Sunday, November 22, 2009

Expectations are disappointments waiting to happen

Experimental - Efficacy - Safety - Titration - Patience - Transient

I have just returned from my 11 months checkup. Although 11 months, probably I was off the first 6 months, so this is month 5.

When I agreed to this, my thinking was very simple: I'll try ANYTHING to get rid of this.

Over the past few months, I have seen some mild (positive) changes. Can I say for sure its the DBS? Absolutely not. Maybe. I'd go so far as to say probably the changes are due to the DBS. But this blog is dealing with reality. My reality.

I made a decision months ago to only report physical problems and to generalize any ups and downs because this is an experiment. My reactions may or may not be the same for anyone else. But (again another but) I feel real compelled to go off on a tangent of expectations and reality and just how new this field is.

Below is a link to a video of Dr. Mayberg discussing the first woman implanted and her reactions, which were remarkable and extraordinary - IN THE OPERATING ROOM. I apologize I wasn't able to embed it, please take the time to listen.

Dr. Mayberg talks about the IMMEDIATE change in this woman.

Next is a video of Dr. Resai and a woman who underwent the surgery. Note the part where after implantation, they bring her in to modify the parameters on her device to zero in on lifting her depression. This is similar to Parkinson's implants where they may spend hours adjusting the generator and choosing which contacts on the leads to use (there are 4 on each wire - 1 wire on each side of the brain). Fascinating and it really really looks like this could be a cure that doesn't take much time.

But back to reality which has to do with bringing this product to FDA approval and that means following rigorous scientific & ethical guidelines. What the researchers actually know about how this is working is baffling little, I'm afraid. For standard FDA research and approval of anti-depressant drugs, there is a 12 week period. The experimental group is given the new drug for 12 weeks and their progress monitored and measured. At the end of the 12 weeks, the results are compared to the control group which was receiving a placebo. Using statistics, the differences are compared and it is decided whether the new drug made a 'significant' change over the control group. There are hundreds of Internet links about various studies and how strong the placebo effect is (18-22%). And how ineffective many of the anti-depressant drugs are. To generalize most studies, 1/3 get remission, 1/3 have some good progress and 1/3 don't get any help over 12 weeks. Then the process may start over at a different dosage - another 12 weeks.

One of the problems with VNS was the ability to figure out what the proper 'dosage' of current to the vegus nerve is for each person. I'm no expert on it, but I know it was controversial - I am sure Herb has plenty of articles and literature on it.

So why am I bringing all this up? As much as my team emphasized "don't get your expectations up", "this is brand new totally completely untested and may not work" it was damn hard not to get them up. And every month when I go for my 'adjustment/checkup' and run through the same questions, it reminds me how bad I have gotten over the years AND maybe this next adjustment will do the trick and next month I'll be CURED. My expectations.

Denise commented in a previous blog:

"From what I've read there seem to be about five sites which could be targeted
to alleviate depression. Therefore, if you were to participate in a DBS trial
and you don't find it of any benefit, what do you do next, opt to attend another
trial where they are targeting another site??? You could go on forever like

Dr Helen Mayberg mentioned that a number of patients noticed acute affects
in the operating room, wouldn't it make sense, whilst they are doing the
operation for them to try stimulating more than one site to see if the patient
reacts better depending on the site that is being stimulated. Or is it not that

Also, Dr Helen Mayberg says that the patients in her study who failed to
respond to treatment showed no subgenial cingulate changes. I'm not sure which
area of the brain they have stimulated in your case but if it is the "Brodmann
area 25" have they noticed any changes in the Subgenial Cingulate area of your

All good questions Denise, and I hope to find out the answers - but for now, we're following the 'protocol' of the experiment. This phase is more about safety of the device than the efficacy. I would LOVE for them to play with the settings for a few hours and fine tune the response, but that's not the protocol. (My apologies to the experimenters if this sort of stuff was supposed to be under wraps - I think the followers need to understand this is SLOW going for a reason. I don't like it - at all - but I understand it and I want to make sure anyone dreaming of having this done understands there is a LOT of work to do before it comes to market and gets approved).

Let me be very very clear - the informed consent was clear and I understood what they were saying - but my own desire kept thinking about the internet stories of miraculous change. One reader here, PsyFi, shared a little of her experience and it was nothing short of miraculous. Another reader and follower shared that though it took quite awhile to find the settings that seemed to help him, it was worth it.

So what am I going on and on about? With any luck, the FDA will approve the next steps for St. Jude's study which to my understanding will include up to 200 more implants. I'm all for it. However, for all of you hoping to get into it, or hoping the medtronics study is for you, or are just plain suffering and expecting this to come and rock your world when it is generally available - be prepared to find out there is more to the story than what the Internet videos/articles discuss. That adjustment phase is done 'by the book' on a rigid adjustment schedule. So even if this is going to work completely for me, getting it 'titrated' is taking a lot of time.

I can completely understand the necessity for a slow pace on such a NEW technology. I just didn't manage my expectations well. As it turns out, from what I've recently been told, a lot of the operating room experiences were transient. i.e. the patient still had to undergo a lot of trials and errors on getting it adjusted for them.

By what I've found on the Internet, including a new German study, there are still fewer than 60 of us. (Medtronic rep, feel free to give us a head count if you can - yes head count is a pun). The gizmo has 4 contacts on each wire - 1 wire on each side. Each contact can be negative or positive with different voltage & milliamps & frequency. Thousands of combinations. I don't know how long it took the pioneers of Parkinson DBS to hone in on their protocols, but it is going to take at least that long for us. And although the video above (where the woman is being adjusted) looks like it may be a simple procedure, remember we are dealing with emotions - not physical movements. A Parkinson patient can visibly see and feel whether their tremors are gone and the setting is working. For moods, it may take quite a bit more fine tuning.

Of course, being the optimist and willing to do my part to promote the science, I offered to take the programming gizmo home with me and adjust as necessary. Fat chance. And understandably it will never get to that. Just because someone has a bad day at work, we can't just go home and up our gizmo. But alas, I had to try.

I've added a link about DBS and rats. Interesting about serotonin being more effected than norepinephine (noradrenaline). I am not on any drugs that affect serotonin - I'm on drugs that affect norepinephine. Possibly I will see more rapid change when I'm able to switch drugs. (Supposedly after awhile, the study allows more testing of combinations etc). BUT - I'm not going to get my expectations up.... ya right.

Overall, putting my expectations rant to the side, I have had some interesting effects. Again, I wouldn't swear they're from the DBS, but probably are. Some of my 'blah' emotions seem to be shifting. I don't want too get detailed, but I am having 'some' different reactions emotionally than I was. I have been able to maintain 20-25 hours working however I did have some bad days and dropped about 5 hours at the last minute - just couldn't do it.

Psyfi, others, or the original Canadians care to comment? Or you can contact me if you want to be anonymous. Note the comments on the last post. A U.K. DBS patient has put together a group for "us". (I hate google groups, FYI, Yahoo would have been my choice). I think allowing us Guinea pigs to share may not be a good idea - but I will say - knowing there are others out there who have gone through this makes me feel wonderful. Maybe the sponsors should consider their own controlled groups - hint hint to the IP address in Plano). There is also another USA DBS person who has put up his own site. That should be interesting as well.

I hope everyone has a good turkey day and thanks for letting me vent.