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Amitriptyline - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

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Amitriptyline - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

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Amitriptyline is an antidepressant drug. Learn about its uses, dosage, drug warnings, side effects, precautions, drug interactions, and more.

Written by

Dr. Lochana .k

Medically reviewed by

Dr. Awadhesh P. Singh Solanki

Published At December 21, 2020
Reviewed AtNovember 8, 2022


Amitriptyline is an oral tablet and a prescription drug given for depression. Depression is a common clinical condition associated with sadness, loss of interest, self-neglect, anorexia, sleep disturbances, suicidal feelings in severe cases, etc. Keep this drug away from kids, as it can be fatal even if they consume a few tablets. This tablet can affect your vision by damaging the eyes. So, it is essential to take these medications cautiously. It could lead to other side effects if you stopped abruptly.

Amitriptyline is a tricyclic antidepressant, and an FDA (Food and Drug Administration) approved drug used in treating depression in adults. It affects certain chemicals called neurotransmitters in the brain, thereby regulating mood. Amitriptyline was first discovered in the late 1950s by scientists at Merck and was approved by the US (United States) FDA in 1961. It is included in the World Health Organization’s (WHO) list of essential medicines.

Drug Group:

Amitriptyline belongs to a group of drugs called antidepressants. It is known that patients who are under depression might have a low level of serotonin in their bodies. When the optimum level of serotonin is not seen, there will be instability in the mood. This will lead to severe conditions of mood disorders. It is known to improve the mental health of the person. However, it will take time for the drug to show its actions. Amitriptyline is also known to enhance the level of noradrenaline.

How Does Amitriptyline Work?

Amitriptyline has a specific mechanism for its action. These drugs get absorbed well in the gastrointestinal system (stomach). After absorption, they are highly bound to plasma proteins. They are distributed well to all body tissues, including the central nervous system. The metabolism of these drugs produces some products called metabolites. The complete metabolism of Amitriptyline happens in the liver. These active metabolites are responsible for the long duration of action Amitriptyline has. After the course of action is over, the active metabolites are converted into inactive metabolites. The inactive metabolites are excreted in the urine. These medications can drastically increase the chemicals in the brain. The substances that are raised by these drugs are serotonin and norepinephrine. The mechanism of action for sleep has not been appropriately identified. But some of these mechanisms have the potential to block histamine.

Amitriptyline belongs to the drug group tricyclic antidepressants (TCA). It works by blocking the reuptake of neurotransmitters serotonin and norepinephrine. Amitriptyline is a tertiary amine with a strong binding affinity to alpha-adrenergic, muscarinic (M1), and histamine (H1) receptors. Amitriptyline blocks the norepinephrine or serotonin transporter at presynaptic channels, thereby increasing noradrenergic or serotonin transmission. The sedative effect caused by Amitriptyline is more when compared to other TCAs. Also, the therapeutic impact begins two to four weeks after the start of treatment. Long-term treatment with Amitriptyline desensitizes presynaptic auto and heteroreceptors that produce long-lasting changes in monoaminergic neurotransmission.

Chronic treatment with antidepressant drugs increases the levels of BDNF (brain-derived neurotrophic factor), which plays a role in developing neurons and synaptic plasticity. This helps improve the symptoms in patients with major depressive disorder.

Indications and Uses:

Amitriptyline is primarily used for the treatment of depression. The off-label uses of the drug include:

  • Anxiety.

  • Post-traumatic stress disorder (PTSD).

  • Diabetic neuropathy.

  • Insomnia.

  • Irritable bowel syndrome.

  • Prevention of migraine.

  • Interstitial cystitis.

  • Sialorrhea.

The other uses of the drug include:

  1. It helps in improving the mood that has been depressed for an extended period.

  2. It helps to ease tension and anxiety.

  3. It improves the sleeping pattern of the individual.

  4. It is used for major depression disorder, anxiety disorder, ADHD (attention deficit and hypersensitivity disorder), and bipolar disorder.

  5. It is also known to ease pain by lowering the signals of distress.

  6. Amitriptyline is known to be helpful in the treatment of migraine. A migraine refers to a headache on one side. It will be very severe. Noise, chocolate, and alcohol will aggravate this headache.

Dosage and Administration:

The dosage of Amitriptyline will be decided by the doctor, depending on the patient’s age, weight, and other medical conditions. The drug is initially started with a low dosage; once the body accepts it, the health care provider may recommend continuing it. It is suggested to follow the regular timings and dosage of Amitriptyline.


Amitriptyline dosage for adults:

In patients with liver, heart, and kidney diseases, the doctor will change the dosage depending on the pulse rate, creatinine clearance, and liver function tests.


Amitriptyline is contraindicated in the below cases:

  • Hypersensitivity to the active or inactive ingredients of the drug.

  • Patients with a history of arrhythmias, QTc prolongation, heart failure, or recent myocardial infarction (MI). Also, Amitriptyline can precipitate acute MI.

  • The drug must be used cautiously in patients with urinary retention, seizures, and angle-closure glaucoma.

  • The drug must not be used within 14 days of monoamine oxidase inhibitors.

  • The use of Amitriptyline concomitantly with other drugs that increase QTc, like Cisapride, Astemizole, Ibutilide, Disopyramide, Indapamide, Pentamidine, Procainamide, Pimozide, Sotalol, Quinidine, and Terfenadine that can cause cardiac problems like arrhythmias.

  • Certain drugs that enhance serotonin concentrations, like Isocarboxazid, Phenelzine, Safinamide, Selegiline, Sertraline, and Tranylcypromine, when used along with Amitriptyline, can precipitate serotonin syndrome.

  • Low doses of Amitriptyline are advised in patients with hepatic and renal impairment.

  • Amitriptyline can interact with anesthetic agents, causing an increased risk of arrhythmia. It is advised to discontinue the drug before elective surgery.

Warnings and Precautions:

There are a few things that need to be considered before taking this tablet, and tell your doctor if you have any of the following conditions:

  • Pregnancy: Taking antidepressants like Amitriptyline is not recommended during the pregnancy period. A gynecologist should be consulted before taking these medicines.

  • Breastfeeding: Amitriptyline should not be taken by breastfeeding mothers unless necessary. However, this drug is known to be a little safe to use if the infant is more than two months old. A doctor's advice is mandatory before taking the drug.

  • Diabetes: This drug can elevate blood sugar levels in a diabetic patient. The medicine must be started only after a doctor's prescription.

  • Glaucoma: Glaucoma can worsen with Amitriptyline use.

  • Heart Problems: Amitriptyline should be taken with caution in patients with heart problems because both these drugs are highly influential for the body. Proper dosage recommendations from the doctor are necessary.

  • Hearing Impairment: Severe tinnitus is noticed in some patients on Amitriptyline.

  • Driving or Operating Heavy Machinery: Patients with dizziness and visual disturbances are advised not to drive or operate any other heavy machinery.

  • Muscle Weakness: Numbness and muscle weakness are noticed in some patients. Doctors must consider prescribing them to patients with skeletal problems.

  • Kidney Problems: Taking medicines without a doctor's advice can worsen the condition in renal impairment patients.

  • Liver Diseases: This drug is not recommended for patients with liver diseases. You should ask your doctor before taking medications because abnormalities are known to occur.


The doctor must be informed if the patient develops suicidal thoughts or depression gets worse, particularly during the first couple of months of therapy. Also, symptoms of serotonin syndrome must be closely observed.

Things that the patient or caregiver has to keep in mind include the following:

  • Inform of any unusual side effects to a doctor.
  • Withdrawal symptoms may occur if the medications are dropped suddenly. An advisable method is to reduce the dosage slowly over weeks to months.
  • It is not advisable to take other medications with Amitriptyline until your doctor or pharmacist approves that these are compatible.
  • The risk of sunburn may increase; therefore, protect yourself from the sun outdoors.

Adverse Effects:

The following are the adverse effects noted with Amitriptyline use:

  • Weight gain.

  • Headache.

  • Somnolence.

  • Constipation.

  • Dizziness.

  • Xerostomia.

The other serious adverse effects of Amitriptyline use include:

  1. Orthostatic hypotension, dizziness, and sedation due to alpha-adrenergic receptor blocking.

  2. Slow intracardiac conduction, arrhythmias, and heart rate variability due to QT prolongation.

  3. Anticholinergic side effects like dry mouth, blurred vision, tachycardia, urinary retention, confusion, delirium, and acute angle glaucoma.

  4. Antihistamine side effects like increased appetite, weight gain, sedation, confusion, and delirium.

  5. Decreasing seizure threshold in a dose-dependent manner.

  6. Liver function tests are three times the upper limit of normal. However, the effects on the liver are mild and transient, that reverse with discontinuation of the drug. Cases of acute liver injury are rare.

  7. Increased risk of fractures and bone marrow suppression (rare).

  8. The CYP3A4 enzyme system metabolizes Amitriptyline. The patient medication regimen must be thoroughly checked for CYP3A4 inducers and inhibitors, and the dosage must be adjusted accordingly.

  9. Suicidal ideation and behavior are more prevalent with Amitriptyline use in adolescents and young adults (less than 24 years of age).

  10. In patients with a family history of mania, bipolar disorder, or pharmacologically induced hypomania, the use of Amitriptyline can rarely cause mania.

For Patients:

What Is Depression, and How Is It Managed?

Depression is a mood disorder that causes a feeling of persistent sadness and loss of interest in regular activities that one used to enjoy previously. It affects how a person thinks, feels, or behaves. A person with depression feels challenged to carry out day-to-day activities and feels that life is not worth living. Speaking out about what a person is going through and seeking help can help manage the condition.

Depression is managed with psychotherapy and medications. Medications include selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCA), monoaminoxidase inhibitors (MAOIs), and mood stabilizers. Psychotherapy or talk therapy involves talking about the emotions to a psychotherapist who gives tips and helps tackle the condition. Alternative treatments include electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), in which electric currents or magnetic pulses are sent into the brain for brief periods.

For Doctors:

Drug Interactions:

All drugs tend to interact with foods and drugs. The common drug interactions of Amitriptyline are:

With Medicines:

  • Aspirin.

  • Diphenhydramine.

  • Duloxetine.

  • Hydrocodone.

  • Gabapentin.

  • Zolpidem.

  • Lamotrigine.

  • Escitalopram.

  • Cyclobenzaprine.

  • Pregabalin.

With Diseases:

  • Liver disease.

  • Diabetes.

  • Glaucoma.

  • Cardiac problems.

  • Hearing impairment.

With Alcohol:

Chronic alcoholism can contribute to a fatty liver condition. This liver condition can worsen the health condition if it is consumed along with Amitriptyline.

During concomitant use of tricyclic antidepressants and drugs that inhibit the cytochrome P450 2D6 enzyme system, lower doses of either the TCA or the other drug must be planned as the serum concentrations of either of the drugs can be higher than expected for usual doses. Also, a higher TCA dose must be prescribed when the other drug from co-therapy is withdrawn.

  • Amitriptyline, administered with anticholinergic drugs, including epinephrine with local anesthetics, is necessary for close supervision and adjustment of dosages.

  • Hyperpyrexia has been reported when Amitriptyline has been administered with neuroleptic drugs or anticholinergics, particularly during hot weather.

  • Paralytic ileus has been reported in patients who were co-administered TCAs and anticholinergics.

  • Cimetidine was found to reduce the hepatic metabolism of TCA, thereby increasing the steady-state concentrations of the drugs. Increased frequency and severity of anticholinergic side effects have been reported with Cimetidine and TCA co-therapy.

  • Large doses of Ethchlorvynol and Amitriptyline have caused delirium in a few patients.

Use in Geriatric Patients:

The dose must be selected carefully in geriatric patients and started with a low dose due to a possible hepatic impairment, concurrent use of other drugs, or concomitant diseases in the elderly. Anticholinergic side effects are common in geriatric patients.

Central anticholinergic effects include:

  • Cognitive impairment.

  • Psychomotor slowing.

  • Sedation.

  • Delirium.

  • Confusion.

Peripheral anticholinergic side effects include:

  • Dry mouth.

  • Urinary retention.

  • Constipation.

  • Tachycardia.

  • Blurred vision.

  • Exacerbation of narrow-angle glaucoma.

Use in Pediatric Patients:

The safety and effectiveness of the drug in pediatric patients have not been established.


Amitriptyline HCl, a dibenzo cycloheptadiene derivative, is a white, odorless, crystalline compound freely soluble in water and alcohol.

Chemical Name:

It is designated chemically as 10,11-Dihydro-N, N-dimethyl5H-dibenzo[a,d] cycloheptene-Δ5, γ-propylamine hydrochloride.

Active Ingredient:

Amitriptyline hydrochloride.

Inactive Ingredients:

Colloidal silicon dioxide, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose (monohydrate), magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized starch (corn), and titanium dioxide.


10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg.

Clinical Pharmacology:

Amitriptyline inhibits the membrane pump mechanism responsible for the uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically, this Action may potentiate or prolong neuronal activity since the reuptake of these amines is vital in physiologically terminating the transmitting activity. This interference with the reuptake of norepinephrine and serotonin causes the antidepressant activity of Amitriptyline.


Amitriptyline has a half-life of 10 to 28 hours and is metabolized to Nortriptyline. CYP3A4 and CYP32 2C19 enzyme systems primarily metabolize it. Amitriptyline can also be administered by intravenous or intramuscular routes (with maximum concentrations reached within 2 to 12 hours of administration). As Amitriptyline can cause sedation, it is advised to administer the drug at night.


The following parameters have to be monitored when administering Amitriptyline:

  1. ECG (electrocardiogram) to assess baseline QTc in patients with a cardiac history or those above 50.

  2. Body mass index (BMI).

  3. Thyroid function tests.

  4. Liver function tests.

  5. Serum Amitriptyline concentrations.

Patients on Amitriptyline must be monitored for increased suicidal tendencies or unusual behavior changes during the first one to two months of therapy or during dose adjustments.


Amitriptyline symptoms can be toxic and fatal. The neurological symptoms of toxicity include seizure, sedation, and coma. Cardiac symptoms include hypotension, tachycardia, and cardiac abnormalities like QTc prolongation. Anticholinergic symptoms include dry mouth, dilated pupils, urinary retention, and decreased bowel sounds.

In treating toxicity, the patient must be admitted to the ICU (intensive care unit) and stabilized. Airway, breathing, and circulation must be monitored. Few patients may require tracheal intubation and oxygen supplementation. Gastric lavage with activated charcoal for gastric decontamination is necessary for all overdosage patients. Seizures should be managed with Diazepam or Lorazepam. An IV (intravenous) bolus of isotonic crystalloid is advised for hypotension post-overdose. Intravenous sodium bicarbonate (cardioprotective) is administered when QRS exceeds 100 msec.

General Instructions to the Patients:

How to Use Amitriptyline?

Amitriptyline comes as a tablet for oral consumption. It is usually taken one to four times a day. Amitriptyline should be taken around the same time every day to avoid side effects. Higher doses must be consumed late in the afternoon or evening to avoid dizziness during the daytime. This might also help escape from tiredness the next day.

Missed Dose:

Once a dose is missed, the patient may experience withdrawal symptoms. The drug must not be taken once remembered, as taking these drugs in an abnormal pattern can be harmful. Reminders on the phone or specific applications help the patient to take the prescribed doses on time.

The Onset of Action:

The onset of Action depends on the individual. But generally, the drug takes around four to eight weeks to prove its power. The drug's therapeutic effect can be achieved within one to three weeks.


Long-term usage of these drugs can make it a habit for the person consuming them. The dosage should be strictly followed as instructed by the doctor. Habit formation of these drugs can cause many serious side effects.

Expiry Date:

The expiry date will be printed on the back of the pack. Avoid taking the medicine Amitriptyline after it expires.

What Are the Side Effects of Amitriptyline?

Get emergency medical help or advice if you have signs of an allergic reaction to Amitriptyline, such as difficulty breathing, hives, or swelling of your face, throat, tongue, or lips.

Report any new or worsening symptoms to the doctor, such as

  • Behavior changes.

  • Panic attacks or anxiety.

  • Hyperactivity, both mentally and physically.

  • Restlessness.

  • Depression and suicidal thoughts might accompany them.

  • Have thoughts about hurting oneself (self-harm).

Common side effects of Amitriptyline are:

  • Vomiting.

  • Nausea.

  • Stomach upset.

  • Diarrhea and constipation.

  • Weight changes or appetite.

  • Unusual taste, black tongue, and mouth pain.

  • Rashes or itching.

  • Urinating less than usual.

  • Decreased sex drive, difficulty having an orgasm, or impotence.

  • Breast swelling in men or women.

Frequently Asked Questions


What Are the Chemicals Amitriptyline Deals With?

It works on two chemicals, serotonin, and noradrenaline, that are found in nerves.


How Does Amitriptyline Help With Pain?

When Amitriptyline is consumed to treat nerve pain, it lowers the pain signals to the brain. This helps to decrease the level of pain you experience, enabling you to get back to your routine activities and lead a better quality of life.


What Is Amitriptyline Used For?

Amitriptyline 25 mg is used to treat mood or mental health problems such as depression. It might also improve moods and feelings. It improves the quality of sleep.


Is Amitriptyline a Sleeping Pill?

Amitriptyline is from a group of antidepressants named tricyclic antidepressants. It is thought to work by enhancing a chemical called serotonin in the brain, which can improve your anxiety, pain, mood, and sleep. It is the one reason why doctors prescribe Amitriptyline medication for sleeping. However, it is not used when a person does not get proper sleep. You should consult your doctor before taking these medications.


What Drugs Should Not Be Taken With Amitriptyline?

Other medications are known to affect Amitriptyline effectiveness. They are known to cause the removal of Amitriptyline from your body. Those drugs are:
- Terbinafine.
- Cimetidine.
- Medicines to treat irregular heart rate (such as Propafenone, Flecainide, Quinidine).
- Antidepressants (such as SSRIs, including Paroxetine, Fluvoxamine, Fluoxetine).


How Long After Taking Amitriptyline Will I Feel Sleepy?

Amitriptyline can make you feel tired and sleepy soon, so it is best to take it in the evening or two to three hours before going to bed. You may notice a difference after a couple of weeks, but it can take six weeks for Amitriptyline to work as a painkiller. Amitriptyline can lead to other side effects if you stop taking it suddenly. So consult your doctor if you are taking these medications.


How Does Amitriptyline Make You Feel?

Antidepressants like Amitriptyline help to gradually enhance your mood, which makes you feel better. You may feel that you sleep better and connect with people more easily because you are less anxious. Some may feel worse during the first few weeks of treatment.


Can I Take Amitriptyline Occasionally?

Amitriptyline is a drug that shows its effect in the long run. So it only needs time to act efficiently. If you take the drug occasionally, you might lose the benefits. So you should ask your doctor for a proper schedule.


What Are the Common Side Effects of Amitriptyline?

The most common side effect of Amitriptyline is drowsiness. It is best to take it 1-2 hours before bedtime. However, Amitriptyline can cause insomnia, and if this happens, it is better to take it in the morning.


Is Amitriptyline a Muscle Relaxer?

By raising the serotonin levels, Amitriptyline will change the body's reaction to pain. The low dosage would not treat depression, but it can reduce the pain, improve your sleep, and relax your muscles.


What Does Amitriptyline Do to the Brain?

Amitriptyline is from a group of antidepressants named tricyclic antidepressants. It works by enhancing a chemical called serotonin in the brain, which can improve your mood. Serotonin can also modify the way that your nerves receive pain signals, so the pain gets eliminated.


Does Amitriptyline Make You Tired the Next Day?

It is common to take Amitriptyline once a day before bedtime because Amitriptyline can make you feel sleepy. Some patients experience drowsiness even the next day.


What Should I Do If I Feel Drowsy During the Day Time?

If you are still feeling drowsy in the morning, try taking the Amitriptyline earlier in the evening. This medication does not usually upset your tummy.


Does Amitriptyline Cause Weight Loss?

No, consuming Amitriptyline leads to weight gain. Following the diet, adjustments in eating habits, and engaging in regular physical exercises can counter this effect.


Can You Drink Alcohol While Taking Amitriptyline?

Consumption of alcohol with Amitriptyline can lead to drowsiness and affect concentration, putting them at risk for falls and other accidents. It can also cause agitation, forgetfulness, and aggression. If required, drink only small amounts of alcohol and see how you feel, But do not stop taking your medication.


What Are the Long Term Effects of Taking Amitriptyline?

Long term usage can cause increased eye pressure, urinary retention, and constipation. Other long-term effects of Amitriptyline medication include the ability to affect the body's hormonal balance.
Dr. Awadhesh P. Singh Solanki
Dr. Awadhesh P. Singh Solanki



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