Nortriptyline vs. Amitriptyline: Similarities and Differences
Medically reviewed by Mary Choy, PharmD
Nortriptyline and amitriptyline are orally administered, generic tricyclic antidepressants (TCAs) that are approved by the Food and Drug Administration (FDA) to treat major depressive disorder (MDD), or, in an off-label setting, nerve pain or migraine prevention.
Pamelor is a brand name of nortriptyline. Conversely, amitriptyline is sold only as a generic.
Generally, healthcare providers view these two tricyclic antidepressants as closely related. Amitriptyline is metabolized, or processed, by the body into nortriptyline.
However, nortriptyline and amitriptyline have some notable differences.
For example, amitriptyline is preferred for MDD when the side effect of mild sedation is desired, while nortriptyline is preferred when its stimulatory (energizing) effects are desired.
This article will provide an in-depth analysis of nortriptyline and amitriptyline, examining their respective uses, dosing requirements, potential side effects, and more.
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Understanding Tricyclic Antidepressants (TCAs)
TCAs are a type of antidepressant.
TCAs work on several chemicals in the brain to help with depression (or other off-label uses, such as nerve pain), which include the following:
Serotonin is involved in mood, appetite, memory, sexuality, many behaviors, and many organ and system functions, including those of the heart, bladder, and bowels.
Norepinephrine, or noradrenaline, helps with focus, energy, and alertness. It is also involved in the fight-or-flight response and other systems in the body, such as metabolism.
TCAs are an older group of antidepressants.
Although they are effective, they have more side effects and may take longer to work than some newer types of antidepressants.
Furthermore, TCAs should be avoided by some people, such as those with glaucoma or an enlarged prostate. These drugs' potential side effects may worsen these conditions.
What Is Nortriptyline?
Nortriptyline is FDA-approved to treat MDD in adults.
While generic nortriptyline comes in both a capsule and liquid solution taken by mouth, brand-name Pamelor, however, only comes in capsule form.
How It Works
Nortriptyline is thought to work by increasing levels of norepinephrine and serotonin in the brain.
Off-Label Uses
Nortriptyline is FDA-approved only for use in adults,
However, some healthcare providers prescribe it off-label, meaning for use or at a dosage for which it has not been FDA-approved, such as in children or teenagers.
Examples of off-label uses of nortriptyline are:
Treatment of nerve pain (such as from diabetic neuropathy, shingles, or injury)
Prevention of migraine
Treatment of panic disorder (PD)
What Is Amitriptyline?
Amitriptyline is FDA-approved for depression in adults and is available as an orally administered tablet.
Historically, amitriptyline was sold under the brand name Elavil, but this brand is no longer available in the United States.
How It Works
When amitriptyline is converted to nortriptyline in the body, it increases levels of norepinephrine and serotonin in the brain.
Off-Label Uses
While amitriptyline is not FDA-approved for non-adults, some healthcare providers prescribe it off-label in children or teenagers.
Some examples of off-label uses of amitriptyline include:
Insomnia (trouble falling and/or staying asleep)
Nerve pain
Migraine prevention
Amitriptyline in Other Products
While this article focuses on single-ingredient amitriptyline, this active ingredient is also available as an ingredient in several combination drugs, including:
Perphenazine/amitriptyline: This medication, sold under brands such as Duo-Vil and Etrafon, treats people with anxiety and depression.
Chlordiazepoxide/amitriptyline: This medication is used to treat people with moderate to severe anxiety and depression.
Dosing Guidelines
When prescribing these drugs, healthcare providers generally start with a lower dose and gradually increase the dose if necessary, while paying close attention to any side effects.
Nortriptyline Dosing
Nortriptyline capsules are available in the following strengths: 10 milligrams (mg), 25 mg, 50 mg, and 75 mg.
Nortriptyline solution is available as 10 mg/5 milliliter (mL).
Dosing for depression includes the following:
The usual dose is 25 mg by mouth three or four times daily. The healthcare provider will likely start at a lower dose and then gradually increase this dose.
Alternatively, the healthcare provider may prescribe a higher dose (such as 100 mg) once daily.
The maximum recommended dose is 150 mg daily.
Older adults will be prescribed a lower dosage, generally no more than 50 mg daily.
Dosing for nerve pain includes the following:
The initial dose is generally 10 or 25 mg orally once daily at bedtime.
The healthcare provider may gradually increase the dose to a target dose of 75 to 150 mg daily.
Older adults require lower doses and a more gradual increase in dose.
Amitriptyline Dosing
Amitriptyline tablets are available in the following strengths: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg.
Dosing for depression includes the following:
A typical dose is 75 mg by mouth daily in divided doses (for example, 25 mg three times daily)
The healthcare provider may gradually increase the dose to a maximum daily dose of 150 mg.
An alternate dosing regimen is 50 to 100 mg once daily at bedtime.
The healthcare provider may gradually increase the dose to a maximum once-daily bedtime dose of 150 mg.
Older adults will require lower doses, such as 10 mg three times daily or 20 mg once daily at bedtime.
Dosing for nerve pain entails:
The starting dose is generally 10 or 25 mg by mouth daily at bedtime.
The healthcare provider may gradually increase the dose to a target of 75 to 150 mg daily.
Side Effects and Safety
Call your healthcare provider immediately if you experience severe side effects that fail to go away or worsen over time.
Furthermore, dial 911 if your symptoms feel life-threatening or if you think you have a medical emergency.
Boxed Warning
All antidepressants, including nortriptyline and amitriptyline, carry a boxed warning—the most severe warning issued by the FDA.
For both drugs, the warning states that people who take antidepressants are at risk for suicidal thoughts and behaviors. In clinical studies, such suicidal tendencies primarily affected children, teenagers, and young adults.
People of any age who take an antidepressant, however, should be closely monitored for changes in mood or behavior or suicidal thoughts and behaviors.
Help for Depression Is Available
No one should suffer from depression. If you are experiencing symptoms of depression, talk to your healthcare provider. If you or someone you know is in a suicidal crisis or emotional distress, you can call or text 988 for the 988 Suicide & Crisis Lifeline.
The line is open 24 hours a day, seven days a week in the United States, and provides free, confidential support.
Call 911 or go to the nearest emergency room if you or someone you know is in a life-threatening crisis.
Nortriptyline-Specific Side Effects
Common side effects associated with the use of nortriptyline include:
Stomach problems, such as nausea or constipation
Appetite or weight changes
Lethargy
Difficulty urinating or urinating more frequently
Severe side effects associated with the use of nortriptyline include:
Anaphylaxis (severe allergic reaction): Seek emergency medical help if you experience urticaria (hives), difficulty breathing, or swelling of the face, lips, tongue, or throat
Spasms of the jaw, neck, and/or back
Problems with speech and/or walking
Uncontrollable shaking of a part of the body
Fever
Amitriptyline-Specific Side Effects
Common side effects associated with the use of amitriptyline include:
Stomach problems, such as nausea, vomiting, or constipation
Lethargy
Appetite or weight changes
Nightmares
Dry mouth
Difficulty urinating
Pain, burning, or tingling of the hands and/or feet
Changes in sex drive or ability
Excess sweating
Severe side effects associated with the use of amitriptyline include:
Anaphylaxis
Numbness or weakness of an arm or leg
A fast, pounding, or irregular heartbeat
Spasms of the jaw, neck, and/or back
Uncontrollable shaking of a part of the body
Unusual bleeding or bruising
Guidelines for Safe Use
Here are some tips for safely taking either nortriptyline or amitriptyline:
Before taking nortriptyline or amitriptyline, tell your healthcare provider about all of your medical conditions and all of the medications you take. If you recently had a heart attack, make sure you notify the prescribing healthcare provider.
Carefully read the prescription label, information leaflet, and medication guide. Ask your healthcare provider or pharmacist if you have any questions.
Take your medication exactly as directed. Do not take more of this medication than prescribed. Your healthcare provider may gradually increase the dose of your medicine. Follow instructions closely.
If you miss a dose, take it as soon as you remember. However, skip the missed dose if it is almost time for the next dose. Do not take extra medication to make up for a missed dose.
Never share your medication with anyone else, even if they have the same symptoms.
Keep the bottle tightly closed when not in use. Keep out of reach and out of sight of children and pets.
Nortriptyline or amitriptyline can cause drowsiness. Do not drive until you know how the medicine affects you.
Consult your healthcare provider regarding alcohol use if you drink alcohol.
Who Should Avoid Nortriptyline or Amitriptyline?
Nortriptyline and amitriptyline are not appropriate for everyone.
Before taking nortriptyline or amitriptyline, notify your healthcare provider of all preexisting medical conditions, your medical history, and your family's medical history.
You should not take nortriptyline or amitriptyline if you are allergic to either medication, other tricyclic antidepressants, or any inactive ingredients in nortriptyline or amitriptyline.
Other people who should avoid taking nortriptyline or amitriptyline include:
Individuals who have recently had a heart attack
Individuals who have taken a medication in a drug class called monoamine oxidase inhibitors (MAOIs) within the past 14 days
Potential Drug Interactions
Tell your healthcare provider about all of the medicines you take, including:
Prescription medications
Over-the-counter (OTC) medicines
Vitamins
Supplements
While taking nortriptyline or amitriptyline, do not start any new medications without approval from your healthcare provider.
Some drug interactions that apply to both medications include:
MAOIs, such as Nardil (phenelzine)
Selective serotonin reuptake inhibitors (SSRIs) antidepressants, such as Lexapro (escitalopram)
Serotonin and norepinephrine reuptake inhibitors (SNRIs) antidepressants, such as Cymbalta (duloxetine)
Muscle relaxants, such as Flexeril (cyclobenzaprine)
Natural herbs used for the treatment of depression, such as Saint-John's-wort
Mood stabilizing medications, such as Lithium
Antihistamines, such as Tagamet (cimetidine)
Solid forms of potassium, such as potassium tablets
Blood-thinning medications, such as Jantoven (warfarin)
This is not a complete list of drug interactions. Other drug interactions may occur with nortriptyline or amitriptyline.
Consult your healthcare provider for more information about drug interactions and how they may affect you.
Summary
Nortriptyline and amitriptyline are orally administered generic TCAs that are FDA-approved to treat MDD or, in an off-label setting, nerve pain or migraine prevention.
In the case of nortriptyline, a brand-name, non-generic form exists, known as Pamelor.
Nortriptyline and amitriptyline are very similar. In fact, amitriptyline metabolizes into nortriptyline after taking it.
Both medications are FDA-approved for depression, and they both have other off-label uses, such as for nerve pain or migraines.
Talk to your healthcare provider for more information and medical advice about these medications.
Frequently Asked Questions
How do I store nortriptyline or amitriptyline?
Store orally administered nortriptyline or amitriptyline at room temperature (68-77 degrees F), away from direct light, heat, and moisture.
Do not store either medication in the bathroom or any area susceptible to high levels of heat or moisture.
Keep all medications out of the sight and reach of children and pets.
What are the most common side effects of TCAs?
TCAs are known for anticholinergic side effects because they block the action of a chemical messenger called acetylcholine.
This leads to common side effects such as constipation, dry mouth, blurry vision, difficulty urinating, and confusion.
Read the original article on Verywell Health.
