What to Do When Antidepressants Are Not Working: 5 Proven Options for Depression
Intro: When Medications Aren’t Enough
If you’ve tried antidepressants without lasting relief, you are not alone. Research shows that up to one-third of people with depression don’t respond to standard treatments like SSRIs or SNRIs. This is often called treatment-resistant depression (TRD) — and while it can feel discouraging, it does not mean you’re out of options.
At Redbud Behavioral Health in Fredericksburg, VA, we specialize in helping adults with difficult-to-treat depression. The good news is that there are several evidence-based treatments that can help when medications alone aren’t enough. In this article, we’ll explore five proven options that may provide the breakthrough you’ve been waiting for.
1. Advanced Medications
When standard antidepressants fail, psychiatrists can use a range of augmentation strategies — adding or switching medications in ways supported by research. These include:
Lithium augmentation: Long considered the “gold standard” add-on for treatment-resistant depression. Lithium can enhance the effectiveness of antidepressants and may also help regulate mood more broadly.
MAOIs (monoamine oxidase inhibitors): Although older and less commonly used today, MAOIs remain one of the most effective classes of antidepressants. For certain patients, they can be life-changing when other medications fail.
Thyroid hormone supplementation: Low doses of thyroid hormone (T3) can boost the effect of antidepressants, even in patients without thyroid disease.
Atypical antipsychotics: Medications like aripiprazole or quetiapine are FDA-approved as add-on treatments for depression.
Dopamine agonists (such as pramipexole): Originally used in Parkinson’s disease, pramipexole has shown promise in improving motivation, energy, and mood in patients with TRD by directly targeting the dopamine system. This option is rarely discussed but can be transformative for some individuals.
👉 The takeaway: Many people never hear about these evidence-based options. At Redbud, we carefully review your treatment history to identify whether advanced medication strategies may be appropriate for you.
👉 [Learn more about Advanced Medication Management at Redbud Behavioral Health]
2. TMS Therapy (Transcranial Magnetic Stimulation)
If medications haven’t helped, it may be time to consider a non-drug treatment option.
TMS therapy uses gentle magnetic pulses to stimulate areas of the brain involved in mood regulation. By “resetting” these circuits, TMS can help restore healthier brain activity and reduce depression symptoms.
✅ FDA-approved since 2008
✅ Non-invasive, no anesthesia, no downtime
✅ Covered by most major insurance, including Anthem/BCBS & Cigna
✅ Sessions take less than an hour, and you can return to normal activities right away
At Redbud Behavioral Health, we offer TMS with both standard and accelerated protocols available. Accelerated TMS may provide results in weeks instead of months.
👉 [Learn more about TMS in Fredericksburg]
3. Spravato® (Esketamine Nasal Spray)
Spravato is one of the most exciting breakthroughs in depression treatment in decades. Unlike traditional antidepressants, Spravato works through the NMDA receptor system in the brain, helping to rapidly improve symptoms for many patients with TRD.
✅ FDA-approved in 2019 for adults with treatment-resistant depression
✅ Administered in-office under medical supervision for safety
✅ Can provide relief in hours to days, instead of weeks
✅ Covered by most major insurance, including Anthem/BCBS & Cigna
During a Spravato session, patients self-administer the nasal spray and then relax in a comfortable setting while our team provides monitoring and support. Most people require 2 sessions per week initially, with frequency decreasing over time.
👉 [Learn more about Spravato in Fredericksburg]
4. Metabolic Psychiatry
Depression is not just about neurotransmitters. Increasingly, research shows that metabolic health plays a major role in mood. Factors like insulin resistance, inflammation, and sleep quality can all contribute to depression symptoms and treatment resistance.
At Redbud Behavioral Health, we take a whole-person approach:
Assessing metabolic health and chronic medical conditions
Looking at risk factors for nutritional deficiencies
Evaluating sleep patterns and circadian rhythms
Considering inflammation as a driver of mood symptoms
By addressing these underlying issues, we can often improve how patients respond to other treatments — or even reduce depressive symptoms directly.
👉 [Learn more about Metabolic Psychiatry at Redbud Behavioral Health]
5. Comprehensive, Personalized Care
The truth is, there’s no single “magic bullet” for depression. What makes the difference is a treatment plan that’s built around your unique history, biology, and goals.
At Redbud Behavioral Health, every new patient begins with a 60-minute consultation where we review:
Current symptoms and mood history
Past treatments and how you responded
Physical health factors like sleep, inflammation, and insulin resistance
Your personal goals for recovery
From there, we design an individualized plan that may include advanced medications, TMS, Spravato, metabolic strategies — or a combination. Most importantly, you’ll work with a small, consistent care team who knows your story and supports you every step of the way.
Closing: A Message of Hope
If antidepressants haven’t worked for you, don’t give up hope. There are proven, FDA-approved, and evidence-based treatments available — right here in Fredericksburg.
At Redbud Behavioral Health, we specialize in helping people with difficult-to-treat depression find relief, often after years of frustration.
📍 Located in Fredericksburg, VA | In-network with Anthem/BCBS & Cigna
