If you are thinking about harming yourself, call or text 988 (Suicide & Crisis Lifeline, 24/7) or go to your nearest emergency room.
What Can I Do When Depression Treatment Isn't Working?
If you have tried antidepressant medication, therapy, or both and your symptoms have not adequately improved, you are not out of options. Persistent symptoms after appropriate treatment may lead a clinician to evaluate for treatment-resistant depression and discuss other evidence-based approaches. The next step is a conversation with a qualified healthcare professional who can review your history and recommend what may be appropriate for you.
Key Takeaways
- Persistent symptoms after adequate treatment may indicate treatment-resistant depression.
- Do not stop medication on your own — talk to your prescribing clinician first.
- Options include medication adjustments, psychotherapy, TMS, SAINT®, SPRAVATO®, and ECT.
- Eligibility for any treatment is determined by a qualified healthcare professional.
- Having tried multiple treatments does not mean no options remain.
When Medication Hasn't Worked
If one or more antidepressant medications have not produced adequate improvement, a psychiatrist can review whether each trial was at a therapeutic dose for a sufficient duration, check for contributing factors such as comorbid anxiety, bipolar disorder, or substance use, and discuss options including medication optimization, augmentation, or non-medication treatments. Learn what to try when antidepressants don't work.
When Therapy Hasn't Worked
If psychotherapy alone has not produced adequate improvement, it does not mean therapy has failed — it may mean that a combination approach is needed. Depression that has not responded to therapy may benefit from adding medication, or from neuromodulation treatments like TMS or SAINT® that address brain circuitry directly. Discuss with your clinician whether a combined approach is appropriate.
When Medication and Therapy Haven't Worked
When both medication and therapy have not produced adequate relief, a psychiatrist may evaluate for treatment-resistant depression and discuss neuromodulation and interventional options. These include FDA-cleared TMS, the accelerated SAINT® protocol, and FDA-approved SPRAVATO® (esketamine). For severe or psychotic depression, ECT remains an option with the highest remission rates but with anesthesia and cognitive considerations.
What Treatment-Resistant Depression Means
Treatment-resistant depression is major depressive disorder that has not responded adequately to at least two antidepressant medication trials of adequate dose and duration in the current episode. It describes treatment history, not a separate diagnosis, and it does not mean the depression cannot be treated. Learn more about treatment-resistant depression.
Treatment Options to Discuss With Your Psychiatrist
TMS Therapy
FDA-cleared, non-invasive brain stimulation for depression that has not responded to medication. ~36 sessions over 6 weeks.
SAINT® Accelerated TMS
FDA-cleared, fMRI-guided, 5-day accelerated protocol for eligible adults with major depressive disorder.
SPRAVATO® (Esketamine)
FDA-approved nasal spray for treatment-resistant depression, administered in-office with monitoring.
Medication Management
Review and optimization of current medications, augmentation strategies, and careful adjustments.
Questions to Discuss With Your Psychiatrist
- Were my previous medication trials at an adequate dose for a sufficient duration?
- Could a comorbid condition (anxiety, bipolar disorder, ADHD, substance use) be affecting my response?
- Would a medication adjustment or augmentation strategy be appropriate?
- Am I a candidate for TMS, SAINT®, or SPRAVATO®?
- What are the risks, benefits, and time commitment for each option?
- What is the plan if the next treatment does not work?
Frequently Asked Questions
What does it mean when depression treatment isn't working?
If your symptoms have not adequately improved after an appropriate course of treatment — such as one or more antidepressant medications taken at a therapeutic dose for a sufficient duration, with or without psychotherapy — a clinician may evaluate whether your depression meets common definitions of treatment-resistant depression and discuss other evidence-based options. This is a clinical determination made by a qualified healthcare professional.
What should I do if my antidepressant isn't working?
Do not stop your medication on your own. Talk to your prescribing clinician. They can review whether the dose and duration were adequate, check for contributing factors like comorbid conditions or medication interactions, and discuss options such as medication optimization, augmentation, psychotherapy, or non-medication treatments like TMS or SAINT®.
What comes after medication and therapy for depression?
When medication and therapy have not produced adequate improvement, options a psychiatrist may discuss include medication adjustments or augmentation, FDA-cleared TMS, the accelerated SAINT® protocol, FDA-approved SPRAVATO® (esketamine), or, for severe cases, ECT. The right next step depends on your individual history and is determined by a qualified clinician.
Is there hope after multiple depression treatments fail?
Yes. Having tried multiple treatments without lasting relief does not mean no options remain. Treatment-resistant depression has a range of evidence-based approaches, including neuromodulation treatments like TMS and SAINT® that are specifically indicated for adults whose depression has not improved on antidepressant medication. A psychiatric evaluation can help identify the next appropriate step.
What is treatment-resistant depression?
Treatment-resistant depression is major depressive disorder that has not responded adequately to at least two antidepressant medication trials of adequate dose and duration in the current episode. It describes treatment history, not a separate diagnosis, and it does not mean the depression cannot be treated.
Medically reviewed by Daniel Pietras, MD. Last updated November 3, 2026.
Talk With Our Team About Your Options
If depression treatment hasn't worked, a consultation can help you understand what may be appropriate for your situation.
Related Resources
When Antidepressants Don't Work
What to try when medication isn't enough
What Is Treatment-Resistant Depression?
Definition and options
SAINT® Accelerated TMS
5-day fMRI-guided TMS for eligible adults
TMS Therapy
FDA-cleared TMS for depression
SPRAVATO®
FDA-approved esketamine for TRD
Am I a Candidate?
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