Major Depressive Disorder (MDD) remains one of the most difficult psychiatric conditions to treat, especially when patients do not respond adequately to medication. Repetitive transcranial magnetic stimulation (rTMS) has become a well-established, non-invasive treatment option for patients with treatment-resistant Depression, but a practical question often comes up for patients considering it: do the medications a patient is already taking affect how well rTMS works?
A study published in Brain and Behavior in 2019 examined this question directly by reviewing outcomes for patients undergoing rTMS while taking a range of psychiatric medications. Here is what the study found, and what it means for patients considering TMS at Mid City TMS.
Understanding rTMS and Its Role in Depression Treatment
rTMS is an FDA-approved treatment for Major Depressive Disorder, particularly for patients who have not responded adequately to antidepressant medication. It works by delivering targeted magnetic pulses to brain regions involved in mood regulation, most commonly the left dorsolateral prefrontal cortex. Unlike medication, rTMS does not rely on systemic drug metabolism and does not carry the same risk of cognitive impairment, weight gain, sedation, or sexual side effects. Because most patients undergoing rTMS are already taking psychiatric medication, understanding how these drugs interact with treatment is a meaningful part of clinical planning.
The Study: Medications and rTMS Outcomes
Researchers at UCLA conducted a retrospective chart review of 181 patients with MDD who completed a standard six-week course of rTMS between 2009 and 2017. All patients received 10 Hz stimulation to the left dorsolateral prefrontal cortex, with some also receiving 1 Hz stimulation to the right side if they did not respond adequately to left-sided treatment alone. Depression severity was tracked using the Inventory of Depressive Symptomatology Self Report (IDS-SR30) at two, four, and six weeks. Researchers then examined whether patients taking specific categories of medication, including antidepressants, benzodiazepines, antipsychotics, and psychostimulants, showed different patterns of improvement than those who were not.
Key Findings
Benzodiazepines were associated with less improvement. Patients taking benzodiazepines (such as lorazepam, clonazepam, or alprazolam) showed less symptom improvement at two weeks, an effect that held up after accounting for age, baseline severity, and anxiety symptoms. By six weeks, the response rate, meaning at least a 50% reduction in symptoms, was 16.4% among benzodiazepine users compared with 35.5% among non-users. One proposed explanation is that benzodiazepines enhance inhibitory GABA signaling in the brain, which may work against the excitability and plasticity that rTMS is thought to depend on. This remains a hypothesis rather than a confirmed mechanism.
Psychostimulants were associated with greater improvement. Patients taking psychostimulants (such as methylphenidate or amphetamine-based medications) showed greater improvement both at two weeks and across the full six-week course. By six weeks, the response rate was 39.2% among psychostimulant users compared with 22.0% among non-users. Researchers speculated that these medications, which increase dopamine and norepinephrine activity, may enhance the cortical plasticity that rTMS relies on, though this too remains an open question.
Antidepressants showed no significant association, favorable or unfavorable, with outcomes. This is a useful data point for patients who are currently taking an SSRI, SNRI, or other antidepressant and are weighing whether to continue that medication while starting rTMS.
Atypical antipsychotics and anti-epileptic medications showed no significant association with outcomes either. The study did not have enough patients taking lithium or other mood stabilizers to draw a reliable conclusion about that category, so it would be inaccurate to describe mood stabilizers as having been shown to be neutral. That question remains open.
Why These Findings Should Be Interpreted Carefully
The study’s authors were direct about its limitations, and those limitations matter for how patients and clinicians should use this information. This was a retrospective, observational chart review, not a randomized controlled trial, so patients were not assigned to medication groups. Differences in outcome could reflect underlying differences between patients rather than a direct medication effect. The findings also were not statistically corrected for the number of medication categories examined, which the authors themselves note means the results should be considered hypothesis-generating rather than confirmed. In their own words, the study’s authors concluded that it remains premature to make clinical recommendations based on this evidence alone, and called for controlled, prospective research to determine whether these associations are causal.
Practical Implications for Patients
A full medication review is a standard part of TMS planning. At Mid City TMS, this evaluation is part of the intake process for every patient, regardless of what this or any single study has found.
Questions about benzodiazepine use should go through your prescribing physician. If you are taking a benzodiazepine and considering rTMS, this research may be worth discussing with your psychiatrist as one factor among several, but benzodiazepines should never be stopped or reduced abruptly, since doing so can cause withdrawal symptoms. Any change in dosing should be individualized and medically supervised.
rTMS remains effective for many patients on multiple medications. Most patients pursuing rTMS have complex treatment histories, and this study’s overall sample showed meaningful improvement across the full six-week course regardless of most medication categories.
Personalized treatment planning matters. At Mid City TMS, treatment planning takes into account a patient’s full medication regimen, symptom profile, and prior treatment response.
Why rTMS Remains a Strong Option
Independent of how any particular medication may interact with treatment, rTMS offers real advantages for patients with Depression. It is non-invasive, and patients remain awake and alert throughout each session with minimal side effects. It does not carry the systemic effects of medication, since treatment is localized to specific brain circuits. It is effective for many patients who have not responded to multiple medications, and many patients experience durable improvement after completing a full course.
TMS at Mid City TMS
At Mid City TMS, we provide evidence-based, individualized rTMS treatment for Depression and related conditions. Our approach includes a comprehensive psychiatric evaluation, a careful medication review, an individualized treatment protocol, and ongoing symptom monitoring throughout the course of care.
TMS and Medications Looking Forward
This study adds useful, if preliminary, information to how clinicians think about medication use during rTMS treatment. Benzodiazepine use was associated with less improvement, and psychostimulant use was associated with greater improvement, while antidepressants showed no negative association at all. These findings come from a retrospective study that its own authors describe as hypothesis-generating, not a basis for changing medication decisions on its own. For patients with Depression who have not found relief with medication, rTMS remains a well-supported option worth discussing with a qualified provider.
If you or a loved one is living with Depression and considering TMS, learn how Mid City TMS can help, or contact us today to schedule a comprehensive evaluation.
Sources
- Hunter, A. M., Minzenberg, M. J., Cook, I. A., Krantz, D. E., Levitt, J. G., Rotstein, N. M., Chawla, S. A., & Leuchter, A. F. (2019). Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder. Brain and behavior, 9(5), e01275. https://doi.org/10.1002/brb3.1275
- Mann SK, Malhi NK. Repetitive Transcranial Magnetic Stimulation. [Updated 2023 Mar 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK568715/
- Rush, A. J., Giles, D. E., Schlesser, M. A., Fulton, C. L., Weissenburger, J., & Burns, C. (1986). The Inventory for Depressive Symptomatology (IDS): preliminary findings. Psychiatry research, 18(1), 65–87. https://doi.org/10.1016/0165-1781(86)90060-0