What Happens When Antidepressants Aren’t Enough?
For many, depression is an invisible battle — a daily weight that colors every thought, decision, and moment. While some find relief through therapy or antidepressants, others continue to struggle despite trying multiple medications. This is known as treatment-resistant depression (TRD), and it affects a significant number of people diagnosed with Major Depressive Disorder (MDD).
What Is Treatment-Resistant Depression?
Treatment-resistant depression occurs when a person doesn't respond adequately to at least two different antidepressants taken for a sufficient duration and dosage. According to the National Institute of Mental Health (NIMH), TRD is not rare — nearly 30% of those with MDD experience it1.
Recognizing the Symptoms
Even when on medication, people with TRD may still experience:
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Persistent sadness or emptiness
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Low energy or fatigue nearly every day
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Trouble concentrating or making decisions
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Feelings of worthlessness or guilt
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Changes in sleep or appetite
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Loss of interest in once-enjoyed activities
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Thoughts of death or suicide
If these symptoms continue even after trying more than one antidepressant, it may be time to explore other options.
Why It Matters
Living with TRD can lead to a deep sense of hopelessness. It’s not just about “being sad.” TRD can interfere with work, relationships, and the ability to function day-to-day. That’s why researchers and clinicians are actively investigating new ways to support individuals facing TRD, including integrative care models, neuromodulation, and novel compounds supported by clinical guidance.
Looking Ahead
If you've been prescribed two or more antidepressants with little to no improvement, you may qualify for a clinical research study exploring a new approach to Treatment-Resistant Depression. This option involves a monitored, single-dose session alongside professional clinical support — designed to better understand care alternatives for people who haven’t responded to traditional treatment.
