Next steps after antidepressants fail, compared in Wentzville

Adjusting medication, therapy, TMS, esketamine and off-label ketamine compared for the caregiver keeping the calendar and the receipts.

The second antidepressant did not work either. Your husband says he does not want to try a third. Your daughter says she is tired of being a science experiment. And you, the one keeping the calendar and the pharmacy receipts, are wondering what is actually left on the menu.

Quite a lot, as it turns out. This is a side-by-side look at the paths a clinician might raise once standard medication has stalled, written for caregivers around Wentzville and the western edge of St. Charles County. Think of it as a map rather than a recommendation, so the next appointment feels less like guessing.

First, a number that should make you feel less alone

Our commissioned survey of 443 Midwest adults put one blunt question to them: had depression, anxiety, or PTSD resisted standard medication for them or for someone close? Nearly three quarters, 72 percent, answered yes.

For caregivers, 22 percent of the sample had watched it happen to someone else without living it themselves, and 13 percent had been on both sides. The figures are final, and the direction is clear: what is happening in your house is statistically ordinary, even if it never feels that way.

Why a comparison helps

When one treatment fails, families tend to hear about the next one only if a clinician happens to bring it up. Most people cannot bring it up themselves because they have never heard of the options. In our survey, 73 percent had no familiarity at all with the name Spravato, and TMS was a known quantity for just 25 percent. You cannot ask about what you do not know exists. So here is the landscape.

Path one: adjust the medication plan

What it is. Switching to a different class of antidepressant, raising a dose, or layering a second medication on top of the first. This is usually the first move after a medication falls short.

What it asks of the family. Patience, mostly. Each change can take weeks to evaluate. Your role is often tracking side effects and mood changes that your loved one may not notice or report.

Where it tends to fit. Early on, or when a specific change has a clear rationale.

Path two: add or change therapy

What it is. Structured psychotherapy, such as cognitive behavioral therapy, alongside or instead of medication changes. For PTSD, trauma-focused therapies are a core option.

What it asks of the family. Weekly appointments and homework between sessions, which depression can make hard to keep up.

Where it tends to fit. Alongside nearly any other path.

Path three: TMS

What it is. Transcranial magnetic stimulation uses magnetic pulses aimed at specific brain areas. It is FDA-cleared for major depression and involves no medication and no anesthesia.

What it asks of the family. Time: sessions most weekdays for several weeks, though your loved one can usually drive afterward.

Where it tends to fit. For people who want to avoid another drug, or who have struggled with medication side effects. That preference is common: just over half of our sample did not know TMS but still cared about going drug-free.

Path four: esketamine (Spravato)

What it is. A prescription nasal spray, FDA-approved for adults whose depression outlasted earlier drugs. Patients use it themselves while staff watch, inside a certified clinic, and stay for monitoring before they leave.

What it asks of the family. Rides: no driving after a session, and the early weeks bring frequent visits.

Where it tends to fit. Adults whose depression has not lifted after earlier antidepressant trials. Whether it fits your person is a clinician's call. An overview of what Spravato treatment involves can help you prepare questions.

Path five: ketamine outside the FDA label

What it is. Generic ketamine, either infused by IV in a clinic or prescribed through certain telehealth services for home use. Because ketamine lacks FDA approval for depression, both routes are off-label.

What it asks of the family. Often out-of-pocket payment, since coverage is less common. With at-home versions, the family may become the only people present during a dose, which is a real responsibility.

Where it tends to fit. This is a different category from esketamine, with different oversight. Do not treat the two as interchangeable. If your loved one is considering at-home ketamine, raise it with their regular clinician first.

How families in our survey weighed the tradeoffs

When people choose a provider, coverage dominates. The share who placed insurance among their two biggest priorities was 85 percent. Location came next at 43 percent, which matters in Wentzville, where the nearest specialized clinic may be a highway drive east. FDA approval and speed of results trailed further back, picked by 27 and 24 percent.

We also asked whether people would rather use insurance and tolerate more steps, or pay themselves to move faster. Just over half picked the insurance route. Paying out of pocket appealed to 23 percent, and the last 26 percent had not decided. Deciding as a family which camp you are in will narrow the list quickly.

Questions to bring to the next appointment

• Which of these paths do you think is realistic for my loved one, and which are off the table?
• Can more than one be combined?
• How many visits per week would each involve, and for how long?
• Which ones are likely covered on our plan, and what paperwork will be needed?
• Who would you refer us to, and how far would we be driving?

That is where most would begin anyway; primary care was the opening move for 56 percent of everyone we surveyed. Bring questions, not a decision.

Take care of the driver, too

Every one of these options leans on someone at home. If that is you, build in help, like a sibling who covers one ride a week, and tell your own doctor how you are holding up.

If at any point your loved one says something that frightens you, about ending their life or not wanting to wake up, act that day. The Suicide and Crisis Lifeline at 988 takes calls and texts for free, never closes, and welcomes caregivers calling for someone else. Veterans can press 1.

Methodology

Pollfish ran our survey on its consumer panel, and 443 adults aged 18 to 64 had completed it when the window shut on June 23, 2026. They came from Oklahoma, Iowa, Missouri, Ohio, Minnesota, Kansas, Indiana, Wisconsin, Illinois, and Nebraska. We cite top-line results, and every one is from the validated final export. This site's publisher commissioned and funded the work. Nothing here is medical advice.