There is a particular kind of discouragement that comes with the first antidepressant not working. You waited the six or eight weeks you were told to wait, you put up with the side effects, and the result is that you feel roughly the same. It is easy to read that as evidence that nothing will work, or that your depression is somehow different.
The data says something else. Needing more than one attempt is the normal shape of depression treatment, not the exception.
The numbers most people are never shown
STAR*D remains the largest real world study of what actually happens when people are treated for depression in sequence. Participants who did not reach remission on one treatment moved to the next step, and the remission rates at each step looked like this:
- Step 1 (first antidepressant): about 36.8 percent reached remission
- Step 2 (switch or augment): about 30.6 percent
- Step 3: about 13.7 percent
- Step 4: about 13 percent
Read the first line again. Roughly two out of three people do not reach remission on their first antidepressant. If that is where you are, you are in the majority, and you have not run out of options. You have finished step one.
The second thing those numbers show is that the returns get smaller as you go. That is not a reason for despair, but it is a good reason not to spend years cycling through minor variations of the same approach without reassessing.
Before changing anything, a few questions worth asking
Quite often a medication gets labelled a failure when it was never given a fair test. Before moving on, it is worth checking:
- Was the dose ever optimized? A starting dose is a starting dose. Plenty of people conclude a drug does not work for them while sitting at the lowest dose in the range.
- Was it given long enough? Meaningful assessment usually needs six to eight weeks at an adequate dose.
- Was it taken consistently? Missed doses are extremely common and rarely volunteered. It is not a character failing, it is worth knowing.
- Is the diagnosis complete? Bipolar depression, ADHD, PTSD, an anxiety disorder or a substance issue running underneath will all blunt the response to a standard antidepressant.
- What else is in the way? Untreated sleep apnea, thyroid dysfunction, heavy alcohol use and chronic pain all suppress response.
A careful psychiatric evaluation exists to catch these before more medications get stacked on top of an incomplete picture.
The four common next moves
1. Optimize what you are already on
If there is partial benefit and tolerable side effects, raising the dose within the approved range is often the first and simplest step. Partial response is a meaningfully different situation from no response at all.
2. Switch
If there was no response at all, or the side effects were not liveable, switching makes sense. Sometimes that means another drug in the same class, sometimes a different mechanism entirely. Which direction depends on what the first trial actually showed.
3. Augment
Rather than replacing the first medication, a second agent is added to strengthen the response. This is a reasonable strategy when there has been genuine partial improvement worth preserving.
4. Bring in something that is not a medication
Structured psychotherapy has good evidence and works well alongside medication. And once two adequate medication trials have not produced remission, it becomes reasonable to evaluate for TMS therapy, which works through a different route entirely rather than adding another compound to the mix.
Where TMS fits
TMS is not a last resort and it is not a first line treatment. It occupies a specific place: depression that has not responded adequately to medication, in someone who is otherwise a reasonable candidate.
Because it is not a drug, it avoids the systemic side effects that make people give up on antidepressants, including weight change, sexual side effects and emotional blunting. The trade off is the schedule. A standard course means daily sessions over several weeks. Whether that trade is worth making is a real conversation, not a foregone conclusion. Our page on TMS compared with medication goes through it in more detail.
What treatment resistant actually means
The phrase sounds like a verdict on you. In practice it is a technical description, usually meaning depression that has not responded adequately to two or more appropriate treatment trials at adequate dose and duration.
It is a description of what has been tried so far. It is not a statement about how treatable your depression is, and it is not permanent. We have written more about this in understanding treatment resistant depression.
The point worth holding on to
An inadequate response to one antidepressant is information, not a conclusion. It tells you something about which direction to go next. What it should prompt is a careful reassessment of the whole picture, not resignation and not an indefinite series of small adjustments.
If you have been through one or more medication trials without getting where you wanted to be, you can read about our approach to depression treatment and medication management, or request an appointment to have the full picture reviewed properly.
This article is for general education and is not medical advice. Do not start, stop or change a prescribed medication without speaking to your prescriber.
Talk it through with someone
Jersey Shore Psychiatric Services provides psychiatric care for adolescents from age 12 and adults at 432 Avenel St, Avenel, NJ 07001. Care is led by Dr. Muhammad Ali Abbas, a triple board-certified interventional psychiatrist who directs the Neuromodulation Division at Raritan Bay Medical Center. Telepsychiatry is available for patients in New Jersey and New York, and new patients are usually seen within a day.
Call or text (732) 426-7030, email info@jshealth.org, or request an appointment online.