Loading...
Loading...
Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice.
Phenothiazine [EPC]
Amitriptyline is a tricyclic antidepressant (TCA) used primarily to treat major depressive disorder and various off-label chronic pain conditions. It works by increasing levels of norepinephrine and serotonin in the brain while also exhibiting significant anticholinergic properties.
Name
Amitriptyline
Raw Name
AMITRIPTYLINE HYDROCHLORIDE
Category
Phenothiazine [EPC]
Salt Form
Hydrochloride
Drug Count
4
Variant Count
212
Last Verified
February 17, 2026
RxCUI
856762, 856773, 856783, 856834, 856845, 856853, 856706, 856720, 856797, 856825, 856840, 856769, 856792
UNII
26LUD4JO9K, FTA7XXY4EZ, 6RZ6XEZ3CR
About Amitriptyline
Amitriptyline is a tricyclic antidepressant (TCA) used primarily to treat major depressive disorder and various off-label chronic pain conditions. It works by increasing levels of norepinephrine and serotonin in the brain while also exhibiting significant anticholinergic properties.
Detailed information about Amitriptyline
This page is for informational purposes only and does not replace medical advice. Consult a qualified healthcare professional before using any medication containing Amitriptyline.
Amitriptyline is a potent tricyclic antidepressant (TCA) that has been a cornerstone of psychiatric and neurological pharmacotherapy since its approval by the U.S. Food and Drug Administration (FDA) in 1961. Chemically, it is a dibenzocycloheptadiene derivative, often categorized as a tertiary amine TCA. While newer classes of antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs), have largely superseded TCAs for the first-line treatment of depression due to a more favorable side effect profile, Amitriptyline remains an essential therapeutic agent for treatment-resistant depression and a wide array of off-label indications.
In clinical practice, Amitriptyline belongs to a class of drugs called tricyclic antidepressants (TCAs), so named for their three-ringed molecular structure. It is primarily utilized to restore the balance of certain natural chemicals (neurotransmitters) in the brain, specifically serotonin and norepinephrine. Beyond its psychiatric applications, Amitriptyline is highly regarded in the medical community for its efficacy in managing chronic pain syndromes, including neuropathic pain (nerve pain), fibromyalgia, and migraine prophylaxis (prevention). Your healthcare provider may prescribe this medication for conditions ranging from severe mood disorders to complex pain management strategies.
The mechanism of action for Amitriptyline is multifaceted and involves the modulation of several neurotransmitter systems. At its core, Amitriptyline acts as a potent reuptake inhibitor of both serotonin (5-HT) and norepinephrine (NE). By blocking the reuptake pumps (transporters) on the presynaptic neuron, the drug increases the concentration of these neurotransmitters within the synaptic cleft (the space between nerve cells). This prolonged presence of serotonin and norepinephrine enhances signal transmission, which is thought to alleviate the symptoms of depression and modulate pain pathways in the spinal cord.
However, Amitriptyline’s pharmacological profile is not limited to reuptake inhibition. It also acts as an antagonist (blocker) at several other receptor sites, which contributes to both its therapeutic effects and its side effect profile. These include:
Understanding how the body processes Amitriptyline is crucial for optimizing therapy and minimizing adverse events. The pharmacokinetic profile of Amitriptyline is characterized by significant inter-individual variability, often necessitating careful dose titration by your healthcare provider.
Amitriptyline is FDA-approved for the treatment of Major Depressive Disorder (MDD), particularly in patients where sedation is desired. However, its clinical utility extends far beyond its primary indication. Healthcare providers frequently prescribe Amitriptyline 'off-label' (for uses not specifically approved by the FDA but supported by clinical evidence) for the following conditions:
Amitriptyline is most commonly available in the following oral dosage forms:
> Important: Only your healthcare provider can determine if Amitriptyline is right for your specific condition. The choice of dose and form depends on your medical history, the condition being treated, and your response to the medication.
The dosage of Amitriptyline must be highly individualized. Healthcare providers typically start with a low dose and gradually increase it (titrate) to achieve the desired therapeutic effect while minimizing side effects.
Amitriptyline is generally not recommended for the treatment of depression in children under the age of 12.
While the kidneys primarily excrete Amitriptyline metabolites, significant renal impairment may require cautious dosing. Your doctor will monitor your kidney function and adjust the dose if necessary to prevent metabolite accumulation.
Since Amitriptyline is extensively metabolized by the liver, patients with liver disease (hepatic impairment) should be treated with extreme caution. Lower doses and slower titration are typically required to avoid toxicity.
Geriatric patients (those over 65) are more sensitive to the anticholinergic and sedative effects of Amitriptyline. Healthcare providers often follow the 'start low and go slow' mantra, beginning with 10 mg to 25 mg per day. Doses above 100 mg are rarely recommended for the elderly due to the risk of falls and cognitive impairment.
To ensure the best results and safety, follow these guidelines:
If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and return to your regular schedule. Do not double the dose to catch up, as this increases the risk of side effects and toxicity.
An overdose of Amitriptyline is a life-threatening medical emergency. It is one of the most dangerous medications in overdose due to its effects on the heart and central nervous system.
> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking the medication without medical guidance, as sudden discontinuation can lead to withdrawal symptoms.
Many patients taking Amitriptyline will experience 'anticholinergic' side effects. While often bothersome, these frequently diminish as the body adjusts to the medication over several weeks.
> Warning: Stop taking Amitriptyline and call your doctor immediately if you experience any of these serious reactions.
Prolonged use of Amitriptyline may be associated with certain risks that your healthcare provider will monitor:
The FDA has issued a Black Box Warning for Amitriptyline regarding suicidality.
Report any unusual symptoms or persistent side effects to your healthcare provider immediately. Your doctor may adjust your dose or suggest ways to manage these effects.
Amitriptyline is a powerful medication that requires careful management. It is not suitable for everyone, and several critical safety factors must be considered before and during treatment. Patients must be aware that the therapeutic effects of Amitriptyline—especially for depression—may take 2 to 4 weeks to become apparent, even though side effects may begin almost immediately.
Suicidality and Antidepressant Drugs:
In short-term studies, antidepressants increased the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (under age 24) with major depressive disorder and other psychiatric disorders. Anyone considering the use of Amitriptyline or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Amitriptyline is not FDA-approved for use in pediatric patients for depression.
Your healthcare provider will likely require regular check-ups and laboratory tests, including:
Amitriptyline causes significant impairment of mental and physical abilities. You should not drive, operate heavy machinery, or engage in hazardous activities until you know how this medication affects you. The sedative effects are particularly strong during the first few weeks of treatment.
Do not consume alcohol while taking Amitriptyline. Alcohol significantly increases the sedative effects of the drug and can lead to dangerous levels of respiratory depression (slowed breathing) and impaired coordination.
Never stop taking Amitriptyline abruptly. Doing so can cause a 'withdrawal syndrome' or 'discontinuation syndrome,' which includes symptoms like nausea, headache, malaise (feeling generally unwell), irritability, and sleep disturbances. Your healthcare provider will provide a tapering schedule to slowly reduce the dose over several weeks.
> Important: Discuss all your medical conditions, especially heart problems, glaucoma, or a history of seizures, with your healthcare provider before starting Amitriptyline.
Amitriptyline can interfere with certain medical tests, potentially leading to false results:
For each interaction, the primary mechanism is usually either pharmacodynamic (additive effects on the brain or heart) or pharmacokinetic (interference with liver enzymes like CYP2D6). Management usually involves dose adjustment or choosing an alternative medication.
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter cold or allergy medicines.
There are specific circumstances where Amitriptyline must never be used because the risks far outweigh any potential benefits:
In these cases, a healthcare provider will perform a careful risk-benefit analysis and monitor the patient closely:
Patients who are allergic to other tricyclic antidepressants (TCAs) are highly likely to be allergic to Amitriptyline. This is known as cross-sensitivity. If you have had a rash, hives, or breathing trouble with drugs like Clomipramine, Desipramine, or Doxepin, inform your doctor immediately.
> Important: Your healthcare provider will evaluate your complete medical history, including any history of heart issues or eye problems, before prescribing Amitriptyline.
Amitriptyline is generally classified as FDA Pregnancy Category C. This means that animal studies have shown adverse effects on the fetus, but there are no adequate, well-controlled studies in humans.
Amitriptyline and its metabolite, nortriptyline, are excreted into breast milk. While the amounts are generally considered low, the drug can accumulate in a nursing infant's system.
Amitriptyline is not FDA-approved for the treatment of depression in children.
The elderly are at the highest risk for adverse effects from Amitriptyline.
While the parent drug is metabolized by the liver, the metabolites are cleared by the kidneys. In patients with significant renal failure, these metabolites can build up, potentially causing increased side effects or toxicity. Dosing should be conservative.
The liver is the primary site of Amitriptyline metabolism. Patients with cirrhosis or hepatitis will have a much slower clearance of the drug. Healthcare providers typically use the Child-Pugh score to assess liver function and will significantly reduce the starting dose in these patients.
> Important: Special populations require individualized medical assessment and frequent monitoring by a healthcare professional.
Amitriptyline hydrochloride is a tricyclic antidepressant with a complex pharmacological profile. Its primary mechanism of action is the inhibition of the presynaptic reuptake of the neurotransmitters Norepinephrine and Serotonin (5-HT). By binding to the norepinephrine transporter (NET) and the serotonin transporter (SERT), Amitriptyline prevents these chemicals from being reabsorbed into the nerve cells. This increases their availability in the synaptic cleft, enhancing neurotransmission. Over time, this is thought to lead to downstream changes in receptor sensitivity (such as beta-adrenergic downregulation), which correlates with the clinical improvement of mood.
Additionally, Amitriptyline acts as a potent antagonist at:
The dose-response relationship for Amitriptyline is well-documented but varies by indication. For depression, a 'therapeutic window' for plasma levels (Amitriptyline + Nortriptyline) is often cited between 80 and 200 ng/mL. The onset of the sedative effect is rapid (within hours), but the antidepressant effect typically requires 2 to 6 weeks of continuous dosing. Tolerance to the sedative and anticholinergic effects often develops over the first few weeks of treatment.
| Parameter | Value |
|---|---|
| Bioavailability | 30% to 60% (due to first-pass metabolism) |
| Protein Binding | ~95% (primarily to albumin) |
| Half-life | 10 to 28 hours (Amitriptyline); 18 to 44 hours (Nortriptyline) |
| Tmax (Time to Peak) | 2 to 12 hours |
| Metabolism | Hepatic (CYP2C19, CYP2D6, CYP3A4) |
| Excretion | Renal (>90% as metabolites), Fecal (minor) |
Amitriptyline is a member of the Tricyclic Antidepressant (TCA) class. It is structurally related to other TCAs like Imipramine and Clomipramine. Within the TCA class, it is considered one of the most sedating and most anticholinergic options, which influences its selection for patients with co-occurring insomnia or certain pain types.
Medications containing this ingredient
Common questions about Amitriptyline
Amitriptyline is primarily FDA-approved for the treatment of Major Depressive Disorder, particularly in cases where symptoms like anxiety or insomnia are present. However, it is also widely used 'off-label' by healthcare providers to manage chronic pain conditions such as fibromyalgia, neuropathic (nerve) pain, and the prevention of migraine headaches. In some instances, it may be prescribed for interstitial cystitis or even bedwetting in children, though this is less common today. Because it is an older medication with significant side effects, it is often reserved for patients who have not responded well to newer antidepressants like SSRIs. Always consult your doctor to understand why this specific medication was chosen for your treatment plan.
The most common side effects of Amitriptyline are related to its 'anticholinergic' activity and its effect on histamine receptors. Patients frequently report experiencing a very dry mouth, significant drowsiness or sedation, and constipation. Other frequent issues include blurred vision, weight gain due to increased appetite, and a feeling of lightheadedness when standing up too quickly. While these side effects can be bothersome, they often become more tolerable as your body adjusts to the medication over the first few weeks. If these symptoms become severe or persistent, your healthcare provider may suggest adjusting your dose or taking the medication specifically at bedtime.
No, you should strictly avoid drinking alcohol while taking Amitriptyline. Alcohol is a central nervous system depressant, and when combined with Amitriptyline—which is also highly sedating—it can lead to dangerous levels of drowsiness and impaired coordination. This combination significantly increases the risk of accidents, falls, and severe respiratory depression (dangerously slow breathing). Furthermore, alcohol can worsen the symptoms of depression and interfere with the therapeutic benefits of the medication. If you have a history of alcohol use, it is vital to discuss this with your doctor before starting treatment.
Amitriptyline is generally not the first choice for treating depression during pregnancy and is classified as Category C. While it is not definitively known to cause major birth defects, animal studies have shown potential risks, and human data is limited. Use of the drug during the third trimester has been linked to withdrawal symptoms in newborns, such as irritability, tremors, and breathing difficulties. However, untreated depression also poses significant risks to both the mother and the baby. Therefore, the decision to use Amitriptyline during pregnancy must be made through a careful risk-benefit discussion with your healthcare provider.
The timeline for Amitriptyline's effects depends on the condition being treated. For sleep and certain types of acute pain, you may notice an effect within just a few days due to the drug's sedative properties. However, for its primary use in treating depression, it typically takes 2 to 4 weeks—and sometimes as long as 6 weeks—to feel the full therapeutic benefit. It is important to continue taking the medication as prescribed, even if you do not feel better right away. If you do not notice any improvement after 4 to 6 weeks, your doctor may consider adjusting the dose or switching to a different medication.
No, you should never stop taking Amitriptyline abruptly without consulting your healthcare provider. Stopping the medication suddenly can lead to 'discontinuation syndrome,' which involves symptoms like nausea, headache, extreme tiredness, irritability, and vivid dreams. This is not an addiction, but rather a result of your brain adjusting to the sudden absence of the chemical changes the drug provides. To stop the medication safely, your doctor will provide a tapering schedule to gradually reduce your dose over several weeks or even months, which helps minimize these withdrawal-like symptoms.
If you miss a dose of Amitriptyline, you should take it as soon as you remember. However, if it is already close to the time for your next scheduled dose, you should skip the missed dose entirely and continue with your regular schedule. Never take two doses at once to make up for a missed one, as this can significantly increase the risk of toxic side effects or an overdose. Since Amitriptyline is often taken at bedtime to help with sleep, missing a dose may affect your sleep quality for that night. If you frequently forget your doses, consider using a pill organizer or a phone alarm.
Yes, weight gain is a well-known and relatively common side effect of Amitriptyline. This occurs for several reasons, including an increase in appetite (particularly cravings for sweets) and changes in the body's metabolism. Some studies suggest that the drug's effect on histamine and serotonin receptors plays a role in these changes. While not everyone will gain weight, those who do may see a significant increase over several months of treatment. Managing your diet and maintaining regular physical activity can help, but you should discuss any significant weight changes with your doctor, as they may want to monitor your blood sugar or cholesterol levels.
Amitriptyline has a high potential for interacting with other medications, so it must be used with caution. It can interact dangerously with MAOIs, other antidepressants, certain heart medications, and even over-the-counter cold medicines that contain antihistamines. Combining it with other drugs that affect serotonin can lead to the life-threatening Serotonin Syndrome. Additionally, because Amitriptyline is processed by the liver, drugs that inhibit or induce liver enzymes can change the amount of Amitriptyline in your blood. Always provide your doctor and pharmacist with a complete list of all prescriptions, supplements, and herbal products you are taking.
Yes, Amitriptyline is widely available as a generic medication (Amitriptyline Hydrochloride). Generic versions are typically much less expensive than brand-name versions (like Elavil, which is no longer widely marketed in the U.S.) and are required by the FDA to have the same active ingredient, strength, and effectiveness. Because it has been off-patent for many decades, it is one of the most affordable options for treating depression and chronic pain. Most insurance plans cover generic Amitriptyline, but you should check with your pharmacist to ensure you are receiving the most cost-effective version of your prescription.