Up early again

I’m still getting used to the incredible idea of being up before other people are.  Yesterday I woke up, got onto the computer, looked at my to-do list, thought, “I must ring the council about that damaged pipe in the main stairwell,” and then realised that it was still only 8.45.  Right now I’ve been up for an hour, my partner is still having a lie-in, and I should give it another half-hour or so before ringing my mother.  I never even knew what time she woke up before.

You know how it is when you are newly and mutually in love with someone, and you exist in a state of delighted astonishment that it’s really happening?  I’ve been like that about being able to sleep at conventional hours, and sleep more deeply at that.  Now I’m starting to come out of the honeymoon period and look more seriously at my sleep and energy patterns.

My sleep pattern is mostly solid to the point of being occasionally inconvenient.  I disgraced myself by falling asleep in the middle of a TV episode last night at midnight, and there have been quite a few times recently when my partner’s wanted to stay up later than I can and we’ve not been able to spend that time together.  I’m getting up at the same time as him on workdays, but he tends to go to bed later (he’s allowed to have a social life, after all, and is generally a night owl) and then pay off his sleep debt by having a long lie-in on his days off.  Maybe we’ll be able to work around this better with practice.

What has been more of an issue recently is that instead of getting more energetic as the day goes on, to the point where I’m bouncing around at 11 pm, my energy peak seems to have moved to the morning and I’ve been sleepier than I’d like in the afternoons and evenings.  One problem is that this makes me terribly anti-social when my partner gets home from work, and the other is that I just don’t like being sleepy for that much of the day, and have a feeling that my overall energy levels are less than they were a few weeks ago.  I’ve been waking at 6.30 and then going back to sleep or dozing for the last three days, although yesterday I gave in and got up at 7.30; no idea why, or whether it’s just a temporary blip, but this is not where I’d like my energy to be, especially since I’ve been even more tired than usual later in the day.

Of course, the ME goes up and down all the time anyway, and it’s been a stressful week, so perhaps that is what’s causing this.  Ten days ago I decided to try a little experiment just before bed.  I’d had my orange specs on since 9, but just before midnight I tried taking them off and putting the twig lights on instead.  These are fairy lights on twigs in a vase by the other side of the bed, and as they’re rice lights rather than LED lights, it’s a soft, warm light which I didn’t think would have enough blue in it to keep me awake.  I was wrong.  I suspect that by now I’ve sensitised myself to light levels, which is great when I’m deliberately manipulating them but means that I have to be more careful about accidental changes.  I missed that sleep wave and the next one, and at four was lying in bed tossing and turning, in the way that used to be normal for me for years but now seems intolerable.  I woke up at the usual time a few hours later, and in the interests of not losing my hard-won sleep pattern, stayed awake.  Sleep deprivation always  makes me groggy and generally worse the next day, and in particular heightens pain.  Usually the pain is a stabbed-in-the-eye-sockets type headache, but for some reason it’s gone for my joints and in particular my hands.  The pain has mostly gone if I don’t overdo it, but it’s still causing enough trouble that I haven’t gone back to quilting yet, and this is a very long hangover from one bad night’s sleep.  Ah well, the mysteries of ME, who knows.

However, this has made me wonder exactly what’s going on with ME and my levels of melatonin/serotonin/other relevant hormones.  I never did find a sleep specialist who knew a thing about circadian rhythm disorders, so I’m going to ask my GP, who is not a specialist in sleep or ME but is generally wonderful, open-minded, and interested in how I’ve been fixing my sleep.  I’m currently going for 11 hours of darkness plus 1 hour of dawn simulation, which is a fairly substantial change from what my body was used to for all those years before.  Perhaps it’s more melatonin than is actually optimal for me?  The general idea behind darkness therapy is that we’re evolved to need 12 hours of darkness and 12 of light in the 24, but I suppose that’s for healthy people, not people whose entire systems are in a mess and behaving differently.

Alternatively, it could be that 12 hours of darkness is exactly what I need, it’s just that I’ll have to go through an adjustment period.  There’s a lesser-known treatment for ME called the Marshall Protocol in which light is almost entirely restricted for the first two years of treatment.  This is done along with other major changes such as high doses of antibiotics, so it doesn’t reflect my situation that closely, but I think it’s worth popping into a Marshall Protocol forum and asking them about this.

I wish I had a nice friendly specialist to consult who knew about all of this.  All I can recall from my reading at the moment is that sleep disorders are the norm in ME, to the point where it’s been proposed that ME is actually a type of sleep disorder, and that morning cortisol levels are low in women with ME, which is where I hope that the dawn simulation (which raises cortisol levels in the preferred way) will be useful.  From what’s happened so far, I am getting the feeling that light and darkness could affect my health quite profoundly, and I’d love to know the best way to utilise them.  I don’t even know how much sleep would be the ideal amount for me, for all I know it’s more than 8 hours.

Meanwhile, yesterday I tried a second lightbox stint at 3.30pm, and I think it did the trick.  I had the odd energy dip, but I wasn’t tempted to fall asleep until helplessly doing so at midnight.  I’ll keep this up for a few days, and if it doesn’t continue to be helpful, I’ll follow my partner’s suggestion of starting the darkness therapy later.  My gut feeling is that brighter daytime light is a better approach to this particular issue than shorter nighttime darkness.

How to shift your bedtime/waking time to earlier

When I was using light therapy alone, I found that my 25 hour pattern shifted to 24 hours beautifully but that sooner or later, I would stay up too late and would end up stuck on falling asleep at 4 am or so again.  DSPS is a tough nut to crack.  This was in the days before I found darkness therapy, which has made my sleep/wake pattern rock solid, so here’s how I treated it at the time.

My preferred sleeping tablet when I need one is 20mg temazepam; many people find that 10mg is enough, but I need a higher dose.  While my GP advised me that I should be able to take it for up to a week, I found that taking it for a week straight caused rebound insomnia when I stopped, presumably because the ME/CFIDS makes me over-sensitive to medication.  I find that taking it for three consecutive nights is fine, so I work with that.  It’s entirely possible that I’d be fine with five nights, but I’ve never needed to try.

I would always recommend strongly that you discuss this with your GP.  They should be made aware of your sleeping problems anyway, even if you’re trying to solve them yourself, and sleeping tablets are fairly serious things, even the over-the-counter ones.  Discuss which sleeping tablets will best meet your needs, and if you’ve had a sleep problem for a while you’ve most likely tried several by now anyway.  Do tell them that you will only be using the tablets for a few nights in order to shift your sleep pattern, as otherwise they will be a lot more reluctant to let you have any meds.  I’ve managed to convinced a GP who’d never met me before to let me have four sleeping tablets for this purpose when it was an emergency (missed flight, unexpected night flight), and I doubt that he’d have let me have anything at all if I’d just wandered in to say that I was a bad sleeper and wanted some drugs please.

I’ve always been able to move my sleep back enough over three days using this method, but if I had needed to control a larger shift I would probably have done three days, waited a week, and then repeated the process.  My general lightbox treatment time is 45 minutes, but for this I would sometimes use a longer treatment time to help reinforce the circadian shift.  As far as I can recall, I used an ordinary alarm clock to make sure I got my light therapy at the right time the next morning, but dawn simulation would probably be even better.

Let’s assume that my bedtime is usually 1 am but has shifted to 4 am.

Day 0 – bed at 4 am, wake the next day at 12 pm.
Day 1 – sleeping tablet at 2.30 am for 3 am bedtime, bright lightbox at 11 am.
Day 2 – sleeping tablet at 1.30 am, lightbox at 10 am.
Day 3 – sleeping tablet at 12.30 am, lightbox at 9 am.
Day 4 – no sleeping tablet, lightbox at 9 am.

After that I would relax and use the lightbox whenever I woke up, instead of setting an alarm clock.  This method worked for me every time, including when I had to go on a night flight and deal with a 3 hour time difference to boot.

If you are using darkness therapy, you may not need the sleeping tablets at all.  Just put on the tinted glasses/switch over to orange lighting an hour earlier every evening.  The usual recommendation is to commence darkness therapy three hours before your desired bedtime, though some people find that they get sleepy too early if they do this.  Obviously getting sleepy too early is not a deterrent for DSPS sufferers!

For the above problem, I’d suggest starting the darkness therapy three or four hours before your current bedtime to begin with, and seeing what happened.  It may take a few nights to kick in fully.  Use the bright lightbox when you wake up.  You can wait until you wake up naturally, depending on how effective the darkness therapy is for you, or you can set an alarm so that you make yourself use the lightbox an hour earlier every day.  Since you’re not using sleeping tablets and therefore don’t need to worry about getting the process completed in a hurry, you can try shifting your sleep more slowly, even by 15 min a night.  Keep a diary of what you’re doing so that you don’t lose track.

If you have Non-24 Sleep-Wake Disorder, I’d suggest waiting until your circadian clock has shifted around to your ideal bedtime and waking time before trying anything, then hitting it with light therapy, darkness therapy and/or sleeping tablets to stabilise it there.  The sleeping tablets are a short-term measure, but the light and darkness therapies can be continued full-time and indeed should if you have a circadian rhythm disorder.

If your problem is jet lag or shift work, rather than a misbehaving body clock, you’ll have to experiment to find out what suits you best, and you may only need to use light/darkness therapies occasionally.  Sleeping tablets are best reserved for occasional use, so if you are going to be moving your sleep pattern every week or so, I wouldn’t advise them, and I would certainly suggest that you discuss this with your doctor.  Some companies give their night shift workers yellow safety goggles to wear when they go home in the daytime, so that the light on their journey won’t keep them awake.

If your problem is instead Advanced Sleep Phase Syndrome, then use bright light therapy in the evenings instead to keep you awake for longer.  I have absolutely no idea how darkness therapy would factor in here, but if you’re using it for other purposes (e.g. sounder sleep), I would imagine you would want to be careful not to start it too early in the evening, and remember that darkness therapy alone is unlikely to shift your body clock in the desired fashion.  Light therapy will be the key here.

For any of these problems, dawn simulation alone is unlikely to be enough to shift your body clock, at least in my experience, but may be very helpful in sticking to a good pattern once you have one in place.  I recently went back to dawn simulation, and while I had already stabilised my body clock using light therapy and darkness therapy by now, I think it may be adding a little extra help, and my partner is certainly finding that the dawn simulation makes it much easier to get up in the mornings.

Darkness therapy

The idea behind this is that humans do best when they have melatonin being produced for half the time (averaged out over a year, it won’t be 12 hours all the time unless you’re living on the equator), and that it’s useful both for aiding sleep and for other things such as fertility and cancer risk.  I’m a little warier of claims that a yellow light bulb will fight cancer/get you pregnant than I am of the claims that it will improve sleep, so I’d treat that side of things as rather more speculative, but there does seem to be a fair amount of research backing it all up, if indirectly.  While darkness therapy itself may be fairly new, the various roles of melatonin have been studied a great deal by now.    There have been studies using 12 hours of complete darkness to treat bipolar disorder, but this is difficult to implement and is generally thought not to be necessary, though I’ve read a website by one guy who feels that it is essential and discusses washing up in the dark!  So while there appears to be a great deal of research on melatonin and sleep in general, for instance how shift work affects breast cancer risk, or on populations who do not have artificial lighting (and have many other major difference from industrialised countries), there is as yet little where researchers have directly studied darkness therapy by taking a group of people and changing nothing except the amount of darkness they get at night.  Hopefully this will be remedied before too long, although since there’s nothing in it for pharmaceutical companies, it may take a while.  All the research that I do know of can be found at LowBlueLights.com.

Since it’s blue light which affects circadian rhythms and tells the body that it should be awake and not producing melatonin, you can practise darkness therapy by simply omitting or filtering out blue light for several hours before you go to bed and while you are in bed.  There are a few ways of doing this, but the crucial thing is that once you have begun the darkness therapy in the evening, you do not get any white or blue light until the next morning, not even the tiniest bit.

Coloured light bulbs. For general use while awake, I prefer yellow-coated incandescent bulbs.  If you’re in the UK, they’re just sold as yellow bulbs.  If you’re in the US, they’re more likely to be called bug lights.  The bulb should be painted completely yellow, with a solid coating rather than a translucent one, and will produce an amber light which I find pleasant but which my partner, who generally dislikes coloured light, can’t stand. You can also get amber, red, or pink-coated bulbs, which you may prefer.  I’m not entirely sure whether the pink ones will filter out all blue light when used in an ordinary lamp, as I’ve only ever tried a 15W one inside a salt lamp, where the thick salt already filters out most of the blue.

Unless you live alone or are only planning to use these lights while alone (e.g. while breastfeeding or if you need to get up in the night because you can’t sleep), this is a potential snag.  As the coating is substantial, it will reduce the overall light output so that a 60W yellow bulb may be only as bright as a 40W white bulb, or even dimmer than that. You can buy fluorescent versions of these yellow-painted lights as well.  I haven’t tried them yet as I respond so badly to all fluorescent light, but I’m curious about how the yellow coating changes the level of visual comfort by filtering out certain bandwidths.  I tried buying an LED bulb that was sold to me as yellow, but it turned out to be a really nasty street-light orange; same goes for the two types of LED tea lights that I’ve tried.  I’ve been told by several lighting merchants that oranges and yellows are problematic for LEDs, it’s hard to get a pleasant colour.  I haven’t tried yellow halogen bulbs, but from the photos the yellow coating doesn’t look  strong enough to block all blue light.

For use when I’m going to the toilet at night, I bought a couple of red bike lights.  Since I’m an evening bather, showering was a problem.  I originally tried a red bike light, but while I can cope relatively well in near-darkness, it just wasn’t safe.  After puzzling over this for some time, I put a couple of lamps with 60W yellow bulbs on the hall, so that when the bathroom door is open, there’s a decent amount of light.

Even with coloured light bulbs, it’s best to keep the lighting in the evening fairly low.  At one point I had a 60w yellow bulb in a desk light by the bed for reading by, and a 25w bulb hidden behind a vase in the corner on my partner’s side of the bed for ambient background lighting.  Once I got the orange glasses, I eventually stopped using those, though I did acquire a salt lamp for ambient lighting which provides a nice orange glow.   (As far as I can tell,  the salt lamp filters out most blue light but not all, so you may need to get a coloured bulb for it if you’re going to be using it without tinted glasses on.)  If you do get tinted glasses, I’d recommend keeping on one lamp with a yellow bulb by the bed, for the occasions when you need a bit of light during the  night and don’t want to put your  glasses on.  There are various forms of gentle ambient lighting which are naturally low in blue light, such as candles or fairy lights, and for some people these will be an acceptable compromise.  If you go for fairy lights and you’re not going to be using tinted glasses, go for rice lights, which are a warm white, instead of LED lights, which are a cold light containing a lot of blue.  Unfortunately, I’ve found that even the small amount of light from fairy lights can be enough to halt melatonin production and keep me awake for hours if I don’t have my orange glasses on.  I may try “golden” LED fairy lights some time, but since all of the LEDs I’ve bought as yellow turned out to be a nasty orange, at the moment I’m using the salt lamp for my one yellow lamp.

Monitor filters. Computers and television screens emit an awful lot of blue light, and using them in the evening can really mess up your sleep all on its own.  Low Blue Lights and its friends sell expensive amber filters, but I simply got some samples of amber gels from a theatrical lighting company and cut them to size.  They stick on fairly well by static, unless you have the computer screen tilted quite far forward, and are easy to take off for daytime use.  I have a 17″ widescreen laptop and there are several inches to spare, so these would probably do you for up to 19″ or 20″ widescreen.  They’re a bit of a nuisance, they won’t work for larger monitors, and again my partner doesn’t like looking at them (some people just don’t get on with coloured light), but they’re cheap.  Brown filters should theoretically do the same job with minimal colour distortion if you can’t stand orange, though they will need to be fairly dark.

If you’re looking at a monitor through an amber filter or glasses, colours will be quite strongly affected.  The general effect is golden yellow more than orange, oddly enough.  Whites will be yellow, blues will be greens, everything will be a bit different.  This may annoy you, and it may restrict your activities.  I can’t do any quilting that requires me to select colours, and it’s not the time to go internet shopping for clothes.  This isn’t entirely a bad thing, as it forces me to wind down in the evenings and look at those hours during darkness therapy as relaxation time.

Tinted glasses.  There are two ways of doing this.  You can buy ready-made tinted glasses which will block all blue light, for instance from the range at Optima Low Vision, or you can get prescription glasses made up with a tint that will block blue light.  If you want to try standard sunglasses in brown, orange, yellow or red, check with an optician to find out whether they block 100% of blue light, as apparently most of them don’t.  You also want these glasses to provide good coverage, as opposed to some of the tiny lenses you can get these days.

If you’re going for anything expensive, try out darkness therapy with coloured bulbs and optionally monitor filters first to see whether you get on with it and whether it helps.  Since I can’t see without glasses, I decided to try some fitover glasses in amber which had the advantage of very good coverage.

Unfortunately I found them horribly uncomfortable, and they looked terrifying on me, being huge and so dark (much darker than the image shows) that my eyes were utterly obscured, along with half my face.  My partner and I didn’t want our evenings together spoilt by this, so I gave up on the fitover school of thought and had some prescription glasses made up instead.

On my optometrist’s advice, they were tinted with Wratten Tint 21, which is a pleasant orange.  Optical Express (who do some rather nice cheap frames) don’t do that tint as standard, but they could get that orange in 50% light transmission, which was more than enough to block 100% of blue light but still not so dark that my eyes were obscured to someone looking at me.  They called it 500 Orange 50%, and it cost the same as an ordinary tint. (Remember that brown is just orange with black added, so while they will look more conventional and may distort colours less, brown-tinted glasses will need to be darker.)  The glasses are rather fetching, if I say so myself, and I’ve had no complaints that they make me odd to be around.

I still keep the ambient lighting low when possible, as there will be a bit of light creeping in around the edges, and sometimes I put on the salt lamp so that the light is a soft orange.  However, I’ve spent enough time wearing these glasses with ordinary indoor lighting to confirm that they work beautifully in any conditions, and you don’t need to worry too much about what your light bulbs are up to.

I generally put on the glasses at about 9.30 for a bedtime of midnight, and have been using them for four months.  I’m getting sleepy earlier in the evening, sometimes I even fall asleep at 11ish, and I’m sleeping more solidly.  I’d estimate the effect of the darkness therapy to be similar to that of taking a sleeping tablet in terms of getting a good night’s sleep, but without the potential side effects or grogginess the next day.  I find the glasses very relaxing to wear.  If my partner comes home late in the evening, in the past I’d be so thoroughly woken up that I couldn’t get back to sleep for hours.  Now he’s lucky to get a coherent “hello darling” out of me, and I go straight back to sleep.  I haven’t had an episode of not being able to sleep until unholy o’clock in the morning, or waking up at night and not being able to get back to sleep for well over an hour, since I started using the glasses. There have been a few nights where I’ve forced myself to stay up until 2, yawning all the time, but where in the past (using bright light therapy alone) I would have messed up my sleep cycle by doing that and would be unable to sleep before 2 (or worse) for the nights afterwards, now (using bright light therapy, dawn simulation and darkness therapy) my sleep pattern snaps right back into place.  The only exception to this is the one night where I made the mistake of having the fairy lights on for half an hour around midnight when my orange glasses were off, as I’d hoped that they were yellowy and dim enough not to disrupt melatonin production.  The ensuing insomnia made me realise just how dreadful my sleep was in the old days, and how enormously it’s improved since then.

Light and darkness: an overview

Arguably the biggest factors in sleep pattern regulation are light and darkness.  Humans evolved outdoors, getting plenty of strong daylight during the day and complete darkness at night, and averaging 12 hours of each.  It’s this light/dark signal that keeps the body on a 24 hour schedule: people who are completely blind almost all have sleep disorders, as the natural body clock runs on a 25 hour schedule for some bizarre reason and they don’t have the light/dark signals to keep it at 24 hours.  Now we sleep indoors, we mostly work indoors where the lighting is nowhere near as strong as sunlight, many of us barely get any   sunlight (and those of us with ME, or housebound due to other medical conditions, may not get any), and instead of following the natural pattern of darkness, we are in darkness only for the time we sleep and that may not even be complete darkness, and we will be under artificial light right up until bedtime.  This chart shows the relative light level from various outdoor and indoor conditions.  Even a well-lit office is still only 10% as bright as an overcast sky, and nighttime road lighting is 50 times as bright as a night with a clear full moon.  Our light/dark signals are all mixed up, and this is showing in the  high prevalence today of not only sleep disorders, but medical conditions which are affected by light/dark.

The very basic version is that bright light stimulates serotonin, and a lack of it can cause low serotonin levels and thus depression, as well as daytime sleepiness.  The main antidepressants used today are SSRIs, selective serotonin reuptake inhibitors, and there is a form of depression which is directly caused by low light levels during the winter, SAD (Seasonal Affective Disorder).  Cortisol is another hormone affected by light levels.  Melatonin is the hormone which makes us feel sleepy, along with a host of other roles in the body, and melatonin is produced when we are in darkness, which should average out to 50% of our time over the year but is now nothing of the sort.  The healthy pattern is to start producing melatonin a few hours before going to bed.  By using artificial lighting until right up to bedtime, melatonin production is inhibited, thus ensuring that we are less likely to feel sleepy when we go to bed, and also that we get less melatonin overall than we should.  All the research I’ve read agrees that we need to have melatonin coursing through our bodies for a certain number of hours per day, and that getting insufficient melatonin impacts on various areas of health, such as the immune system, as well as sleep.

Medication for sleep

Short-term medication

Doctors are reluctant to hand out sleeping tablets for good reason.  They’re most often highly addictive and can cause rebound insomnia, as well as the usual risk of side-effects.  They can be used sensibly, however.  If you’re going through a particularly stressful time such as a bereavement, sleeping tablets may be used for a few weeks.  If your bedtime has crept to far too late, sleeping tablets may be used for a short time (no more than a week; I can only do three days, then I get rebound insomnia), preferably in conjunction with bright light therapy, to move it back to where it should be.  Sleeping tablets can be scary things, so research side effects carefully and the first time you take a new med, make sure you can sleep in the next morning if need be.  I’ve tried Zolpidol and Zolpidem (Ambien), and while Ambien seemed to work OK at first, I tried it again and got hallucinations that night and was groggy for the next week.  I now use Temazepam 20mg for no more than three nights in a row, and probably do this a few times a year.  That said, now that I am nicely settled into darkness therapy, it doesn’t seem to be necessary.

Long-term medication

Most people shouldn’t be taking this, but instead improving their sleep hygiene and so forth.  If you have a sleep disorder that can only be helped by medication, it may be possible, though it should always be discussed with your doctor.  My sleep study showed that I don’t get enough deep sleep, as is common with ME.  I can improve my sleep hygiene until the cows come home, I’m never going to get enough deep sleep, so long-term meds make sense for people like me as long as I can tolerate them, and since I have only recently discovered darkness therapy, this is what my GP spent some time trying me on.  Rarely people will take the stronger hypnotics for long-term use, but it’s far from being a first port of call and I would not be able to do it myself.  Antihistamines and low-dose tricyclic antidepressants are common for long-term use.  I didn’t get on well with either: the antihistamines made me a zombie in the day but not particularly sleepy at night, while the amitriptylene (low-dose tricyclic) did great things for my sleep but caused too many side-effects.

I spent several months taking a herbal sleeping aid, Lifeplan Valerian Formula, before I discovered that I didn’t need it once I had the orange glasses for darkness therapy.  If you’ve tried herbal sleeping tablets before and found them useless, check the dosage you were taking, as most of the ones on the market are so low-dose that I doubt there’s more than a placebo effect going on.  The Lifeplan one has a nice reasonable dose, and some people take two capsules at a time.  Some studies suggest that valerian should be taken off and on to avoid building up a tolerance, so for half my cycle I took the valerian formula, and the other half (when I’m premenstrual and more likely to get anxiety) I took 600mg passiflora and 400mg skullcap at bedtime, both in capsule form by Biohealth herbs.  Now that the darkness therapy has kicked in, I’m just using the passiflora and skullcap, as they are useful to treat the PMS, won’t harm my sleep even when taken on top of darkness therapy, and would make me groggy if I took them during the daytime.  The main herbs for sleep are relatively well-researched by now and often come up as effective as benxodiazepines, so again do your research, make sure it’s a reputable manufacturer, and talk to your doctor about what you’re doing.  This should only be used long-term by people who have pretty much no other way of getting a good night’s sleep, however; if you’re reasonably healthy, just keep it for occasional use.

I’ve tried melatonin tablets but they didn’t do a thing for me.  They’re not used in the UK, which makes me fairly cautious of them to begin with, and it’s uncertain how well melatonin works when given in oral tablet form.  This site discusses the problems that can occur from taking melatonin tablets.  I prefer to use darkness therapy instead, where I’m stimulating my body to produce melatonin itself.  If it’s a long-term sleeping problem, I’d suggest trying darkness therapy before medication, unless you need the medication for other reasons anyway, such as low-dose tricyclic antidepressants for pain.