What's Better for Treatment-Resistant Depression? TMS, Ketamine, or Spravato?

Many of my patients who come to me for a treatment resistant evaluation wonder what's wrong with them that the typical antidepressants don't work. They hear about friends, family, co-workers, etc. who get on Prozac, Lexapro, Zoloft or some other such drug and live happily ever after. Except maybe for the myraid of side effects they may experience. Weight gain, sexual problems, insomnia, fatigue, cognitive problems, and the list goes on. 

First thing I tell them is that they are in good company. Research shows that up to 1/3 of those with depression don't respond to standard medication and/or psychotherapy. In my opinion, that number is even higher because there are many who have responded to these treatments but then the therapies stopped working over time. And what about those who don't like how they feel or can not tolerate medication? 

So of our newer interventional therapies, TMS, Ketamine, or Spravato, which is the best? (We will leave shock therapy-ECT- for another time since has its own special place). 

I wish it was a simple answer. But like most things in medicine, and life, it's not. There are very few meaningful studies comparing these treatments. These would be expensive, time consuming studies to do and it is unlikely that science will give us more guidance in the near future. So for now, we have to depend on what us frontline, healthcare providers see, like myself, doing these therapies. 

So my general observations? And I reserve the right to change my mind later. IV ketamine seems to work the fastest and in the most broad range of patients. We have more dosing flexibilty, we know how much is getting into your body and can adjust accordingly. Downside? It's not FDA appproved for depression, rarely insurance will cover it, it is a medicine given through an IV, and the effects seem to wear off if you don't get subsequent boosters or find some medicine to maintain the benefit. 

Spravato is FDA approved and is most like ketamine. Upside? Since it is an approved therapy, it is more likely covered by insurance,  has good long term safety and effectiveness data, and there are specific guideline on how, where, and frequency of dosing. While I think I've seen more people respond to IV ketamine than Spravato, I have had many do well on both, and a number of patients tolerate and/or do better than on IV ketamine. Downside? Intranasal dosing is less reliable, less dosing flexibility, and very expensive if insurance dosen't cover. Also, like ketamine, the effects can wear off quickly without repeated dosing. 

Lastly, TMS. This non-medication therapy is a magnetic pulse delivered to specific area of the brain. It is FDA approved and much easier to get insurance to cover since it has been around longer than Spravato. There is an extensive research database to support its safety and effectiveness. And its not a drug, which is appealing for many. I was quite the skeptic on this initiallly but have become increasingly impressed the more I watch patients go through this treatment. My initial lack of enthusiasm may have been that ketamine/Spravato work so quickly and TMS takes longer to see results, often 4-5 weeks. But the benefits seem more durable than ketamine or Spravato. 

Bottom line. I have had patients not respond to TMS and do great on ketamine or Spravato. Some do poorly on ketamine and do great on TMS or Spravato. And so on. They are all different enough, just like medications and all deserve a look. And we have a number of patients that do both TMS and ketamine/Spravato. This is growing interest in combining these therapies. 

An experienced clinician can guide you as to what the best therapy to start with is but do not discount any of them. They all work. They all have good safety profiles. But as to what is best for you? No one knows for sure. But whatever you do, do something because help is right there for you. 

Michael Banov MD Dr. Banov is the medical director of Psych Atlanta, with locations in Marietta and Roswell, Georgia, and provides comprehensive outpatient psychiatric care for adult patients. Dr. Banov is triple-board certified in adult, adolescent, and addiction psychiatry as well as a certified clinical research investigator. Dr. Banov completed his Bachelor of Arts in Religion at Duke University in Durham, North Carolina. He went on to earn his Doctor of Medicine at the Emory School of Medicine in Atlanta. He completed his psychiatry residency at McLean Hospital, Harvard Medical School. Dr. Banov has conducted over 150 clinical research studies in all aspects of psychiatry, including anxiety, depression, bipolar disorder, and post-traumatic stress disorder (PTSD). He has written over 25 scientific papers and articles. Dr. Banov shares his experience and knowledge as an assistant clinical professor at the Medical College of Georgia.

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