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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.

Further Resources

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.

Rating: 3.64/5. From 28 votes.
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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

Rating: 2.73/5. From 11 votes.
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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.

Rating: 3.33/5. From 9 votes.
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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

Rating: 3.88/5. From 8 votes.
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Ruth Connolly

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

Rating: 4.00/5. From 5 votes.
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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.

Rating: 2.67/5. From 3 votes.
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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.

Rating: 3.00/5. From 9 votes.
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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.

Rating: 3.67/5. From 9 votes.
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Hello, you statet that a lower dosis is more effective than a higher. Do you have sources that prove that?

Rating: 3.00/5. From 3 votes.
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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.

Rating: 3.67/5. From 3 votes.
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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

Rating: 3.25/5. From 4 votes.
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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.

Rating: 1.75/5. From 4 votes.
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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!

Rating: 4.50/5. From 8 votes.
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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!

Rating: 3.13/5. From 8 votes.
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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!

Rating: 3.57/5. From 7 votes.
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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.

Rating: 3.00/5. From 5 votes.
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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.

Rating: 2.83/5. From 6 votes.
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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%.

Rating: 3.50/5. From 2 votes.
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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

Rating: 3.00/5. From 4 votes.
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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

Rating: 4.00/5. From 11 votes.
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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?

Rating: 3.83/5. From 6 votes.
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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

Rating: 2.00/5. From 3 votes.
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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.

Rating: 3.80/5. From 5 votes.
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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.

Rating: 3.43/5. From 7 votes.
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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.

Rating: 5.00/5. From 4 votes.
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