Your depression treatment may not be working if, after a fair trial, you are only partly better, the side effects are costing you more than the medication gives back, your symptoms have returned, or you are still struggling to get through work and home life. A "fair trial" generally means 4 to 6 weeks at an effective dose, taken consistently. None of these signs means you are out of options. They mean it is time for an honest review with your prescriber, ideally backed by numbers from a simple symptom questionnaire.
Here are seven signs to watch for, what to ask, and when a different kind of treatment such as TMS starts to make sense.
The 7 signs
1. You are better, but not well
Partial improvement is the most common way treatment falls short, and the easiest to accept without question. In studies, "response" usually means a drop of at least 50% on a depression scale, while "remission" means symptoms are down to a minimal level. Response is real progress, but it can still leave you tired, unmotivated or foggy. A 2023 review in World Psychiatry notes that even among STAR*D participants counted as "in remission", only 10% were fully free of symptoms. Leftover symptoms are worth treating, not just tolerating.
2. Several weeks at a full dose have changed very little
Antidepressants take time, so "I feel nothing after a week" is not a failed trial. But if you have taken a medication consistently at a therapeutic dose for 4 to 6 weeks with little change, that is worth discussing. Some people do respond later: one analysis summarized in the World Psychiatry review found about 20% of people who had not responded by week 4 responded during weeks 5 to 8. Your prescriber may suggest waiting a little longer, raising the dose, or changing course; the right choice depends on how much you are suffering.
3. The side effects outweigh the benefit
Side effects are a legitimate reason to change treatment, not something you are obliged to put up with. A 2009 meta-analysis found sexual side effects in 25.8% to 80.3% of people on several commonly used antidepressants when they were asked directly, depending on the drug. In a 2017 survey of 669 people taking antidepressants, 46% reported emotional blunting, a sense of feeling flat or numb. A large UK cohort study also linked antidepressant use with a higher rate of weight gain over the following years, though the authors note the association may not be causal. If side effects are the main problem, our article on where TMS fits after stopping antidepressants because of side effects goes deeper.
4. Your symptoms came back
Feeling well for a while and then sliding back deserves attention rather than a shrug. Relapse is more likely the more treatment steps someone has needed: in STAR*D, people who required more steps had higher relapse rates. A return of symptoms is a reason to review the diagnosis, any new stressors, sleep, substance use and medical changes, not only the prescription.
Relapse rarely announces itself all at once. People often notice small changes first, so it helps to know your own early pattern:
- sleep shifting (waking early, or sleeping much longer than usual)
- pulling back from friends, texts or plans you would normally keep
- work or chores taking noticeably more effort
- losing interest in things that were enjoyable a month ago
- more irritability, guilt or self-criticism than usual
Writing down two or three of your personal warning signs, and sharing them with someone close to you, makes it easier to act early rather than months later.
5. Your scores improved, but your life did not
Questionnaires measure symptoms, not whether you can concentrate in a meeting, enjoy your kids or keep up with friends. The World Psychiatry review points out that none of the common definitions of treatment-resistant depression account for quality of life, and that people who remit on antidepressants but still report poor quality of life are at greater risk of relapse. Bring examples: tasks you are avoiding, days missed, things you used to enjoy and no longer do.
6. Your PHQ-9 is not moving
The PHQ-9 is a nine-question form that rates each core symptom of depression from 0 ("not at all") to 3 ("nearly every day"). Scores of 5, 10, 15 and 20 mark the thresholds for mild, moderate, moderately severe and severe depression. If your score has hovered in the same band for several visits, the treatment is probably not doing enough, even if you have gotten used to feeling this way. More on this below.
7. You have already tried two or more medications
The definition of treatment-resistant depression used by the FDA and the European Medicines Agency is an inadequate response to at least two antidepressants despite adequate dose, duration and adherence. If you are there, it is reasonable to ask about a wider set of options instead of a third or fourth drug of the same kind. Our guide to what treatment-resistant depression means explains the definition and its gray areas.
One sign that cannot wait
New or worsening thoughts of suicide, especially after starting or changing a medication, need same-day attention. Antidepressant prescribing information, including the current Spravato label, carries a boxed warning about an increased risk of suicidal thoughts and behaviors in children and young adults, and calls for close monitoring of everyone taking antidepressants for worsening. Tell your prescriber right away.
If you are thinking about suicide or are in crisis, call or text 988 (the 988 Suicide & Crisis Lifeline) or go to the nearest emergency room.
Measure, do not guess: measurement-based care
Measurement-based care means filling out a validated rating scale, often the PHQ-9, at each visit and using the scores to guide decisions. It turns a vague "a bit better, I think" into a trend line you and your prescriber can both see.
It appears to change outcomes. In a 2015 randomized trial of 120 outpatients with moderate to severe depression, the group whose treatment decisions followed rating scales and guidelines had higher response (86.9% vs 62.7%) and remission (73.8% vs 28.8%) than standard care, and got there faster. That was one trial with only two medications allowed, but the principle is simple and low-cost.
| PHQ-9 total | Severity band | What it can suggest |
|---|---|---|
| 0 to 4 | Minimal | Close to remission in many studies |
| 5 to 9 | Mild | Better, but residual symptoms remain |
| 10 to 14 | Moderate | Treatment is probably not doing enough |
| 15 to 19 | Moderately severe | A change in plan is usually warranted |
| 20 to 27 | Severe | Needs prompt review; ask about safety |
Severity bands follow the original PHQ-9 validation study. One FDA-reviewed analysis of a TMS registry defined remission as a PHQ-9 below 5 after treatment. The questionnaire is a tool, not a diagnosis, and question 9 asks about thoughts of self-harm, so any positive answer should be discussed with your clinician. Scales matter for insurance too: several insurers ask for scores from a validated depression scale: Optum wants a documented baseline score, and Cigna wants scales at the beginning and end of each TMS course. Our guide to tracking your progress with the PHQ-9 and other scales shows how to keep a simple log.
What to ask your prescriber
| Question | Why it helps |
|---|---|
| Is this dose high enough, and has it been long enough? | Rules out an under-dosed or too-short trial |
| Could something else be driving this, such as thyroid, sleep apnea, alcohol, or a bipolar pattern? | Misdiagnosis and untreated medical problems are common causes of apparent resistance |
| What are our options: raise, switch, add, or try something non-medication? | Puts every path on the table, not just the next pill |
| Can we track a scale at every visit? | Makes progress, or the lack of it, visible |
| At what point would you consider TMS, esketamine or other treatments? | Sets a shared threshold for changing direction |
The World Psychiatry review lists misdiagnosis (including missed bipolar disorder), inadequate treatment trials and non-adherence among the most common reasons depression looks treatment-resistant when it is not. Please do not stop or taper a medication on your own. In a 2024 meta-analysis, 31% of people who stopped an antidepressant had at least one discontinuation symptom, compared with 17% of those stopping a placebo, and about 3% had severe symptoms. The site's article on getting off psychiatric medications safely explains why a plan matters. If side effects are the sticking point, this piece on reducing medication side effects may help you frame the conversation.
When TMS enters the conversation
TMS is FDA-cleared for adults with major depression who have not improved enough with prior antidepressant medication in the current episode. In practice, it usually comes up after one or more medication trials have fallen short. CANMAT 2023 rates rTMS as first line for treatment-resistant depression and says it can be a first-choice treatment when there are concerns about medication tolerability. Insurers generally want to see a documented history of failed or poorly tolerated medication trials; Medicare's local policy in New York, for example, also requires a trial of evidence-based psychotherapy.
TMS is not the right first step for everyone. If depression includes psychotic symptoms or acute suicidal thinking, expert consensus points toward treatments such as ECT first. And if one medication has only just been started, giving it a proper trial may make more sense. To weigh your options, read TMS or another antidepressant?, check the TMS candidate checklist, and use our guide to bringing up TMS with your psychiatrist. You can also browse the full TMS guide or read about TMS treatment for depression.
Sources
- Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry, 2023. pmc.ncbi.nlm.nih.gov
- The PHQ-9: validity of a brief depression severity measure. Journal of General Internal Medicine, 2001. pubmed.ncbi.nlm.nih.gov
- Measurement-Based Care Versus Standard Care for Major Depression: A Randomized Controlled Trial With Blind Raters. American Journal of Psychiatry, 2015. pubmed.ncbi.nlm.nih.gov
- Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. Journal of Clinical Psychopharmacology, 2009. pubmed.ncbi.nlm.nih.gov
- Emotional blunting with antidepressant treatments: A survey among depressed patients. Journal of Affective Disorders, 2017. pubmed.ncbi.nlm.nih.gov
- Antidepressant utilisation and incidence of weight gain during 10 years' follow-up: population based cohort study. BMJ, 2018. pubmed.ncbi.nlm.nih.gov
- Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. The Lancet Psychiatry, 2024. pubmed.ncbi.nlm.nih.gov
- SPRAVATO (esketamine) nasal spray, CIII – Prescribing Information (dosage, contraindications, warnings and adverse reactions sections). Janssen / DailyMed (U.S. National Library of Medicine), 2026. dailymed.nlm.nih.gov
- Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. American Journal of Psychiatry, 2006. pubmed.ncbi.nlm.nih.gov
- K231926 510(k) Summary – NeuroStar Advanced Therapy System. U.S. FDA, 2024. accessdata.fda.gov
- Transcranial Magnetic Stimulation (Coverage Policy EN0383). Evernorth Health Services (Cigna), 2026. a.static.cigna.com
- Behavioral Clinical Policy: Transcranial Magnetic Stimulation (BH803TMS112025). Optum Behavioral Health Solutions, 2026. providerexpress.com
- 510(k) K160703 (NeuroStar TMS Therapy System). U.S. FDA, 2016. accessdata.fda.gov
- Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults. Canadian Journal of Psychiatry, 2024. pmc.ncbi.nlm.nih.gov
- Transcranial Magnetic Stimulation (LCD L33398). CMS Medicare Coverage Database, 2026. cms.gov
- Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. Journal of Clinical Psychiatry, 2018. pmc.ncbi.nlm.nih.gov
FAQs
How long should I give an antidepressant before deciding it is not working?
Generally 4 to 6 weeks at an effective dose, taken consistently, though some people respond later. If you are getting worse or having troubling side effects, do not wait; call your prescriber.
Is it my fault if the medication did not work?
No. Non-response is common and has many causes, including the wrong drug for your biology, a missed diagnosis, or side effects that made consistent use hard. Saying honestly how you took it helps your prescriber plan the next step.
Can I take the PHQ-9 at home?
Yes. It is a short self-report form. Taking it at the same point each week or before each visit gives you and your prescriber a trend line. It does not replace an evaluation, and any thoughts of self-harm should be discussed right away.
Should I switch medications or try something different, like TMS?
It depends on how many trials you have had, how well you tolerated them, and how severe things are. After two adequate trials, guidelines support considering non-medication options such as TMS. See TMS or another antidepressant?
Does feeling emotionally numb mean the antidepressant is working too well?
Not necessarily. Emotional blunting can be a medication side effect, but researchers have found it also tracks with depression severity, so it can be a sign of residual depression. Describe it to your prescriber in your own words.
