Managing Serotonin Update

It’s been just over 4 weeks since I cut down on the drugs that affect the serotonin levels in the brain. I was taking trazadone for sleep, tramadol for pain and daily doses of Celexa for depression. I cut out the tramadol and the trazadone and, after consultation with my hepatologist Dr. Bzowej, replaced them with Ambien and Vicodin. The results have been significant.

I have noticed that I am physically calmer. My hands are steadier and the random muscle twitching I have been experiencing has receded a bit. I still have all the hyperactivity behaviors I’ve had all my life (leg bouncing, pacing, etc.) but I am not as physically tense and tight as I was 4 weeks ago. My teeth-clenching and grinding have both subsided and the tendency to get caught in negative mental feedback loops (or to put it another way, become obsessed with other people’s irritating behavior) has also declined. Not to be continually catching myself thinking about other people and their foibles really reduces the stress load.

Among the downside to the change is that I am now using Vicodin for pain. Tramadol was relatively mild in its mental effects compared to vicodin. The days I have to take two doses to relieve the aching and allow sleep leave me loopy while I’m taking it and groggy the next morning. Given that serotonin overload can result in seizures and occasionally death, I’ll deal with vicodin’s side effects, it’s just that losing even more mental acuity while I’m taking it means I have even less to work with.

Ambien works differently as well. It is not as strong as trazadone. That means that I don’t wake up groggy, but I also wake up much more during the night. Trazadone would generally allow me to get at least one stretch of 3-4 hours of sleep during the night. The ambien puts me to sleep more gently but also not as deeply and I generally sleep for no more than 2 hours at a time. I wake up feeling rested so it is apparently having the desired effect, it just accomplishes it differently.

The change in medications has done me good. This reinforces the fact that you have to pay close attention to your own physical state and close attention as well to your drugs, their doses and their interactions. Don’t be afraid to talk to your doctor about any symptoms you think may be related to any of your drugs. They can’t help you if you don’t talk to them. Make sure that you get your questions and concerns are answered in any meetings you have with your doctors and nurses.

Now that my mental state is calmer and steadier and my energy is returning after the emotional roller coaster of the San Francisco Giants World Championship drive, I hope to have more frequent postings. Thanks to all of you who have commented and offered support. I hope the rally thong ends up in Cooperstown…

Managing The Serotonin Complex

My previous post discussed the problems I have been having because I am taking Celexa, Trazadone and Tramadol to manage side effects of my chemotherapy. I had a scheduled appointment with my hepatologist this past Friday and decided to bring these issues up at the meeting.

That plan was derailed from the start. When I got to the doctor’s office, my appointment had been cancelled. It was irritating as hell, but they did immediately contact my nurse practitioner Alex who called in the overall Hep C treatment nurse Tammy for a three-way consult. I explained my symptoms and my worries about serotonin overload. Tammy agreed with me that my symptoms could be some level of serotonin syndrome and she and Alex both said I should stop the Tramadol. I told them that the only effective means I had of dealing with the muscle pain I get each injection cycle was to take 800 mg of Ibuprofen every 4 hours. I said it worked fine, but that I had been told it was bad for my kidneys. They agreed but said that in the hepatology department they do not prescribe any opiate-based painkillers. I would have to talk to my primary care doctor in order to get anything prescribed. This sets me up for a great meeting with Dr. K to engage in some classic drug-seeking behavior. I need that stress like I need another hemorrhoid.

I also told them I wanted to change from Trazadone to something else for sleep. They were both resistant to that suggestion. Apparently Trazadone is prescribed along with Celexa and other antidepressants fairly commonly and without problems. I explained that my nervous system is sensitive to drugs and perhaps we should cut back to only one serotonin reuptake inhibitor. They told me that we should eliminate one at a time. Not a bad idea, but then they don’t feel as jumpy as I do.

That was five days ago and it has been a nasty five days indeed. I decided to stop the trazadone as well as the tramadol to try to get my serotonin levels done more quickly. The first 3 days were especially rough at night. My legs were so twitchy that I had to keep getting out of bed to walk around and tire them out. When I got back to be, I had a ten minute window to fall asleep before the twitching would start again and I would have to start pacing, It was a great deal like the symptoms described in this post, but they lasted longer and were more intense. I managed to get about four hours of sleep a night.

The past few days have been better. I have less general jumpiness, irritability and nervousness during the day. The nights are still difficult, but I have been able to get five to six hours of sleep. I am going to try some over-the-counter sleep stuff of some kind if this goes on much longer.

I think I made the right choice to get off the tramadol and the trazadone, but I certainly wish I had a better idea of how long it’s going to take for my body to settle down a bit. I have dealt with restless leg syndrome all my life, but if this goes on much longer I’ll need stronger drugs than celexa to keep me sane…

Minding Your Drug Interactions

Among the disadvantages of being in a drug research study is the tendency for discontinuity in your medical care. The RO5024048 Roche study that I participated in was run by Dr. Natalie Bzowej. It was administered by the Hepatology Center at California Pacific Medical Centers (CPMC). CPMC is a first rate institution and they do cutting edge Hepatitis C research. The doctors are excellent, but as is true with specialists everywhere, they are busy people with many patients. When I screened for the study, I was examined by Dr. Frederick. For early symptoms of rash, sweats etc, I was examined by Dr. Merriman. When I had difficulty with pain issues I was examined by Dr. Bonacini and prescribed Tramadol. Later, when I was having trouble with sleep, I was examined by Dr. Frederick and prescribed Trazadone. When depression issues cropped up, I was examined by Dr. Bzowej and prescribed Paxil. and added Ativan for use as needed. After I reported difficulties with the Paxil, I was seen by Dr. Frederick again and he changed the antidepressant to Celexa Finally, my thyroid function was affected by the research meds and I was put on Levothyroxine by my primary care doctor.

Over time, this can add up to a significant number of medications creating their own set of interactions with each other that have to be carefully attended to. This is something that you should not be leaving solely to the doctors treating you. All the doctors in the hepatology center work on the same team. They are all involved in doing research and, to the limits imposed by patient and study confidentiality restrictions, they communicate with each other and share patient information. However, each doctor has preferred medications they are familiar with and prescribe regularly. This creates a situation in which each doctor is thoroughly familiar with certain meds and they may not be conversant in the effects and interactions of meds preferred and prescribed by the other doctors. You have to do your own research on the drugs you are taking and the potential interactions between them all. I found the drug interaction database at drugs.com to be particularly helpful. If you find something, contact your doctor and get their response. If you feel you need to change drugs, tell them. Keep at it until you get answers that satisfy you.

In my case, I was prescribed tramadol, trazadone and celexa. All have the effect of inhibiting serotonin reuptake in the brain. While this is a good thing for combating depression, if it results in an overabundance of serotonin in the brain, it can cause serious problems: irritability, confusion, tremor, stronger reflex reactions, sweats and potentially even seizures. I do not think these would have been prescribed together if all my symptoms had manifested at the same time. But as each was prescribed for a symptom that was occurring at separate times in the study, I ended up taking them all. There are days when I have to take all three and it is on those days that I have been noticing an increase in my some of my symptoms.

I have increased irritability, a general increase in physical tension and in activities like rubbing my hands, pacing, grinding my teeth, etc. This is all symptomatic of serotonin syndrome which I thought I experienced a few months ago. I am seeing both my primary care doctor and my hepatologist this week and will bring this all up with them both. I would like to see another painkiller substituted for the tramadol and perhaps another sleep aid substituted for the trazadone. I am not sure which way the doctors will want to go but I am tired of feeling this way and need a change.

Careful Planning Meets Chaos Theory

When Chaos Theory first became widely discussed years ago, there was a quick and dirty example of it that made the rounds: Chaos Theory can be illustrated as your typical day. You wake up in the morning with a certain plan or pattern for your day. You have places to be and tasks that need to be accomplished and you think that they can all fit into your day. Then your day happens.

As you get dressed, your shoelace breaks and you realize you don’t have any spares. You unthread one from another pair of shoes and go to make breakfast. You find that someone has used the last of the ground coffee and you have to grind some. There is no orange juice for your smoothie, so you have to hustle up some English muffins for breakfast. You find that the deli meat and tomato you were going to use for your lunch sandwich are gone and that means you have to buy something for lunch. All this combines to get you out the door a touch late and there is a bus stall on your way to work. You are late to work and that pushes back your first meeting. The meeting runs long. There is not enough time to complete the spreadsheet work you were going to do before you need to check in with the contractor working on the office. Lunch gets pushed back and you have to take additional time to go out and get food. All this shortens your afternoon and you absolutely have to be at little league practice (you’re the coach) or 16 kids will be standing around. Etc, Etc, Etc. By the end of the day, the resemblance to your morning plan may be only a passing one.

The same thing occurs when you attempt to plan your activities around your treatment regimen. Chaos has the same domino-like effect. It ambushed me just two days ago.

I had a fairly heavy day at work, packing and moving many boxes of books, rearranging inventory and working through floor plans for a 400,000-book sale. I felt all right when I got home, but I realized I had pushed it and decided to stay home instead of making a run to my studio. I knew that my wife worked late the next day and I could handle what I needed to do tomorrow evening. At 1:30 a.m. that night however, tired as I was, I was wide awake. I had to get some sleep and broke down and took a Trazadone. I took about an hour to work, so I managed to get 4 hours of sleep and woke up with a logy feeling from the sleeping pill. By the time I got home after work, I went right to bed and slept for 3 hours. I was still tired enough that I went to bed early and slept for 8 hours (as treatment veterans know, 8 hours sleep can be a miracle). I did not even manage to get much done at work much less do any of the small tasks I had hoped to accomplish in the evening. The lack of accomplishment that day affected the next and it is only now that I can plan to get what I wanted to do yesterday done tomorrow evening, if all goes well.

Planning is good, lists are good, notes to yourself to remember that you forget are good, but the best-laid plans can definitely be put paid by a bout of treatment-derived chaos…

Restless Sleep

I wrote a couple of postings ago about being prescribed trazadone for insomnia. It is an anti-depressant that is also prescribed as a sedative. You can take 50 up to 100 mg per dose if you use it as a sedative and I definitely have to take the higher dose. It does work. There is one side effect that can be a bit aggravating especially as it intensifies a characteristic I’ve had all my life.

I have restless feet, and legs and hands. I have had this all my life. I am sure that if I were growing up today, I would be diagnosed as hyperactive or ADD or whatever the current fashionable term is. When I was about 14 my younger brother was diagnosed with ADD by the family doctor. When he asked my mother if she hadn’t noticed that he was a bit over-energetic and hard to control, she said, “Oh no, I have another one just like him at home.” Whenever I sit down, my feet are tapping, or my knees are jiggling and it goes on 24 hours a day.

I did not know that I did it at night until I was 18. Three high school buddies and I drove to Mexico City from Minneapolis to visit one of the guy’s uncles. That is an innocuous sounding statement until you realize that it is about 2500 miles, 4 guys in one car, driving straight through until we got there. We were young…

The first night we were in Mexico City, we were all bunked in one large room. The next morning, my three friends looked bleary-eyed and haggard. They had been awakened all night long by the sound of my feet rubbing together under the sheets. They thought it might be mice or bugs and it was not for several hours that they traced the noise to my feet. They could not believe that I could sleep through the noise I was making. I was exiled to a small room next door for the duration of our visit.

Trazadone makes my legs jumpy. It doesn’t happen till about 30 minutes after I take it, then it sets in. There is a strange feeling of tension build up in my leg and then it twitches sharply. This goes on until I fall asleep. When I took 50 mg, the jumpy leg defeated the sedative, but when I went to 100 mg. the sedative effect put me to sleep despite the twitching. Luckily for me, and more notably my wife, the twitching subsides shortly after I fall asleep and reverts back to my normal foot rubbing. I can usually get a reasonable night’s sleep after taking it without feeling logy in the morning.

One small, twitchy, step against side effects, one great leap for enduring treatment…

Second Opinions

I visited my gastroenterologist, the fabulous Doctor C, to keep him up to date on the progress of my treatment. I took him all my latest lab results, the two prescriptions the research doctors have given me to treat my pain and insomnia and the questions I had been accumulating about what I have been going through.

Doctor C is a great listener and takes as much time as needed to deal with his patients’ questions and problems. He went over my file and the latest test results I brought with me. He had a number of questions about the physical side effects of treatment. He asked about the nature and severity of them as well as any measures that were being taken to either counteract or mitigate their effects. I also asked him for his opinion of the drugs they had given me for the muscle pain (tramadol) and for insomnia (trazadone). He immediately pulled up his drug reference app on his smartphone and gave me the details. He told me that the tramadol was fairly standard for the pain. He went into more detail about the trazadone. He told me it was an antidepressant that had been around for over 20 years and that it was a very safe drug. He said that it had also demonstrated good results as a sedative. He told me that as an antidepressant the dose went up to 300 mg. and that as a sedative the dose was either 50 or 100 mg. I was prescribed one 50 mg tablet as needed. He told me that if it was not working at that dose to take two. It was perfectly okay and would probably be very effective.

He also questioned me quite extensively about my state of mind. He is very concerned about the side effects of interferon. He has had extensive experience in prescribing it for various conditions and has seen that it can be devastating to some patient’s mental state. He mentioned that his father had taken it for a lung condition and had become extremely depressed. He was a bit surprised that I was not on any antidepressants. He mentioned that when he prescribed the standard therapy for Hep C for his own patients he usually started a prophylactic regime of antidepressants right at the start. He suggested that I pay close attention to my mental state and that I should keep both the study doctors and him informed of any changes.

It was a good meeting and I think it shows the importance of having someone you trust on your team going into treatment, whether it be a research trial or the standard of care.
The books and advice sites all say that you should have a hepatologist as well as your primary care or personal physician in your medical team. I am not sure it is absolutely essential that you have a hepatologist. Doctor C is a gastroenterologist who has extensive experience with Hep C. As a hepatologist is a sub-specialty of gastroenterology, an experienced gastro person should be familiar with Hep C. If not, look around until you find one if you can.

You need to have a doctor who listens to you. That is the most important characteristic you need to find. You need to find the best mix of attention and knowledge in your doctor. This is especially true for a research trial. The research trial doctors are very good and want their patients to succeed, but I have never talked to a trial doctor for more than four or five minutes. The conversations are about specific reactions and not about the general state of my health, my state of mind or my progression of symptoms. Thus, you need to have a doctor outside the trial to backstop the questions, the decisions and the information you are getting in the trial. You need someone who is on your side.

Unless you don’t have a choice, and unfortunately there are lots of people in that situation, don’t go into a research trial unless you have a personal or primary care doctor who knows exactly what you are planning to do and what to watch for because of it. If you can, get a referral to a gastro person with Hep C experience or a hepatologist before the trial. You can give them the details of the trial, they can get your history and you can forward your results to them as you receive them. This way you can get the support you need when you have questions and concerns that may not be met by the study doctors.

Never be afraid to ask for a second opinion. It is your right as a patient. Get all the information you need to feel comfortable proceeding with your treatment be it drug trial or standard of care. You are the only person who has only your best interests at heart, so do whatever you need to defend those interests.

Week 18 – On A More Personal Note…

Yesterday I passed on the news about the expansion of the RO5024048 combination drug trial. Today I’ll pass on the personal news about my condition.

They did all the usual blood draws (only 14 vials this time), and various vitals but no EKG. I didn’t notice that they were not doing it and therefore never asked why it did not happen. When they checked my weight, it turned out I have lost 12 pounds in the last 8 weeks. I had noticed my belt being a bit loose, but I didn’t think I had lost that much weight. I don’t have the energy to exercise heavily so I guess I am eating less than I think.

I’m still undetectable as of week 14 (which was 4 weeks ago) which is the best news of the day. 8 official weeks of no detectable virus levels is encouraging and definitely helps during the various bouts of side effects. About 3 weeks ago they dropped my Copegus dose to 1000mg from 1200mg per day. My Hemoglobin has popped up very slightly but I am still down 35% over normal. The only new development with the shortness of breath associated with the anemia is that now I occasional get out of breath while talking. Thankfully it only tends to happen when I have to project a bit to be heard in a noisy room or in a large group, the usual day-to-day nattering is unaffected (to the occasional chagrin of those subjected to it). White blood cells are low but just above the cutoff line.

About 3 weeks ago, my neutrophil count increased enough that they restored me to a full dose (180mg) of Pegasys from the 3/4 dose (135 mg) that I had been on for about 6 weeks. This brought back a whole raft of side effects that had moderated during the lower dose of interferon. Headaches, rash with itching (thankfully mild), nausea and more intense insomnia all were once again daily, or at least several times weekly, features of life. I had actually thought that my body had begun to acclimate to the treatment drugs, but with the return of all of these side effects, I believe the lower occurrence was due to the lower dose.

I have been having bouts of insomnia for several weeks and given that they have increased with the increase in my interferon dose, the consulting doctor to the study decided to proscribe trazodone to help me sleep. I have taken it twice and while on the first night it did not seem to help at all, the second night found it working better and I think I got a decent night’s sleep. I will report back on the results in the future.

As for reports, taking acetaminophen instead of ibuprofen, just before my Pegasys (interferon) injection has had no effect on my fatigue in the 24-36 hours after the injection. I feel just as crappy taking Tylenol as I do taking Motrin, so much for the miracles of modern pharmacology.

Time to head out the door to the support group. Best of all, I can listen to the Giants game on the way there and maybe on the way back…if I don’t forget they’re playing before I get to the car.