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Nortriptyline vs. Amoxapine: Which Should I Take?


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Living with symptoms of depression is exhausting, especially if you have tried multiple medications with minimal relief. Everyone reacts to psychotropic medication differently, and finding the right treatment option may take time.

In this article, we take a deeper look into two commonly prescribed antidepressant medications, Nortriptyline and amoxapine. We will discuss what they are used for, 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 unhappy with your current medication regimen or have not taken the next steps to address your depression symptoms, let Klarity can help. Start by taking our brief online self-assessment, and we will connect you with an experienced healthcare provider in your state within 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 separate medications and have unique properties that we will discuss below. 

What Are Tricyclics?

Antidepressant medications have been used since the 1950s, and 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 first-line medications or for those who have treatment-resistant depression and cannot achieve adequate relief of their symptoms.  

Tricyclics (TCAs) act by increasing two important neurotransmitters, norepinephrine and serotonin. These chemical messengers play an important role 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.

Amoxapine and Nortriptyline Are Both Used To Treat Major Depressive Disorder

Major depressive disorder is one of the most common psychiatric disorders and is 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, worthlessness, helplessness, and hopelessness. 

What Else Does Amoxapine Treat?

Amoxapine is a unique tricyclic medication because it has an effect on dopamine, in addition to 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 useful in treating insomnia.  

What Else Does Nortriptyline Treat?

Nortriptyline 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 Pamelor 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

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

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 daily maximum 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 changes in mental status 
  • 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 any TCA medication, including amoxapine and Nortriptyline. As we 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 who have a history of suicide attempts or are actively suicidal. 

In addition, TCAs should be avoided or used with great caution in the elderly population for a number of reasons. Firstly, the risk of developing serious side effects is much higher in those over the age of 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. 

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. 

What is Nortriptyline?

Nortriptyline, also known by its brand name, Pamelor, is a tricyclic antidepressant that is used to treat a number of conditions, including headaches, anxiety, and various forms of nerve pain like diabetic neuropathy, and post-herpetic neuralgia. Pamelor is also used off-label to treat ADHD, bedwetting, and for smoking cessation.  

What is Amoxapine?

Amoxapine or Asendin is also a tricyclic antidepressant and has unique effects on dopamine in the brain, which results in mild antipsychotic properties and can be used to treat more severe forms of depression with psychotic features or agitation. It can also be helpful in treating insomnia and chronic nerve pain. 

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 separate, 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 that are used to treat anxiety. Pamelor can still be effective in some patients who are unable to tolerate first-line drugs. 

What’s better for anxiety? Nortriptyline or Amoxapine?

Although neither medication is FDA-approved or considered a first-line treatment for anxiety, Pamelor 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 a couple of 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?

Yes, 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. 

How Klarity Helps You Access Depression Treatment

There is a substantial number of effective antidepressants available in today’s pharmaceutical market, and this can act like a double-edged sword. 

With such a wide variety of different treatment options available, there is a medication for just about anyone who suffers from depression. But with so many different drugs available, it can be overwhelming to understand what makes each drug unique and which medication would be best for you. 

The providers on Klarity specialize in depression treatment and will help navigate this process with you, all from the comfort of your own home. Our unique telehealth service is fast, convenient, and affordable, allowing you to be in control of your care. 

Schedule an appointment on Klarity today, and we will match you with a licensed healthcare professional in less than 48 hours who will help you get the care you deserve. 

Start today, and discuss your symptoms with a specialist who can help.

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