Management of AOPVFS in Adults

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Development of Modified Activity Programme for both Physical and Mental Activity

In the course of treating the majority of illness processes in human beings, doctors encourage patients to do as much as they can, to struggle against their infirmity, to progress; don’t sit around doing nothing because that makes your problem worse.  This is the advice given to the majority of patients with CFS and there is no doubt that the vast majority of patients with this condition do exactly that; they tend to try and do as much as they can.

On a bad day they have to rest more and whilst resting, both physically and mentally, the symptoms begin to settle and they wake the following day feeling, perhaps, a little better. On a good day patients, I suppose quite naturally, tend to try and do as much as they can and play catch-up. Inevitably in doing so they overdo it and that gives them a bad next day, two days or three days or maybe even a week.  Patients work this out for themselves. They will tell me they can’t simply sit around doing nothing so they go out for a party, or they go to a family dinner, spend too long there, do too much and suffer for one, three, seven maybe ten days for doing so.  They have these bad days, good days, bad weeks, good weeks and bad months and good months as a result.  Their illness process tends to fluctuate

They can usually identify what they do that is too much and makes them suffer, especially when they look at the physical aspect of it. If they walk too far they know the following day their muscles are likely to ache, their knees are going to ache, their joints ache and their fatigue increases.  They also know that when they read for too long their concentration is poor. To some extent therefore, what I am about to enlighten you with is already fairly obvious.   

It is very important to realise that by doing too much one makes oneself more unwell, but what one may not realise is that every time you do too much today (for which you suffer tomorrow), you also put extra days on the end of the illness; you actually perpetuate the problem.  If you have been ill for a year and do a little bit too much, so that you suffer tomorrow, then you also put an extra day on the end. If you have been ill for two years and you do too much today, you will suffer not only tomorrow but you also put two days on the end of your illness process and so the story continues to compile.  If you have been ill for three years and overdo it you will put three times as long on the end, ten years and it is ten times as long on the end. Thus, if you do too much today and, consequently, suffer for a week and you have already been ill for five or six years, then you are going to put five or six weeks on the end of your illness and that suddenly becomes like chasing rainbows; you simply never get there.

It becomes evident, therefore, that the prognosis in patients who have been ill for four years tends to be extremely poor because they can’t stick to a programme for as long as it is necessary to get better.  Life tends to get in the way, major family events get in the way, people get married, people give birth to babies, grandchildren arrive, etc. It is very difficult to hang onto a modified activity programme indefinitely, but on the whole, treatment programmes from my point of view take somewhere between eighteen months and three years.  You can get the vast majority of people a great deal better in three years or less, but sticking to the programme is the most important thing of all. Drugs don’t work until you have got the programme right. You have stop making yourself worse before I can help you get better.

HOW DO YOU DEVELOP A MODIFIED ACTIVITY PROGRAMME?

 Let us start with the physical side of things. When you were well, before all of this started, you had a normal sized battery, charged to say a 100 Volts. If you went out and did some training you could make your battery bigger, 110 or 120 Volts, you would then go to bed at this time, sleep well and wake up in the morning with your 110 Volt battery fully recharged ready for another day.  Now because of Chronic Fatigue Syndrome your battery size is reduced, let us say by 40% to 60 Volts. Neither you nor I can actually measure this, so the best way of starting out with a programme is to assume that your battery is smaller than the 60 Volts it actually is, and we work with a 50 Volt output.

Let us assume therefore, that your battery is smaller than it actually is, just to be on the safe side; so to start any programme I want you to do less than you can achieve.  I might say to you,

 “How far can you walk?” and you might reply by saying,

 “On a good day I can walk XX metres.”

Unfortunately that is not the whole question. The question that I am asking is,  

“How far can you walk every day;  not on a good day, not on a bad day, but on an average sort of day?  Furthermore, is this a distance that you can consistently walk every day; i.e. that is less than you can achieve and, therefore, would not make your illness process worse?” 

I might ask you if you can walk a mile and you may say,

 “No, not every day.” 

“Could you walk 100 metres?” to which the answer may be,

 “Yes.”

So the actual answer then lies somewhere between 100 metres and one mile.  I want you to be absolutely sure that you can walk a certain distance before you say “Yes”. 

“Could you walk 800 metres?” and the answer might be,

“Probably, yes.”

I don’t want a ‘probably’ to come into it. I would rather you walked  the 400 metres each day to which the answer is ‘yes’ as opposed to the ‘probable’ 800 metres.

So your modified activity programme for a physical walking point of view would be 400 metres every day.  Having decided that it is 400 metres every day then that is what you walk.  You might not wish to do it every day and I am perfectly happy that you don’t do it every day but you have to be capable of doing it every day.  I will then ask the question as to whether you can do a quarter of an hour’s washing-up every day and quarter of an hour ironing, a quarter of an hour cooking, a quarter of an hour homework each day, can you play a little bit of football every day, as a young adolescent male, can you phone somebody and talk to them each day, every day?  So the answer is really to search for a programme which you can reproducibly do every day.  It is not difficult to develop a programme for such physical ‘pottering’.

As this illness process is purely inside the central nervous system, within the brain, then, of course, it is very important to make sure that the amount of mental activity is also measured and it is with this aspect that the vast majority of people have the biggest difficulty.  As I have already indicated patients can readily tell me that too much physical activity makes them worse but they haven’t worked out that too much mental activity can also perpetuate the problem. Most patients will also be able to tell me that they can’t read for as long as they used to before their concentration goes, but they haven’t worked out that watching television also makes them ill.  The majority of sufferers that are children, who are not well enough to be at school, (or at work in the case of adults), tend to get up in the morning, at a random hour, get washed and dressed, have some breakfast and then almost invariably turn the television on.  They will watch this intermittently during the day and the evening without realising that this is the biggest potential source of disaster.  Children also have computers, Playstations and X-Boxes, to play with ,chat rooms and telephones to occupy their time, and they tend to lie on the sofa in their dressing gowns watching television for hour after hour.

Chronic Fatigue Syndrome is a disorder of intellectual processing dysfunction with 70% of all of the information going into your brain through the eyes. Each eye has a million nerve fibres and each optic nerve works at 1000 cycles per second.   You are putting two gigabytes of information into your brain every second.  With all of this visual input, your brain automatically processes it up to the level at which it is presented with a picture; this is automatic and doesn’t require processing.  If then you tend to concentrate on this picture you are said to ‘attend’ the picture. Your brain is now on a timer, normally for about ten minutes, after which the picture is disassembled and you have to concentrate to hold it in focus. At this point you have just made your illness process worse.  The more you try to concentrate the worse it gets and the more you will suffer for it.  This is something that the majority of patients will tell you is a ‘reading span of ten to fifteen minutes’ but they haven’t realised out that watching television is exactly the same process. If you watch television for more than ten or fifteen minutes, then you will make your illness worse.

When you are playing with your computer, using your hand eye co-ordination,  a visual input and a sound input you are three level multiple processing and the concentration span on the computer can go down to as little as just a few minutes. Certainly this will be in single figures, so I always advise patients when we first meet and introduce the concept of the development of a programme, that they should exclude detailed visual input.  They should avoid reading, television, computers and, also, one or two other activities that include visual processing such as crosswords, jigsaws, scrabble, cards, close up needlework, detailed painting; in fact,  anything that makes them have to use their brain.  They then usually ask, “Well what can I do then?”,  and the answer would be to suggest they increase the amount of auditory input into the central nervous system, listen to Radio 4,  talking books or music.  Each one of all of these various activities has an essential time base which is fairly universally similar and I tend to advise patients to do approximately fifteen minutes (or less) of any of these activities at a time. Then, of course, comes the question, “How often can I do these things?” and, generally speaking, the answer is once every hour.

Once you have exhausted one particular part of the brain by, say, listening to a talking book for fifteen minutes it takes approximately forty to fifty minutes for that part of the central nervous system to refresh itself enough for you to be able to repeat the activity.  So, in general terms, you do fifteen minutes of one activity at a time per hour, wait an hour and then you can do it again.

So, the essence of a programme is to do a little bit, stop, change to do something else, do that for fifteen minutes (or less), stop, have a break, a cup of tea or a rest and then do something else.  Pottering around in this way means that your central nervous system is involved in doing different activities, a little bit of physical activity, a little bit of housework, a little bit of cooking, a little bit of gardening, maybe kick a football about or whatever.  The process is then repeated to form a regular balanced cycle.

You should develop a programme that takes up the majority of your day. It should start at the same time each day, say 9am and finish at the same time in the evening, approximately at dinner time, 6pm to 6.30pm, 7pm or something like that and should contain as much as you can reasonably easily achieve and does not, in total, make your illness process worse.

It may be that you should look around to get some new hobbies or some new activities. Always make sure that you spend some time out of the house, maybe not only just going for a walk but going for a ride in the car, go and sit in a café to  have a coffee, go and visit a friend but don’t stay too long; don’t spend too long doing anything in particular - break it up and mix it up. 

This initial development of a programme is, I am afraid, quite difficult. It does take a long time; patients never get it right to start with and it takes me approximately six to nine months to help anybody, who has been ill for approximately two years, to get their programme right. It is restrictive and quite boring.  Once you have got the programme absolutely correct then one can start looking at medication. 

NOW TO GET THE SLEEP PATTERN RIGHT

You have got your modified activity programme, you are pottering around from 9am to 6.30pm doing less than you can achieve, and you have also started to lock yourself into a regular sleeping pattern.  This entails going to bed at the same time every night. I am not at all interested in what time you go to bed, that is for you to decide but whatever it is it should be the same every day.  Let us assume that you are going to bed at 10pm.  Between 6.30pm and 10pm, after you have had your dinner, you start to “dumb down”.  You are not watching television nor doing any visual processing, and you then start to turn off your central nervous system - so what do you do?  Well again, you can potter around in a very simple fashion making sandwiches for tomorrow, do a little bit of tidying away, listen to the radio, listen to some music, listen to a talking book, talk to your parents, partner or husband, phone a friend for a few minutes, go for a stroll round the garden, have a nice hot bath, generally sit down, do not a lot and switch off!

MEDICATION

You would then start looking at introducing sedative tricyclic antidepressants.  The reasons for using antidepressants are discussed elsewhere but I like to make use of the sedative side effect of tricyclics to improve sleep pattern.  The commonest one to start with is Amitriptyline. It is a very old medication which is very sedative and works extremely well the majority of the time and is well tolerated.  You would start off with the smallest dose that is made by the manufacturer and that is 10mg as a tablet, or you can take less if you start with the liquid.  Take 10mg approximately an hour before you go to bed which in our example would be at 9pm. You should notice that it makes you feel a little drowsy before you go to bed and hopefully your sleep will start to improve.  I am not suggesting 10mg is necessarily going to be the right dose for everyone; some people (very few) can’t take as much as that. Normally, as I have said, it is well tolerated and one would need more than 10mg.  You can increase the Amitriptyline to 20mg and then to 30mg increasing at approximately 10mg aliquots at approximately weekly intervals.

HOW MUCH DO YOU NEED?

You need such amount that, if you take medication at 9pm, go to bed at 10pm, are asleep hopefully before 10.30pm, you then sleep all night long and wake by alarm at the same time every morning, let us say 7am, not feeling too groggy.  There is no doubt that Amitriptyline makes you feel groggy, but this hopefully will only last for half an hour or so in the morning and be worn off by the time you finish your cup of tea.  If it makes you groggy for longer or makes you feel bad, dizzy, headachy, drugged or any other horrible side effect then of course you must stop it.  You can try then to take something else such as 10mg of Doxepin or 10mg of Trimipramine. These are also tricyclic antidepressants and are also sedative. They are all the same, yet they are all different! (Cheddar and Gorganzola are both cheeses but they are very different). The side effects are all the same as well but, again, they are all different.  The side effects of tricyclic antidepressants are predictably unpredictable - what works for one person may not work for somebody else, so I suggest that you try all three.  It is also an advantage to be able to take all three; they are all different neurotransmitter regulating substances and they work on different neurotransmitters at different concentrations in the blood.  10mg of all three would be 30mg of tricyclic antidepressant (TCA) in total.  If this works for you then fine, but otherwise adjustments can be made to any one of them, or to all three, by small amounts until the perfect prescription for you is established. 

TCAs are sedative; they tend to improve the sleep but, very occasionally, they sometimes make patients not only feel bad but sometimes a little anxious and nervous Also, they can tend to make people twitchy at night. This happens, I guess, in about 5% of cases in which circumstances these sorts of medications are not for you.  There are very few substitutes for the tricyclics but in this slightly unusual situation it may be appropriate to try a quadrocyclic like Trazodone instead.

 TCAs all make you dream; it is very common. Probably 30% to 50% of the patients that I see get dreams on TCAs; dreams which tend to be quite vivid, certainly colourful, active and sometimes unpleasant. Very occasionally, the dreams are so bad and so horrific that the tricyclic antidepressant has to be discontinued or at least a compromise is struck.  Some improvement in sleep pattern can be achieved without using too much and without making the dreams bad.

Another common nocturnal complaint and side effect is that of visual hallucinations. Patients can wake up in the middle of the night and start seeing all sorts of funny things walking over the bed covers, up the walls or across the ceiling; usually unpleasant, big, creepy crawly things.  The way to cope with this, again, is to reduce the tricyclic, if necessary, or simply switch the light on. On doing this visual hallucinations disappear but, unfortunately, tend to come back when you go back to sleep.   

There are, therefore, as you can see, benefits and down sides and it is always important to make sure that the benefits outweigh the bad.

 TCAs, especially Amitriptyline, are pain killers and they are very good at treating headache and muscle aches and pains. In this case, if one of the principal complaints of the patient is of muscle pain even to the point where the diagnosis might be Fibromyalgia Syndrome, then you should stick to Amitriptyline by itself and take as much as you can tolerate. 

HOW MUCH IS THE MAXIMUM?

The usual maximum dose that I am quite familiar with using is somewhere between 150mg and 250mg of mixed TCA or of any one of them.  The maximum dose is as much as you can tolerate.  Other side effects of the tricyclics are those of a dry mouth, constipation and stimulation of appetite so it as much TCA as you can tolerate for the myalgia without making those side effects intolerable.  The constipation can be relieved symptomatically by using bulk expanders like Fybogel and faecal softeners like Lactulose.

 Two other serious and restrictive side effects are the very infrequent development of epilepsy and of cardiac stimulation and palpitation. Needless to say, if anyone has an epileptic attack on tricyclics then the tricyclic is either stopped or reduced to a minimum.  Cardiac side effects are dose related and, therefore, would need to be monitored by an ECG and even asking for a Consultant Cardiological opinion as to the safety of the medications proposed.  Any patient with known epilepsy and with known cardiac problems should seek relevant Consultant medical opinion as to the safety of using TCAs.

It is very important to take one’s time in developing the correct dose and mixture of the tricyclic antidepressants and can take some four to six months before the ideal prescription can be achieved. 

So, now we have developed a modified activity programme that is less than you can achieve; a well balanced mixed programme of mental and physical activity. You have got your sleep pattern right with the tricyclics, you are probably already feeling a little better and, certainly, if nothing else, you should be in control.

 Now we look at introducing the medication to really begin to sort this problem out and that is the introduction of SSRIs in the morning.  In using the SSRIs you are treating one of the biggest of the neurotransmitter substances inside the central nervous system. Arguably, 35% of all neurotransmission in the brain and the rest of the central nervous system is 5HT.  There are several different sorts of 5HT receptors and there are several available medications to help. The commonest ones that I use are Prozac (Fluoxetine Hydrochloride), Seroxat (Paroxetine Hydrochloride), Cipramil (Citalopram), and Efexor (Venlafaxine).

PROZAC

Using Prozac is really very difficult and must be done with great caution, because there is a potential drug interaction between all the tricyclics and the SSRIs.  In America, many years ago, there was a group of very depressed, institutionalised men   being treated with Trimipramine, at night and in quite large doses of up to 300mg at a time.  Prozac, which was fairly new on the scene, was added to their regime and several died of heart attacks.  Obviously, this combination was immediately stopped.  Further studies revealed that these two groups of antidepressants were metabolised by the liver using the same pathway; to be specific the hepatic cytochrome pathway P45011D6 isoenzyme system.  There was competition for this breakdown pathway which was largely won by Prozac, and the metabolism of the tricyclic medication was inhibited. Therefore the tricyclic, in this case Trimipramine and its active metabolite Desmethyl Trimipramine, slowly went up in the blood and continued to increase to toxic levels. Toxic levels of tricyclics lead to ventricular rhythm abnormalities such as ventricular ectopics, ventricular extra systoles and ventricular tachycardia and death, so a skull and crossbones warning was written on the Prozac prescribing leaflet. This stated that Prozac must not be mixed with tricyclics at the same time or within a couple of weeks of using such other antidepressants. 

Using tricyclics by themselves restores and normalises sleep patterns but does nothing for the fatigue. In fact, if anything, tricyclics increase fatigue in the day in the form of drowsiness and, maybe, have a little bit of a drugging effect.  I realised, therefore, that I must use the wonderful anti-fatigue properties of Prozac and, at the same time, I could get round this potential drug interaction. The answer really is quite simple. When you start using the Prozac you can measure the blood levels of tricyclics and their active metabolites and make sure that you always stay within safe therapeutic limits.  You can’t start using Prozac at the smallest prescribed capsular amount because that is 20mg and there could be an effect on the tricyclic level quite quickly and, of course, I would be in serious trouble if this happened. So I always start off using Prozac liquid.  5ml of Prozac liquid is equivalent to 20mg of Fluoxetine Hydrochloride and the bioavailability and the effects of the capsule and the liquid are the same.  So if you start off with 1ml of Prozac syrup (equivalent to 4mg of Fluoxetine Hydrochloride) this is such a small dose that it is most unlikely to have any effect at all, either good or bad. Certainly one would not expect 1ml of Prozac to have any effect upon the liver and, therefore,to have a knock on effect upon tricyclic metabolism, and that is in fact what I have found.  

 It is also true to say that I have very rarely used large doses of the tricyclics. The average sort of prescription would be 75mg, which is often as low as 10mg at night in total or up to the 200mg that I have used on occasion; however, the average would be 75mg. 

After starting the Prozac syrup at 1ml you would leave that prescription to stabilise itself for about a month and then you would do a blood test to measure the tricyclic and its active metabolite for whatever tricyclic you are using.  This is specifically measured and monitored for me by a Therapeutic Monitoring Service in London.  The blood test is very specialised and is only done in one or two centres in Great Britain.  The result takes about a week to ten days to come back and provided this prescription is then safe and stable, which it would be, I would then increase the Prozac to 2ml, (equivalent to 8mg of Fluoxetine Hydrochloride), wait another month and do another blood test. Then I would use 3ml and another blood test, 4ml another blood test and then 5ml (which would be one capsule), and do another blood test. 

These blood tests are expensive (roughly £50 a go) so, for example, I can spend anything up to £300 just to get to 20mg of Prozac and 75mg of Amitriptyline. Of course, on occasions I have used a little more Prozac and have gone up to 40mg and, of course one continues to do blood testing.  It gets very expensive but that pales into insignificance when you bear in mind that the priority that you have is patients‘ safety, which is paramount. 

My average prescription is 20mg of Prozac and in the fifteen years that I have been using this combination of medications I have never ever seen this potential drug interaction with tricyclics.  I have, on a couple of occasions, had to write to patients to ask them to reduce their tricyclic, but it is not because of the Prozac, but due to the fact that a particular level of a prescription of, say, 100mg of Trimipramine may produce a slightly higher blood level than I would wish. 

Once you have attained this stabilised prescription it remains stable. The competitive inhibition of Prozac with the tricyclic will be at a fixed level and the blood level of tricyclic will not at any point rise by itself.  Of course if you find yourself increasing the tricyclic you would have to repeat the blood test again, but I have very rarely had to do that, so the prescription is safe and stable once you have established it to be so. Furthermore, it will not change unless there is another medication introduced that uses the same metabolic pathway, the cytochrome 3450 system or, of course, if the patient goes down with a liver infection such as hepatitis or they start drinking heavily and produce some kind of alcoholic liver disease.  On the assumption that this doesn’t happen, the prescription can remain stable for several years but of course should be monitored.  There is always potential for problems, human beings are only human   and things never stay the same - they either get worse or they get better and hopefully better - and that is my finding.  The anti-fatigue property of Prozac, its ability to produce this feeling of well-being and the effect of sedation and improved sleep pattern of a tricyclic proves to me to be an ideal prescription. However, during all of this time the single most important thing is for the patient to remain on a stable programme and, providing they do not abuse the fact that they feel better with their Prozac, you can move them forward very slowly.

 There is one very important proviso to this and that is that the patient must not get their programme wrong whilst on this combination of drugs. If they make themselves ill by doing too much and have a significant relapse on Prozac and tricyclics then there is nothing more that you can do, and I have seen this on a couple of occasions.

I remember, very vividly, one lady of about forty-five who had been ill for seven years. It took me several years to get her better and she went away, knowing all of what I’d  advised her to do and she was sticking well to her programme.  She went out and bought herself a new kitchen. It was delivered but they couldn’t install it for twelve weeks and their old kitchen had been ripped out to make way for the new one, so, as her husband was a DIY specialist they decided to try and do it themselves.  After a few days of mess and muck her husband’s back went. She was not a person who was unfamiliar with a screwdriver so she sat her husband in the middle of the room and said, “You tell me what to do and I will do it.”  She didn’t stick to her programme and did a little bit more than she could do, day by day.  She ignored the returning sleep disturbance, she ignored the unrefreshed feeling in the morning, she ignored the aches and pains and the slowly increasing sore throat. She then produced an acute flu-like reaction and found herself being bed-bound.  After a couple of weeks she came back to see me and told me that I had to help her.  I pointed out to her that there was nothing I could do. I couldn’t increase the already maximum doses of drugs and there is no other treatment that I know of. She could only sit back and rest and wait and see what happened.  That was five years ago and I know, for a fact, that she is still chair-bound.  This is a warning and I make sure that everybody understands it. It is not meant to be a ‘scare story’ but you have got to stick to the programme like glue when you are on these medications.  Along the path of recovery the unplanned event could occur that could exacerbate the situation. This might be an contemporaneous flu-like illness, the common cold, a general anaesthetic, a broken leg or an operation. In these circumstances, all you have to do is to rest and don’t push it. Just lock the front door, take the phone off the hook, take an analgesic, go to bed and stay there and wait until whatever it is, has gone away.  Then you slowly return back to where you were.   I find these things never make people significantly unwell. They do not produce an exacerbation although, of course, a minor relapse might be experienced because of whatever has transpired, but that is safe and not a problem. 

On a few occasions I have come across people who just simply do not want to stick to the programme and, therefore, I don’t want to prescribe Prozac.  I tell them this so they can stick to a tricyclic at night and if they relapse then there is not really much of a problem with that.

I stick to Prozac most of the time (at least 90%) and, these days, I only use another SSRI if they can’t tolerate Prozac.  I find that most patients can tolerate Prozac very well indeed but there are one or two who say that they can’t and, in these situations, they usually experience a headache or nausea.  I won’t go into the potential side effects of Prozac simply because these facts and information are widely available to everybody. You can find the side effects on the internet, in doctors’ surgeries, in MIMS, in prescribing journals and the back of every single packet that is prescribed. 

There is some degree of notoriety with regard to Prozac – ‘The happy pill’ - and there is no doubt that this is true. It does lift people’s mood.  It can produce a slightly laissé faire attitude and I’ll tell you about that because I have seen it on at least half a dozen occasions.

Prozac lifts mood and reduces fatigue but, also, on rare occasions, it removes inhibitory features and I have had people come back and tell me that they have found themselves doing things they would not have expected of themselves.  As an example, I had a young lady patient of about twenty two, who always enjoyed shopping. She borrowed her mother’s Debenhams card, one Saturday morning, went out and blew £2,000.  Debenhams’ were very good about it and after an explanation they took all of her shopping back.  I had to stop the Prozac.  I had another lady who came back and told me that she developed road rage. She was finding herself winding the window down and swearing at all the passers by.  One gentleman brought his wife along to see me who, at the beginning, was quite a mouse. He had always encouraged her to be independent but she lived a very reclusive life. After taking Prozac she totally changed. She became flamboyant, quite extrovert, very chatty and in fact the man commented to me on this saying that he liked the lady that had come out of the Prozac bottle better than the one that was there before!!”.  She then looked at me and she said, “Yes and I leant over the fence the other day and told my next door neighbour exactly what I thought of him!”

These side effects are quite unusual but it does mean that they need an eye being kept upon the prescription and its effects. Whatever is going to happen it is not going to become obvious until patients are taking at least 3ml or more, usually 4ml or 5ml of Prozac, and these side effects, good and bad, are dose dependent.  The more you take, the more likely you are to have side effects, so whilst you are taking some six months or more to get the prescription stable, you have got to keep a careful eye, not only upon the potential drug interactions and their potential problems, but also upon the effects of the interactions and of the drug itself upon the patient. It is important to make sure that at all times you are doing good and never doing bad.  I reckon that you can improve CFS/ME at least 80% of the time, probably more with current programmes.  Provided the patient can stick to their programme and tolerate the drugs then you can nearly all always get them better.

There are, however, a few that cannot tolerate the drugs and if they have been ill for a long period of time they become quite stuck.  There are those that can’t tolerate any of my range of drugs used, and they get stuck as well but, fortunately, they are very few. I would always encourage patients to take these medications but I do understand their concerns about taking antidepressants and all the stigmata that go with them.  When used properly they are safe.  

Equally when they have got better they would come off the medication extremely slowly in the reverse order.  Taking them off the Prozac first and then the tricyclics at night, I would then take probably twice as long to withdraw patients from the drugs as I did to put them on.  I have never had a problem getting patients off drugs. They can sometimes be a little bit difficult, and if you have been on these medications for three or four years or so then, of course, you are going to be fairly dependent upon them.  Getting off is not necessarily easy but, certainly, I have never found it to be impossible. 

Whilst I would never advocate stopping these drugs very quickly that may not be the advice if you suddenly found yourself being pregnant.  As I am sure we all know, the most likely time for the worst problems to occur in a pregnancy is within the first sixteen weeks, and I would suggest that you should always try and stop these drugs as soon as you know you are pregnant.  The advice, these days, is that you shouldn’t take even an Aspirin if you are pregnant.  After twenty weeks it is not so much of a problem for the pregnancy and, of course, you must always weigh up the benefits that you have from taking these drugs with the problems that you might have in stopping them. However, as this is an unknown quantity I would suggest you should try stopping them.  It would be unlikely that you would relapse all the way back to as bad as you were before and I have never actually seen that happen.  I have found patients who want to have a family and are not 100% recovered discover that when they stop the drugs to become pregnant, in a planned way,  they do slide back probably 10% or 15% but not all the way back down the hill. I have had approximately ten ladies in this position of wanting to have a family and stopping the drugs. They can restart them after they have finished having their baby and  finished breastfeeding, and this will be an option to be considered.

I would never let anybody else stop your drugs if you are taking the full dose of tricyclic and Prozac. If you find yourself in a hospital having to have an operation there is no problem between these two drugs and an anaesthetic.  You will find yourself being questioned as to why you are taking these two together and, of course, when you process your prescription Pharmacists will and, quite rightly, question why you are taking this potentially dangerous combination.  I will leave it to you to explain.  If at any point you want to stop the drugs then you must always feel free to do so whether that would be my recommendation or not; the choice, of course, is always yours.  However, I would always recommend trying to come off them extremely slowly.  If you come off them very quickly you are likely to have a very rough ride. You will get headache, nausea, dizziness and quite profound sleep disturbances.   

There is no problem in taking these drugs with other mild analgesics for headache or various aches and pains. Aspirin, Paracetamol and Ibuprofen are fine.  On the box you will also see a warning that says do not mix these drugs with alcohol and that alcohol should be avoided. In my opinion that is not a problem with modest amounts. When antidepressants are prescribed for depression then alcohol can take the antidepressant effect away and the depression can become much worse. However, we are not treating depression with these drugs; we are treating CFS/ME.  Small amounts of alcohol and tricyclics, individually, make you drowsy so the combined effect of the two may help      sleep as well.  Too much alcohol, however, can have the opposite effect, and I am not advocating its use as part of the programme but merely commenting on likely effects.

 It is also true that a lot of people with CFS/ME can’t tolerate alcohol as it makes them worse but that is a different situation altogether.

In the event of somebody not being able to tolerate Prozac then (as I have already indicated above) I would go for Paroxetine Hydrochloride (SEROXAT) or CIPRAMIL; probably Cipramil first because it does have a slight anti-fatigue property but nowhere near as much as Prozac.  Cipramil tends to be fairly neutral.

SEROXAT

Seroxat is one of a group of antidepressants that are 5-Hydroxytryptamine reuptake inhibitors and it is a potent one.

Chemically known as Paroxetine Hydrochloride, it comes in 20mg and 30mg tablets and as a liquid 20mg in 10ml. I have been using it now for approximately five years and have often used it in conjunction with Prozac, the properties of which are mentioned elsewhere. Seroxat has recently come under quite a lot of criticism. It has been associated with an apparent increase in suicide in younger depressed patients and this association has resulted in a ban in prescribing it for patients under the age of eighteen. Having said that, if we are using it in CFS/ME in patients who are not necessarily depressed, I can see that there would be no reason to believe that there would be an increase in suicide rate in this group. I am therefore looking at what options we should be adopting in treating children under the age of eighteen with CFS/ME using Seroxat.

It became clearer to me several years ago that by using just Prozac I was excluding groups of patients who had anxiety, because there is no doubt that, in certain situations, Prozac is stimulating and actually increases some of the patients’ anxiety levels. Seroxat is essentially neutral, (ie. it doesn’t sedate and it does not stimulate) and it would therefore be taken in the morning. It also has other properties which can be very useful in treating certain subgroups of patients with anxiety and degrees of obsessional compulsive disorder which I sometimes find in a few patients with CFS/ME. I am not talking about patients who have serious obsessional compulsive disorder (OCD) but in patients with whom it is possible that their anxiety is derived from a tendency to be obsessional, pernickety or precise. This is especially seen in younger people in their approach to some of their schoolwork; they like it exact, they don’t like crossing things out and they tend to re-write things. Also agoraphobia and social phobia are quite common in people who have been ill for long periods of time. They become socially withdrawn and they can get anxiety and even panic attacks, very often directly as part of their personality or the result of being ill from CFS/ME for so long. It became these groups of patients in whom Seroxat would be seen to be more appropriate to be used.

Seroxat is principally an antidepressant but as I have already suggested it has licenses for treating OCD, panic disorder, anxiety disorder and social phobias. Posology suggests doses starting with 10mg (half a 20mg tablet) to 50mg in depression, panic disorder and social anxiety and phobia to a maximum of 60mg in OCD. In my experience it takes several weeks to be effective and as elsewhere in the treatment of CSF/ME I start off with tiny doses because of the possibility of drug intolerance that is found in so many people with this disorder. I would therefore always go for the liquid and start off with 2ml which is equivalent to 4mg of Seroxat and increase by 1ml per fortnight or per month.

Pharmacological Properties

Paroxetine Hydrochloride is a potent selective inhibitor of 5-Hydroxytryptamine. Its metabolites are not pharmacologically active. Seroxat and its metabolites are cleared by the liver through the isoenzyme P450. Thus its use in conjunction with other drugs that also use this pathway of metabolism has to be very carefully controlled, and as I use the tricyclics which also use P450 isoenzyme, blood testing must be done to look at the levels of the tricyclics and their active metabolites to ensure they stay within safe therapeutic limits. It should be used extremely carefully in patients who are known to have renal or hepatic impairment, although in the presence of these two conditions it would be hard to sustain a diagnosis of a CFS/ME. I have rarely had to use more than 20mg or 30mg of Seroxat.

There are known to be several conditions in which special warnings and precautions should be used. Seroxat should not be used with a monoamine oxidase inhibitor, and caution exercised with anticoagulants. It doesn’t have a cardiological or a blood pressure problem. It shouldn’t be used in conjunction with Tryptophan because serotonin syndrome may result.

Side effects are quite common; the ones that I see most often are that patients taking Seroxat have problems sleeping and they get quite frequent gastrointestinal upsets, usually indigestion and diarrhoea. There are lots of other potential side effects and undesirable problems, but I think those should be looked up on the manufacturer’s pamphlet.

In summary, I have found it a very safe medication and I simply haven’t come across the problems that were indicated in the Panorama programme of last year. I haven’t found that anybody has become addicted to it even after two or three years of use, especially if it is withdrawn extremely slowly. It is one of the medications that you shouldn’t come off very quickly but go back through the liquid form and come off a millilitre at a time over weeks or even months to avoid all the withdrawal symptomatology. I have found it most beneficial in patients who have got anxiety with CFS/ME.

VENLAFAXINE

Venlafaxine is specifically good for chronic anxiety and stress. Unfortunately it is also true that the potential problems of prescribing Venlafaxine with tricyclics are greater than the problems that you experience with Prozac, Cipramil or Paroxetine Hydrochloride.  There is a horrible problem with a potential drug interaction that can lead to acute serotonin syndrome; again, fortunately, something I have never seen but it does occur and this is potentially more of a risk with Venlafaxine. So if you are going to use this medication, then you would have to measure the blood levels not only of the tricyclic and its metabolite but also of Venlafaxine itself and make sure that all of these three lie within safe therapeutic monitored boundaries.

 I would also try a different SSRI if, despite a reasonable prescribing dosage, Prozac doesn’t work. On one or two occasions I have found that, if the patient doesn’t improve despite tolerating the drug,  you have got to try something else.

I do understand that there are a large number of people who simply don’t want to try antidepressants for one reason or another. They have a psychological barrier to doing so in which case that is not a problem.  In my opinion, whilst their chances of significant improvement are less, I am happy to continue working using a modified activity programme by itself.