What to Do When Antidepressants Don't Work: Your Next Steps

Taking an antidepressant and still feeling depressed can be frustrating. You might wonder whether you need more time, a different medication, or another approach altogether. A large national STAR-D trial showed that response rate to antidepressant medication with the first medication is 37%, and after the third medication trial it is 67%, which still leaves more than 30% of patients with significant symptoms of depression.

One antidepressant not working doesn't mean depression can't be treated. It may mean your treatment plan needs another look. Your psychiatrist can review your symptoms, previous medications, side effects, and overall health to understand what might help next.

At Family Care Psychiatry, treatment options include medication management, psychotherapy referrals, TMS therapy, and SPRAVATO® for eligible patients.

First, Make Sure Your Antidepressant Has Had Enough Time

Antidepressants generally take several weeks to work. The National Institute of Mental Health notes that it can take around 4–8 weeks to experience their full effects, although some symptoms may improve sooner.

Before changing treatment, your psychiatrist may ask:

• How long have you been taking the medication?
• Are you taking it consistently?
• Has your dose been adjusted appropriately?
• Have you noticed any improvement?
• Are side effects making treatment difficult?

Don't stop or change your medication on your own. Talk to your prescribing clinician before making any changes.

What If Your Antidepressant Still Isn't Working?

If you've given your medication an adequate trial and depression continues to affect your daily life, your psychiatrist may consider a different approach.

Depending on your situation, this could mean adjusting your current medication, switching to another antidepressant, adding psychotherapy, or reviewing your diagnosis and other health factors.

Depression can overlap with anxiety, sleep problems, other psychiatric conditions, and medical issues. Reviewing the bigger picture can help identify factors that may be affecting your response to treatment.

What Is Treatment-Resistant Depression?

Treatment-resistant depression generally refers to depression that hasn't improved adequately after trying at least two antidepressants. However, the number of medications alone doesn't tell the whole story.

Your psychiatrist will want to understand which medications you've tried, their doses, how long you took them, and how you responded.

Treatment-resistant depression doesn't mean untreatable depression. It means previous approaches haven't provided enough relief, so other options may need to be considered.

For some patients, this may include treatments such as transcranial magnetic stimulation (TMS) or SPRAVATO.

Could TMS Therapy Help?

TMS therapy, an FDA-approved treatment, uses magnetic pulses to stimulate targeted areas of the brain associated with mood regulation. It's a non-invasive treatment that doesn't involve adding another antidepressant medication. TMS therapy targets a specific area in the brain identified as the dorsolateral prefrontal cortex. When repeatedly stimulated via magnetic stimulation, it may help strengthen activity in relevant brain networks and reduce depressive symptoms.

TMS may be considered for people whose depression hasn't improved sufficiently with conventional treatments or who cannot tolerate them.

At Family Care Psychiatry, TMS is part of the treatment options available to appropriate patients. Your clinician can explain the treatment schedule, possible side effects, and whether it fits your medical and treatment history.

Could SPRAVATO Be an Option?

SPRAVATO is a prescription nasal spray containing esketamine. The FDA has approved it for adults with treatment-resistant depression.

Unlike a medication taken independently at home, SPRAVATO must be administered under healthcare-provider supervision. Patients are monitored after administration because side effects such as sedation, dissociation, and increased blood pressure can occur.

Eligibility depends on your medical history and clinical evaluation. Your psychiatrist can explain whether SPRAVATO may be suitable and how it compares with other available treatments.

To understand the medication in more detail, read our guide to how SPRAVATO works in the brain.

TMS or SPRAVATO: Which Treatment Is Right for You?

TMS and SPRAVATO work differently, and neither is automatically the better choice for everyone.

TMS Therapy	SPRAVATO
Uses magnetic pulses to stimulate targeted brain areas	Uses esketamine nasal spray
Non-invasive treatment without medication administration	Medication administered under clinical supervision
Involves repeated sessions over several weeks	Requires supervised administration and post-treatment monitoring
Suitability depends on clinical evaluation	Suitability depends on eligibility and clinical evaluation

The right choice depends on your symptoms, previous treatments, medical history, and preferences. A psychiatric evaluation can help you understand which options are appropriate.

What Happens During a Psychiatric Evaluation?

If you've already tried antidepressants without enough improvement, your appointment should look beyond simply prescribing another medication.

Your psychiatrist may review your current symptoms, previous diagnoses, medication history, treatment duration, side effects, therapy experience, medical history, and treatment goals.

At Family Care Psychiatry, this evaluation helps guide an individualized treatment plan. The aim is to understand what you've tried, what hasn't helped enough, and what options make sense now.

Depression Treatment in Ann Arbor, Michigan

Family Care Psychiatry is based in Ypsilanti, near Ann Arbor, and serves patients from Ann Arbor, Canton, Brighton, Plymouth, Chelsea, and surrounding communities across Washtenaw, Wayne, Livingston, and Jackson counties.

For eligible patients, care may include medication management, TMS therapy, or SPRAVATO treatment. Telehealth is also available across Michigan, depending on the patient's needs and the type of care required.

If depression continues despite treatment, you can request an evaluation to discuss your history and possible next steps.

Frequently Asked Questions

What happens if two antidepressants don't work?

Your psychiatrist may assess whether the previous medication trials were adequate and whether you meet the criteria for treatment-resistant depression. Depending on your situation, TMS, SPRAVATO, or another treatment approach may be considered.

Does treatment-resistant depression mean I can't get better?

No. It means previous treatments haven't provided enough improvement. Other treatment options may still be available.

Can I stop taking antidepressants before trying TMS?

Don't stop or change medication without discussing it with your prescribing clinician. Your treatment plan should be based on your individual needs.

Can SPRAVATO be taken at home?

No. SPRAVATO must be administered under healthcare-provider supervision, with monitoring after treatment.

What to Do Next

If antidepressants haven't worked well enough, you don't necessarily need to keep repeating the same approach. A review of your symptoms, treatment history, and overall health can help identify a more suitable next step.

For some people, that may mean adjusting medication or adding psychotherapy. For others with treatment-resistant depression, TMS or SPRAVATO may be worth discussing.

At Family Care Psychiatry, the goal is to understand what hasn't worked and help you explore the next appropriate step in your depression care.