For many older adults, Depression is more than just sadness. It can be persistent, debilitating, and resistant to standard treatment. In fact, a significant number of adults over the age of 60 suffer from treatment-resistant Depression (TRD)—a condition in which traditional antidepressants fail to bring meaningful relief in alleviating symptoms of Depression in older adults.
Countless older adults struggling with TRD are left to wonder where to turn when popular medications aren’t effective. To address this difficult crossroads, a major clinical trial known as OPTIMUM recently offered insights into whether it’s better to add a second medication (augmentation) or switch to a new one completely.
The findings of the OPTIMUM trial hold a deep significance regarding how this complex condition should be addressed moving forward. Increasingly, research and real-world psychiatry are turning to something beyond medications: Transcranial Magnetic Stimulation (TMS).
Let’s explore what the OPTIMUM trial found—and why TMS may be one of the most effective next steps for older adults living with stubborn Depression.
What Is the OPTIMUM Study’s Research in Symptoms of Depression in Older Adults?
The OPTIMUM trial—short for Optimizing Outcomes of Treatment-Resistant Depression in Older Adults—examined patients aged 60 and over who struggled with TRD and whose symptoms had not improved with at least two antidepressants. The study compared two potential treatment pathways:
- Augmentation: Participants were randomised to antidepressant augmentation with another medication (aripiprazole, bupropion, or lithium)
- Switching: Participants were randomised to replace their current antidepressant with a new one (bupropion or nortriptyline)
Researchers wanted to know, which, if any, specific patient characteristics make one approach more effective than the other. The OPTIMUM trial investigated five potential moderators that have been shown to negatively influence antidepressant treatment outcomes: age, executive dysfunction, comorbid medical burden, comorbid anxiety, and degree of treatment resistance. Researchers aimed to discover which, if any, of these factors influenced the advantage of augmentation over switching.
Key Takeaway from the OPTIMUM Study
742 participants were included in the OPTIMUM study; 262 were randomised to switching and 480 were randomised to augmentation and were subsequently treated for ten weeks.
Spanning this ten week period, researchers observed for two main outcomes—symtpom improvement (defined as change in scores on the Montgomery–Asberg Depression Rating Scale) or remission (defined on MADRS as a score of 10 or less at the conclusion of the study).
After the ten week period, the study concluded that the only notable moderator in patient outcome was correlated to the number of different antidepressants a person had already tried, or their “severity of treatment resistance.” For those who had tried fewer than three antidepressants, augmentation worked better.
However, for those who had tried three or more medications, researchers found there was no clear benefit of adding a new medication or switching—both strategies led to modest improvements at best.
These results gesture towards the pressing need for alternative treatment plans beyond just Depression medications for elderly and older adults; medical practitioners continue to seek new solutions that hold the promise of relief for older patients mired in the ongoing struggle against TRD.
One promising pathway for moving beyond a cultural dependence on antidepressants is Transcranial Magnetic Stimulation.
What the OPTIMUM Study Didn’t Include: TMS
Transcranial Magnetic Stimulation (TMS) is a non-invasive, FDA-approved treatment for Depression that uses magnetic pulses to stimulate areas of the brain involved in mood regulation, working to fight against symptoms of Depression in older adults.
While OPTIMUM focused on medication strategies, it did not evaluate TMS, despite strong evidence that TMS is both safe and effective in older populations. In fact, large bodies of research beyond OPTIMUM show that older adults respond well to TMS, often with fewer side effects than medications—which is of particular importance for patients struggling with:
- Polypharmacy (taking many medications simultaneously)
- Medical comorbidities (such as heart disease or diabetes)
- Cognitive concerns (foggy thinking or drug-related confusion)
Key Benefits of TMS for Older Adults:
- TMS is proven to be highly effective in remediating treatment-resistant Depression and diminishing symptoms of Depression in older adults.
- It is non-systemic; it doesn’t involve pills nor does it elevate the risk of potential drug interactions.
- TMS has minimal side effects, especially compared to Depression medications for elderly and older adults.
- It is covered by Medicare (which covers TMS for anyone who has failed to respond to just one antidepressant) along with most insurance plans.
- Most importantly, for those over 60, TMS can be safely used in older adults, even for individuals with multiple medications and/or medical conditions.
So When Is It Time to Consider TMS?
TMS may be the logical next step if you or your loved one has tried one or more antidepressants with little or no improvement or experienced significant side effects from antidepressant medication.
If you’ve observed only partial responses to combination drug strategies, struggled with drug interactions, or experienced medication fatigue, then TMS may prove to be a life-altering treatment option.
To be clear, the OPTIMUM trial indicates that fighting TRD is not about “giving up” on medication altogether, but rather emphasizing the need for an expansion of the treatment toolbox to include modern, evidence-based options that move beyond a sole reliance on pills.
Rethinking the Treatment Ladder
The traditional treatment model often looks like this:
Antidepressant #1 → Antidepressant #2 → Augmentation → Switch again → Add more medications → Continued waiting…
But because of studies such as OPTIMUM, we now know that continuing to cycle through medications after multiple failures often leads to diminishing returns. A more modern, patient-centered ladder might simply be reimagined as:
Antidepressant #1 → TMS
In this more direct and effective model, TMS becomes the next logical step in treatment as opposed to the last resort. TMS holds a deep level of synergistic potential when integrated with antidepressant therapy, and its life-altering effects hold deep significance for those who have tried and failed to respond to other treatment modalities.
The Need for Personalized, Collaborative Care
The real message from the OPTIMUM study is that no single strategy works for everyone—and treatment plans should be based on the individual’s history and needs rather than on blanket solutions that ignore multiplicity and variation.
TMS allows clinicians and patients to shift from a trial-and-error medication model toward targeted, brain-based care that doesn’t rely on the body processing more drugs, especially meaningful for those ages 60 or older overcoming late-life TRD.
At our practice, we integrate these insights by:
- Carefully reviewing a patient’s history with Depression medication for elderly and older adults
- Considering the number of failed antidepressant trials
- Evaluating suitability for TMS
- Offering compassionate, evidence-based guidance at each step
TMS vs. Medications: What the Research Shows:
Whether TMS is being used as an augmentation to an existing treatment plan or supplanting the use of antidepressants altogether, comparing the key differences between the two will provide a more holistic picture of their respective effects on treating TRD.
| Factor | TMS | Augmentation/Switch |
| Response Rate | 70-80% (after 4-6 weeks) | ~30-35% in OPTIMUM |
| Remission Rate | 30-40% | <25% |
| Side Effects | Mild (scalp discomfort, fatigue) | Can include weight gain, sexual dysfunction, sedation, etc. |
| Drug Interactions | None | Many |
| Cognitive Effects | Often improves clarity/cognition | Sometimes worsens (especially with lithium, tricyclics) |
Uncertain Whether TMS is Right for You?
Our clinical team offers personalized consultations to assess:
- TMS eligibility
- Insurance coverage
- Realistic expectations
- How it compares to other next-step treatments (like ketamine/Spravato, psychotherapy, or newer medications)
TMS Deserves a Place at the Table in Fighting Symptoms of Depression in Older Adults
The OPTIMUM study helps psychiatrists make smarter medication decisions, but it also reveals the limits of these medications overall—especially when a patient’s Depression has persisted through multiple trials.
Mid City TMS is proud to offer patients new solutions, and with them, new hope. Our TMS services are safe, effective, and finally accessible through insurance, including Medicare.
If you or a loved one is 60 or older and facing treatment-resistant Depression, don’t assume you’re “out of options.” You may just need a different kind of solution—one that focuses on brain stimulation, not just the addition of more pills.
Contact our office today to schedule a TMS consultation. No matter your age, we’re here to answer your questions and help you find the solution in the next stage of your wellness journey.
Sources
- Bender, K. J. (2025, July 25). Advantage of augmenting antidepressant over switching qualified in new analysis. Psychiatric Times. https://www.psychiatrictimes.com/view/advantage-of-augmenting-antidepressant-over-switching-qualified-in-new-analysis
- Kim, H. K., Karp, J. F., Lavretsky, H., Blumberger, D. M., Brown, P. J., Flint, A. J., … Mulsant, B. H. (2025). Moderators of antidepressant augmentation versus switch in the OPTIMUM randomised controlled trial. The British Journal of Psychiatry. https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/moderators-of-antidepressant-augmentation-versus-switch-in-the-optimum-randomised-controlled-trial/4AB4A560C293C66D1C6E713331C73FCB
