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Many peo­ple liv­ing with chron­ic pain are daunt­ed by the prospect of long term or even per­ma­nent drug ther­a­py. What are these drugs, are they safe and how do they work? Con­cerns such as these can stop peo­ple per­se­ver­ing with med­i­cines that may offer a real, life-enhanc­ing solu­tion to their con­di­tion. Dr Mick Ser­pell explains how amitripty­line works and gives reas­sur­ance about the side effects that you might expe­ri­ence, espe­cial­ly in the ear­ly stages

The aims in man­ag­ing chron­ic pain are obvi­ous­ly to relieve or to reduce the pain as much as pos­si­ble, but this is not always achieved to the lev­el patients would wish. Just as impor­tant then, is to improve over­all qual­i­ty of life by improv­ing phys­i­cal func­tion, sleep, mood and psy­cho­log­i­cal func­tion. There are four main approach­es to pain management:

1) phys­i­cal ther­a­py (phys­io­ther­a­py, acupunc­ture, TENS (tran­scu­ta­neous elec­tri­cal nerve stim­u­la­tion), etc.
2) drug ther­a­py
3) region­al anal­ge­sia (injec­tion of drugs around nerves, joints or oth­er tis­sues)
4) psy­cho­log­i­cal ther­a­pies (tech­niques which improve cop­ing with the pain).

Two types of pain

Doc­tors describe pain as either noci­cep­tive (tis­sue dam­age), neu­ro­path­ic (nerve dam­age), or a com­bi­na­tion of the two. It is impor­tant to dis­tin­guish between the two types of pain, as they respond to dif­fer­ent med­i­cines. Noci­cep­tive pain is the most com­mon form of chron­ic pain, and exam­ples include mechan­i­cal low back pain and degen­er­a­tive or inflam­ma­to­ry joint pain. Although these pains may begin as pure­ly noci­cep­tive, over time there may be changes with­in the ner­vous sys­tem. Neu­ro­path­ic pain often results from nerve dam­age that makes the nerve over­ac­tive. There­fore the drugs used for neu­ro­path­ic pain are aimed at sta­bil­i­sa­tion or ‘calm­ing’ of these nerves. Per­haps it should be no sur­prise, then, that drugs used in oth­er con­di­tions where ner­vous tis­sue is over­ac­tive or ‘excit­ed’, such as epilep­sy or depres­sion, have turned out to be use­ful med­i­cines for chron­ic pain.

Drug ther­a­py

Con­ven­tion­al painkillers such as codeine and ibupro­fen are used for noci­cep­tive pain. They are often not effec­tive for neu­ro­path­ic pain. Most of the drugs used for the relief of neu­ro­path­ic pain were orig­i­nal­ly devel­oped to treat dif­fer­ent con­di­tions. For instance, amitripty­line is an anti­de­pres­sant drug but is now used much more com­mon­ly for pain than for its orig­i­nal use. The sit­u­a­tion is the same for some anti­con­vul­sant drugs, such as gabapentin, which are used more fre­quent­ly for neu­ro­path­ic pain than epilepsy.

Change your lifestyle

Always remem­ber that the med­i­cine alone will not be enough. While drug ther­a­py can play a role in the man­age­ment of pain, chang­ing your lifestyle (such as build­ing up your fit­ness and get­ting more exer­cise), as well as learn­ing to man­age and cope with your pain bet­ter, are also vital to a suc­cess­ful outcome.

Gen­er­al prin­ci­ples of drug therapy

Your doc­tor will start you off at a low dose of your med­i­cine and this is increased up to a suit­able dosage and tak­en for suf­fi­cient dura­tion until you obtain notice­able pain relief (or expe­ri­ence severe side effects). This pro­ce­dure of increas­ing the dose step by step while mon­i­tor­ing the effect is called ‘titrat­ing the dose’. If there is insuf­fi­cient pain relief or trou­ble­some side effects, the drug will be stopped. Your doc­tor is like­ly to grad­u­al­ly wean you off the med­ica­tion over sev­er­al weeks, in order to avoid poten­tial sud­den with­draw­al effects. If you get par­tial, but inad­e­quate pain relief, some­times your doc­tor will add in anoth­er dif­fer­ent drug, because ‘com­bi­na­tion’ ther­a­py can be more effec­tive for pain than sin­gle drug ther­a­py. How­ev­er, there is an increased risk of side effects when more drugs are taken.

Once you are on the right dose and drug com­bi­na­tion, then you may con­tin­ue on the med­ica­tion indef­i­nite­ly. How­ev­er, this should always be reviewed by you and your doc­tor, every three to six months. It may be that you decide the med­ica­tions are no longer help­ing enough, or that you are now expe­ri­enc­ing prob­lem­at­ic side effects. In this case you should wean your­self off the med­ica­tions grad­u­al­ly (one at a time) to ensure they are still ben­e­fit­ting you.

Most doc­tors agree that med­ica­tion for chron­ic pain should be tak­en reg­u­lar­ly ‘round the clock’ rather than ‘as required’ for break­through pain. It is eas­i­er to keep pain at bay rather than try­ing to chase it after it has been allowed to get out of control.


The tri­cyclic anti­de­pres­sants, such as amitripty­line, are the ‘gold stan­dard’ for neu­ro­path­ic pain as they are the most effec­tive and best-known drugs for this con­di­tion. They can also be use­ful for chron­ic noci­cep­tive pain, espe­cial­ly if there is a neu­ro­path­ic com­po­nent to it. They appear to work in the ner­vous sys­tem by reduc­ing the nerve cell’s abil­i­ty to re-absorb chem­i­cals such as sero­tonin and nora­dren­a­line. These chem­i­cals are called neur­al trans­mit­ters. If they are not reab­sorbed they accu­mu­late out­side the nerve cell and the result is sup­pres­sion of pain mes­sages in the spinal cord.

All in the mind?

The way anti­de­pres­sants give pain relief is com­plete­ly sep­a­rate from the anti-depres­sant effect. The dose required for treat­ing depres­sion is much high­er (150–250 mil­ligrams (mg) a day) rather than the dos­es used for pain relief (25–75 mg/d). Amitripty­line also works in patients who are not depressed. Also, there are over twen­ty dif­fer­ent anti­de­pres­sant drugs avail­able for treat­ing depres­sion, but only a small num­ber can also be effec­tive pain killers.

It is impor­tant that the patient is giv­en a full expla­na­tion of the ratio­nale for using anti­de­pres­sant ther­a­py. It is not the case that the doc­tor believes your pain is due to the depres­sion. So do not think that you are not being tak­en seri­ous­ly, or that the pain is ‘all in your mind’.
Depres­sion can occur with chron­ic pain, it is usu­al­ly ‘reac­tive’ or in response to the pain, suf­fer­ing and loss of func­tion, and often improves as the chron­ic pain improves. How­ev­er, if severe, it may require simul­ta­ne­ous treat­ment with oth­er anti­de­pres­sant ther­a­pies such as psy­chol­o­gy tech­niques or anoth­er anti­de­pres­sant drug.

Start­ing amitriptyline

One in four peo­ple will get sig­nif­i­cant pain relief with amitripty­line. This is regard­ed as an excel­lent result for chron­ic pain con­di­tions. It is start­ed at a low dose (10 or 25 mg a day) and grad­u­al­ly increased in 10 or 25 mg incre­ments each week up towards 75 mg if side effects are tol­er­a­ble. Your doc­tor may advise you to go high­er than this dose. The tablets are small and dif­fi­cult to cut in half, and will often pro­duce numb­ness of the tongue due to a local anaes­thet­ic effect, but it is avail­able as a syrup. It is bet­ter to use the syrup if small increas­es of dose are required dur­ing the titra­tion (dose build-up) phase.

Keep tak­ing it!

You may notice pain relief as quick­ly as two weeks after start­ing, but often amitripty­line requires to be tak­en for six to eight weeks at the opti­mal dose lev­el before one can say the drug has been giv­en a fair tri­al. Many peo­ple stop tak­ing the med­i­cine because they expe­ri­ence side effects ear­ly on but do not feel any ben­e­fit. How­ev­er, if you can per­se­vere, you will often get tol­er­ant to most of the side effects after a few days to weeks and you may then start notic­ing the ben­e­fits of the medicine.

Although there are a num­ber of side effects asso­ci­at­ed with amitripty­line most of them are extreme­ly uncom­mon. The most com­mon ones, expe­ri­enced by only 5–15% of peo­ple, include dizzi­ness, drowsi­ness, dry mouth, nau­sea and con­sti­pa­tion. These side effects are gen­er­al­ly harm­less and, pro­vid­ed you do not exceed the dose, will not cause any dam­age. Most peo­ple find they adapt to these and even­tu­al­ly they go away. Amitripty­line is not addic­tive but if dis­con­tin­ued, it should be with­drawn slow­ly over sev­er­al weeks in order to avoid with­draw­al symp­toms of headache and malaise. Your doc­tor can advise on this.

Not for everyone

Your doc­tor will not pre­scribe this drug for you if you have had an aller­gic reac­tion to amitripty­line or relat­ed drugs; a recent heart attack; or recent admin­is­tra­tion of drugs that can inter­act with amitriptyline.

When should I take it?

Amitripty­line is long act­ing, so only needs to be tak­en once a day. As one of the most com­mon side effects is drowsi­ness, it is best to take it one to two hours before bed­time. This effect can be par­tic­u­lar­ly use­ful if you suf­fer lack of sleep from your pain. Some­times there is a ‘morn­ing after’ type of hang­over feel­ing, but this usu­al­ly wears off with time. Occa­sion­al­ly amitripty­line can cause insom­nia; if this hap­pens it is bet­ter to take it in the morning.

Worth try­ing

If side effects are a prob­lem, there are oth­er sim­i­lar drugs (for exam­ple, nor­tripty­line, imipramine, and now dulox­e­tine) that are worth try­ing as they are near­ly as effec­tive, and often have less side effects,. Many of the patients I have seen have stayed on amitripty­line for years and say that it has trans­formed their lives. When deal­ing with pain, it is worth giv­ing drug ther­a­py a chance. Best results are achieved in com­bi­na­tion with the non-drug ther­a­pies men­tioned above. It is impor­tant to work with your doc­tor to try the dif­fer­ent approach­es so that you find the par­tic­u­lar approach that is right for you. The opti­mal result is rarely com­plete pain relief. It is often that which brings you the best bal­ance of pain relief, improved func­tion, and min­i­mal side effects, to give you the qual­i­ty of life that you and your doc­tor both want.

Mick Ser­pell is a Con­sul­tant in Anaes­the­sia & Pain Med­i­cine for Greater Glas­gow & Clyde NHS, and Senior Lec­tur­er at Glas­gow University. 

If you would like to know more about the sources of evi­dence con­sult­ed for this pub­li­ca­tion please click here.

Amitripty­line © Michael Ser­pell. All rights reserved. Revised April 2019. To be reviewed April 2022. First pub­lished April 2013.


Been on this for a few years to help me sleep was tak­ing 2 10mg .In june pain in leg got real­ly bad told it was pulled ham­string by doc and physio.In sept had to have month off recent­ly went ae ‚plus told by them to keep tak­ing pills basically.Been tak­ing 5 at night sleep­ing bet­ter for me but still in alot of pain .Been tak­ing high­er dose for 2Wks plus 8codine 8 paraceac­mol and ibro­fufen in between.just had bloods done and mri wait­ing for results .Feel ive been messed about since june legs gone numb now since high­er dose so fedup real­ly not help­ing my depres­sion at all sor­ry thks

This drug is evil, I had ter­ri­ble side effects from the almost min­i­mal dose 20mg. The with­draw­al was so strong that I still have symp­toms after 2 years off the med­ica­tion, it worked for pain but it gave me oth­er prob­lems that per­sist, I do not rec­om­mend it, there are safer alternatives.

Hi Maria I have been told for months now to start tak­ing this med­ica­tion for pain but I am very wary and after read­ing com­ments here I feel my con­cerns are for a good rea­son. You say there are safer alter­na­tives can I ask you what those are. Are you tak­ing an alter­na­tive and is it work­ing for you. Thank you

Ruth Connolly

What we’re the side effects for you can I ask?

Ruth Connolly

Hi Maria, can I ask what side effects you had? I am 4 weeks off it now and still very upset by the tin­gles in my left arm and hip. It’s very wor­ry­ing. I had ter­ri­ble reac­tion to the drug whilst on it.

After near­ly 20 years of back pain due to an acci­dent I final­ly found some­thing that works.
I take 10mg each night and while the pain hasn’t gone I am much bet­ter I think it’s a com­bi­na­tion of less pain, more sleep and more exer­cise. One helps the oth­er and so on ‑my wife thinks my mood is bet­ter too since tak­ing them do for me it’s been a life saver.

Amitripry­line pre­scribed for pain is an “off label” use for the drug in the States, but my psy­chi­a­trist pre­scribed it as a result of very severe pro­tract­ed insom­nia (120 min­utes or less of sleep a night from severe lum­bosacral pain for past two years). Titrat­ing dose up from 10mg to 100mg, at 100mg I devel­oped a dan­ger­ous lev­el of con­sti­pa­tion which sud­den­ly cre­at­ed painful hem­or­rhoids and intesti­nal block­age. Upon low­er­ing the dose to 50mg the bow­el issues resolved and there was notice­able improve­ment in my abil­i­ty to fall back asleep after repeat­ed awak­en­ings from pain. A pain man­age­ment spe­cial­ist was review­ing my L5-S1 pain man­age­ment plan and indi­cat­ed that research had shown that the effec­tive­ness of amitripty­line for pain fol­lows a curve where more is not bet­ter. A low­er dose is more effec­tive for pain than a high­er dose. Also it has improved my over­all state of mind that had become plagued by anx­i­ety from liv­ing with such intense intractable pain and sleep depri­va­tion for so long. For me, 50 to 60mg night­ly appears to be the thresh­old above which side effects become unmanageable.

Hel­lo, you statet that a low­er dosis is more effec­tive than a high­er. Do you have sources that prove that?

Hi, how can I wean off amitripty­lene? I’m on 20mg and have been on this med­ica­tion for 14 years. I’ve sud­den­ly start­ed get­ting tremors in my hand and doc­tor thinks it could be adverse effects of the drug so has sug­gest­ed to Wean off them. I’m feel­ing quite anx­ious about com­ing off them now.

Speak to your Dr I had to low­er mine Grad­u­al­ly. I stopped them over a week ago and feel absolute­ly awful!
Appar­ent­ly you can feel rough for a few weeks. Good luck

I’ve been on amitripty­line since Dec 2017 for chron­ic blad­der pain. I am in the process of increas­ing my dose from 30mg (til March 2020) and am now on 60mg but feel­ing real­ly grog­gy in the morn­ings (my rea­son for not increas­ing it pre­vi­ous­ly was the grog­gi­ness as I work.but dur­ing lock down I haven’t had to go in every­day) How­ev­er, my pain is final­ly bear­able. The only oth­er side effects are dry mouth and snor­ing. I’ve been on 60mg for a week and a half but the grog­gi­ness is still too much for when life goes back to nor­mal work wise. How­ev­er I am also on gabapentin, which I am grad­u­al­ly reduc­ing so that may not be help­ing. I need to find a hap­py medi­um between pain and func­tion­ing! I’ve also tried pre­scrip­tion codeine, tra­madol, gabapentin and mor­phine. Mor­phine was cer­tain­ly effec­tive but unsuit­able for long term use, the rest did noth­ing to relieve the pain.

Maby you went to fast? I know doc­tors say that it’s no prob­lem to increase the dose with 20 mg or more at the time. But to my opin­ion 10 mg or maby 5 mg is better.
I’m on 10 mg Amitripty­line for over 10 years and start­ing with 10 mg was too much, I felt real­ly bad in the morn­ing, like hav­ing a huge hang­over. So I began with 5 mg and when I got used to it I went to 10 mg.
Because of an increase in pain and lack of sleep I decid­ed tho increase the Amitripty­line. The first week I used 15 mg a day (cut a pill in half). And since Yes­ter­day I’m on 20 mg (2x 10 mg). I felt fine this morn­ing, no prob­lems what so ever. Sor­ry for my Eng­lish, Im no native speak­er. Take care!

Is any­one tak­ing low dose (10mg nocte) Amit­ryp along with Pre­ga­balin (Lyri­ca) to deal with fibromyal­gia? I’m cer­tain­ly sleep­ing bet­ter now, praise the lord, and feel a gen­er­al ground­ed­ness Ive missed for years, and a lot of the time my stiff­ness is improved, but Ive the impres­sion that my over­all pain is actu­al­ly undiminished.
I guess it’s still worth it for the oth­er improve­ments, but I’d rather hoped for more!

Ulner nerve injury to hand-delayed allo­graft and repair surgery-unbear­able pain & hyper­sen­si­tiv­i­ty from fin­ger tips to shoul­der-ten­sion… caus­ing migraines which caused nau­sea-light sen­si­tiv­i­ty and bloody noses-dif­fi­cult to do any­thing that requires one hand or both hands.. Ther­a­py was near impos­si­ble-lit­tle improve­ment. Took gabapentin, then lat­er weaned off and took pre­ga­balin both made me sick-yel­low blood shot eyes & skin pain in my side and I had a idc atti­tude. I felt the meds were killing me. Hired attor­ney who filed a com­plaint with State on work­ers comp and I was allowed after nine refer­rals to final­ly see a pain man­age­ment dr. He and his pa helped me incred­i­bly. Phys­io­ther­a­py, Ztli­do lido­caine pad under a com­pres­sion glove 12 hours dai­ly and Amitripty­line 25mg am and 50 mg pm 12 hours apart same time each day.
I feel more like myself than I have in two + years. For me, the med­ica­tion has been a God Send and with­out it I think I would not be able to have hope that mobil­i­ty & func­tion will increase. Still hurts still hyper­sen­si­tive but the Amitripty­line has reduced it by half. I have zero side effects although at first it made me sleepy. It took a few weeks but each day was bet­ter than the day before. I’m sor­ry it didn’t work for some of you & that you even need it. Was also on Cele­brex For the swelling — upset my stom­ach and had heart­burn with indi­ges­tion Glad I’m on the upside. Thank­ful for Amitripty­line and the lido­caine pads!, gloves and my care­givers. Best wishes!

I have been ordered amitripty­line 25–50mg at bed­time for insom­nia, and gabapentin 300mg morn­ing, noon, and 600mg in evening after bone graft in left ankle, am also under pain man­age­ment for Spinal Steno­sis with radicu­lopa­thy, DJD, and Fibromyal­gia, i wear back brace when sit­ting long & stand­ing at all. I think the Amitripty­line is help­ing insom­nia but cer­tain­ly not depres­sion, Gabapentin is def­i­nite­ly help­ing with the nerve dam­age & pain, but also caus­es a sur­re­al feel­ing, which i do not like that side effect and it is not get­ting bet­ter with time. I like the sug­ges­tion of just try­ing low­er dos­es. I know it’s true for some oth­er meds that the low­er dos­es are effec­tive differently.

I have been tak­ing amitripty­line for about 15 years for trigem­i­nal neu­ral­gia. The pain is like an elec­tric shock down the right side of my face. I start­ed on 10mg. I worked my way up to 120mg and still the pain was over­bear­ing. My gp said this was too much to be tak­ing, he reduced it by 45mg and start­ed me on anoth­er drug, car­ba­mazepine. Ide­al­ly they shouldn’t be tak­en togeth­er but needs must. I am now down to 40mg of amitripty­line. My qual­i­ty of life is suf­fer­ing at the moment. Both the side effects have the same symp­toms so I don’t k is if I’m suf­fer­ing side effect of com­ing down with the amitripty­line or increas­ing the car­ba­mazepine. I’m see­ing a neu­rol­o­gist on Wednes­day so hope to have some answers then.
The side effects are mem­o­ry loss, itch­ing, I feel like I have brain fog, feel­ing drowsy most of the time but not sleepy if that makes sense, for­get­ting stuff, my speech is also affect­ed as in say­ing stuff back to front.

I have been tak­ing a vari­a­tion of Amitripty­line called Trepi­line for about two years now. I start­ed get­ting painful pins and nee­dles in both my upper arms and it felt like my bones were on fire. Also could­n’t use my arm when that hap­pened, thank­ful­ly it was only one arm at a time. 

My doc­tor pre­scribed the Trepi­line 10mg and all of that went away after about a month. I might take 20mg in the future if I feel more of that but atm it’s work­ing real­ly well, it’s also real­ly helped my insom­nia so yay. I haven’t had any neg­a­tive side effects, I do take it close to bed time though so not sure if I’d expe­ri­ence any oth­er side effects if I took it earlier.

We’re not sure why I get this nerve pain, it might have been from an op in the past but it’s not 100%.

I’m only new on Amitripty­line ‚30 mg start­ing this week.i can’t believe there are so many side effects.i feel like I want to stop them now before start­ing to get these.First week,I was on 10 mg,second week 20 mg and stayed for 3 weeks on it.Ive had ter­ri­ble migraines,even if it sup­pose to pre­vent migraines.I suf­fer with Carpal Tunel syn­drome that’s why doc­tor pre­scribed me this, for pain.Make no sense to me.Carpal Tunel gives you numb arms in the night(my case)and result­ing pain will wake you up.Now ‚with this tablet,I still wake up few times a night but I feel so drugged up that my body can’t react to shake my hands and get rid of numbness.Really weird feeling.With all this,my stiff neck seems to get bet­ter and no oth­er side effects so far

This med­ica­tion is amaz­ing. I injured my back when weight train­ing and it did­n’t heal. I could­n’t do exer­cise for months and this was depress­ing me plus my job is very phys­i­cal and I was wor­ried that I might not be able to work any more. I tried phys­io­ther­a­py and com­mon pain relief but could­n’t train as I used to be or even walk and work more than one or two hours. I had this med­ica­tion as a sleep­ing aid and I was­n’t using it. My insom­nia led my to start with it (10 mg) and after a few days I noticed my pain is so much less and I could push more in the gym with­out being scared of being in too much pain. and I noticed my mood was so much bet­ter and my anx­i­ety com­ing from life deal­ings turn into calm­ness. Plus those days I start­ed to take big steps for those problems.
My pain is reduced, my sleep is so much bet­ter, and my mood is improved. I think this med­ica­tion is a def­i­nite YES and worth trying

I have tak­en amitripty­line for 3 years to man­age nerve pain. I went up to 10mg a day and then could reduce to 5–10 mg.
This week, I start­ed to suf­fer from tin­ni­tus (ring­ing sound in both of my ears, some­thing like sound of silence) and I sus­pect that it is because of amitripty­line. I am think­ing of stop­ping amitripty­line but I am scared that my nerve pain will return. Has any­one had a sim­i­lar expe­ri­ence? Do you you think that the nerve pain come back quickly?

Hi Bashar,

I’m afraid we can­not give you any advice relat­ed to your spe­cif­ic case, that can only come from your health­care pro­fes­sion­al. How­ev­er, you may find our forum at HealthUn­locked help­ful, where you can dis­cuss your con­cerns with oth­ers who live with pain. Alter­na­tive­ly, our helpline may also be able to help.

James, Pain Concern

I asked for a pre­scrip­tion for Naftidro­furyl to try because of bad cramps in shins, thighs and big toe at night and some­times in the day time. It was flagged up in the Times last month. Was advised this was not suit­able for me and was giv­en Amitripty­line although cramps are not caused by nerve mal­func­tion appar­ent­ly. Am will­ing to give it a try but am anx­ious after read­ing the side effects in this blog. I am a senior and already have idio­path­ic neu­ropa­thy in both feet which can­not be inves­ti­gat­ed any fur­ther. I do not want to feel spaced out or befud­dled nor put my eyes at risk as I am under a glau­co­ma clin­ic for famil­ial reasons.

Patricia Mc Gonagle

I am wor­ried now. I suf­fer from siat­i­ca and it’s been ter­ri­ble, cry­ing try­ing to get out of the bed. I had it last no novem­ber but cleared up. I try to self man­age it nuro­fen exfra, stretch­es, heat pads but went to doc and ge pre­scribed these. Just googled them and saw for Depres­sion. Pan­ick­ing now as although in pain and not sleep­ing l would­n’t say depressed. Wor­ry­ing about being off work and hop­ing l can return to nor­mal for the sake of my young fam­i­ly. I want to get fit­ter and health­i­er but one side effect us weight gain which is already a prob­lem. I am scared to take take them now only 10 mg for a month. Should I trust doc but can’t afford to become addict­ed or put on extra weight.

Hi Patri­cia, we are unable to give you med­ical advice here at Pain Con­cern. We would always sug­gest that if you have wor­ries or con­cerns about your med­ica­tion you should speak to a health pro­fes­sion­al, in this case prob­a­bly your GP.

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