What Can You Try When Antidepressants Aren't Working?
If antidepressants have not produced adequate improvement, you are not out of options. Inadequate response to medication is common — roughly one-third of people do not reach remission after two treatment steps. Options include medication optimization or augmentation, psychotherapy, conventional TMS, accelerated TMS (SAINT®), Spravato (esketamine), and ketamine. A psychiatric evaluation reviews whether past trials were adequate, screens for misdiagnosis (such as bipolar disorder), and recommends the most appropriate next step. Do not stop medication on your own.
Key takeaways
- Inadequate response to antidepressants is common.
- Options include medication changes, therapy, TMS, SAINT®, Spravato, and ketamine.
- A psychiatric evaluation reviews whether past trials were adequate.
- Misdiagnosis — such as bipolar disorder — can mimic treatment resistance.
- Do not stop medication without consulting your prescriber.
Understanding Inadequate Response
Inadequate response means a treatment has not produced enough improvement. It is common: in the STAR*D study, roughly one-third of people did not reach remission after two treatment steps. Inadequate response is a reason to reassess, not a reason to give up.
An inadequate response may be due to an incomplete trial (too low a dose or too short a duration), a missed diagnosis, or genuine treatment resistance. Learn more about treatment-resistant depression.
Treatment-Resistant Depression
Treatment-resistant depression (TRD) is major depressive disorder that has not responded adequately to at least two antidepressant trials of adequate dose and duration in the current episode. It describes treatment history, not a separate diagnosis. It does not mean the depression cannot be treated.
A psychiatrist reviews your medication history — doses, durations, side effects — to determine whether past trials were adequate before labeling depression as treatment-resistant.
Medication Adjustments
If current medication is not working, a psychiatrist may recommend optimizing the dose, switching to a different antidepressant class, or adding an augmentation medication. These changes can take four to eight weeks to assess. Medication remains a first-line option and may be combined with other treatments.
Do not stop or change medication on your own — abrupt discontinuation can cause withdrawal symptoms and relapse.
Psychotherapy
Evidence-based psychotherapies — CBT, behavioral activation, interpersonal therapy — can help when medication alone has not. Therapy addresses patterns of thought and behavior that medication does not. It is often combined with medication or brain stimulation.
Learn more about psychotherapy.
TMS and Accelerated TMS
Conventional TMS is FDA-cleared for adults with major depressive disorder who have not improved on antidepressant medication. It is delivered over about six weeks and is broadly covered by insurance. SAINT® is an accelerated version — five days with fMRI-guided targeting on the Magnus Neuromodulation System — typically self-pay.
Learn more about TMS therapy and SAINT®.
Spravato (Esketamine)
Spravato is an FDA-approved nasal spray for treatment-resistant depression, administered in a certified clinic with monitoring. It may act faster than traditional oral antidepressants. Coverage varies by plan; prior authorization is common.
Learn more about Spravato.
Other Clinician-Directed Options
Other options a psychiatrist may discuss include ketamine infusions (off-label), ECT for severe or psychotic depression, and combinations of the above. The right option depends on your diagnosis, history, eligibility, and preferences.
If you are having thoughts of self-harm, call or text 988 (Suicide & Crisis Lifeline) in the U.S., or go to the nearest emergency room.
Discuss With Your Treating Clinician
The most important step is a full re-evaluation with a psychiatrist. This should include reviewing whether past trials were adequate, screening for bipolar disorder and other comorbidities, and a medical workup. Do not stop current medication on your own.
Neuro Wellness offers TMS, SAINT®, Spravato, ketamine, psychotherapy, and medication management in Coral Springs, Florida. Request a consultation or call 954-827-9793.
Understanding SAINT® TMS: How It Works & What to Expect
SAINT® is an FDA-cleared treatment for adults with major depressive disorder who have not improved on antidepressants in the current episode. These videos explain how it works and how it differs from conventional TMS.
SAINT® is an FDA-cleared, fMRI-guided form of TMS developed at Stanford. Most patients complete treatment in one week — not the six weeks standard TMS requires.
Follow a real patient through the five-day SAINT® treatment week
Is SAINT® TMS Right for You?
Tried antidepressants without enough relief? SAINT® TMS is an FDA-cleared, fMRI-guided treatment for adults with major depressive disorder who have not improved enough with antidepressant medication.
SAINT® uses a personalized brain target and delivers treatment over five consecutive days. It differs from standard TMS in its targeting approach, treatment schedule, and research background. In a small randomized trial, 11 of 14 people receiving active treatment reached remission at the four-week assessment, compared with 2 of 15 receiving sham treatment. Results vary, and a five-day treatment course does not guarantee remission in five days.
How SAINT® Works and How It Differs From Conventional TMS
SAINT® is an FDA-cleared treatment for adults with major depressive disorder who have not improved on antidepressants in the current episode. This video explains how it works, and how it differs from conventional TMS.
Conventional TMS usually means about 30 visits over 6 to 9 weeks. SAINT is five visits over five days.
What makes it different: SAINT is the only FDA-cleared depression treatment that uses an fMRI scan to personalize the stimulation target to your individual brain. A 45-minute scan maps your brain and identifies the specific circuit linked to depression. Treatment is then delivered as ten 10-minute sessions per day, with 50-minute breaks between them, across five consecutive days.
In clinical trials, 79% of participants reached remission, with an average of 2.6 days to remission. SAINT is generally well tolerated; the most common side effects reported were mild headache and temporary scalp discomfort at the treatment site.
SAINT® at Neuro Wellness TMS Centers of America
Coral Springs, Florida
Free benefits check · Self-pay options available
Call or Text: 954-827-9793
Sources: Cole et al., American Journal of Psychiatry 2020;177:716-726 and 2022;179(2):132-141. magnusmedical.com/depression-therapy. PubMed 34711062. FDA 510(k) K220177.
Insurance coverage for SAINT is currently limited and varies by plan. Individual results may vary. This video is educational and is not medical advice. Talk to a qualified clinician about whether SAINT is appropriate for you. If you are in crisis, call or text 988.
Frequently Asked Questions
What can I try when antidepressants don't work?
If antidepressants have not produced adequate improvement, options include medication optimization or augmentation, psychotherapy, conventional TMS, accelerated TMS (SAINT®), Spravato (esketamine), and ketamine. A psychiatric evaluation reviews whether past trials were adequate, screens for misdiagnosis (such as bipolar disorder), and recommends the most appropriate next step.
Does 'not working' mean my depression is treatment-resistant?
Not necessarily. A medication stopped early because of side effects, or never increased beyond the starting dose, is usually considered an incomplete trial rather than a failed one. Treatment-resistant depression generally requires at least two adequate trials — therapeutic dose for about six to eight weeks. A psychiatrist can review your history.
Should I stop taking my antidepressant if it's not working?
No. Stopping abruptly can cause discontinuation symptoms and raises the risk of relapse. If you want to reduce or stop medication, ask your prescriber to plan a gradual taper. Many treatments — including TMS and psychotherapy — are delivered alongside medication, not instead of it.
Can TMS help if antidepressants haven't worked?
Yes. Conventional TMS is FDA-cleared specifically for adults with major depressive disorder who have not improved on antidepressant medication. SAINT® is an accelerated version. Both require a psychiatric evaluation to confirm eligibility.
What is the difference between inadequate response and treatment-resistant depression?
Inadequate response means a treatment has not produced enough improvement. Treatment-resistant depression is a clinical term for depression that has not responded to at least two adequate antidepressant trials. Inadequate response is a reason to reassess; TRD is a pattern that guides the next steps.
Cited Research
SAINT® is delivered only by verified providers on the Magnus Medical system. Programs described as SAINT “alternatives”, “equivalents” or “fMRI-guided accelerated TMS” are not SAINT®, are not affiliated with us, and SAINT® results do not apply to them. Read our SAINT® disclaimer.
Have questions about whether TMS may be appropriate for you?
Speak with our clinical team. A free consultation is the best way to get answers specific to your situation.
Related Patient Education
SAINT® Accelerated TMS
The 5-day, fMRI-guided protocol offered at our clinic
What Is TMS Therapy?
How transcranial magnetic stimulation works for depression
Cost & Insurance
Benefits verification, CPT codes, and self-pay options
Am I a Candidate?
Screening factors for TMS and SAINT® eligibility
Schedule a Consultation
Book a free consultation with our clinical team
Contact & Directions
9734 W Sample Rd, Coral Springs, FL 33065
Treatment-Resistant Depression
What TRD is and the options
Depression Treatment Beyond More Medication
Non-medication treatment options