Ketamine Therapy Vs. TMS: Which One is Right for You?

A Brief History of Ketamine

Ketamine vs. Traditional Antidepressants

Now, traditional antidepressants like SSRIs and SNRIs (think Prozac, Zoloft, Effexor) have been around for decades, and they’re still very useful for many people. But here’s the kicker: they can take weeks to take effect, which can be frustrating if you’re in the thick of depression. Ketamine, on the other hand, can work within hours or days, making it a game-changer for people with treatment-resistant depression.

That said, ketamine isn’t just a quick fix. Many patients report that the positive effects stick around even after their initial doses, thanks to the brain’s boosted neuroplasticity. However, the long-term benefits and how to best maintain them are still being studied.

Ketamine has an interesting effect on what’s known as the Default Mode Network (DMN). The DMN is basically your brain’s “autopilot” mode, which is most active when we are not engaged in much brain activity, when we are idle. It’s also capable of self-referential thinking—that can lead to an endless loop of negative thoughts and rumination that’s so common in depression. If your brain is constantly chewing over the same painful thoughts, your DMN might be overactive.

Ketamine (and TMS) can disrupt this pathological pattern, helping the brain break free from that negative loop. Think of it like rebooting a frozen computer—it gives your brain a chance to start fresh, reducing rumination and increasing mental flexibility.

Now, there are two main ways people get ketamine therapy:

• IV Ketamine:This is the most common method. Ketamine is administered via infusion, usually over a few weeks. The typical regimen includes six infusions over two to three weeks.
• Esketamine (Spravato):This nasal spray form of ketamine was FDA-approved in 2019 and is slightly more potent than IV ketamine. It’s administered under supervision in a clinic, but works just as fast. I have experience administering Spravato. I was involved in post marketing research at Suburban Research Associate (https://suburbanresearch.com) with Dr Shivkumar Hatti. I witness great improvement in many of our “subjects”, which is the term the replaces “patients” in the research setting. Some patients would become chatty, quite talkative. Others would almost fall asleep. But I remember one who dissociated, felt quite uncomfortable and paranoid - a “bad trip”, if you will. But these side effects would subsided within 2-3 hours and their depression, like I said, did improve.

Now, just a heads-up: some ketamine clinics are run by non-psychiatrists, like pain specialists or anesthesiologists. These folks are highly skilled at administering ketamine, but if you’re dealing with depression or other psychiatric conditions, it might be helpful to see a psychiatrist. Psychiatrists have specific expertise in mental health and can integrate ketamine therapy into a broader, more holistic approach to your well-being.

One of my patients recently tried oral ketamine through a telemedicine service called Mindbloom. This company prescribes and supervises at-home oral ketamine therapy, and my patient saw significant improvements in mood and clarity. However, he did share that the process wasn’t without its challenges: “I had to take the ketamine pill once a week, and I’d lose a whole day feeling stoned,” he told me. It worked for him, but the logistics weren’t ideal—he had to set aside an entire day.

Ketamine is a powerful antidepressant with rapid clinical effects, making it an effective “rescue” option for individuals experiencing acute depression with suicidal ideation. Additionally, it may benefit those who have not responded to multiple antidepressant trials over a prolonged period. However, ketamine requires more frequent retreatment and may induce a psychedelic experience that can take several hours to wear off, potentially impairing functioning for the remainder of the day. In contrast, TMS provides more durable benefits, enhances cognitive function, and is performed on an outpatient basis, allowing you to immediately resume work, school, or other activities. Both treatments may be used in combination to maximize therapeutic effects. There are many factors to consider when choosing a treatment, and I hope this article supports you on your journey toward recovery.

If you’re considering ketamine therapy and happen to live near Wilmington, Delaware, you’ve got some great options:

• Therapeutic Infusions / Ketamine Therapy in Delaware offers ketamine infusions and Spravato to treat depression and anxiety.
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• Dr. Terrence Boyadjis in West Chester, PA is a close friend and colleague of mine. He offers intranasal ketamine therapy and TMS treatments. I can’t recommend him highly enough—he’s fantastic with patients suffering from severe depression and anxiety.
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• Dr. Sandeep Gupta at Serene Minds LLC is another trusted colleague and personal friend. He provides both ketamine therapy and TMS, and he’s got years of experience helping patients with mood disorders.
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• Dr. John Dougherty of Initia Nova (with offices in Wilmington, DE, and Cherry Hill, NJ) is also a fantastic resource. He’s highly experienced with ketamine therapy, particularly for depression and concussions.
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• Brandywine Therapeutics offers comprehensive mental health services and ketamine therapy for depression.
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• Dr. Rany Abdallah at ApicoPain provides ketamine infusions for pain management but also uses it to help patients struggling with depression.
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References:

1. Ketamine and Depression:
 Duman, R.S., & Aghajanian, G.K. (2012). "Synaptic Dysfunction in Depression: Potential Therapeutic Targets." Science. This study explores how ketamine promotes synaptogenesis and neural plasticity, which forms the biological basis for its rapid antidepressant effects.
2. Ketamine’s Mechanism of Action:
 Krystal, J.H., et al. (2019). "Ketamine for Depression—Part 1: Clinical Summary and Mechanism of Action." The American Journal of Psychiatry. This article provides insights into how ketamine blocks NMDA receptors and its downstream effects on synaptic plasticity and mood improvement.
3. Ketamine vs. Traditional Antidepressants:
 Zarate, C.A., et al. (2006). "A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression." Archives of General Psychiatry. This clinical trial compares ketamine's rapid effects with the slower onset of traditional antidepressants like SSRIs.
4. Ketamine and the Default Mode Network:
 Carhart-Harris, R.L., et al. (2012). "Neural Correlates of the Psychedelic State as Determined by fMRI Studies with Psilocybin." Proceedings of the National Academy of Sciences. This research explains how psychedelics like ketamine disrupt the Default Mode Network, leading to reduced rumination and improved mental flexibility.
5. TMS Therapy and Depression:
 George, M.S., et al. (2010). "Daily Left Prefrontal Transcranial Magnetic Stimulation Therapy for Major Depressive Disorder: A Sham-Controlled Randomized Trial." Archives of General Psychiatry. This study compares TMS to placebo, showing its effectiveness in treating depression.
6. Esketamine (Spravato) and its FDA Approval:
 "Spravato (Esketamine) – A New Antidepressant Option." (2019). The American Journal of Psychiatry Residents' Journal. This article discusses esketamine’s FDA approval for treatment-resistant depression and how it compares to IV ketamine.