Nortriptyline vs Amitriptyline: What's The Difference?

Katelyn Hagerty FNP

Medically reviewed by Katelyn Hagerty, FNP

Written by Our Editorial Team

Last updated 4/20/2022

Names were never the strong point for scientists working on antidepressants, but in the 1950s when tricyclic antidepressants (TCAs) first hit the market, they found a strong point in the treatment and management of depression symptoms. More than half a century later, Nortriptyline and amitriptyline are two of the common TCAs prescribed by healthcare professionals.

These two medications are similar in function, and for years they’ve helped people cope more effectively not just with depression, but with a host of other medical conditions and diseases as well. 

The differences between nortriptyline and amitriptyline are few — but significant. So, whether you’re doing your own due diligence about a doctor’s recommendation or just wanting to understand these medications better, let’s break down the differences.

Nortriptyline and Amitriptyline: Tricyclic Antidepressants

It often helps to understand the differences between two medications by outlining what they have in common, and in the case of amitriptyline and nortriptyline, there’s quite a lot of overlap.

TCAs are a class of antidepressant that in 1959 hit the market running. Regardless of which TCA you’re prescribed, they all operate in similar ways.

When taken as prescribed, TCAs affect the reabsorption of two key neurotransmitters in your brain: serotonin and norepinephrine.

These neurotransmitters generally affect the way your brain regulates mood, but in the brain of a person with depression, it can be the case that the supply of both norepinephrine and serotonin can be reduced by your own brain, sort of the way a bowling alley clears and resets its pins.

TCAs and other antidepressants essentially shut down the mechanics — the neurotransmitters don’t get cleared away, and so there’s a larger volume available the next time your brain needs some.

Both amitriptyline and nortriptyline operate in this way, and in addition to their similar functions, they also share similar benefits. Both drugs have been FDA approved to treat depression, but also function off-label in the management of neuropathic pain and other pain in adults from a variety of conditions and diseases.

They even provide anti-anxiety benefits to some patients.

The Difference Between Nortriptyline And Amitriptyline

It’s actually difficult to find significant differences between nortriptyline and amitriptyline, if we’re being honest. They have similar if not identical common side effects, dosages, drug interactions and risk of adverse effects.

Studies have shown that their effective dosages are even similar.

There’s also not much difference with regards to effectiveness between these two medications, at least when it comes to depression.

A 1977 clinical trial concluded that these two drugs were equally effective when it came to depression treatment. What affected the effectiveness was not the particular TCA in this study, but whether the TCA was delivered at the right concentrations and dosage for the use case.

Why so similar? It comes down to the relationship between the two. Both are a type of chemical compound called an amine, but in practice, one comes before the other. In your body, amitriptyline is actually converted into nortriptyline — from a tertiary amine to a secondary amine — to be used.

There’s an argument being made that, because it has already past that conversion stage, nortriptyline is the better tolerated of the two, sort of the way that chewed food digests better than unchewed food. In practice though, more research seems to be needed to validate this concept.

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Should I Use Nortriptyline or Amitriptyline?

So which one should you be using? The short answer is that it doesn’t seem to matter, at least in terms of perceived benefits for depression. 

There’s the first case in which, according to the research we shared, they’re both equally effective in the treatment of depression. 

The final answer to this question, though, will come from a healthcare professional.

With respect to the study data, antidepressants affect everyone differently, much the same way that depression affects everyone a little differently. Each unique person needs a unique and tailored line of treatment to maximize their results and get the best quality of life. 

This is why it’s perhaps the case that the best treatment for you won’t involve any TCAs at all.

Other Depression Treatment Options

The appropriate treatment for your individual needs may take the form of one (or a combination) of medication, therapy and lifestyle changes. 

There’s plenty more to the options you have for therapy and medication, and you can read more about that in our other guides, but for a quick summary, here are the other options available to treat depression.


Aside from TCAs, there are several other medications on the market that can help regulate mood. The most popular of these is serotonin reuptake inhibitors (SSRIs), which block the reabsorption of serotonin to give your brain a larger supply pool to draw from.

A healthcare provider will guide you to the best medication for your needs, but be warned that it’s not uncommon for someone to try more than one medication to find the best support for their needs.

Therapeutic Practices

A mental health professional might be able to provide much-needed additional support in the form of therapy — something that a general practitioner is not trained to do. 

Therapy is a great way to work through not just the emotions you’re dealing with, but the patterns of thought and ways of thinking that are keeping you depressed. 

One of the most effective forms of therapy for depression is Cognitive Behavioral Therapy (CBT) which helps the patient learn to observe, question, and eventually control those intrusive negative thoughts that give depression so much power. 

Habit and Lifestyle Changes

While therapy and medication are the two most commonly employed treatments for depression, studies provide evidence that a variety of other practices may hold benefits, including meditation.

Mindfulness meditation can help reduce depression symptoms for some people. 

Beyond meditation, changes to your lifestyle that improve your blood pressure, weight, or heart rate, and improvements to your diet and exercise routines can be beneficial for mental and physical health. In fact, some research shows that regular exercise is as effective as drugs in the treatment of mood disorders.

Whether it’s walking, talking, or as-directed pill-popping, the right treatment is about finding what works for you.

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Treating Depression: Beyond Nortriptyline or Amitriptyline

If you’re exploring this information because you want to know more about a recommended medication, we hope this has been helpful in clearing up some of the 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 getting help.

Here’s the thing about depression treatment: if it works, it’s a solution. 

Whether you take nortriptyline, amitriptyline, another TCA, an SSRI or just start jogging, there’s no right answer to the treatment of depression as long as you’re feeling results. 

You can read all you want to (and we hope you do), but what you should be doing it you want to kick depression’s ass is getting the right mental health coach in your corner to help you figure out what works. 

If you’re ready to see what these and other medications can do for you, start the process today. 

8 Sources

Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references.

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This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.