When the first or second antidepressant has not done enough, the usual next step is a third. Plenty of people in O'Fallon and around St. Charles County would rather not have that conversation yet. They want to see the full menu first.
Here are four common paths laid side by side: another antidepressant, psychotherapy, TMS, and esketamine. The comparison grew out of a summer survey we commissioned and is meant to help you prepare questions for a clinician, not to pick for you.
The finding behind this comparison
Our survey reached 443 adults spread over Missouri and nine more Midwest states. When one question asked respondents about TMS and about drug-free care, 64 percent said avoiding medication mattered while only 25 percent were familiar with TMS, and half of everyone landed in a single group: unaware of TMS but interested in a treatment without drugs.
So many people are comparing options without knowing one of the main ones exists. These numbers are final.
Path 1: Another antidepressant
What it is: a different medication, a dose change, or a second drug added to the first.
Drug-free? No.
Time commitment: Few visits: a prescription, a pharmacy stop, and follow-ups. The waiting is the hard part, since antidepressants often need weeks to reach full effect.
Regulatory status: Standard antidepressants carry FDA approval for depression.
Coverage: Usually covered, often cheaply for generics.
Worth knowing: Many people do improve on a new drug or combination, but asking what else exists before another trial is reasonable.
Path 2: Psychotherapy
What it is: Structured talk therapy with a licensed clinician; cognitive behavioral and interpersonal therapy are among the best studied for depression.
Drug-free? Yes.
Time commitment: Typically a weekly session for months. Video visits help it fit around a job or an I-70 commute.
Regulatory status: Therapy is not an FDA-regulated product; the state licenses therapists.
Coverage: Commonly covered, though session caps, referrals, and copays differ by plan.
Worth knowing: Therapy often goes alongside other treatment rather than replacing it, and fit with the therapist matters, so trying more than one is fine.
Path 3: TMS
What it is: Transcranial magnetic stimulation, in which a coil on the scalp pulses a mood-related brain region while you sit awake without anesthesia.
Drug-free? Yes.
Time commitment: High. A standard course runs nearly every weekday for several weeks and then tapers, and most people drive themselves and can head back to their jobs afterward.
Regulatory status: The FDA has cleared it for major depression in adults with too little benefit from antidepressants. Clearance is the review route for many devices and is separate from drug approval.
Coverage: Many plans pay after prior authorization, usually wanting records of earlier medication trials.
Worth knowing: Scalp discomfort and headache are common; seizures are unusual, and a risk screening comes first.
Path 4: Esketamine
What it is: A nasal spray sold as Spravato that patients use themselves under direct supervision at a certified site, followed by on-site monitoring and no driving until the next day.
Drug-free? No, it is a medication.
Time commitment: Moderate to high. Visits cluster at the start and taper later, and each includes a monitoring period, so you need a ride.
Regulatory status: FDA approved for treatment-resistant depression, unlike IV ketamine for depression, which is off label, or home ketamine, which is less regulated.
Coverage: Often covered with prior authorization; plans vary.
Worth knowing: Among our respondents, 73 percent had never heard of Spravato, so it may be new to you as well. Brain Recovery Centers publishes a rundown of the Spravato treatment process for anyone weighing this path.
How respondents weighed these factors
Asked for their two most important considerations in a provider, respondents put insurance first by a mile at 85 percent and closeness to home second at 43 percent; FDA approval and fast results followed, 27 and 24 percent.
In separate questions, FDA approval ranked as decisive or major for 59 percent of respondents, and coverage reached that level of importance for 65 percent.
Mapped onto the four paths, those priorities suggest settling a few questions early. Is it covered, and what does the plan require first? How far is the provider from home or work? And is the treatment approved, cleared, or off label?
The O'Fallon factor: time and distance
For O'Fallon residents, TMS and esketamine ask the most of the calendar: TMS through many short visits, esketamine through fewer, longer ones plus a driver. Before choosing either, look honestly at work hours, childcare, and the commute, and ask clinics about early and evening slots.
Therapy asks least of your map, especially when some sessions are online. Another antidepressant asks least of your calendar but may ask the most patience.
Starting the conversation
Most respondents would begin with their own doctor: 56 percent named primary care as the first stop, and 74 percent said their doctor's recommendation would be what moved them.
Bring this comparison along and ask: "Given my history, which of these should we look at next?" Keep taking current medication until your prescriber says otherwise, and remember that the right choice depends on a health history only a clinician can weigh.
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Methodology
Pollfish carried out this research among its consumer panelists, with the publisher as the commissioning and paying party. By the June 23, 2026 close, 443 adults had completed it; each consented, was aged 18 to 64, and lived in a ten-state Midwest region including Missouri. Where several answers were allowed, each percentage uses the full sample as its base; all results are final.