… and then maybe try Ketamine?

Hey Martin,

TMS (whether dTMS or rTMS) has a great likelihood of getting a patient into full remission from the symptoms of depression and keeping them in a balanced state for an extended period of time. It usually takes 20 treatments for a patient to start to see improvements in function and mood, but many don’t see improvement until they near the end of their treatment course and (in some cases) they don’t see the effects until a month or two after treatments are completed. In short, I think it’s too early for you to tell whether you are benefiting from TMS and you need to be a little more patient with the process.

As for ketamine, it can be a great short term solution to help get you out of the doldrums and on the path to healing, but the benefits are short term and most people need frequent top offs to sustain the benefit. It’s not a cure for depression and the chance of having a sustained benefit from TMS alone is greater than with Ketamine alone

Depending on your financial situation and access to medical care, you can pursue both TMS and Ketamine at the same time. There are doctors that strongly believe that TMS treatments create pathways that help sustain the benefits for Ketamine for the long term. Here’s a case report by Dr. Steven Best, who is a big proponent of combined rTMS/ketamine therapy: His protocol calls for a patient to receive rTMS and a relatively high dose of Ketamine administered via IV bracketed within the first five and last five minutes of the rTMS treatment (which is administered over 37 minutes). Dr. Best’s proposed protocol provides for the patient to be primed with four TMS treatments administered over two days (no Ketamine). On the third day, the patient receives the combined treatment. After the first week (3 days of treatment), the patient returns for combined therapy once a week for 30 weeks. He has done an open label study of 28 patients that suggests that combined therapy is significantly more effective than TMS or Ketamine administered by themselves.

Dr. Best’s protocol hasn’t been studied by anyone else to my knowledge and it’s certainly not a treatment that has been proven to be effective. My wife is, however, seeing another doctor that uses a different combined therapy protocol, where she gets rTMS treatments 5 days a week for six weeks, with ketamine administered via IM injection during twice a week. It’s too early for her to tell whether this treatment is effective, but our fingers are crossed. I also know of other people that are receiving rTMS treatments and ketamine infusions concurrently, but not administered at the same time or by the same doctor.

Anyway, it’s food for thought and maybe something worth looking into. Good luck!!!

Martin,

I am not a doctor and it’s not my place to tell you what treatment is best for you. Opinions are like @ssholes, we all have one and half the time they are wrong. I can only share with you my personal experiences with these treatments. Well, not mine exactly, but my wifes. My wife has been struggling with severe MDD (unipolar) most of her adult life. She used to respond to SSRI’s but that stopped about three years ago and now she is treatment resistant to pretty much every drug combo out there. She has tried them all: cymbalta, prozac, lexapro, viibryd, effexor, wellbutrin, abilifiy, trintellix, latuda, lithium, (and many that I am forgetting at the moment). My wife has been through a living hell, to the point where she told me that she is a drag on everyone she loves and that if it wouldn’t devastate the kids and me, she would end it all now.

My wife has been under the care of 7 different p-docs in the past 5 years and six of them sucked @ss!!!. If they were on our insurance policy, they were getting paid $70 a session to treat my wife and if things were more complicated than just writing a script for prozac, they were out of their depth and weren’t going to do the research needed to help my wife. Doctor 6 came highly recommended and didn’t take insurance. We paid him a fortune and he started my wife on a disastrous course pharma combinations that turned my sweet (but sad) wife into an angry person, full of rage with paranoid delusions. I was scared to leave her alone (and never left her alone with the kids for more than 10 minutes at a time). Doctor’ 6’s answer to these issues was to put her on even higher doses of more toxic meds and he strongly recommended having her placed in inpatient care at a p-ward and thought ECT was her only option. He was against Ketamine because for treating depression because it wasn’t FDA approved (and he couldn’t provide it to her anyway, since he didn’t have the skills) and he thought TMS was a waste of time (he also couldn’t offer that, since he didn’t have the machines and would have to refer my wife to another doctor for treatment–thereby costing him a patient that was paying $400 in cash every two weeks (sometimes more often). We ditched doctor 6 in September.

In October, my wife started seeing Dr. 7, who is a neuropsychiatrist (did his residence in Neurology and fellowship in psychiatry). Our experience with Dr. 7 is a 180 degree difference from any other p-doc my wife has seen (or that I have seen for that matter for my own issues). He didn’t just do the usual psych workup that every other p-doc did (you know the one, “how do you feel today on a scale of 1-10, ten being fantastic—-“. I mean, he did ask my wife those questions, but he also talked to my wife for over 2 hours during the first session and she felt he really understood how she ws feeling. He then had my wife take an MRI, EEG, full blood work and he conferenced with my wife’s OB-GYN to rule out any hormonal issues and her primary care physician. He also took her off all of the meds Doc 6 had her on, and replaced it with a low dosages of Viibryd, Welbutrin, Ritalin (to help her get enough energy to get out of bed and focus on her basic needs) and klonopin for anxiety/panic attacks. He put her on these drugs to try to take some of the edge off of her and to reduce the withdrawal effects from some of the drugs she was on. He didn’t even get into ketamine, TMS or anything else with her at this time.
By making these changes, my wife’s rage and anger were gone in a couple of weeks, but the depression and anxiety were still in full force and effect.

In December, my wife wasn’t doing well so Doc 7 talked about her iother options. In addition to the usual p-doc services (meds, talk therapy etc.), Doc 7 offers ketamine infusion therapy (since 2011), rTMS (since 2009), dTMS (since 2013), tDCS in his offices and ECT through the hospital. One of his partners is a neurosurgeon that performs surgery to implant the electrodes and equipment used for deep brain stimulation and vega nerve stimulation (both require surgical procedures). In short, his practice offers the latest and greatest services, so he has no economic incentive to push patients towards one treatment as opposed to another–which isn’t the case for many clinics. If you go to Ketamine clinic run by an anesthesiologist,he can only offer KIT and has an economic incentive in promoting it over other treatments like rTMS. If you go to a TMS clinic that doesn’t offer KIT (which is usually the case), they’ll push TMS as the preferable course of treatment. So, when doc 7 gives advice based on his experience with these treatments, it means something to my wife and me because he has no incentive in promoting one over the other.

In January he started my wife on Ketamine infusion therapy and, at the same time, he started the paperwork to get her approved for rTMS from our insurance carrier. He explained to us that Ketamine is a wonderful short term solution, but TMS is more likely to provide my wife with a durable, lasting remission. He also offered us the option to pursue both treatments in a combined therapy protocol his practice has developed. There’s not a lot out there on this, but there are other neuropsych clinics doing research in this area with solid preliminary results. There’s no increase risk facts when compared to TMS or ketamine administered alone, the only issue is whether the combined therapy will result in a better treatment outcome than either TMS or Ketamine alone. We felt it was worth a shot. (He also isn’t charging us more for the combo therapy than the rTMS alone, after we paid for the initial 6 ketamine treatments alone–so, he’s not making more money off of us, but pushing the combination therapy [which is refreshing]).

As of now, my wife had a full course of six ketamine infusions (2 a week for three weeks) without rTMS. The ketamine, by itself was very helpful—but it did not put my wife into remissions. She is still depressed, still has anxiety attacks, still cries a lot—but the intensity and frequency is less. She also has a lot more good moments, when she is actually smiling and laughing. She even sings along with music again. She has also had 5 TMS treatments without Ketamine for the first week of TMS treatments and she just had treatment 9 today (there was a delay after treatment 5 due to an insurance snag, but we’re back on track now).

After 9 TMS treatments (2 combined tms/ketamine), my wife’s mood is still very low and she is still having panic attacks and is getting fixated on her fears and worries (like what will she do if this treatment doesn’t work etc.). If you ask her, she’ll tell you she doesn’t feel better and doesn’t see any change. That’s her perception of things, but mine perspective is different. While I don’t any major improvements in mood, I do see some noticeable improvements in function for her. For example, she doesn’t get as frustrated as easily or as quickly as she normally would. If my daughter spilled juice on the floor a month ago, my wife would have flipped out (three months ago it would have been very serious incident). This morning, my wife got a little annoyed, but said, “honey, you need to be more careful and let’s clean this up. Go get some paper towels…..” That’s a major improvement. While my wife is still having panic attacks, there have only been two significant ones since treatment began (instead of daily). She seems to sleep better–more deeply and it’s easier for her to get up in the morning (relative to how she was before). She also isn’t getting caught up in thought loops (that’s what I call them anyway), when she gets an thought or idea in her head and can’t get it out of mind. She’ll start a thought loop, but I can change the topic or create some distraction and it gets her thoughts “unlocked”. She also laughs at stupid stuff on tv on occasion–which is great and she is singing along to music in the car at times. She is also more willing to consider different ideas. I was trying to convince her to try mindfulness meditation techniques a few months ago and you would have thought I was asking her to cut off her right arm. I mentioned it last night and I downloaded a mindfulness program for her and she actually said she would give it a try.

In short, I am not describing miracles or major events. These are signs of improved function relative to how my wife was functioning in the recent past. Things are not good by any means. She is still emotionally fragile and I would not be surprised if she experiences one or more set backs along the way. People don’t heal in a straight line of constant improvement. It’s all ups and downs that hopeful trend upward as a general pattern over time, like the stock market.

Before you give up on dTMS, think about how your ability to function may have improved in small ways over the past couple of weeks. Ask people who know you and see you regularly if they notice any changes or improvements. Whether you seek treatment with Ketamine, dTMS, rTMS or some other form of therapy, you never going to wake up one day feeling on top of the world with a cheerleaders jumping around your bedroom celebrating the end of your depression. It’s more like watching an analog clock. Stare it for a few minutes and you barely see the time change, but come back after taking a shower and the difference is noticeable.

Hi Martin,

Thanks for the good wishes. I started responding to your post and ended up with a ridiculously long post, some of which is just me processing all the crap we have been through the past few years and regurgitating all the stuff I have studied and read trying to find an answer to our problem. I’ll put in headings so you can read what the parts that interest you and skip my self-reflection sessions

Hitting the Bottom and Finding New Hope

Our family has been through a lot over the past couple of years and it hasn’t been easy for anyone. You said you’re surprised my wife was able to sustain hope through these bad experience with her doctors and her illness–well, she didn’t for a while. She pretty much gave up and just wanted to handle it all on her own–which meant isolating herself from the rest of the world because she needed time to think. Obviously, this didn’t help the situation and any attempt on my part to help her or discuss the situation with her turned into WWIII. Things just continued to get worse over time—much worse. She became verbally abusive towards me and the kids and very selfish and self-centered.

After dealing with her declining depression for two years and months of abusive behavior, I started to sink into my own depression. I gained a lot of weight and started having panic attacks. I couldn’t sleep and I was having issues at work. I started seeing a therapist and my p-doc put my on lexapro and klonopin. After doing more research, I found doc no. 6 for my wife and started doing research on TMS and ketamine treatments. When I tried to discuss these new therapies with her, she told me to go f—- myself. As much as I loved my wife, I couldn’t take the situation any longer. Either she was going to get become an active participant in her recovery and get the help she needs or she had to find a new place to live because the kids and I deserve to live in a healthier environment.

I guess she got the point because, after that conversation, she made an appointment to see doc no. 6. After meeting with doc 6, something clicked for her. She finally found a doctor that listened to her and understood how she felt. She thought he was really kind and smart. He seemed to under the issues and he had a real plan for her. It always seemed like her other docs were basically throwing darts at a wall in the hope of getting some random drug combo that might help—but she never felt like they gave a sh!t about her or put much thought into her treatment (and they really didn’t). Doc 6 was different. Even without taking a single pill, her outlook changed after that first visit and he gave her hope and faith that things can get better.

TMS Clinics and TMS Techs

I have definitely been in situations where you go to a doctor or some other professional and just get a bad feeling. Some of these insurance companies have their approved providers and they pay them next to nothing for these treatments so the only way they can earn a living is to limit the doctor’s involvement in the treatment and run the place like a mill. As effective as dTMS is (and it is known to work and it has some advantages over rTMS), but Brainwaves main selling point to doctors is the fact that they treatments take only 20 minutes (which is 17.5 minutes faster than rTMS) and their machines have heat sinks and cooling mechanisms so they can run without a cool down period. In Brainwaves’ sales material, they brag about the fact that doctors can treat three patients an hour with their machine compared to 1.5 patients an hour with the neurostar (rTMS) machine. In other words, it’s ideal for running a TMS mill.

So everything you’re saying about this TMS center is probably right–but doesn’t mean it won’t work. My wife’s doctor isn’t an insurance mill and he’s a great guy, but he’s still running a very successful and profitable business. The fact is you don’t need a doctor to run these machines. TMS in his office is also run by a tech. The doctor prescribes the treatment and dosage, but he’s not there when it’s administered–except on mondays and thursdays when he gives her the ketamine injections. My wife was a little disappointed that he wasn’t the one administering the treatments, but that’s just not the way this works. A good tech can do the same job and free the doc up to see other patients–that’s the only profitable way to administer these treatments and keep the costs in the realm of reason.

DIY Ketamine Treaments??? Really???

Now, as for your little DIY project, please be careful. I understand why you wanted to go the DIY route with Ketamine, since it’s not officially covered by insurance and it can be expensive. Nevertheless, this stuff can be dangerous, not to mention it can land you in jail.. Putting my public service announcement to the side, if you’re going to play doctor with ketamine (don’t do it!!), the dosage you are giving yourself sounds really high!! You also didn’t mention how you are you’re self administering (injection, snorting, eating etc.).

The protocol used the first big study by Yale on treating TRD with ketamine (published in 2000) used a protocol based on dosage of .5mg/kg administered via IV over 40 minutes. No one knows if this is the best or most desirable default treatment, but it has been the default treatment in every published study since 2000. When I say default, this is generally where all treatments begin and/or its used as a reference point for ketamine infusion therapy. There have been studies on the efficacy of lower dosages and higher dosage but it always seems to come back to the .5mg/kg formula. Based on patient response, doctors often adjust their dosage and duration of treatment–but the variation for treating depression is generally between .1mg/kg to .75mg/kg with during of infusion between 2 and 100 minutes. The same type of dosage is used when administering KIT by IM or SC injection, with an upward adjustment in dosage to compensate for a lower absorption rate when compared to IV infusion.

For example, if you were a man that weighs 200 pounds (just to use a round number), the baseline therapeutic dose for you would be 45mg administered IV push with saline solution over a 40 minute period. If administered through Intramuscular injection, subcutaneous injection. If the ketamine is administered via IM injection, the absorption rate is 92% (compared to 100% if administered via IV), so you can expect that your brain would receive 41mg of the drug. A doctor administering ketamine via IM would increase the dosage to 45mg to compensate for the difference in absorption rates for the patient’s first treatment. Based on patient response to the baseline dosage, doctors will adjust the duration of the infusion and dosage amount to achieve the desired response–the dosage for this 200 pound guy via IM shouldn’t really go above 75mg. If you’re taking 200mg, for our 200 pound guy, that would be 2.2mg/kg–which is way too high (It’s getting closer to a recreational drug dosage).

My wife’s doctor is administering ketamine to her via IM injection She weights 110 and the doctor started her out at 25mg for her first session, which he administered in two separate injections (10mg for the first injection and 15mg for the second injection, which were spaced ~30 minutes apart). For her second treatment, he bumped her up to 30mg (15mg/15mg, spaced around ~30 minutes apart). For her third treatment and each treatment thereafter, she has been getting 40mg (20mg/ 20mg, spaced about ~25 minutes apart–which is right at the .75mg/kg mark). On her “optimized” dosage, my wife is not having any real “trips”—she’s not seeing her body from the outside or anything like that. She just feels very relaxed and heavy–like she can’t move her body, but it’s not unpleasant for her. She can’t really talk when the injections are kicking in, but that only lasts for 10 minutes or so, then it wears off pretty quickly. There have been times when her doctor has had to delay the second injection because my wife’s BP was too high or low and he won’t give her the second injection until her BP returns to near baseline.

Ketamine Treatment Costs

In addition to not being a great idea to self-administer, ketamine treatments don’t have to be outrageously expensive. Some of the big NYC and California clinics run by anesthesiologists charged outrageous prices for their services, but competition for ketamine treatments has risen sharply over the past 2 years, so prices have dropped. One major NYC clinic was charging $750 for an infusion around this time last year, but now its down to $450 an infusion–which is a big drop. IM injections are just as effective and cost much less than IV infusions

My wife’s doctor generally charges $300 for a ketamine treatment via IM. If you’re a referral from another doctor and are just seeing him for ketamine treatments, it’s a straight charge. If, however, your his patient, his office will process out-of-network insurance claims (he’s not on any insurance network) and he bills the ketamine treatments as therapy sessions with an injection (since there’s no code for ketamine infusion/injection thereapy). Insurance carriers will generally reimburse some of the treatment cost this way. Although we paid $300 on the day of each of my wife’s six induction ketamine treatments, we got back $110 dollars for each treatment from our insurance carrier. So the actual cost of each treatment was only $190. Your mileage may vary, but $190 as the net cost per treatment is pretty reasonable and, given the significant and quick improvements it can make for someone with TRD, it’s a no brainer. I am not a rich guy, $1140 for the initial six treatments that have such a profound health benefit seems like a bargain (I spent more on a flat screen television 10 years ago). If you need a monthly booster treatment (and most people do), , $190 every month is very doable (I pay more than that for cable tv-which provides much less benefit to my family!).

While Ketamine is a big help to my wife, it doesn’t pull her completely out of the depression. For us, it’s an adjuct to other treatments and I sense that’s how it’s used by most people. We hope TMS (with ketamine) gives us a better result. While my wife worries that this might not happen for her (you know how those negative thoughts are!), there are more treatments and options coming down the line–so no need to despair.

New Treatments

1. Esketamine

Johnson & Johnson has a new breakthrough drug in the pipeline called “esketamine”, which is a derivative of Ketamine, but is 3 to 4x more potent. It has been designed to be delivered intransally and can be prescribed for use at home. Patients take it twice weekly In November 2017, J&J completed its phase III studies and it published the results of its phase II studies. The Phase II study included 67 patients, which were divided into 4 groups. Three of these groups receiver low, medium and high doses of eskatemine, with group 4 receiving a placebo. The esketamine was administered twice a week for 8 weeks. The study showed that the highest dose resulted in the greatest benefit (but also had dissociative side effects associated with ketamine). However, at the 14 day point (4 treatments into the therapy) in the study, 50% percent of patients in the high dose group had significant improvement in depression symptoms and 40% achieved full remission from symptoms. This is a substantial improvement over Ketamine via IV, which only has a 30% response rate and 14% full remission rate at this point in treatment.

In a second part of the study, patients continue to participate for 74 days (receiving treatments 2x weekly, than titrating down to 1x weeks and 1x biweekly). The responders continued to respond throughout the treatment process and continued to show the same level of response 8 weeks after treatment was discontinued. These are significantly better results than those shown in IV ketamine studies.

J&J just completed its Phase III studies, which includes a much larger sample group and were conducted over an 18 month period to determine optimal dosage and duration of treatment and to study long term safety. The results from the phase III study will be published in April or May. Assuming the phase III results are consistent with phase II (which rumor suggests they are), J&J will probably file for FDA approval sometime in June or July. Since this drug has been designated as having breakthrough status (which expedites the approval process based on a dire need for the population), approval should happen quickly and industry experts estimate that the drug may be on the market as early as July, but definitely sometime in the second half of 2018.

2. Rapastinel

Rapastinel is the name of drug under development by a company called Allergan which is in the middle of phase III studies (should be completed pretty soon). Rapastinel is also a derivative of Ketamine and acts on the same receptors, but it’s function is different from Ketamine and esketamine in that it has no dissociative effects, but phase II studies indicate that it may be more powerful than either Ketamine or Eskatamine. Rapastinel is administered via IV infusion. In phase II studies, patients that received a Rapastinel infusion a significant response within 24 hours and improvement in depression scores that were double the improvement of SSRI responders after 8 weeks of treatment and the benefits from a single infusion lasted between 7 days and 10 week–which is an improvement over ketamine. Interestingly, Rapastinel also appears to be a “smart” drug because appears to improve memory and cognitive functions.

Anyway, I wish you the best and you have plenty of reason to stay hopeful.

Hey Martin,

I hope you’re having a good day. I am sorry to hear that you don’t have any friends or family to help you through this process. That can’t be easy. What state/city are you living in?

As for the Diy, I am definitely not one to judge people. If the DIY ketamine is giving you relief, it’s your body and mind, so you do what you need to do. That said, snorting is probably the riskiest way to go. Ketamine can be really potent stuff and it’s hard to regulate dosage when you’re snorting powder. If you can’t make it to a clinic or doctor that can administer ketamine via IV or IM, why don’t you ask your p-doc for a prescription for intranasal ketamine. While you can’t get it a Rite Aid or CVS, most compounding pharmacies can fill it for you. https://www.pavilioncompounding.com/blog/ketamine-nose-spray-for-depression-and-pain-management At least this way you’re getting a metered dosage and it would be legal. It is also possible to get a bottles of medical grade ketamine online in liquid form and you can buy syringes. At least this would enable you to try to follow a medical protocol. You can give it to your via IM–just watch a youtube video on how to give an IM injection. While none of these are good options, they are better than snorting powder.

Hey Martin,

Hope you’re having a good day. I agree that there’s no harm in asking for a prescription and that would be much more preferable than the the DIY treatment you are doing. As for that pharmacy, I have no experience with it but there are doctors that administer ketamine to their patients intranasally and they do write prescriptions for this stuff. Whether your doc will give you a prescription is another story. Some of those docs will administer it to their patients in their office, others will let their patients do it at home. He definitely will not give you a prescription for a bottle to inject. I can’t imagine any doctor in their right mind doing something like that. Anyway, let me know what happens after you ask. 🙂

–Eric

Hi Martin. I tried Ketamine twice with 2 different doctors. After 2nd treatment, doc told me that since I was taking ativan for anxiety that the treatment would not be effective. So, if you take any benzo’s, ask or read up. Wasted $800.

• This reply was modified 6 years, 5 months ago by  Tse.