can help, and you deserve a treatment plan that honors the full complexity of what you’re experiencing — mind and body.

You are not broken. You are not beyond help. And the fact that you’re still searching for answers? That’s not a sign of weakness. That’s resilience.

Justine Framularo, MA, LMHC, HMIP, is the owner of Heartfelt Healing Institute, LLC, a psychotherapy and biofeedback practice in Warwick, RI. She specializes in somatic therapy, DBT, trauma treatment, and chronic pain counseling. To learn more or schedule a consultation, visit heartfelthealing.us or call 401-584-2837.

Works Cited

1. Gaynes BN, Lux L, Gartlehner G, et al. Defining treatment-resistant depression.

Depression and Anxiety. 2020;37(2):134-145.

• Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. American Journal of Psychiatry. 2006;163(11):1905-1917.
• Ijaz S, Davies P, Williams CJ, et al. Psychological therapies for treatment-resistant depression in adults. Cochrane Database of Systematic Reviews. 2018;5:CD010558.
• Giguère S, Fortier A, Azrak J, Giguère C-É, Potvin S, Dumais A. Effectiveness of psychological therapy for treatment-resistant depression in adults: a systematic review and meta-analysis. Journal of Personalized Medicine. 2025;15(8):338.
• Melnikov MY. The current evidence levels for biofeedback and neurofeedback interventions in treating depression: a narrative review. Neural Plasticity. 2021;2021:8878857.
• Pizzoli SFM, et al. A meta-analysis on heart rate variability biofeedback and depressive symptoms. Scientific Reports. 2021;11:6650.
• McIntyre RS, et al. Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry. 2023.