Amitriptyline (Tryptanol) increases the levels of serotonin and norepinephrine in the presynaptic terminals of the neurons.

It is used to treat the following disorders:

• Treatment of unipolar major depressive disorder

• Off-Label Uses of amitriptyline in Adults include:

  • Chronic fatigue syndrome related to sleep disturbances and pain

  • Fibromyalgia

  • Functional dyspepsia

  • Headache

  • Prevention of chronic tension-type headache

  • Interstitial cystitis

  • bladder pain syndrome

  • Irritable bowel syndrome

  • Prevention Migraine

  • Neuropathic pain including diabetic neuropathy

  • Postherpetic neuralgia

  • Sialorrhea

Amitriptyline (Tryptanol) Dose in Adults:

Note: Use a lower starting dose and increase the dose by 10 mg at 3 - 7 days interval to minimize adverse drug reactions especially in patients who are sensitive to the adverse effects of amitriptyline.

• Off-label use in Chronic fatigue syndrome related to sleep disorders and pain:

  • 10 mg once a day one hour before bedtime. Increase the dose gradually based on response and tolerability in 10 mg increments up to 50 mg/day at bedtime for sleep disorders
  • For patients with pain, titrate up to 100 mg/day given once daily at bedtime or in divided doses

    ---

• Amitriptyline (Tryptanol) Dose in Fibromyalgia:

  • 10 mg once daily, 1 to 3 hours before bedtime.
  • Increase the dose gradually based on the response and tolerability in 5 to 10 mg increments at intervals of more than 2 weeks up to 75 mg/day.

    ---

• Amitriptyline (Tryptanol) as Off-label use in the treatment of functional dyspepsia (alternative agent):

  • 10 to 25 mg once daily at bedtime.
  • Increase the dose gradually based on response and tolerability at intervals of 2 weeks or more up to 75 mg/day
  • Allow for an 8 to 12-week trial before discontinuing due to ineffectiveness.
  • In patients who respond to therapy, reassess at 6 months interval with an attempt to discontinue treatment.

    ---

• Amitriptyline (Tryptanol) Dose as in the prevention of chronic tension-type Headache (off-label):

  • 10 to 25 mg once daily at bedtime;
  • may increase the dose based on response and tolerability in 10 to 25 mg increments at intervals of 1 week or more up to 125 mg/day
  • To minimize adverse effects, use a lower starting dose and increase the dose gradually.

    ---

• Amitriptyline (Tryptanol) Dose in bladder pain syndrome of Interstitial cystitis (off-label):

  • 10 mg once daily at bedtime.
  • Increase the dose after 1 week to 25 mg once daily and then at weekly intervals in 25 mg increments to a target dose of 75 to 100 mg/day
  • A maximum dose of up to 75 mg/day as tolerated is suggested by some experts.

    ---

• Amitriptyline (Tryptanol) Off-label use as an alternative agent for  Irritable bowel syndrome:

  • 10 to 25 mg once daily at bedtime
  • may increase the dose gradually based on the response and tolerability up to 75 mg/day.

    ---

• Amitriptyline (Tryptanol) as an alternative agent in unipolar Major depressive disorder:

  • 25 to 50 mg/day as a single dose at bedtime or in divided doses
  • Increase the dose based on response and tolerability in 25 to 50 mg increments at intervals of 1 week or more up to a usual dose of 100 to 300 mg/day.
  • According to the Manufacturer's labeling (may not reflect the current clinical practice)
    • 75 to 100 mg/day as a single dose at bedtime or in divided doses

      ---

• Amitriptyline (Tryptanol) Off-label use in the prevention of Migraine:

  • 10 to 25 mg once daily at bedtime
  • may increase the dose gradually based on response and tolerability in 10 to 25 mg increments at intervals 1 week or more up to 150 mg/day given once daily at bedtime or in 2 divided doses
  • A lower maintenance dose range of 20 to 50 mg once daily at bedtime is often adequate and better tolerated

    ---

• Amitriptyline (Tryptanol) Off-label use as an alternative agent for chronic Neuropathic pain (including diabetic neuropathy):

  • 10 to 25 mg once daily at bedtime
  • may increase the dose gradually based on response and tolerability in 10 to 25 mg increments at intervals 1 week or more up to 150 mg/day given once daily at bedtime or in 2 divided doses

    ---

• Amitriptyline (Tryptanol) Off-label use in Postherpetic neuralgia:

  • 10 to 25 mg once daily at bedtime
  • may increase the dose gradually based on response and tolerability in 10 to 25 mg increments at intervals of 1 week or more up to 150 mg/day given once daily at bedtime or in 2 divided doses.

    ---

• Amitriptyline (Tryptanol) Off-label use in excessive salivation:

  • 10 to 25 mg once daily at bedtime.
  • may increase the dose gradually based on response and tolerability up to 100 mg/day

    ---

How to discontinue Amitriptyline (Tryptanol)?

• Amitriptyline should be gradually tapered off in patients who have been using it for more than three weeks.
• The dose should be gradually reduced by 5 – 10 mg over a period of 2 – 4 weeks. If the patient’s symptoms reappear, restart the previous dose on which the patient was stable and then start tapering more slowly.
• Patients using amitriptyline and other antidepressants for more than six months may benefit from tapering it over a period of three months.

How to switch from amitriptyline to another antidepressant?

Although data regarding switching strategies from one antidepressant to another antidepressant is limited, some of the important points are listed here:

• Cross-titration:
  • This method is usually followed especially when amitriptyline or another antidepressant has been used for more than 2 – 4 weeks.
  • One drug is gradually tapered while the dose of the other drug is increased gradually at the same time.
• Direct switch:
  • The direct switch is the abrupt discontinuation of one drug and initiating the other drug at an equivalent dose.
  • This method may be appropriate in cases where the drug has been used for less than 1 – 2 weeks or when the drug is discontinued because of the adverse effects.

    ---

Switching to or from an MAOI:

At least a 14 days drug-free interval should be allowed when switching from an MAOI to amitriptyline and vice versa. Cross titration is contraindicated when switching from an MAOI to an SSRI and vice versa.

Amitriptyline (Tryptanol) Dose in Children

• Amitriptyline (Tryptanol) dose in Chronic pain management:

  • Children and Adolescents:
    • 0.1 mg/kg at bedtime.
    • may increase the dose over 2 to 3 weeks to 0.5 to 2 mg/kg at bedtime based on the response and tolerability.

      ---

Amitriptyline (Tryptanol) dose in children with a Depressive disorder:

Note: Not recommended as a first-line treatment for depression in children.

• Children 9 to  less than 12 yearsofage:
  • 1 mg/kg/day in 3 divided doses
  • Increase the dose after 3 days to 1.5 mg/kg/day in 3 divided doses if indicated.
• Children older than 12 years and Adolescents:
  • Manufacturer's labeling:
    • 10 mg three times daily and 20 mg at bedtime.
    • Lower doses of amitriptyline should be used compared to adults. (the maximum daily dose is 200 mg/day)
  • Alternate dosing:
    • 30 to 100 mg at bedtime or in divided doses twice daily
    • maximum daily dose is 200 mg/day.

Amitriptyline (Tryptanol) dose in children for Migraine prophylaxis:

Older children and Adolescents:

• 0.25 mg/kg/day at bedtime
• increase the dose by 0.25 mg/kg/day every 2 weeks to 1 mg/kg/day.

  ---

How to discontinue Amitriptyline (Tryptanol)?

• Amitriptyline should be gradually tapered off in patients who have been using it for more than three weeks.
• The dose should be gradually reduced by 5 – 10 mg over a period of 2 – 4 weeks. If the patient’s symptoms reappear, restart the previous dose on which the patient was stable and then start tapering more slowly.
• Patients using amitriptyline and other antidepressants for more than six months may benefit from tapering it over a period of three months.

Amitriptyline (Tryptanol) Pregnancy Risk Factor C

• Amitriptyline crosses over the placenta. In some studies on animal reproduction, adverse events were observed.
• In case reports, CNS effects, limb defects, and developmental delay were noted. However, no causal relationship has been established.
• The symptoms of neonates can include irritability, jitteriness, and rare cases of seizures.
•  Neonatals exposed to pregnancy may experience nausea, constipation and urinary problems as well as crying.
• Women at high risk for postpartum depression after delivery may want to restart their medication.
• Pregnant women should not take tricyclic antidepressants. Amitriptyline, which is a preferred agent, is the best choice if a TCA is required. 
• Monitoring of serum amitriptyline levels during pregnancy is important. Pregnancy should be avoided while on migraine prophylaxis.
• However, it can be used in cases where other agents are not effective or contraindicated.

You can use amitriptyline while breastfeeding

• The WHO considers amitriptyline compatible with breastfeeding when taken in amounts equal or below 150 mg/day (WHO 2002).
• Manufacturers recommend that you weigh the risks and benefits of breastfeeding with amitriptyline.
• Patients who have been stabilized on amitriptyline can continue to breastfeed and monitor the neonate for any adverse effects such as sedation or growth.
• Similar to the previous, prophylaxis for migraines with amitriptyline while breastfeeding is not recommended. However, in the absence other agents, it can be used with caution. 

Amitriptyline (Tryptanol) Dose in Kidney disease:

Although the manufacturer does not recommend any dosage adjustment for patients with kidney disease, patients with severe to moderate renal impairment should still be aware that it is excreted in their bodies.

Amitriptyline (Tryptanol) Dose in Liver disease:

Although the manufacturer does not recommend any dosage adjustment for patients with liver disease or other liver diseases, it should still be used with caution.

Side effects of amitriptyline (anapsique):

Anticholinergic effects and mild to moderate sedation are common adverse effects of amitriptyline

• Cardiovascular:
  • Atrioventricular conduction disturbance,
  • Cardiac arrhythmia,
  • Cardiomyopathy (rare),
  • Cerebrovascular accident,
  • nonspecific ECG changes,
  • Edema,
  • Facial edema,
  • Heart block,
  • Hypertension,
  • Myocardial infarction,
  • Orthostatic hypotension,
  • Palpitations,
  • Syncope,
  • Tachycardia
• Central nervous system:
  • Anxiety,
  • Ataxia,
  • Cognitive dysfunction,
  • Coma,
  • Confusion,
  • Delusions,
  • Disorientation,
  • Dizziness,
  • Drowsiness,
  • Drug withdrawal
    • Nausea,
    • Headache,
    • Malaise,
    • Irritability,
    • Restlessness,
    • Dream and sleep disturbance,
    • Mania [rare], and hypomania [rare],
  • Dysarthria,
  • EEG pattern changes,
  • Excitement,
  • Extrapyramidal reaction (including abnormal involuntary movements and tardive dyskinesia),
  • Fatigue,
  • Hallucination,
  • Headache,
  • Hyperpyrexia,
  • Insomnia,
  • Lack of concentration,
  • Nightmares,
  • Numbness,
  • Paresthesia,
  • Peripheral neuropathy,
  • Restlessness,
  • Sedation,
  • Seizure,
  • Tingling of extremities
• Dermatologic:
  • Allergic skin rash,
  • Alopecia,
  • Diaphoresis,
  • Skin photosensitivity,
  • Urticaria
• Endocrine & metabolic:
  • Altered serum glucose,
  • Decreased libido,
  • Galactorrhea,
  • Gynecomastia,
  • Increased libido,
  • SIADH,
  • Weight gain,
  • Weight loss
• Gastrointestinal:
  • Ageusia,
  • Anorexia,
  • Constipation,
  • Diarrhea,
  • Melanoglossia,
  • Nausea,
  • Paralytic ileus,
  • Parotid gland enlargement,
  • Stomatitis,
  • Unpleasant taste,
  • Vomiting,
  • Xerostomia
• Genitourinary:
  • Breast hypertrophy,
  • Impotence,
  • Testicular swelling,
  • Urinary frequency,
  • Urinary retention,
  • Urinary tract dilation
• Hematologic & oncologic:
  • Bone marrow depression (including agranulocytosis, leukopenia, and thrombocytopenia),
  • Eosinophilia
  • Purpura
• Hepatic:
  • Hepatic failure
  • Hepatitis (rare; including altered liver function and jaundice)
• Hypersensitivity:
  • Tongue edema
• Neuromuscular & skeletal:
  • Lupus-like syndrome
  • Tremor
  • Weakness
• Ophthalmic:
  • Accommodation disturbance
  • Blurred vision
  • Increased intraocular pressure
  • Mydriasis
• Otic:
  • Tinnitus

Contraindications to amitriptyline (anapsique):

• Allergy reactions to any component of the formulation or the drug
• Within 14 days of MAOIs, coadministration
• Coadministration with Cisapride
• After myocardial injury, acute recovery phase
• Grave liver disease
• Acute heart failure

Warnings and Precautions

• Suicidal thoughts/behavior [US Boxed Warning]

  • AmitriptylineThis product is not FDA-approved for use in children.
  • Families and caregivers should be advised to notify any behavior change and watch for the following behaviors:
  • Anxiety
  • Agitation
  • Panic attacks
  • Insomnia
  • Irritation
  • Hostility
  • Impulsivity
  • Akathisia
  • Hypomania is a condition that causes depression.
  • Mania.

• Anticholinergic effects

  • Patients with the following conditions should not take Amitriptyline:
  • Reduced gastrointestinal motility
  • Increased intraocular pressure
  • Narrow-angle glaucoma
  • Paralytic ileus
  • Urinary retention
  • Benign prostatic hyperplasia
  • xerostomia
  • Visual problems

• Depression in the CNS:

  • CNS depression can result in mental or physical impairments from Amitriptyline. It is important to warn patients about tasks that require mental alertness.

• Fractures

  • Undiagnosed bone pain, swelling, bruise, or tenderness after taking amitriptyline should prompt a physician to examine the patient for possible bone fractures. Fragility fractures have been linked to long-term TCA use.

• Hematologic effects

  • Rarely, TCAs such as amitriptyline can cause bone marrow suppression. Any signs and symptoms of infection should be checked on patients.

• Ocular effects

  • This could increase angle-closure glaucoma due to pupillary dilation.

• Orthostatic hypotension

  • Those with hypotension, cardiovascular illness, and concomitant drug use should utilise amitriptyline with caution.

• Hyponatremia and the Syndrome of Inappropriate Antidiuretic Hormone Secretion

  • Hyponatremia and SIDH are more common in elderly patients. TCA is less likely to develop hyponatremia than SSRIs.

• Cardiovascular disease

  • Patients who have had a stroke, myocardial injury, stroke, tachycardia or other conduction abnormalities in the past should be cautious about taking this drug.

• Diabetes:

  • Amitriptyline can alter glucose regulation. Patients with diabetes should not take it.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious.

• Hypomania & Mania:

  • Bipolar depression is not treated with amitriptyline. It is important to screen patients for signs of hypomania or mania, and then treat them accordingly.

• Renal impairment:

  • Patients with severe to moderate renal impairment should be cautious.

• Seizure disorder

  • Patients at high risk for seizures such as those with seizures due to head trauma, brain damage or alcoholism should be cautious.

• Discontinuation syndrome

  • After abruptly stopping amitriptyline, patients who have been taking the drug for a long time may experience a discontinuation syndrome.
  • The symptoms of discontinuation syndrome include nausea, vomiting and diarrhea, headaches, anorexia and tremors.
  • Other symptoms include: imbalance, electric shock-like sensations; myalgias; arrhythmias; myalgias; irritability and aggressive behavior; mood instability; confusion and difficulty concentrating.

• The electroconvulsive treatment:

  • Amitriptyline can increase the risk of electroconvulsive treatment. It should be stopped as soon as possible before starting ECT.

• Do not continue before elective surgery:

  • Because of the risk of hypotension and cardiac arrhythmias, the manufacturer suggests that you discontinue the drug before elective surgery.

Amitriptyline: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Notice: Drug Interaction Categories  

Monitoring Parameters:

• MonitorClinically indicated serum sodium for at-risk populations
• Evaluate:
  • Mental status
  • Suicidal thoughts or ideation, especially during therapy and after dose adjustments.
  • Anxiety
  • Social functioning
  • Mania,
  • Panic attacks and other unusual behavior changes.
• Monitor:
  • Heart rate
  • Blood pressure
  • ECG for patients with heart disease and older people
  • Electrolyte panel to evaluate the risk of conduction abnormalities
  • Blood glucose
  • BMI and weight

How to take Amitriptyline (Tryptanol)?

• It should best be taken in the late afternoon or at bedtime to minimize day time sedation.
• It should be taken with food to minimize the gastrointestinal side effects.

Mechanism of action of Amitriptyline (Tryptanol):

• Amitriptyline decreases the synaptic concentrations of serotonin, norepinephrine and neurotransmitters in the central nervous systems by inhibiting their reuptake through the presynaptic neural membrane pump.

The therapeutic response you desireIt may take up to 3 weeks. Patients with depression must undergo a trial period of between 4 and 8 weeks before being deemed non-responsive to treatment. For migraine prophylaxis, it takes 8 to 12 weeks.

Amitriptyline can be absorbed quickly and has more than 90% protein binding. The liver rapidly processes it.Nortriptyline is the active form of nortriptyline.

Bioavailability can vary betweenThe half-life elimination ranges from 13 to 36 hours. It takes between 2 and 5 hours for peak serum concentration to reach its maximum. It is mostly excreted through urine.

Amitriptyline Brand Names International:

• Adepril
• Adt
• Amicon
• Amilab
• Amilit
• Amineurin
• Amiprin
• Amiptril
• Amiram
• Amirol
• Amirol 25
• Amitrin-25
• Amitrip
• Amitriptylinum
• Amytril
• Amyzol
• Anapsique
• Antalin
• Deprelio
• Domical
• Elatrolet
• Elavil
• Enafon
• Endep
• Entrip
• Etravil
• Fortyline
• Granityllin
• Lantron
• Laroxyl
• Miketorin
• Modup
• Neurotol
• Pinsaun
• Polytanol
• Protanol
• Psiquium
• Qualitriptine
• Reptylin
• Sarotard
• Saroten
• Saroten Retard
• Sarotena
• Sarotex
• Sarotex Retard
• Seronil
• Teperin
• Teperinep
• Trepiline
• Tridep
• Tridep-25
• Trilin
• Trip
• Tripgen
• Tripta
• Triptanol
• Triptil
• Triptizol
• Triptyl
• Tryptal
• Tryptanol
• Tryptizol
• Trytomer
• Uxen
• Zinotroval
• AG-Amitriptyline
• Amitriptyline-10
• Amitriptyline-25
• APO-Amitriptyline
• BIO-Amitriptyline
• Elavil
• JAMP-Amitriptyline
• Levate
• Mar-Amitriptyline
• NOVO-Triptyn
• PMS-Amitriptyline
• TEVA-Amitriptyline

Amitriptyline Brand Names in Pakistan: