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Active Ingredient: Amitriptyline
Brand(s): Elavil, Endep

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What is Amitriptyline

Amitriptyline additionally has a blocking impact on the sodium, potassium and NMDA ion channels, each on the central degree and within the spinal twine. This induces the analgesic impact within the therapy of neuropathic ache, prophylaxis of persistent tension-type headache and prophylaxis of migraine.

Amitriptyline Drug Recommendation

When treating a depressive episode, select an antidepressant primarily based on comorbidity, uncomfortable side effects, interactions, expertise and worth. When prescribed normally observe, a tricyclic antidepressant (TCA) or selective serotonin reuptake inhibitor (SSRI) is really useful. There’s a slight desire for the SSRIs attributable to a barely extra beneficial side-effect profile. Within the specialized psychological well being care setting, a TCA, an SSRI, a non-selective serotonin reuptake inhibitor (SNRI), mirtazapine or bupropion could also be began. In clinically admitted sufferers, a TCA is most well-liked. When utilizing a TCA, desire is given to medicine with which a lot expertise has been gained:

  • amitriptyline
  • nortriptyline
  • imipramine
  • clomipramine

The place of an antidepressant within the therapy of a depressive episode of bipolar dysfunction is mostly controversial because of the restricted proof for efficacy. If an antidepressant is added, SSRIs (besides paroxetine) and bupropion are most well-liked. Solely take into account including a serotonin-noradrenaline-reuptake inhibitor (SNRI) or a tricyclic antidepressant if different antidepressants haven’t confirmed efficient. Antidepressants can set off a mania. 

Amitriptyline Indications


  • extreme melancholy;
  • neuropathic ache;
  • prophylaxis of persistent tension-type headache (CTTH);
  • Migraine prophylaxis;
  • offlabel: (diabetic) polyneuropathy.

With youngsters:

  • enuresis nocturna in youngsters ≥ 6 years, when natural causes (equivalent to spina bifida) have been excluded and within the absence of response to all different (non-medicinal/medicinal) remedies.

What Should You Discuss To Your Doctor Before Using This Medicine

  1. Being pregnant
    • Amitriptyline and its lively metabolite nortriptyline cross the placenta.
    • Teratogenesis: In depth expertise with amitriptyline throughout being pregnant doesn’t recommend an elevated threat of congenital abnormalities.
    • Pharmacological impact: With persistent use and after administration within the final weeks, neonatal withdrawal signs might happen
      • irritability,
      • hypertonia,
      • tremours,
      • irregular respiratory,
      • poor ingesting and crying and generally anticholinergic signs
        • urinary retention
        • constipation
    • Recommendation: Use solely on strict indication. Abrupt discontinuation or switching of an antidepressant throughout being pregnant shouldn’t be really useful. On account of altering pharmacokinetics in being pregnant, it’s advisable to find out plasma ranges often. Within the second eand notably the third etrimester, plasma ranges might drop and a dose improve could also be obligatory.

  2. Lactation
    • Transition in breast milk: Sure, in small quantities (amitriptyline, nortriptyline), comparable to 0.6-1% of the maternal dose.
    • Pharmacological impact: There was one report of extreme sedation and poor ingesting within the toddler at a dose of solely 10 mg/day.
    • Suggestion: Can in all probability be used safely. To be on the protected facet, test the toddler for:
      • poor sleeping
      • drowsiness
      • irritability
      • frequent crying
      • poor ingesting
      • poor progress throughout the first few weeks

  3. Contraindications
    • Hypersensitivity to tricyclic antidepressants;
    • latest myocardial infarction, coronary heart block, cardiac arrhythmia, coronary insufficiency;
    • extreme hepatic impairment.

Amitriptyline Drug Interactions

Amitriptyline is principally a substrate for CYP2D6 and CYP2C19. Concomitant use of amitriptyline with MAOIs (non-selective and selective -A (moclobemide) and -B (selegiline)), attributable to threat of serotonin syndrome together with agitation, confusion, tremor, hyperthermia and myoclonus.

Remedy with amitriptyline ought to solely be began 14 days after the final dose of an irreversible non-selective MAOI and no less than sooner or later after the final dose of the reversible MAOI moclobemide. Don’t begin the MAOI till 14 days after discontinuation of amitriptyline.

Concomitant use with sympathicomimetics together with adrenaline, isoprenaline, noradrenaline and phenylephrine might potentiate cardiovascular results. TCAs scale back the blood stress reducing impact of centrally appearing antihypertensive medicine equivalent to methyldopa and clonidine.

Use warning when combining with different medicinal merchandise that extend the QT interval, equivalent to:

  • amiodarone
  • quinidine
  • disopyramide
  • sotalol
  • domperidone
  • some antipsychotics
  • methadone
  • macrolide antibiotics
  • fluoroquinolones
  • some antimycotics
  • selective serotonin 5HT3– receptor antagonists (granisetron, ondansetron).

TCAs improve the impact of anticholinergics on the attention, central nervous system, bowel and bladder. There’s additionally an elevated threat of hyperpyrexia, particularly in scorching climate. In instances of enuresis nocturna, don’t use amitriptyline similtaneously an anticholinergic.

Antimycotics: terbinafine will increase plasma ranges and secondary toxicity of TCAs by way of inhibition of CYP2D6. Syncope and torsade de pointes have been reported. Fluconazole will increase plasma ranges of amitriptyline by numerous mechanisms.

Concomitant use with serotonergic medicinal merchandise will increase the danger of serotonin syndrome, which can be life-threatening. With concomitant use, particularly at initiation and with every dose improve, intently monitor the affected person for adjustments in psychological standing, autonomic instability, neuromuscular abnormalities and gastrointestinal signs. Concomitant use with tramadol will increase the danger of seizures and serotonin syndrome. Concomitant use with the robust CYP1A2 inhibitor fluvoxamine might improve plasma concentrations of amitriptyline.

Different interactions

Concomitant use with valproic acid might improve plasma concentrations of amitriptyline; scientific monitoring is really useful.

The impact of alcohol, barbiturates and different central inhibitors could also be potentiated. A rise in free plasma concentrations of amitriptyline and nortriptyline has been reported within the presence of ethanol.

Electroconvulsive remedy might improve therapy dangers.

Anaesthetics might improve the danger of arrhythmias and hypotension when used along with tri-/tetracyclic antidepressants. If doable, this drugs needs to be discontinued just a few days earlier than surgical procedure. In case of emergency surgical procedure, the anaesthetist needs to be knowledgeable that the affected person will probably be handled with it.

CYP2D6 inhibitors, together with sure antipsychotics, SSRIs, β-blockers and anti-arrhythmics could cause a major improve in plasma concentrations. Examples of robust CYP2D6 inhibitors embrace bupropion, fluoxetine, paroxetine and quinidine. Take into account measuring TCA plasma ranges when co-administering with CYP2D6 inhibitors. Mixture with terbinafine is contraindicated.

Different CYP inhibitors equivalent to cimetidine, methylphenidate and calcium channel blockers (e.g. diltiazem and verapamil) might improve plasma ranges of TCAs and related toxicity.

CYP-inductors equivalent to rifampicin, phenytoin, barbiturates, carbamazepine and St. John’s wort (Hypericum perforatum) might result in decrease plasma ranges and decreased response to TCAs attributable to elevated metabolism of TCAs.

Amitriptyline Dosage

Not all dosing regimens might be achieved with the accessible strengths. Select the suitable energy for the dose will increase.

  • Extreme melancholy
    • Adults
      • Beginning dose: 25 mg 2×/day. If obligatory, improve by 25 mg each 2 days to a most of 75 mg 2× day by day; then titrate to the bottom efficient dose.
      • Proceed therapy for a adequate time period, often as much as 6 months after restoration; then taper off step by step over a interval of a number of weeks.
    • Aged individuals (> 65 years) and sufferers with cardiovascular ailments
      • Preliminary dose: 10-25 mg within the night. Relying on particular person response and tolerability, improve day by day dose to 100-150 mg, divided into two doses, if obligatory. Use warning with doses above 100 mg. Thereafter, titrate to the bottom remaining efficient dose.
      • Proceed therapy for a adequate time period, often as much as 6 months after restoration; then taper off step by step over a interval of a number of weeks.

  • Neuropathic ache, prophylaxis of persistent tension-type headache (CTTH) and of migraine
    • Adults
      • Beginning dose: 10-25 mg within the night, step by step improve by 10 or 25 mg/day each 3-7 days. Really helpful doses are 25-75 mg/day. Warning needs to be exercised with doses above 100 mg. Give the dose 1×/day within the night or cut up into 2 doses; a single dose above 75 mg shouldn’t be really useful. The upkeep dose is the bottom efficient dose. The analgesic impact is often noticed after 2-4 weeks of administration.
      • Based on the NHG commonplace Ache (2016), for neuropathic ache: beginning dose: 10-25 mg within the night, step by step improve by 25 mg/day each 1-2 weeks, to a most of 125 mg/day, based on impact and uncomfortable side effects.
      • Period of therapy for neuropathic ache: often a therapy interval of a number of years is critical, it is strongly recommended that this be evaluated often.
      • Remedy period prophylaxis of persistent tension-type headache (CTTH) and migraine: it is strongly recommended to often consider whether or not the therapy remains to be applicable.
    • Aged individuals (> 65 years) and sufferers with cardiovascular ailments
      • Preliminary dose: 10-25 mg within the night. Relying on particular person response and tolerability, improve day by day dose as obligatory. Use warning with doses above 75 mg, these could also be divided into 2 doses.
      • Based on the NHG-Customary Ache (2016), for neuropathic ache: within the aged, begin with a low dose (10 mg) and improve slowly.
      • Remedy period for neuropathic ache: often a therapy period of a number of years is critical, it is strongly recommended to judge this often.
      • Remedy period prophylaxis of persistent tension-type headache (CTTH) and migraine: it is strongly recommended to often consider whether or not the therapy remains to be applicable.

  • Enuresis nocturna
    • Kids 6-10 years
      • 10-20 mg, administered 1-1.5 hours earlier than bedtime. Enhance dose step by step. Most period of therapy is 3 months; section out step by step. After medical evaluation, such a therapy cycle might be repeated if obligatory.
      • Based on the paediatric formulary of the NKFK: 1-1.5 mg/kg/day in 1 dose.
    • Kids from 11 years
      • 25-50 mg, administered 1-1.5 hours earlier than bedtime. Enhance dose step by step.
      • Most period of therapy is 3 months; section out step by step. After medical evaluation, such a therapy cycle might be repeated if obligatory.
      • Based on the paediatric formulary of the NKFK: 1-1.5 mg/kg/day in 1 dose.

  • Offlabel: (Diabetic) polyneuropathy
    • Adults
      • Based on the NVN guideline polyneuropathy (2005): Beginning dose: 25 mg 1×/day within the night earlier than going to sleep. Enhance by 25 mg every time. Most 75-125 mg/day. In a big proportion of sufferers, therapy over a lot of years could also be obligatory.
      • Within the aged: beginning dose: 10 mg 1×/day within the night earlier than going to mattress.

  • In case of CYP2D6 polymorphism, modify the dose or the drug, if obligatory, in session with the pharmacist.
  • Together with robust CYP2D6 inhibitors: relying on the person response of the affected person and primarily based on the plasma degree, take into account a decrease dose of amitriptyline. Mixture with terbinafine is contraindicated. 
  • Diminished liver operate: In case of gentle and reasonable hepatic impairment, dosing is really useful and plasma ranges needs to be decided if doable. In case of extreme hepatic impairment, use is contra-indicated.
  • Decreased renal operate: no dose adjustment is required.
  • Administration: Swallow the tablets complete with water.

Signs of Overdose

  • Mydriasis
  • urinary retention
  • dry mucous membranes
  • decreased intestinal motility
  • extreme hypotension
  • hyponatraemia
  • hypokalaemia
  • convulsions
  • respiratory melancholy
  • extreme arrhythmias
  • cardiac shock
  • metabolic acidosis
  • coma
  • Kids are notably prone to cardiotoxicity and seizures
  • Change in ECG is a crucial indicator of toxicity

Amitriptyline Precautions

A CYP2D6 polymorphism could also be concerned if there’s a marked lack of efficacy or if uncomfortable side effects are extra frequent or extreme.

  1. Verify-ups: It is strongly recommended to test the blood depend within the first 10 weeks of therapy if sore throat and fever happen.

  2. Comorbidity: Use with warning in cardiac problems, vascular problems, hypotension, epilepsy, natural mind harm, urinary retention, prostatic hypertrophy, pylorus stenosis, hyperthyroidism, therapy with thyroid treatment, hepatic and renal impairment.

  3. Cardiovascular toxicity: Cardiac arrhythmias (together with QT prolongation) and extreme hypotension are comparatively widespread at excessive doses. They could additionally happen at regular doses in pre-existing coronary heart illness. Common blood stress monitoring is required. Earlier than beginning therapy, take into account an ECG to exclude a long-QT syndrome (carried out routinely in therapy of enuresis nocturna). Use warning with threat elements for QT prolongation equivalent to:
    • hypocalcemia
    • hypokalemia
    • hypomagnesemia
    • related cardiac illness
    • bradycardia
      comedication with medicinal merchandise that extend the QT interval and congenital or acquired QT prolongation; use further warning within the aged as they could have proarrhythmic circumstances. Cardiac arrhythmias may additionally happen in instances of hyperthyroidism or when taking thyroid treatment. For different interactions that will trigger dysrhythmia. Within the presence of non-treatable threat elements, often test electrolytes and assess ECG. Inquire about sudden dying of younger family, as this can be a sign of congenitally extended QT time.

  4. Danger of suicide: In case of suicidal behaviour or suicidal ideas previously, in addition to in sufferers youthful than 25 years, further monitoring is really useful, particularly within the first weeks of remedy (when the drug remains to be insufficiently efficient) and after dose changes. There’s a larger threat of suicide within the early levels of restoration. As well as, the affected person mustn’t have giant portions of antidepressants at his disposal. If the situation worsens, if suicidal tendencies happen or if there are different psychiatric signs, take into account altering the remedy. Sufferers (and caregivers) needs to be knowledgeable to hunt medical recommendation instantly if such signs happen. Don’t use TCAs for melancholy in individuals < 18 years of age; research have proven no useful impact of TCAs on this age group, and suicidality and hostile behaviour had been extra widespread.

  5. Psychiatric results: In a manic-depressive affected person, a shift to a manic section might happen. If this happens, discontinue therapy with amitriptyline.

  6. Ocular results: An assault of acute glaucoma could also be provoked by pupillary dilation in sufferers with a uncommon ocular dysfunction, equivalent to a shallow anterior chamber or a slender chamber angle.

  7. Enuresis nocturna: Earlier than beginning therapy with amitriptyline, exclude long-QT syndrome by the use of an ECG. For this therapy amitriptyline shouldn’t be mixed with an anticholinergic. On this indication, too, use of amitriptyline can result in suicidal ideas/behaviour; in that case, take the identical precautions as described beneath the paragraph “Suicide”. In case of enuresis nocturna, don’t use in youngsters < 6 years of age. Electroconvulsive remedy might improve the dangers of therapy.

  8. Aged: Use warning within the aged attributable to elevated susceptibility to orthostatic hypotension, anticholinergic and cardiovascular uncomfortable side effects. On account of elevated threat of caries, dental management is indicated.

  9. Lower: Withdrawal signs equivalent to headache, malaise, nausea, irritability and sleep disturbance might happen with sudden discontinuation of therapy after extended administration; due to this fact, lower the dose slowly.

  10. Glucose metabolism: Despair and amitriptyline itself affect glucose metabolism. An adjustment of antidiabetic treatment could also be obligatory.

  11. Driving: This drugs might have an effect on the flexibility to drive and use machines.

Amitriptyline Side Effects

A CYP2D6 polymorphism could also be concerned if the quantity or severity of uncomfortable side effects is considerably larger.

  • anticholinergic results
    • equivalent to dry mouth
    • nausea
    • constipation
    • lodging dysfunction
    • palpitations and tachycardia
  • hypotension
  • Weight acquire
  • sedation
  • drowsiness
  • dizziness
  • headache
  • tremor
  • speech dysfunction
  • Nasal congestion
  • extreme perspiration
  • aggression
  • cardiovascular abnormalities
    • conduction defect
    • ventricular dysfunction
    • atrioventricular block
    • irregular ECG equivalent to:
      • extended QT
      • QRS complicated)
  • Focus dysfunction
  • style dysfunction
  • paraesthesia
  • ataxia
  • confusion
  • agitation
  • restlessness
  • Fatigue
  • thirst
  • Decreased libido
  • erectile dysfunction
  • Mydriasis
  • micturition problems
  • hyponatraemia


Information concerning psychotic disorders, included within the review of Amitriptyline, is used for the informative features exclusively as well as should not be thought-about to alternative to licensed healthcare or referral of the well being treatment distributor.


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Frequently asked questions

  • What is Amitriptyline?

    Amitriptyline works on the central nervous system (CNS) and helps to relieve the symptoms of OCD. This medication belongs to a class of so-called tricyclic antidepressants.

  • What to do if you miss a dose?

    If you miss a dose of Amitriptyline, take it as quickly as potential. However, whether it is virtually time to your subsequent dose, skip the missed dose and return to your common dosing schedule. Do not double doses.

  • What if u take too much Amitriptyline?

    If an overdose happens, name your physician or call your nearest hospital. You might have pressing medical care. You might also contact the poison management at your local hospital.

  • How to store Amitriptyline?

    Store your medicines at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. 

  • What Should I Avoid While Taking Amitriptyline?

    Marked drowsiness may occur avoid alcoholic drinks alcohol, sedatives, and tranquillizers may increase drowsiness excitability may occur, especially in children be careful when driving a motor vehicle or operating machinery 

  • What are the side effects of Amitriptyline?

    The most common side effects are dizziness, dry mouth, drowsiness, constipation, stomach upset, nausea, vomiting, sweating etc. Anxiety symptoms may temporarily worsen when you first start using Amitriptyline. 

  • What are the Contraindication?

    The medication cannot be used in patients with hypersensitivity to the components of Amitriptyline, in patients during acute recovery phase of myocardial infarction, and in patients treated by MAO inhibitors.

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Last Updated on December 15, 2021 by Toni El Clikos

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