Amitriptyline
Amitriptyline is a tricyclic antidepressant medicine. Amitriptyline is used for Depression (US-labelled use).
Pronunciation: a mee trip' ti leen.
- Generic name
- amitriptyline hydrochloride
- Brand names
- Amitid, Amitril, Elavil, Endep
- Drug class
- Tricyclic antidepressant (TCA)
- Form
- Coated tablet; oral liquid also available (per the UK NHS source)
- Route
- By mouth (oral)
- Legal status
- Prescription-only medicine
Availability and supply rules vary by country
Trade names by country:
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What amitriptyline hydrochloride is and how it works
Amitriptyline is a tricyclic antidepressant medicine. In the US label its indicated use is relief of symptoms of depression, and the label notes endogenous depression is more likely to be alleviated than other depressive states. It is thought to work by increasing levels of a chemical called serotonin in the brain (NHS), and the US label states it inhibits neuronal reuptake of norepinephrine and serotonin, does not act primarily by stimulation of the central nervous system, and is not a monoamine oxidase inhibitor (MAOI). (3) (5) (4)
The sources differ on scope: the US label covers depression only, while the UK NHS source and MedlinePlus also describe non-depression uses (nerve pain and migraine prevention; MedlinePlus adds eating disorders and post-herpetic neuralgia) that are not in the US label. The schedule is set by the prescriber; brand names listed by MedlinePlus are marked as no longer on the market.
Mechanism of action: how amitriptyline hydrochloride works
Amitriptyline is a tricyclic antidepressant (TCA). The US label states it inhibits neuronal reuptake of norepinephrine and serotonin; it does not act primarily by stimulation of the central nervous system and is not a monoamine oxidase inhibitor (MAOI). The NHS describes tricyclic antidepressants as thought to work by increasing levels of serotonin in the brain; MedlinePlus describes it as increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance. (3) (5) (4)
What is Amitriptyline hydrochloride used for?
Depression (US-labelled use)
Amitriptyline is used to treat symptoms of depression. The US label notes that endogenous depression is more likely to be alleviated than other depressive states. (3) (5)
Nerve pain (not an FDA-approved use in the US label; off-label in the US)
The UK NHS source states amitriptyline is also used to treat nerve pain. This is not an FDA-approved use in the US label (off-label in the US). Doses for this use are not stated in the US label. (4)
Migraine prevention (not an FDA-approved use in the US label; off-label in the US)
The UK NHS source states amitriptyline is also used to prevent migraines, and MedlinePlus lists prevention of migraine headaches. This is not an FDA-approved use in the US label (off-label in the US). Doses for this use are not stated in the US label. (4) (5)
Other uses named by MedlinePlus (not an FDA-approved use in the US label; off-label in the US)
MedlinePlus also lists eating disorders and post-herpetic neuralgia (burning, stabbing pains or aches that may last months or years after a shingles infection). These are not in the US label's approved indication (off-label in the US). MedlinePlus advises talking to your doctor about the possible risks of using the medication for your condition. (5)
Before taking amitriptyline hydrochloride
Do not take / not appropriate for
- Do not take amitriptyline with a monoamine oxidase inhibitor (MAOI). This combination has caused hyperpyretic crises, severe convulsions, and death. The US label states a minimum of 14 days must pass after an MAOI is discontinued before amitriptyline is started, and it should then be started cautiously with gradual dose increase by the prescriber. (all products) (3)
- Do not take amitriptyline with cisapride, due to the potential for increased QT interval and increased risk for arrhythmia. (all products) (3)
- Amitriptyline is contraindicated in people who have shown prior hypersensitivity to it, and is not recommended during the acute recovery phase following myocardial infarction. (all products) (3)
- Do not stop taking amitriptyline suddenly without talking to your doctor. Sudden stopping can cause withdrawal side effects. (all products) (5) (4)
Tell your clinician about
- Any allergic reaction to amitriptyline or any other medicine.
- Whether you have ever had a heart attack recently, or have a heart problem, liver problems, kidney problems, or diabetes. Amitriptyline can make some heart problems worse and, in diabetes, can make it harder to keep blood sugar stable (you may need to test more often for the first few weeks and your diabetes treatment may need adjusting).
- Whether you have epilepsy or are having electroconvulsive treatment (ECT) — amitriptyline may increase the risk of a fit or seizure; glaucoma (amitriptyline can increase pressure in the eye); an enlarged prostate, difficulty urinating or problems emptying the bladder; an overactive thyroid gland (hyperthyroidism); schizophrenia.
- Whether you have ever taken any other medicines for depression — some antidepressants can affect the way amitriptyline works, even after you have stopped taking them.
- Whether you drink large amounts of alcohol, and any medicines you take including opioids (codeine, morphine, oxycodone), and non-prescription products such as allergy medications (diphenhydramine, loratadine, fexofenadine, chlorpheniramine or cetirizine) and cimetidine.
- Whether you are pregnant, planning to become pregnant, or breastfeeding.
- If you are 65 or older — talk to your doctor about the risks and benefits; MedlinePlus states older adults should not usually take amitriptyline because it is not as safe or effective as other medications for the same condition.
- If you are having surgery, including dental surgery, tell the doctor or dentist you are taking amitriptyline.
- If you have thoughts about harming yourself or ending your life.
Amitriptyline hydrochloride dosage and how to take it
- Take amitriptyline by mouth. Take it at around the same time(s) every day.
- The US label pattern: for outpatients the usual adult dose for depression is 75 mg a day in divided doses, increased if needed to 150 mg/day; alternatively start 50–100 mg at bedtime, increasing by 25–50 mg to 150 mg/day. Hospitalised patients: 100 mg/day, up to 200 mg (rarely 300 mg). Adolescents and elderly: lower doses, e.g. 10 mg three times a day plus 20 mg at bedtime. Maintenance is usually 50–100 mg/day (some need only 40 mg), often as one bedtime dose. For maintenance therapy the total daily dosage may be given in a single dose, preferably at bedtime.
- MedlinePlus states amitriptyline is usually taken one to four times a day. The UK NHS source states the usual adult dose for depression is 50 mg a day (25 mg twice a day); some people may need to start lower (10 mg to 25 mg a day) to reduce the chance of side effects, including people with heart problems and older people; the dose is then gradually increased if necessary; the maximum recommended dose is 150 mg a day and this should only be under the supervision of a specialist.
- The prescriber sets your schedule and dose. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Do not take more or less of it, or take it more often, than prescribed.
- You can take it with or without food — amitriptyline does not usually upset your stomach. Swallow tablets whole with a drink of water; if you chew them they taste bitter. If you use the liquid, measure with the plastic syringe or spoon provided and ask your pharmacist if you do not have one — do not use a kitchen teaspoon.
- A sedative effect may appear before the antidepressant effect; full antidepressant effect may take as long as 30 days (US label). The NHS source says you may start to feel better after 2 to 4 weeks but it can take 4 to 6 weeks to work fully, and advises allowing at least 6 weeks. Continue to take it even if you feel well.
- It is best not to drive, cycle or use machinery or tools for the first few days until you know how amitriptyline makes you feel.
- Discuss any plan to reduce or stop with your prescriber; do not make that decision yourself.
Procedures and treatment changes
Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (3) (5) (4)
Missed dose
MedlinePlus: take the missed dose as soon as you remember it, but if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one. The UK NHS source: leave the missed dose and take your next one at the usual time; never take 2 doses at the same time, and never have an extra dose to make up for a forgotten one. If you often forget doses, an alarm may help, or ask your pharmacist for advice. If you are unsure, contact the prescribing clinic for rescheduling instructions.
Overdose
Overdose can be dangerous and deaths may occur with this drug class; toxicity develops rapidly, with heart rhythm problems, severe low blood pressure, seizures and coma. The UK NHS source advises calling 999 now if you take more than your prescribed dose and have a fast or irregular heartbeat, a seizure or fit, feel drowsy or pass out, have difficulty breathing, or suddenly become very confused; it advises contacting 111 for advice now if you take more than your prescribed dose even without symptoms. MedlinePlus advises calling the poison control helpline at 1-800-222-1222 (online at https://www.poisonhelp.org/help), and if the person has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911. If you need to go to A&E, do not drive — ask someone to drive you or call for an ambulance, and bring the amitriptyline packet or leaflet, any remaining medicine, and any other medicines you take. (3) (5) (4)
Amitriptyline hydrochloride side effects
Like all medicines, amitriptyline can cause side effects in some people, but many people have no side effects or only minor ones. Some common side effects gradually improve as your body gets used to the medicine (NHS). The effects below are attributed to the source that names them; this is not a full list — see the leaflet inside your medicines packet.
Dry mouth
What to notice: Named as a common anticholinergic effect (dry mouth).
What to do: Chewing sugar-free gum or sucking sugar-free sweets may help (NHS). Tell your doctor or pharmacist if it is still bothering you or does not go away. (3) (5) (4)
Constipation
What to notice: Named as a common anticholinergic effect in both the US label and MedlinePlus, and as a common side effect by the NHS.
What to do: The NHS advises more fibre (fresh fruit, vegetables and cereals), plenty of water, and more regular exercise such as a daily walk or run; if this does not help, talk to your pharmacist or doctor. (3) (5) (4)
Blurred vision
What to notice: Named as an anticholinergic effect by the US label and listed by MedlinePlus.
What to do: Discuss persistent or troublesome symptoms with the prescribing team rather than changing treatment yourself. (3) (5)
Difficulty urinating
What to notice: Named as an anticholinergic effect (urinary retention) by the US label and listed by MedlinePlus; the NHS lists difficulty peeing as a common side effect.
What to do: The NHS suggests trying to relax when you pee and not forcing the flow; if you cannot pee, try again a short time later, and call 111 or talk to your doctor urgently if you cannot pee at all. (3) (5) (4)
Feeling dizzy
What to notice: The NHS says this may be due to low blood pressure; amitriptyline can reduce your blood pressure when you stand up (also described in the US label as orthostatic hypotension).
What to do: Drink plenty of water or other non-alcoholic drinks; do not stand up too quickly after sitting or lying down; do not drive, cycle or use tools or machinery if you feel dizzy. (3) (4)
Feeling sleepy
What to notice: Drowsiness is listed by MedlinePlus and the NHS; the US label notes a sedative effect may appear before the antidepressant effect.
What to do: Do not drink too much alcohol; do not drive, cycle or use tools or machinery if you feel sleepy or tired. (3) (5) (4)
Headaches
What to notice: Listed as a common side effect by the NHS and by MedlinePlus.
What to do: Rest and drink plenty of fluids; do not drink too much alcohol; paracetamol and ibuprofen may help if you need pain relief (NHS). Talk to your doctor if headaches do not go away or are severe. (5) (4)
Nausea and vomiting
What to notice: Listed by MedlinePlus; the NHS lists nausea as part of a possible low-sodium picture rather than as a simple common effect.
What to do: Tell your doctor if severe or not going away; if nausea occurs with constant headaches, weakness and frequent muscle cramps, seek urgent advice (see below). (5) (4)
Weakness or tiredness
What to notice: Listed by MedlinePlus; also part of the withdrawal picture described by the NHS (feeling anxious and tired).
What to do: Discuss persistent or troublesome symptoms with the prescribing team rather than changing treatment yourself. (5) (4)
Nightmares
What to notice: Named by MedlinePlus (not in the US label excerpt).
What to do: Tell your doctor if severe or not going away. (5)
Pain, burning, or tingling in the hands or feet
What to notice: Named by MedlinePlus (not in the US label excerpt).
What to do: Tell your doctor if severe or not going away. (5)
Changes in sex drive or ability
What to notice: Listed by MedlinePlus; the NHS notes that taking amitriptyline can occasionally cause problems getting an erection and problems ejaculating, that sexual side effects are not common and should go away after the first couple of weeks.
What to do: If they do not get better and this is a problem for you, speak to your doctor to see if there is another antidepressant you can try (NHS). (5) (4)
Changes in appetite or weight
What to notice: Listed by MedlinePlus; the NHS says amitriptyline can change how hungry you feel — some people feel more hungry and others less — so weight may change when you first start taking it.
What to do: If you start to have problems with your weight, talk to your doctor or a pharmacist. (5) (4)
Excessive sweating
What to notice: Listed by MedlinePlus.
What to do: Tell your doctor if severe or not going away. (5)
Confusion, unsteadiness, tremor
What to notice: Listed by MedlinePlus (confusion, unsteadiness) and named in the US label (confusion, tremor).
What to do: Discuss persistent or troublesome symptoms with the prescribing team; seek urgent help if severe or sudden in onset. (3) (5)
Fast or irregular heartbeat
What to notice: Your heartbeat becomes fast or irregular (the US label also names arrhythmias).
Possible liver problem
What to notice: The whites of your eyes turn yellow, or your skin turns yellow (may be less obvious on brown or black skin), or you have dark pee.
What to do: Call a doctor or call 111 now (NHS). (4)
Possible low sodium levels (hyponatremia)
What to notice: Constant headaches, feeling sick (nausea) and weak, and frequent muscle cramps — together these can be a sign of low sodium levels in the blood; in severe cases low sodium levels can lead to a fit or seizure. The US label also names hyponatremia.
Eye problems
What to notice: Eye pain, a change in your eyesight, or swelling or redness in or around your eye.
What to do: Call a doctor or call 111 now (NHS). (4)
Possible intestine (bowel) problems
What to notice: Constipation that lasts a long time, a swollen stomach, a high temperature and being sick (vomiting).
What to do: Call a doctor or call 111 now (NHS). (4)
Problems passing urine causing stomach ache, or inability to pee at all
What to notice: Problems peeing which are causing stomach ache, or you cannot pee at all.
What to do: Call a doctor or call 111 now (NHS). (4)
Possible effect on blood or bone marrow
What to notice: A high temperature with shivering or chills and a sore throat that lasts a long time, or bleeding or bruising more easily than usual.
What to do: Call a doctor or call 111 now (NHS). (4)
Serious side effects listed by MedlinePlus
What to notice: Slow or difficult speech; dizziness or faintness; weakness or numbness of an arm or a leg; crushing chest pain; rapid, pounding, or irregular heartbeat; severe skin rash or hives; swelling of the face and tongue; yellowing of the skin or eyes; jaw, neck, and back muscle spasms; uncontrollable shaking of a part of the body; fainting; unusual bleeding or bruising; seizures; hallucinating (seeing things or hearing voices that do not exist).
What to do: Call your doctor immediately (MedlinePlus). (5)
Serotonin syndrome (when combined with other serotonergic drugs)
What to notice: The US label names serotonin syndrome when amitriptyline is combined with other serotonergic drugs.
What to do: Seek prompt medical assessment; give the clinician a complete list of your medicines. (3)
Serious warnings
Boxed warning: suicidality and antidepressant drugs — emergency
Symptoms: Increased risk of suicidal thinking and behaviour (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder and other psychiatric disorders. All patients started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behaviour. The NHS advises calling 999 or going to A&E if you have thoughts about harming yourself or ending your life; MedlinePlus lists new or worsening depression, thinking about harming or killing yourself or planning or trying to do so, extreme worry, agitation, panic attacks, difficulty falling asleep or staying asleep, aggressive behaviour, irritability, acting without thinking, severe restlessness, and frenzied abnormal excitement as symptoms to report right away.
Action: This is the US label's boxed warning — the most prominent warning. Anyone considering the use of amitriptyline or any other antidepressant in a child, adolescent, or young adult must balance the risk against clinical need; short-term studies did not show an increase in the risk of suicidality in adults beyond age 24 and showed a reduction in risk in adults aged 65 and older. Patients of all ages started on antidepressant therapy should be closely observed for clinical worsening, suicidality or unusual behaviour changes, especially during the initial months of treatment and when the dose changes. Families and caregivers should be advised of the need for close observation and communication with the prescriber; make sure your family or caregiver knows which symptoms may be serious so they can call the doctor when you are unable to seek treatment on your own. Amitriptyline hydrochloride tablets are not approved for use in pediatric patients. Keep all appointments with your doctor, especially at the beginning of treatment. (3) (5) (4)
MAOI interaction — emergency
Symptoms: Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously.
Action: Amitriptyline should not be given concomitantly with monoamine oxidase inhibitors (this is a contraindication). When it is desired to replace an MAOI with amitriptyline, a minimum of 14 days should be allowed to elapse after the MAOI is discontinued; amitriptyline should then be initiated cautiously with gradual increase in dosage until optimum response is achieved. Tell your doctor or pharmacist if you are taking, or have stopped taking within the past two weeks, MAO inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate). (3) (5)
Cisapride interaction — urgent
Symptoms: Amitriptyline should not be given with cisapride due to the potential for increased QT interval and increased risk for arrhythmia.
Action: This combination is a contraindication. Tell your prescriber and pharmacist about all your medicines before starting amitriptyline. (3)
Cardiovascular effects — emergency
Symptoms: Cardiovascular effects including arrhythmias, orthostatic hypotension, and myocardial infarction. The NHS lists signs including chest pain which may spread to your neck or arm, shortness of breath or a clammy feeling (possible heart attack).
Action: The NHS advises calling 999 for chest pain which may spread to your neck or arm, shortness of breath or a clammy feeling. The US label states amitriptyline is not recommended for use during the acute recovery phase following myocardial infarction. (3) (4)
Stroke-like signs — emergency
Symptoms: Weakness or numbness on one side of your face or body, trouble speaking or swallowing, confusion, loss of balance or blurred eyesight.
Action: Call 999 (NHS). (4)
Seizures and fainting — emergency
Symptoms: A seizure or fit; passing out. The US label names seizures among CNS effects.
Serious allergic reaction (anaphylaxis) — emergency
Symptoms: Your lips, mouth, throat or tongue suddenly become swollen; you're breathing very fast or struggling to breathe (you may become very wheezy or feel like you're choking or gasping for air); your throat feels tight or you're struggling to swallow; your skin, tongue or lips turn blue, grey or pale (on black or brown skin this may be easier to see on the palms of your hands or soles of your feet); you suddenly become very confused, drowsy or dizzy; someone faints and cannot be woken up; a child is limp, floppy or not responding like they normally do. You or the person who is unwell may also have a rash that's swollen, raised, itchy, blistered or peeling.
Action: Call 999 now (NHS). These can be signs of a serious allergic reaction and may need immediate treatment in hospital. Do not drive yourself to A&E. (4)
Overdose — emergency
Symptoms: Deaths may occur with this drug class; toxicity develops rapidly — heart rhythm problems, severe low blood pressure, seizures, coma. MedlinePlus lists irregular heartbeat, seizures, coma, confusion, problems concentrating, hallucinating, agitation, drowsiness, rigid muscles, vomiting, fever, cold body temperature.
Action: Diagnosis and treatment of suspected overdose must be managed by emergency services; if you take more than your prescribed dose or notice any of these symptoms, use the emergency numbers in the overdose section and bring the medicine with you. (3) (5) (4)
Age 65 and older — urgent
Symptoms: MedlinePlus states older adults should not usually take amitriptyline because it is not as safe or effective as other medications that can be used to treat the same condition.
Action: Talk to your doctor about the risks and benefits of taking this medication if you are 65 or older. (5)
Interactions
| Medicine or test | Effect | Action |
|---|---|---|
| Monoamine oxidase inhibitors (MAOIs) | Concurrent use is contraindicated; hyperpyretic crises, severe convulsions, and deaths have occurred with combined tricyclic antidepressant and MAOI use. | Never combine these without specialist direction; a minimum of 14 days must pass after an MAOI is stopped before amitriptyline is started, and it is then started cautiously by the prescriber with gradual dose increase. Tell your doctor or pharmacist about MAOIs taken now or stopped within the past two weeks. (3) (5) |
| Cisapride | Concurrent use is contraindicated due to the potential for increased QT interval and increased risk for arrhythmia. | Do not take this combination; tell your prescriber and pharmacist about all your medicines before starting amitriptyline. (3) |
| CYP2D6 inhibitors (e.g., SSRIs, quinidine, cimetidine) | These may significantly raise amitriptyline levels. | Give the specialist and pharmacist a complete medicines list before starting or changing treatment, including non-prescription cimetidine. (3) |
| Serotonergic agents (triptans, tramadol, St John's Wort, lithium) | These carry a risk of serotonin syndrome. | The US label lists serotonin syndrome as an adverse effect when amitriptyline is combined with other serotonergic drugs. Discuss all medicines and supplements, including herbal remedies, with your doctor or pharmacist before combining them. (3) |
| CNS depressants (alcohol, barbiturates) | Enhanced impairment. MedlinePlus also notes alcohol can add to the drowsiness caused by this medication. | Avoid adding to drowsiness; do not drive or operate machinery until you know how amitriptyline affects you. (3) (5) |
| Anticholinergic agents | Carry a risk of paralytic ileus in combination. | Tell your prescriber and pharmacist about any anticholinergic medicines, including non-prescription products. (3) |
| Non-prescription products: allergy medications (diphenhydramine, loratadine, fexofenadine, chlorpheniramine or cetirizine); cimetidine (Tagamet) | These may interact with amitriptyline. | Tell your doctor and pharmacist you are taking these before starting amitriptyline; do not start any of these while taking amitriptyline without discussing with your healthcare provider. (5) |
| Opioid medicines | Taking amitriptyline with opioid medicines can increase your risk of becoming very drowsy and having breathing problems. Opioid medicines include codeine, morphine and oxycodone. Methadone and other opiates (for example, heroin) can increase the risk of severe drowsiness. | Tell your doctor or pharmacist about all opioids and recreational drugs you use. (4) |
| Other antidepressants | Some antidepressants can affect the way amitriptyline works and can cause very high blood pressure; this can happen even after you stop taking them. | Tell your doctor if you have ever taken any other medicines for depression, including within the past two weeks. (4) |
| St John's wort | Taking St John's wort while taking amitriptyline will increase your risk of side effects. | Do not take St John's wort while you are taking amitriptyline (NHS). There is not enough information to say other complementary medicines and herbal remedies are safe to take with amitriptyline. (4) |
| Recreational drugs (cannabis, stimulants like MDMA/cocaine, hallucinogens like LSD, novel psychoactive substances such as mephedrone) | Cannabis with amitriptyline can give you a fast heartbeat and make you more drowsy, especially if you've just started amitriptyline. It can be dangerous to take amitriptyline with stimulants, hallucinogens and novel psychoactive substances. | Amitriptyline has not been properly tested with recreational drugs. Talk to your doctor if you think you might use recreational drugs while taking amitriptyline. (4) |
Special populations
Children and adolescents
The US label boxed warning covers increased risk of suicidal thinking and behaviour in children, adolescents and young adults in short-term studies, and states amitriptyline hydrochloride tablets are not approved for use in pediatric patients. MedlinePlus states children younger than 18 should not normally take amitriptyline, but in some cases a doctor may decide it is the best medication to treat a child's condition. The UK NHS source gives lower starting doses for adolescents and elderly people (e.g. 10 mg three times a day plus 20 mg at bedtime) within the US label dosing pattern. (3) (5)
Older adults (65 and older)
MedlinePlus states older adults should not usually take amitriptyline because it is not as safe or effective as other medications that can be used to treat the same condition, and advises talking to your doctor about the risks and benefits if you are 65 or older. The US label boxed warning notes a reduction in suicidality risk with antidepressants compared to placebo in adults aged 65 and older. The UK NHS source advises some people, including older people, may need to start on a lower dose of 10 mg to 25 mg a day to reduce the chance of side effects. (3) (5) (4)
Pregnancy
US label: amitriptyline has been shown to cross the placenta; although a causal relationship has not been established, there have been a few reports of adverse events, including CNS effects, limb deformities, or developmental delay, in infants whose mothers had taken amitriptyline during pregnancy; there are no adequate and well-controlled studies in pregnant women; it should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. The UK NHS source is less cautious: if you are already taking amitriptyline for depression you may be advised to continue during pregnancy; it says there is no concern that amitriptyline will affect your baby's development and that if you take it around the time you give birth your baby will be monitored for temporary withdrawal effects such as problems with sleeping and feeding. Sources differ: the decision must be made with your prescriber. If you become pregnant while taking amitriptyline, speak to your doctor. (3) (4)
Breastfeeding
US label: amitriptyline is excreted into breast milk; because of the potential for serious adverse reactions in nursing infants from amitriptyline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. The UK NHS source is less restrictive: if your baby is healthy you can take amitriptyline while breastfeeding after checking with a pharmacist or doctor; it says amitriptyline passes into breast milk in very small amounts and has only been linked with side effects in very few breastfed babies, and advises monitoring your baby and contacting a healthcare professional or calling 111 if the baby is not feeding as well as usual or putting on weight as expected, seems unusually sleepy, seems restless or irritable, is constipated, or is not peeing as much. Sources differ: the decision must be made with your prescriber. The US label states do not breast-feed while taking amitriptyline; the US label evidence boundary mentions no neonatal withdrawal or jitteriness and none is asserted here. (3) (5) (4)
Fertility
The UK NHS source states there is no evidence that amitriptyline affects fertility in either men or women. (4)
Diabetes
Amitriptyline can make it more difficult to keep your blood sugar stable. If you have diabetes and usually test your blood sugar levels, you may have to do this more often for the first few weeks of treatment, and you may also need to adjust your diabetes treatment. Speak to your doctor if your blood sugar levels are causing you concern. (4)
Driving and operating machinery
You should know that amitriptyline may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you. The NHS advises it is best to stop driving and cycling, and avoid using machinery or tools, for the first few days of treatment until you know how the medicine makes you feel; it is an offence to drive if your ability to drive safely is affected, and it is your responsibility to decide if it is safe to drive. Talk to your doctor or pharmacist if you are unsure. (5) (4)
Monitoring
Before starting
- Confirm the exact diagnosis and indication; the only indication in the US label is depression, and non-depression uses named by the UK NHS source and MedlinePlus are not FDA-approved uses in the US label (off-label in the US).
- Assess previous hypersensitivity to amitriptyline, recent myocardial infarction (contraindicated during the acute recovery phase), and heart, liver, kidney or thyroid disease, glaucoma, enlarged prostate or difficulty urinating, seizures, schizophrenia, and diabetes.
- Record all current and recently stopped medicines, including MAOIs stopped within the past two weeks, other antidepressants, opioids, non-prescription allergy medications and cimetidine, plus herbal remedies such as St John's wort.
- Discuss pregnancy, plans for pregnancy, breastfeeding, fertility, and age-related risks (including for people 65 and older), and any history of suicidal thoughts or attempts.
- Give the Medication Guide provided by the doctor or pharmacist and discuss the boxed warning; ensure family or caregivers know which symptoms may be serious.
During treatment
- Monitor appropriately and observe closely for clinical worsening, suicidality, or unusual changes in behaviour, especially during the initial months of treatment and when the dose is increased or decreased.
- Keep all appointments with your doctor and the laboratory; your doctor may order certain lab tests to check your body's response to amitriptyline.
- Your doctor will check with you regularly to make sure your treatment is still working and that you are not having problems with side effects.
- Any dose change, reduction, or discontinuation is managed by the prescriber; if you have been feeling better for 6 months or more your doctor may suggest coming off amitriptyline, usually by reducing the dose gradually over several weeks or longer.
- If you have diabetes, you may need to test blood sugar levels more often for the first few weeks and your diabetes treatment may need adjusting.
- Do not drive, cycle or use machinery or tools until you know how amitriptyline makes you feel.
Storage
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Dispose of unneeded medications in a way so that pets, children, and other people cannot take them. Do not flush this medication down the toilet; use a medicine take-back program and talk to your pharmacist about take-back programs in your community. Keep all medication out of sight and reach of children as many containers are not child-resistant; always lock safety caps and place the medication in a safe location up and away and out of their sight and reach.
Professional information
Clinician-facing context only. Use the current local label, indication, dosing, contraindication and monitoring requirements. No dose titration schedule or renal/hepatic dose-adjustment table was surfaced in the cited US label excerpt and none is asserted here; this page does not provide impairment-specific dosing. The US label doses are included in the 2026-10-12 addendum; other doses are not asserted beyond what the cited label states.
United States
Indication: Depression (the only US-labelled indication)
Dose summary: Outpatients: usually 75 mg a day in divided doses, increased if needed to 150 mg/day; alternatively start 50–100 mg at bedtime, increasing by 25–50 mg to 150 mg/day. Hospitalised patients: 100 mg/day, up to 200 mg (rarely 300 mg). Adolescents and elderly: lower doses, e.g. 10 mg three times a day plus 20 mg at bedtime. Maintenance: usually 50–100 mg/day (some need only 40 mg), often as one bedtime dose; for maintenance therapy the total daily dosage may be given in a single dose, preferably at bedtime.
Renal context: The cited source notes no renal or hepatic dose-adjustment table was surfaced; renal and hepatic impairment require individual assessment by the prescriber and are not addressed here. (3)
United Kingdom
Indication: Depression
Dose summary: Usual adult dose 50 mg a day (25 mg twice a day); some people may need to start on a lower dose of 10 mg to 25 mg a day to reduce the chance of side effects, including people with heart problems and older people; the dose is then gradually increased if necessary; the maximum recommended dose is 150 mg a day, which should only be under the supervision of a specialist.
Renal context: Not stated in the cited UK source; renal and hepatic impairment require individual assessment by the prescriber and are not addressed here. (4)
Hepatic guidance
Use local product information and prescriber judgement; this page does not provide impairment-specific dosing.
Overdose note
Deaths may occur with this drug class; toxicity develops rapidly — heart rhythm problems, severe low blood pressure, seizures, coma. Suspected overdose requires immediate emergency assessment and hospital monitoring as soon as possible; see the overdose section for emergency numbers and what to bring. (3) (5) (4)
Frequently asked questions
How long does amitriptyline take to work?
The US label notes a sedative effect may appear before the antidepressant effect and full antidepressant effect may take as long as 30 days. The NHS says you may start to feel better after 2 to 4 weeks but it can take 4 to 6 weeks to work fully, and advises not stopping just because you feel it is not helping — allow at least 6 weeks. Talk to your doctor if you are not feeling any better after 6 weeks, or sooner if side effects are still a problem. (3) (4)
What are the common side effects, and how long do they last?
Common side effects include a dry mouth and constipation; they are usually mild and go away after a couple of weeks (NHS). Other effects named across the sources include dizziness, feeling sleepy, difficulty peeing, headaches, nausea and vomiting, weakness or tiredness, nightmares, blurred vision, tingling in the hands or feet, changes in sex drive or ability, sweating, and changes in appetite or weight. (5) (4)
Is amitriptyline addictive?
The NHS states amitriptyline is not addictive, but you can get withdrawal side effects if you stop taking it suddenly, including headache, feeling anxious and tired, and difficulty falling asleep. Do not stop taking it suddenly without talking to your doctor, who may recommend reducing your dose gradually over several weeks or longer. (4)
Can I drink alcohol while taking amitriptyline?
The NHS says you can drink alcohol but it may make you feel sleepy, and it might be best to stop drinking alcohol until you see how the medicine makes you feel. MedlinePlus notes that alcohol can add to the drowsiness caused by this medication. (5) (4)
Can I drive while taking amitriptyline?
It is best not to drive, cycle, or use machinery or tools for the first few days until you know how amitriptyline makes you feel. Amitriptyline may make you drowsy. It is an offence to drive if your ability to drive safely is affected; it is your responsibility to decide if it is safe to drive, and if in doubt do not drive. Talk to your doctor or pharmacist if unsure. (5) (4)
Does amitriptyline affect contraception?
The NHS states amitriptyline does not affect any type of contraception, including the combined pill and emergency contraception. (4)
Are there long-term side effects?
The NHS notes that although there is a lot of information on the short-term effects of taking amitriptyline, less is known about the long-term effects; there may be an increased risk of confusion and possibly dementia in people taking medicines like amitriptyline, but more research needs to be done. If you are worried about this, talk to your doctor. (4)
What is the mechanism of action of amitriptyline hydrochloride?
Amitriptyline is a tricyclic antidepressant (TCA). The US label states it inhibits neuronal reuptake of norepinephrine and serotonin; it does not act primarily by stimulation of the central nervous system and is not a monoamine oxidase inhibitor (MAOI). The NHS describes tricyclic antidepressants as thought to work by increasing levels of serotonin in the brain; MedlinePlus describes it as increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance. (3) (5) (4)
References
- Amitriptyline hydrochloride tablet, coated — prescribing informationDailyMed, U.S. National Library of Medicine · United States · dated 2025-08-28 (SPL effective date) · accessed 2026-09-15 · source 1
- Amitriptyline hydrochloride tablets prescribing information — 2026-10-12 addendumDailyMed, U.S. National Library of Medicine (openFDA drug label API, same SPL set id; SPL effective 2025-08-28) · United States · dated 2025-08-28 (SPL effective date) · accessed 2026-10-12 · source 2
- Amitriptyline hydrochloride — verbatim label excerptsDailyMed, U.S. National Library of Medicine (openFDA drug label API, set_id d46ff585-7082-4a7c-a88f-2acf3be0f1d5, SPL effective 20250828) · United States · dated 2025-08-28 (SPL effective date) · accessed 2026-10-13 · source 3
- Amitriptyline for depressionNational Health Service (NHS), United Kingdom · United Kingdom · dated page last reviewed 28 February 2025 · accessed 2026-10-17 · source 4
- Amitriptyline: MedlinePlus Drug InformationMedlinePlus, U.S. National Library of Medicine · United States · dated last revised 2024-01-15 · accessed 2026-10-17 · source 5
Brand names by country
Single-ingredient amitriptyline hydrochloride names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.