Ketamine & TMS

It is always good to have options.  Until recently, people suffering from depression could see a psychotherapist, take a classic antidepressant medication, or get ECT (commonly known as "shock treatments").  Of course, everything has its pros and cons.  Psychotherapy works well for milder forms of depression, but the more serious the depression is, the less likely it is to be helpful. Plus it can take a long time to produce results.  ECT works better than anything we know of for depression, but is very inconvenient, involves running an electrical current through the brain to induce a seizure, and appears to be capable of causing memory problems.  The classic antidepressants work well for many people, but do have a moderate amount of side effects (nausea, headaches, drowsiness, sexual problems among others). Also, a substantial number of people can go through multiple medications without finding one that is both tolerable and effective enough.

And then there is the issue of what to do when these measures are not working, or work only partially.

Fortunately, in the last several years a couple of new clinically proven options have been developed; Transcranial Magnetic Stimulation (TMS) or ketamine (Spravato).. They are both very different from previous forms of treatment.  “Different” is important here.  Although we have around 20 different antidepressants, they tend to be from three different broad classes, and even these classes have many similarities.  When someone tries one antidepressant and fails, we may try another and another, but after a while we are basically going down the same road, hoping for a different result. Each time you fail a medication trial, the chances the next medication will work diminishes.

TMS and ketamine (including Spravato, intravenous ketamine and intramuscular ketamine), and transcranial magnetic stimulation (TMS)are both so different from previous therapies that they represent game changers in the treatment of depression.  Let's take a look at both and see where they might fit in for you, since they are also very different from one another.  Keep in mind that if one doesn't work, the other one is still an option, and still very different from anything that has been tried previously. Also, note that, for reasons described below, Southeastern Psychiatric Associates administers TMS, but not ketamine. 

TMS

TMS is not a medication at all, and therefore operates on very different principles.  Fundamentally, it is the same physics as a cordless cell phone charger. But here we are not charging a battery, but rather making an important region of the brain more active and stronger.  In TMS, magnetic pulses bring brain cells (neurons) closer to their trigger threshold. They therefore start firing more.  When the neurons “fire together they wire together”, forming connections that persist after the treatment has ended.  The region of the brain that we are strengthening is called the dorsolateral prefrontal cortex.  It is an important node in a network of brain regions.  When your conscious mind is trying to fight off depression, you are using your dorsolateral prefrontal cortex to push back against deeper parts of the brain that are generating the depression.  By strengthening it, we make you more able to bring yourself to an even keel.

TMS was cleared by the FDA in 2008 for treatment resistant depression, and has solid scientific evidence confirming its effectiveness.  Recent research reveals that after only two antidepressant failures, TMS is more likely to be effective than a third medication trial.  Unlike ECT, no electricity is actually passing through the brain.  It is merely a magnetic field coming from a device outside the head.  Treatments last up to 15 minutes, and you remain awake and alert during the treatment. The only sensation is a somewhat loud noise and a tapping feeling against the forehead.  When the treatment ends, you are able to resume normal activities immediately, even drive yourself home or back to work.  A course of TMS typically involves 36 treatments, usually delivered five times a week for 6 weeks, then a week of three treatments, a week of two treatments and a week of one treatment.

Over 50% of patients respond to TMS, and about half of those go into full remission.  We generally start to see results in about 2-4 weeks which is similar to standard antidepressant medications.  Unlike ECT, there is no evidence of memory damage, in fact there is some suggestion that TMS has a pro-cognitive effect.  The benefit tends to be durable.  Most patients do not require follow-up treatments or maintenance, although some do.  If retreatment is required, research indicates that 84% will respond a second time.  If maintenance treatments are required, this typically takes place every 2-4 weeks. TMS is covered by all major insurance companies.

KETAMINE

Unlike TMS, ketamine is a medication, but it is a very different medication than any antidepressant that has previously been in common use, because it works on a completely different brain chemical system than any of the others. Perhaps its most distinguishing feature is how fast it works. Whereas other antidepressants and TMS take weeks to work, ketamine can start working in as little as a couple of days, but it wears off quickly also, so it is given twice weekly at first, then indefinitely every week or two.

Its effect is also unusual. It has a 2 hour “trippy” effect which feels different from classic psychedelics like LSD or magic mushrooms. Patients often listen to music during those two hours. In the doses used it is not a strong “trip”. 

Ketamine comes in several forms, and the amount of medical and regulatory oversight varies widely as a result. The version that is FDA approved for depression is a nasal spray under the brand name Spravato. It is usually covered by insurance. But there is an older version, just called “ketamine”, that can be administered IV or IM by a clinician. This version is not covered by insurance and can therefore be quite pricey. The FDA regulates Spravato, so it is administered in a clinician's office, and the patient has to be driven home by someone else. Because it can raise blood pressure, this has to be monitored by clinical staff. Because “ketamine” is not regulated and is being used “off label”, the same restrictions are not required-but responsible clinicians should (though don’t always) follow them.

There is a sketchier ketamine market, where compounding pharmacies, which are only lightly regulated, make up their own batches of nasal, or even oral ketamine. Unscrupulous physicians then write prescriptions for this. It is then mailed directly to the patient’s house, where it is taken without direct clinical supervision. This carries tremendous potential for abuse and I STRONGLY URGE PEOPLE NOT TO DO THIS! 

Ketamine has been used for many years as an illegal street drug, often under the name”Special K” or just “K”. This raises the concern among some clinicians that perhaps we aren’t exactly treating people with an antidepressant, but are merely “getting them high.” A related concern is that ketamine is active at one of the opioid receptors. In fact , in one study, an opioid blocker, Narcan also blocked the therapeutic effect of ketamine. Ketamine is not an opioid per se, but I worry that it is opioid-adjacent. Lastly, chronic ketamine use, especially in high doses can damage the bladder (as Elon Musk has self-reported). As a result, Southeastern Psychiatric Associates is not currently administering any form of ketamine. 

SO WHICH ONE SHOULD I TRY FIRST?

There is no right or wrong answer here.  Bear in mind that whether you start with ketamine or TMS, if one doesn't work out, the other treatment will probably be your best option, (unless you want to take the high risk/high reward path of ECT).  Let's look at some important considerations which may help you choose:

• EFFECTIVENESS: Unfortunately, there are no head-to-head studies which might give us a clue as to which treatment may be more effective.  Even the ways in which the data was analyzed don't lend themselves to easy comparisons.  However, keep in mind that once people have failed a number of classic antidepressants, both of these treatments are likely to be more effective than taking yet another standard antidepressant.

• MECHANISM OF ACTION: Ketamine is a medication, whereas TMS is not.  But ketamine is a very different medication, working through a very different chemical system than the other antidepressants.  TMSis not a chemical at all; it affects the brain via a magnetic field.

• TIME TO RESPOND: Ketamine is the fastest treatment for depression that we have, often producing a response within a couple of days. TMS typically takes 2-4 weeks although it can be longer or shorter than that.  

• DURABILITY: Most patients who do respond to TMS do not require follow-up or maintenance treatment, but some do.  Ketamine does require ongoing treatments every 1-2 weeks indefinitely.

• FREQUENCY OF TREATMENTS: Ketamine begins as a twice weekly treatment and is then gradually decreased to every week or every other week. A course of TMS involves treatments five times a week for 6 weeks followed by a 3-week taper.  It is okay to miss some treatments, they just get added on at the end. 

• LOGISTICS: Patients can drive themselves to and from TMS treatments, and resume normal activities immediately.  Patients are not allowed to drive themselves home from ketamine treatments, so will either need a friend, relative or rideshare to get themselves to and from the office.

• SIDE EFFECTS: TMS can cause twitching of the muscles of the jaw or around the eyes, but only during the treatment. Some people experience headaches or drowsiness afterwards. One in a thousand people may have a seizure; a rate similar to antidepressants. Ketamine can cause a “trippy” experience, carries some abuse potential, can raise blood pressure and (generally with high doses and long term use) cause bladder damage.

• INSURANCE/OUT OF POCKET COST: Spravato and TMS are covered by insurance.  Each visit is therefore generally a standard co-pay.  IV and IM ketamine are not covered by insurance and so can be very costly. 

We are fortunate to be living in an era when we have more options at our disposal, when it starts to look like standard treatments for depression are not working.  Both ketamine and TMS offer dramatically different solutions from the old antidepressants and from each other.  WIth these two solutions, we can offer real hope that those who have not had good results in the past, can find a satisfying solution to this very debilitating illness.

Learn more about TMS