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Nortriptyline vs Amitriptyline: What's The Difference?

Katelyn Brenner FNP

Reviewed by Katelyn Hagerty, FNP

Written by Geoffrey Whittaker

Published 04/19/2022

Updated 04/20/2022

If you’re one of the estimated 21 million US adults affected by some form of depressive illness every year, your healthcare provider may have suggested taking an antidepressant medication to reduce the severity of your symptoms.

Names were never a strong point for scientists working on antidepressants, and as such, there are countless medications for depression that, as well as being challenging to pronounce, look and sound almost identical.

Nortriptyline and amitriptyline are two such examples. These tricyclic antidepressants, or TCAs, have been around for more than half a century and remain common options for treating certain depressive disorders.

Although there are some minor differences between nortriptyline and amitriptyline, these drugs work in the same way to treat depression and have very similar rates of effectiveness.

However, if you have a depressive disorder, this doesn’t necessarily mean that nortriptyline, or amitriptyline, is the right medication for you.

Below, we’ve covered what nortriptyline and amitriptyline are, as well as how these drugs work for the treatment of depression.

We’ve also discussed alternatives to nortriptyline and amitriptyline, including newer medications for depression such as selective serotonin reuptake inhibitors (SSRIs).

Although the term antidepressant is often used to refer to any medication that treats depression, the reality is that there are many different types of antidepressants available.

Nortriptyline and amitriptyline both belong to a class of drugs called tricyclic antidepressants. An older class of antidepressant medications, tricyclics work by blocking the reuptake of chemicals such as serotonin and norepinephrine.

These naturally-occurring chemicals are neurotransmitters -- chemical messengers that help to carry signals between your nerve cells.

Serotonin and norepinephrine both play key roles in managing several aspects of your thinking, emotions and behavior, including your mood.

For example, serotonin is thought to regulate your moods, anxiety levels and happiness, as well as your ability to maintain normal sleep habits. Research has linked low levels of serotonin to a higher risk of mood disorders such as depression and anxiety.

Norepinephrine, on the other hand, is involved in regulating your heart rate, blood pressure and blood sugar levels. It plays a key role in giving you the energy you need to function throughout the day, as well as regulating certain aspects of your sleep cycle.

In addition to its physical effects, norepinephrine is associated with concentration, memory and certain emotions, such as happiness. Like serotonin, low norepinephrine levels might be linked to clinical disorders that can affect your mental health, including depression.

Your brain naturally reduces the concentration of these neurotransmitters via a process called reuptake, kind of like how a bowling alley clears and resets its pins. Tricyclic antidepressants stop this process, resulting in higher levels of serotonin and norepinephrine in your brain.

Both amitriptyline and nortriptyline operate in this way, and in addition to their similar functions, they also share similar benefits. 

Both medications have been approved by the FDA to treat clinical depression. However, as with many other antidepressants, they’re both also commonly used off-label to treat a variety of other conditions.

These include several types of chronic pain in adults, such as neuropathic pain syndromes and issues such as muscle pain, bladder pain syndrome and migraines.

Since nortriptyline and amitriptyline belong to the same class of antidepressants and function in the same way inside your body, it’s actually difficult to name any significant differences between the two medications. 

Nortriptyline and amitriptyline are both similarly effective as antidepressant drugs. In one clinical trial published in the late 1970s, researchers found that both medications worked equally well as treatments for depression. 

Other research has found that their effective doses -- the dose at which a medication produces a biological response -- are also very similar.

Put simply, nortriptyline and amitriptyline are similar medications in numerous ways, resulting in a similar range of effects within your body. 

Why are nortriptyline and amitriptyline so similar? Both drugs are chemical compounds referred to as amines -- compounds that contain a nitrogen atom with a lone pair. However, in practice, one medication comes before the other. 

Amitriptyline is a tertiary amine, meaning as a chemical, it has three carbon atoms bonded to its nitrogen atom. Nortriptyline, on the other hand, is a secondary amine, meaning it features two carbon atoms bonded to its nitrogen atom.

Although amitriptyline is chemically distinct from nortriptyline, your body converts amitriptyline to nortriptyline to be used.

There’s an argument being made that, since it’s already passed the conversion stage before it’s entered your body, nortriptyline is the better tolerated of the two, similar to the way that chewed food digests better than unchewed food.

However, both medications are still used to treat depression and other conditions, and there’s a need for more research in order to validate this concept. 

So, since nortriptyline and amitriptyline are chemically similar and have almost identical effects within your body, which one should you be using? 

If you have depression, it’s best to speak with your healthcare provider and use the medication they suggest. It’s also important to closely follow their instructions regarding dosage, as well as the right time to use your medication. 

However, if you have a condition other than depression, your healthcare provider may suggest one medication over the other.

Nortriptyline is commonly prescribed off-label to treat the following conditions:

  • Diabetic neuropathy

  • Persistent myofascial pain

  • Postherpetic neuralgia

  • Trigeminal neuralgia

  • Neurogenic cough

  • Chronic pain

  • Migraines

It’s also sometimes prescribed as a smoking cessation agent -- a medication used to make the process of quitting smoking easier.

Amitriptyline is commonly prescribed off-label to treat the following conditions:

  • Anxiety

  • Insomnia

  • Post-traumatic stress disorder (PTSD)

  • Interstitial cystitis (bladder pain syndrome)

  • Irritable bowel syndrome (IBS)

  • Sialorrhea (excessive saliva flow)

  • Postherpetic neuralgia

  • Diabetic neuropathy

  • Fibromyalgia

  • Migraines

If you’re prescribed nortriptyline or amitriptyline off-label, your healthcare provider will inform you about how to use your medication effectively. 

Because nortriptyline and amitriptyline are similar antidepressants, they tend to cause a similar range of side effects.

Common side effects of nortriptyline include:

  • Drowsiness

  • Constipation

  • Dizziness

  • Blurred vision

  • Impaired coordination

  • Physical weakness

  • Nausea and vomiting

  • Xerostomia (dry mouth)

  • Excessive sweating

  • Disorientation

  • Confusion

  • Insomnia

  • Anxiety

  • Agitation

  • Restlessness

  • Skin rash and/or itchy skin

  • Galactorrhea (nipple discharge)

  • Changes in blood sugar levels

  • Breast gland tissue growth 

  • Increased need to urinate

  • Sensitivity to sunlight

  • Urinary retention

  • Abnormal sensations

  • Tremoring

Common side effects of amitriptyline include:

  • Nausea

  • Vomiting

  • Drowsiness

  • Confusion

  • Dry mouth

  • Headaches

  • Physical weakness

  • Unsteadiness

  • Tiredness

  • Confusion

  • Nightmares

  • Blurred vision

  • Constipation

  • Urinary retention

  • Excessive sweating

  • Changes in appetite 

  • Changes in weight

Both medications can potentially cause sexual side effects, such as changes in your sex drive or sexual performance issues such as erectile dysfunction (ED). 

Nortriptyline and amitriptyline can both cause drug interactions, particularly when they’re used at the same time as other medications that affect serotonin levels. They may also cause or worsen issues if you have an existing medical condition.

Stopping antidepressant treatment can cause withdrawal side effects. These can occur if you’re prescribed nortriptyline or amitriptyline and adjust your dosage or stop taking your medication.

Our guide to tricyclic antidepressants goes into more detail about the adverse effects of this type of medication, as well as other key safety issues. 

To keep yourself safe while using either medication, make sure to tell your healthcare provider about any medications you currently take or have recently taken, as well as any existing health issues.

It’s also important to inform your healthcare provider if you experience any side effects or signs of an allergic reaction while using either type of medication. 

Although nortriptyline and amitriptyline are both effective medication for depression, they tend not to be used as first-line treatments.

This is because newer antidepressants, such as SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) offer similar benefits for treating depression with a lower risk of causing side effects.

Other Medications for Depression

If you have depression, your healthcare provider will likely prescribe an SSRI or SNRI as your first medication, and only switch to a TCA like nortriptyline or amitriptyline if you don’t feel any improvements from your initial antidepressant. 

Your healthcare provider will guide you to the best medication for your needs. However, it’s far from uncommon to try more than one antidepressant, often over the course of several months, before finding one that works well for you. 

We offer several SSRis online, including fluoxetine (the active ingredient in Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®) and escitalopram (Lexapro®), in addition to SNRIs such as duloxetine (Cymbalta®) and venlafaxine (Effexor®). 

These medications are available through our online psychiatry service, following a consultation with a licensed psychiatry provider who will determine if a prescription is appropriate.

Psychotherapy (Talk Therapy)

Whether you’re prescribed nortriptyline, amitriptyline or a different antidepressant, taking part in therapy and making changes to your habits can help you improve your results and make faster progress towards recovering from depression. 

One of the most effective forms of therapy for depression is cognitive behavioral therapy (CBT), which involves learning to identify and change the thoughts, emotions and behaviors that play a role in the development of depression.

We offer online counseling as part of our range of mental health services, allowing you to talk to a licensed therapist from the comfort and privacy of your home.

Habits and Lifestyle Changes

While therapy and medication are the two most commonly employed treatments for depression, research suggests that making changes to your habits and lifestyle can also provide benefits for your mental health and wellbeing. 

These include taking part in meditation, which has been shown to reduce the severity of anxiety and depression symptoms for many people.

Other habits and lifestyle changes that can help with depression include eating a balanced diet, exercising regularly, maintaining a regular bedtime and wake-up schedule, reaching out to your friends and family members, setting goals and avoiding alcohol, nicotine and illicit drugs.

You can also find out more about making changes to your daily habits to overcome depression in our guide to the best ways to help depression

Nortriptyline and amitriptyline are similar antidepressants with similar effects. They both reduce the severity of depression symptoms, but generally aren’t used as first-line treatments because of their side effect profiles. 

If you’re exploring this information because you want to know more about a certain medication, we hope this has been helpful in clearing up some of the common questions about amitriptyline and nortriptyline. 

But if you’re three hours down a rabbit hole about the subtle differences in medication, we have some advice: stop procrastinating on reaching out for help. 

Here’s the thing about depression treatment -- if it works, it’s a solution. Whether you get results from a TCA, an SSRI or a form of treatment other than medication, anything that gives you real improvements is a good thing when it comes to depression. 

If you’re interested in seeking help for depression, anxiety or any other mental disorder, you can connect with a psychiatry provider using our online psychiatry platform.
You can also learn more about dealing with depression and other common mental health issues with our free mental health resources and content.

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