For decades, antidepressant medications have been the first-line treatment for major depressive disorder (MDD). While they have helped millions of people, the reality is that they often fall short—with new research illuminating the low rate of long-term antidepressant success. Patients may try multiple prescriptions, switch between SSRIs, SNRIs, or tricyclics, and still feel trapped in cycles of relapse or non-response.
A groundbreaking 2024 Danish study recently shed light on this issue; by analyzing outcomes from over 100,000 patients across a two-year period, researchers compared the effectiveness of 17 different antidepressants in real-world settings. The results were eye-opening: not all antidepressants are equal, and even the most effective ones still leave many patients without relief.
At Mid City TMS, where we provide innovative, evidence-based treatment for Depression in New York City, these findings reinforce an important truth: when medications fail, Transcranial Magnetic Stimulation (TMS) is a proven next step.
Why Long-Term Antidepressant Success Matters
Most clinical trials on antidepressants focus on short-term results—usually 6–12 weeks. But Depression is usually a chronic illness. What often matters to patients and clinicians is not just whether a medication helps for a few months, but whether it works over years without frequent relapses, switches, or hospitalizations.
This is exactly what the Danish research team set out to measure in 2023. By using a nationwide health registry and “emulating” the structure of a randomized clinical trial, they were able to follow patients for two full years—a far more realistic timeframe for evaluating long-term success.
The Study: 17 Antidepressants, Over 100,000 Patients, 2 Years of Comparison
The study included 106,920 patients diagnosed with major depressive disorder who began treatment with one of 17 commonly prescribed antidepressants. A patient was considered a “non-responder” if they had ever switched to another antidepressant, added an additional antidepressant to supplement their treatment, began treatment with antipsychotics or lithium or required hospitalization for Depression. By tracking long-term outcomes, the researchers could compare real-world effectiveness across drug classes and specific medications.
Key Findings: Which Antidepressants Held Up Best?
The results of the study showed a few clear differences and distinctions between the long-term responses produced by the medications in question:
- Sertraline (Zoloft) stood out as one of the most reliable SSRIs for long-term response.
- Citalopram (Celexa) performed similarly to sertraline, but escitalopram (Lexapro)—often thought of as superior—actually had a higher rate of non-response over two years.
- Fluoxetine (Prozac) and paroxetine (Paxil) also showed weaker long-term results compared to sertraline.
- Among SNRIs, venlafaxine (Effexor) performed better than duloxetine (Cymbalta).
- Mirtazapine (Remeron) was a stronger option compared to some of its peers, especially when used for patients with insomnia or appetite issues.
- Among older tricyclic antidepressants, amitriptyline surprisingly outperformed others like clomipramine and nortriptyline.
While sertraline, mirtazapine, and venlafaxine showed relative strengths in two-year outcomes, escitalopram, fluoxetine, and duloxetine were less effective long-term than expected. Overall, the takeaway of this study is that no single antidepressant guarantees long-term success; even the most effective medications still left many patients cycling through multiple treatments, searching for a better solution.
The Implications of this Study for Patients
For patients in New York City and beyond, these results highlight a few important realities:
- Trial and error is common. Many people will not respond to the first, second, or even third antidepressant.
- Medication classes are not interchangeable. Even within SSRIs, one drug may work much better—or much worse—than another.
- Non-response is frustrating but not unusual, and remains common across all medications tested in the study. If you’ve tried several medications without sustained relief, you are not alone.
This is where patients often feel stuck. The study confirms that while some antidepressants perform better than others, a significant number of people remain untreated by medication alone. For them, it’s time to consider alternatives. Here is where the conversation shifts—and where Mid City TMS offers a lifeline.
TMS Offers Hope as a Strategic Next Step for Non-Response to Low Antidepressant Success
The Danish study underscores a harsh truth many patients already know from experience: even the best antidepressants fail for a large portion of patients, and long-term success is uncertain. Instead of endlessly switching medications and enduring side effects, patients now have another option—Transcranial Magnetic Stimulation (TMS).
TMS is an FDA-approved, non-invasive treatment for major Depression that uses magnetic pulses to stimulate underactive regions of the brain involved in mood regulation. When compared against medications, which circulate throughout the body, TMS acts directly on the brain’s neural circuits—targeting the source of Depression without systemic side effects.
Why Patients Choose TMS After Non-Response to Antidepressants
- Proven effectiveness: Clinical studies show that TMS can help patients who have failed multiple antidepressant trials achieve meaningful remission.
- Durable results: Many patients report lasting improvement months or even years after TMS treatment.
- Fewer side effects: The most common side effect of TMS is mild scalp discomfort during sessions—far less disruptive than weight gain, fatigue, or sexual dysfunction from medications.
- Compatible with medication: TMS can be used alone or alongside ongoing antidepressant treatment to achieve the best possible results.
Too often, patients are told to “try just one more medication” with little to no antidepressant success before exploring TMS. The Danish study shows why this mindset must change. If multiple antidepressants have failed, continuing to switch medications may not provide better outcomes. TMS is not a last resort—it’s a proven next step forward.
What the Patient Experience Looks Like at Mid City TMS
At Mid City TMS, we believe patients shouldn’t have to suffer through years of trial and error. At our Manhattan clinic, we make the TMS journey as comfortable and effective as possible by offering the following:
- An in-depth consultation: We review your history, past medications, and goals. During this initial meeting, we’ll discuss whether TMS is right for you and answer any questions you may have about the treatment process. We also coordinate with your current providers to ensure comprehensive, collaborative care.
- A personalized treatment plan: Sessions are typically five times per week for 7-8 weeks. We tailor the specific TMS protocol to your individual needs, adjusting parameters based on your response to treatment. For patients with significant anxiety components, we may recommend bilateral TMS to target both brain hemispheres.
- Safe, comfortable sessions: Each lasts about 4 minutes; you can return to normal activities right after. You’ll remain awake and alert throughout the procedure, and there’s no need for anesthesia or recovery time. Most patients find they can drive themselves to appointments and go directly back to work or daily responsibilities.
- Ongoing support: Our team monitors progress closely and integrates TMS with your broader treatment plan. We’ll meet weekly to monitor progress and address concerns and questions. We maintain regular communication with your psychiatrist, therapist, or primary care provider to ensure coordinated care throughout your treatment journey.
Charting a Path Towards Healing with Mid City TMS
At Mid City TMS, our mission is to help patients in New York City find relief from their Depression when their antidepressant success stories fail to stand the test of time. The Danish study on antidepressants proves that while medications play an important role, they often leave patients cycling through options without ever obtaining lasting, meaningful improvement.
TMS therapy offers hope. It is safe, effective, and uniquely suited for patients who have experienced antidepressant non-response. If you or a loved one has tried multiple medications without success, now is the time to explore a different path.
Contact Mid City TMS today to learn how TMS can help you break free from the cycle of trial-and-error and move toward lasting recovery.
Sources:
1. Kessing, L. V., Ziersen, S. C., Andersen, F. M., Gerds, T., & Budtz‐Jørgensen, E. (2024). Comparative responses to 17 different antidepressants in major depressive disorder: Results from a 2‐year long‐term nation‐wide population‐based study emulating a randomized trial. Acta Psychiatrica Scandinavica, 149(5), 378–388. https://doi.org/10.1111/acps.13673