Nortriptyline vs. Amoxapine: Which Should I Take?

Living with depression can be exhausting, especially if you have yet to find relief from your symptoms. It can take time to find the right treatment for you, and with all of the available medication options available, it can be difficult to understand which one will work best for your depression.

This article looks deeper into two commonly prescribed antidepressant medications, Nortriptyline and Amoxapine. We will discuss what they are used for, their potential side effects, and warnings associated with each so that you can be better informed when discussing treatment options with your healthcare provider. 

If you are experiencing depression symptoms, medications like Nortriptyline or Amoxapine may be able to help. To determine if these drugs or another form of antidepressant is right for you, find a provider on Klarity today for online depression treatment in as little as 48 hours.

Amoxapine and Nortriptyline Are the Same Class of Drugs (Tricyclics)

Amoxapine and Nortriptyline are two commonly prescribed medications that belong to the same class of drugs called tricyclic antidepressants (TCAs). Although they share many characteristics, they are two different medications with unique properties, which we will discuss below. 

What Are Tricyclics?

Tricyclics were among the first antidepressant medications to be developed. While they are no longer considered to be first-line agents for the treatment of depression, they are still used in certain cases, such as those who cannot tolerate other antidepressants or for those who have treatment-resistant depression and cannot find relief from their symptoms with other methods.  

Tricyclics act by increasing two important neurotransmitters, norepinephrine and serotonin. These chemical messengers are important in many bodily functions, such as mood regulation, sleep, appetite, and sex drive. Decreased levels of these neurotransmitters are responsible for the symptoms of depression, and tricyclic antidepressants work to correct this imbalance.

Tricyclics are not selective in the neurotransmitters that they target unlike SSRIs and SNRIs. For this reason, TCAs can affect other parts of the brain unrelated to mood, which can cause an increased risk of negative side effects. 

Amoxapine and Nortriptyline Are Both Used To Treat Major Depressive Disorder

Major depressive disorder is one of the most common psychiatric disorders, characterized by a loss of interest in pleasurable activities and feelings of sadness. Depression presents differently from person to person, but some shared symptoms include:

• Changes in appetite
• Changes in sleep
• Feelings of guilt
• A sense of worthlessness, helplessness, or hopelessness

What Else Does Amoxapine Treat?

Amoxapine is a unique tricyclic medication because it affects dopamine, serotonin, and norepinephrine. Dopamine plays a role in hallucinations and delusional thought processes, which makes this medication useful in treating depression with psychotic features. 

In addition to treating anxiety and depression, Amoxapine is commonly prescribed to treat nerve pain. Because of its sedating effects, it may be a better choice for patients who have agitation associated with their depression. 

Off-label Uses for Amoxapine 

Like most TCAs, Amoxapine has sedative effects and, therefore, can be potentially useful in treating insomnia.  

What Else Does Nortriptyline Treat?

Nortriptyline is only FDA-approved to treat depression. However, it has several off-label uses, which is a term used to describe any indication that has not been approved by the FDA. This does not mean that the medication is not effective for the given condition but that the drug manufacturer has not gone through the extensive FDA research process. 

Off-label Uses for Nortriptyline   

The most common off-label uses for Nortriptyline include: 

• Migraines 
• Diabetic neuropathy or nerve pain caused by uncontrolled diabetes 
• Postherpetic neuralgia or nerve pain caused by the virus that causes shingles
• Neurogenic cough 
• Chronic pain 
• Trigeminal neuralgia or nerve pain involving the 5th cranial nerve in the face 
• Smoking cessation

What is Nortriptyline?

Nortriptyline, also known by its brand name, Pamelor, is a tricyclic antidepressant that is used to treat depression. It is used off-label to treat a number of other conditions as well, including headaches, anxiety, and various forms of nerve pain. 

Doses, Dosage Form, and Side Effects of Nortriptyline   

Common Nortriptyline Doses and Forms

Nortriptyline is also known by its brand name, Pamelor, and is available in capsules as well as an oral solution. The capsules come in the following dosages: 10 mg, 25 mg, 50 mg, and 75 mg, while the oral solution is one concentration of 10 mg/5mL and is typically reserved for those who have difficulty swallowing pills.  

As with most psychotropic medications, the initial starting dose is low, around 25 mg, and is taken multiple times throughout the day. The dose can then be titrated up every week until the desired dose is reached, but it should not exceed 150 mg per day. 

Common Nortriptyline Side Effects

As with most TCA medications, there are a number of side effects that are associated with Nortriptyline. This unfavorable side effect profile is one of the main reasons TCA medications are no longer considered first-line agents for depression treatment. 

Some common side effects associated with Nortriptyline include: 

• Weakness 
• GI upset, including nausea, vomiting, abdominal pain, and constipation
• Insomnia
• Agitation, anxiety, or restlessness 
• Drowsiness
• Dry mouth 
• Dizziness, which can lead to impaired coordination 
• Blurred vision
• Excessive sweating 
• Gynecomastia or breast tissue growth, nipple discharge 
• Sensitivity to sunlight 
• Urinary retention or increased need to urinate 
• Tremor 
• Skin rash or itching 
• Confusion or disorientation 

Common Nortriptyline Drug Interactions

Due to extensive drug interactions associated with TCA medication, disclose all medications and supplements you are currently taking with your healthcare provider before starting a new medication.  

Some common drug interactions with Nortriptyline include: 

• MAO inhibitors should be avoided two weeks prior to and after taking Nortriptyline 
• Anticholinergic medications
• Certain antihypertensive medications: Clonidine, Guanabenz, Lisinopril
• Thyroid medications and supplements
• Opioid or other analgesic medications 
• Blood thinning medications, such as Warfarin or Coumadin 
• Muscle relaxers: Flexeril 
• Medications used to treat nerve pain: Cymbalta, Gabapentin, Lyrica 
• Other medications that increase serotonin levels: SSRIs, SNRIs, ADHD medications, St. John’s Wort, and recreational drugs like MDMA

How Much Does Nortriptyline Cost?

Pamelor is the brand name of the generic drug Nortriptyline. The cost of your monthly supply of medication will dramatically vary based on your insurance coverage, which dose you are on, and what pharmacy you use. 

Most insurance plans cover Nortriptyline, and coupon codes can significantly lower the cost of your prescription if you are underinsured or uninsured. The retail price of name brand Nortriptyline is typically over $1200 for a 30-day supply, but using a generic formulary and coupons, you can reduce the cost to under $15 per month.   

What is Amoxapine?

Amoxapine, or Asendin, is a tricyclic antidepressant with unique effects on dopamine in the brain. Amoxapine’s properties result in mild antipsychotic effects, making it useful in treating more severe forms of depression with psychotic features or agitation. It can also be helpful in treating insomnia and chronic nerve pain. 

Doses, Dosage Form, and Side Effects of Amoxapine  

Common Amoxapine Doses and Forms

Amoxapine is also known by its brand name Asendin, and is available in tablets with the following dosages: 25 mg, 50 mg, 100 mg, and 150 mg. Similar to Nortriptyline, the initial dose is typically started low, around 25 mg, and it can be increased weekly to the targeted dose.  

The maximum daily dose of Amoxapine is 400 mg per day and 600 mg per day in patients who are in a hospitalized setting and are being closely monitored by healthcare professionals. 

Common Amoxapine Side Effects

Nortriptyline and Amoxapine share many side effects because they belong to the same class of medication and work in a similar way in the body. 

Some common side effects of Amoxapine include: 

• Sedation 
• Drowsiness 
• GI upset, including nausea, vomiting, diarrhea, or constipation
• Dry mouth 
• Fatigue 
• Weakness
• Increased anxiety or restlessness 
• Insomnia or difficulty sleeping 
• Increased appetite, which may result in weight gain over time
• Blurred vision
• Tremor 
• Confusion or memory impairment 
• Palpitations, arrhythmias, or changes in EKG patterns 

Common Amoxapine Drug Interactions

Similar to side effects, Amoxapine and Nortriptyline share many drug interactions as well. When starting a new medication, it is important to disclose all medication you are currently taking with your healthcare provider, including all over-the-counter medications and supplements. 

Some common drug interactions seen with Amoxapine include: 

• Anticholinergic medications
• Certain medications for high blood pressure, such as Clonidine or Lisinopril
• MAOI medications, including isocarboxazid, linezolid, methylene blue, or phenelzine, to name a few 
• Drugs that increase serotonin in the body: SSRIs, SNRIs, ADHD medication, St. John’s Wort, and recreational drugs like MDMA 
• Thyroid supplements
• CNS depressants, such as alcohol, benzodiazepines, and barbiturates 

How Much Does Amoxapine Cost?

The cost of your Amoxapine or Asendin prescription varies based on your insurance coverage, dosage, and pharmacy. For those who are uninsured, there are coupon codes available at most commercial pharmacies that can significantly lower the cost of your prescription from its retail price of $42 to around $20 for a 30-day supply. 

Do I Need A Prescription for Amoxapine or Nortriptyline?

Yes, you need a prescription from a state-licensed healthcare provider for all tricyclic antidepressant drugs, including Amoxapine and Nortriptyline. As discussed, there are a number of serious side effects and drug interactions associated with TCAs, making this class of medication not the best choice for certain groups of people. 

Your healthcare provider will determine if you may benefit from starting a TCA medication. 

Other Tricyclic Side Effects

The unfavorable side effect profile of TCA medications is one of the main reasons why they are no longer considered first-line agents in the treatment of depression. There are a few rare but serious side effects associated with TCAs as a class that will be discussed below. 

What is Serotonin Syndrome?

Serotonin syndrome is an uncommon but serious and potentially life-threatening condition that occurs when there are dangerously high levels of serotonin built up within the body. This most commonly occurs when someone is taking more than one medication that increases the level of serotonin in the body. 

It is important to closely monitor yourself when starting a TCA medication for the following signs and symptoms and seek out urgent medical attention if you begin to experience: 

• High fever
• Fast heart rate 
• High blood pressure 
• Dilated pupils
• Excessive sweating or shivering  
• Diarrhea 
• Headache 
• Insomnia 
• Increased agitation or restlessness
• Muscle twitching or rigidity 
• Altered state of consciousness or confusion 

Pregnancy and Breastfeeding on Tricyclics

Tricyclic antidepressants should be avoided during pregnancy because of the potential complications during gestation: 

• Spontaneous loss of pregnancy 
• High blood pressure, preeclampsia, or eclampsia 
• Preterm birth 
• Postpartum hemorrhage
• Postnatal effects: withdrawal, hypoglycemia, jaundice, decreased respiratory drive

If you are taking a TCA medication when you get pregnant, your healthcare provider can provide alternative medication options that are safe during pregnancy. If you restart your TCA medication immediately after birth, it is generally considered safe to breastfeed while taking your medication because there are low levels of the drug found within breast milk. 

Black Box Warning With Antidepressants

The majority of antidepressant medications are associated with a black box warning for worsening depression and suicidal ideation once starting a new medication. While this is rare and most commonly seen in those under the age of 24, it is important to monitor yourself for negative changes in mood or thought process when starting a new antidepressant. 

Warnings of Improper Use of Medication

You should always follow your healthcare provider’s instructions on how to take your medication, but this is particularly important with tricyclic medications. We have previously discussed how TCAs are no longer considered first-line treatment because of their side effects, but they are also considered to be dangerous if not taken as prescribed. 

When TCAs are taken in high doses, there is a serious risk of heart arrhythmias or irregular heartbeats that can be deadly if not treated immediately. For this reason, TCAs should be avoided in those with a history of suicide attempts or who are actively suicidal. 

In addition, TCAs should be avoided or used with great caution in the elderly population for several reasons. Firstly, the risk of developing serious side effects is much higher in those over 65, particularly fatal cardiac events. In addition, cognitive decline is inevitable with age, and elderly patients are more likely to struggle with remembering if or when they took their medications, resulting in a risk of accidental overdose. 

How Klarity Helps You Access Depression Treatment

With so many antidepressant options available, each with its own benefits and side effect profiles, it can be difficult to find the right one for you without the help of an experienced healthcare provider. For this reason, you should never attempt to self-medicate your symptoms and should always consult with a psychiatric expert to receive a safe and effective prescription.

Klarity has connected thousands of patients nationwide with healthcare providers for affordable and straightforward online mental health treatment. Find a provider today and discuss your symptoms in a private telehealth appointment to determine if Nortriptyline, Amoxapine, or another antidepressant is right for you. 

Nortriptyline and Amoxapine Frequently Asked Questions

We understand that comparing two medications from the same class of drugs can get confusing, so we have answered some of the most frequently asked questions about Nortriptyline and Amoxapine below. 

Are Nortriptyline and Amoxapine the same drug?

Although they belong to the same class of medications and have many similarities, Nortriptyline and Amoxapine are two unique drugs. 

Why is Nortriptyline an off-label treatment for anxiety?

Nortriptyline is not a first-line treatment for anxiety because there are newer, safer, and more effective medications used to treat anxiety. Pamelor can still be effective in some patients who cannot tolerate first-line drugs. 

What’s better for anxiety? Nortriptyline or Amoxapine?

Although neither medication is FDA-approved nor considered a first-line treatment for anxiety, Nortriptyline is a better choice for treating anxiety when compared to Amoxapine.  

What’s better for depression? Nortriptyline or Amoxapine?

While both medications are used to treat depression, Asendin may be a better treatment option for severe depression with psychotic features or with agitation. Pamelor would likely be a better option for mild depression, as it has a better side effect profile. 

Can I drive on antidepressants like Nortriptyline or Amoxapine?

Due to the sedating effects of TCAs, you should not drive or operate heavy machinery after taking Nortriptyline or Amoxapine. 

Can I drink alcohol on Nortriptyline or Amoxapine?

Drinking alcohol should be avoided when taking a TCA medication for several reasons, including the increased risk of adverse effects. There is also a greater potential for dangerous CNS depression and sedative effects when combining the two drugs. 

Does it matter what time of day I take Nortriptyline or Amoxapine?

Because of their sedative effects, TCA medications are typically taken at night before bed. Your healthcare provider will instruct you on how to take your medication as they see fit.