Is Using Ketamine and TMS Together More Effective Than Either Alone for Treatment Resistant Depression?

Picture two of the newest and most effective therapies for treatment resistant depression in modern psychiatry: magnetic pulses that can awaken specific brain circuits, and a medication that can rapidly lift the heaviest of depressions. Now imagine combining them. This is not science fiction, but rather an emerging frontier in treating what we call treatment-resistant depression (TRD)– those cases that have stubbornly refused to yield to our usual approaches. Upwards of 30% of people suffering from depression do not respond to standard antidepressants medication. Or cannot tolerate the side effects of these treatments. The combination of transcranial magnetic stimulation (TMS) and ketamine may be a transformative combination that can offer rapid and lasting benefits for those suffering from TRD. Think of it as a symphony where each instrument alone makes beautiful music, but together they create something transcendent. TMS is a FDA approved treatment for TRD that is well tolerated and highly effective but may take up to 4-6 weeks to work. The benefits however appear to be long lasting. Ketamine, which is not FDA approved for depression, is being increasingly used in patients who have not responded to standard medication and counseling and is known to work rapidly but the effects may be short lived unless one continues to receive treatment.

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The magnetic pulses of TMS gently coax the brain toward health, while ketamine – once known primarily as an anesthetic – acts like a reset button for neural circuits gone awry. What's particularly fascinating is how these treatments seem to amplify each other's benefits. In one recent study, doctors found that patients could tolerate stronger magnetic stimulation when ketamine was on board – as if the medication created a more receptive environment for healing. These weren't just temporary improvements. Many patients maintained their gains for two years or more, a remarkable achievement in treating persistent depression.

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It's reminiscent of the way certain medications work better in concert than alone – a phenomenon we've seen throughout medical history. What makes this combination so potent? The answer lies in the brain's remarkable ability to rebuild itself. Both treatments independently promote what we call neuroplasticity – the brain's capacity to forge new connections and heal old wounds. Together, they appear to create a more robust environment for this healing process, like preparing soil before planting seeds. Most encouraging is the safety profile we're seeing. Both treatments side effects tend to be mild and temporary – a fair trade-off for the profound relief many patients experience. This matters enormously because when you're fighting severe depression, the risks of not treating effectively far outweigh the modest risks of treatment.

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To date, there are no large well controlled studies exploring the benefits of combining these treatments, but at PsychAtlanta we are having more patients take advantage of combining these two therapies with the hopes of rapid and lasting improvement. A 2019 retrospective review of 28 patients with TRD revealed significant and sustained reductions in depressive symptoms following concurrent TMS and intravenous ketamine infusions. Remarkably, the improvements persisted for at least two years after treatment. The combined therapy also allowed for higher TMS intensities than typically tolerated, potentially enhancing its overall effectiveness. Similarly, a 2022 case report documented a patient with bipolar TRD achieving complete and lasting remission when TMS and ketamine were used together, despite limited response to either treatment alone. These findings suggest a synergistic effect that amplifies therapeutic outcomes.

Building on these clinical observations, a 2023 review explored the underlying mechanisms driving the enhanced efficacy of this combination therapy. Both TMS and ketamine independently promote neuroplasticity and regulate neurotransmitter activity, but their combined use appears to deliver more robust and longer-lasting antidepressant benefits. Additionally, a systematic review from the same year confirmed that the combination therapy outperformed either treatment alone, with only mild and transient side effects reported. These encouraging results underline the potential of TMS and ketamine as a powerful tool against TRD, emphasizing the need for further research to refine treatment protocols and fully understand their synergistic mechanisms.

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Of course, we still have much to learn. Science moves forward carefully, and larger studies are needed to fully understand this promising approach. But for those who have walked the long, dark road of treatment-resistant depression, this combination offers new hope – not just for temporary relief, but for lasting wellness.