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Amoxapine vs Trimipramine


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Amoxapine and trimipramine are two different medications that are commonly used for the treatment of depression. While they are the same class of drug, they have many differences that can complicate the process of choosing one over the other.

In this article, we give a full comparison guide, including how each medication works, potential side effects, drug interactions, and costs.

For more information on TCA antidepressants and other treatment options, schedule an appointment on Klarity. We connect you with a local healthcare provider who will discuss your symptoms and find the personalized depression treatment plan that’s best for you. 

This article discusses suicide, suicidal ideation, and self-harm. If you or someone you know is experiencing suicidal thoughts or is in crisis, contact the Suicide Prevention Lifeline immediately at 800-273-8255.

Trimipramine and Amoxapine are the Same Class of Drugs (Tricyclics)

One class of medications that are commonly prescribed for the treatment of depression is tricyclics (TCAs). Amoxapine and trimipramine are two of these TCA medications, and although they have similar effects, there are different side effects and uses for each medication we will discuss.

What Are Tricyclics?

Tricyclic antidepressants (TCAs) are a class of medications that are named for their chemical structure and are commonly used for the treatment of depression and anxiety. They act on a number of different chemical neurotransmitter pathways in the brain and work to improve mood. 

Specifically, TCAs block the reuptake of serotonin and norepinephrine, resulting in increased levels of these neurotransmitters in the brain. These two neurotransmitters have been found to be decreased in depressed patients, and TCAs help to increase the levels of these two neurochemicals to restore balance. 

A few commonly prescribed TCAs include:

Amitriptyline or Elavil 

Elavil (amitriptyline) is a commonly prescribed drug used to treat migraine headaches and major depressive disorder. It is one of the most commonly prescribed tricyclic medications. Amitriptyline is only available as a generic drug, and in addition to Elavil, generic names include Amitid, Amitril, and Endep. 

Amoxapine or Asendin 

Asendin (amoxapine) is used to treat depression and anxiety disorders. This drug is typically taken once before bedtime due to drowsiness.

Trimipramine or Surmontil

Surmontil (trimipramine) is another tricyclic medication used to treat depression. This medication is available as a capsule and is taken one to three times a day. 

 Vivactil or Protriptyline Hydrochloride  

Vivactil (protriptyline) is used to treat depression. This medication is less popular because it is more expensive than other tricyclics and is typically prescribed for multiple doses per day. 

Trimipramine and Amoxapine are Both Used To Treat Major Depressive Disorder

Trimipramine and amoxapine are two different TCA medications that are commonly used in the treatment of major depressive disorder, as well as various anxiety disorders. Although these medications have a similar mechanism of action, there are important differences between the two that should be considered. 

What Else Does Trimipramine Treat?

Aside from treating major depressive disorder, trimipramine is also known to have weak antipsychotic effects and can be used in patients with delusional depression or depression with psychosis symptoms. 

Off-label Uses for Trimipramine  

Off-label use simply describes any use for a medication that is not FDA-approved. Yet this does not mean they are not effective for a given cause. Due to the sedative effects of trimipramine, it can help with insomnia or difficulty sleeping. 

What Else Does Amoxapine Treat?

Amoxapine is unique compared to other antidepressants due to its effect on norepinephrine and serotonin, as well as dopamine. Therefore, this medication can be useful for 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  

Similar to trimipramine, amoxapine has sedating effects that can be useful in patients that have trouble sleeping. 

Doses, Dosage Form, and Side Effects of Amoxapine  

Amoxapine is available as a tablet and has generic equivalents in the US. There are four different dosage forms available, and the medication is typically prescribed for multiple doses per day. As with most TCA medications, there are a number of side effects associated with the medication, and they are listed below. 

Common Amoxapine Doses and Forms

The initial recommended dose of amoxapine typically starts at 25-50 mg at bedtime but can vary, with multiple doses throughout the day. Dosing for older adults over 65 years of age should start at 25 mg, 2-3 times a day. 

The medication can be titrated up over the course of 1-2 weeks, with a target dose of 200 to 300 mg per day. The maximum daily dose is 400 mg per day and 600 mg per day for hospitalized patients. 

Amoxapine is available as a tablet in the following dosage forms: 

  • 25 mg 
  • 50 mg 
  • 100 mg 
  • 150 mg 

Common Amoxapine Side Effects

As with any medication, there are a number of side effects associated with amoxapine. Of note, amoxapine is considered a high-risk medication in elderly patients over the age of 65 due to its potential for sedation, lowering blood pressure, and lowering sodium levels in the blood. Therefore, this medication should be used with caution and requires close monitoring with initiation or dose adjustments in older adults. 

Some of the most common side effects include:

  • Sedation or drowsiness
  • Dry mouth
  • Constipation, nausea 
  • Fatigue or weakness 
  • Blurred vision 
  • Anxiety or restlessness
  • Insomnia or difficulty sleeping 
  • Confusion or altered consciousness
  • Palpitations or changes in EKG patterns 
  • Tremors 
  • Increased appetite causing changes in weight over time 

There are some rare but serious conditions that may occur and if you experience any of the following, contact your healthcare provider immediately: 

  • Signs of Neuroleptic Malignant Syndrome (NMS): mental status changes, fever, muscle rigidity, or unstable vital signs when taking the medication. 
  • Serotonin syndrome: agitation or restlessness, insomnia, confusion, increased heart rate, and blood pressure, muscle twitching, fever, muscle rigidity
  • Increased suicidal thoughts or self-harm behaviors. 

Common Amoxapine Drug Interactions

Before starting any new medication, it is important that you discuss all current medications that you are taking with your healthcare provider, including over-the-counter medications and supplements. 

Some common drug interactions with amoxapine include:

  • Other anticholinergic medications, including atropine 
  • Medications for high blood pressure, such as clonidine & guanethidine 
  • Alcohol and barbiturates, increasing CNS depressants 
  • Monoamine oxidase inhibitors, including isocarboxazid, linezolid, methylene blue, phenelzine, or safinamide to name a few
  • SSRIs
  • Thyroid supplements 

How Much Does Amoxapine Cost?

Amoxapine is available in brand name and generic forms. Although most prescriptions are covered by most health insurance, the average price without insurance and the use of a coupon code is around $20 per month. Coupon codes are widely available and easy to use at most commercial pharmacies.

Doses, Dosage Form, and Side Effects of Trimipramine   

Trimipramine comes in a capsule and is available in generic and name-brand forms in 3 different strengths. Unlike amoxapine, this medication is typically taken once a day before bed but can also be taken in multiple doses throughout the day. 

Common Trimipramine Doses and Forms

Similar to amoxicillin, the initial recommended dose of trimipramine is 25 mg at bedtime, although this can vary depending on the severity of symptoms. The starting dose in hospitalized patients can range as high as 100 mg but requires close supervision. 

The typical dose of trimipramine ranges from 50 mg – 150 mg by mouth daily, either taken as a single dose at bedtime or divided throughout the day. The typical maximum dose is 200 mg per day. 

Trimipramine is available in capsule form in the following dosages: 

  • 25 mg 
  • 50 mg 
  • 100 mg 

Common Trimipramine Side Effects

As with any medication, there are associated risks and benefits with trimipramine. These should be considered and discussed with your healthcare provider before starting any medication. 

Some common side effects of trimipramine include: 

  • Drowsiness, fatigue 
  • Nausea, vomiting, abdominal cramping, or constipation 
  • Dry mouth 
  • Changes in blood pressure
  • Blurred vision 
  • Changes of sensation, such as feeling “pins and needles” in your extremities 
  • Loss of appetite 
  • Decreased sex drive 
  • Headache 
  • Skin rash 

There are a number of rare but serious side effects associated with trimipramine, and you should contact your healthcare provider immediately if you experience the following: 

  • Suicidal thoughts or self-harm behaviors 
  • Serotonin syndrome: changes in mental status, high fever, high blood pressure, irregular movements 
  • Signs of heart attack: new or severe chest pain, fast or irregular heartbeat, increased sweating, dizziness, nausea, or vomiting 
  • Signs of stroke: tired or weakness, difficulty speaking, imbalance, headache, confusion, paralysis of one side of your body 

Common Trimipramine Drug Interactions

Trimipramine is known to interact with certain medications. You should discuss all your current prescriptions with your healthcare provider before starting this medication, including over-the-counter medications and supplements. 

Some common drug interactions with trimipramine include: 

  • Anticholinergic medications, such as atropine 
  • MAO inhibitors, such as isocarboxazid, linezolid, metaxalone, methylene blue, phenelzine, selegiline
  • Certain medications for high blood pressure: clonidine, guanadrel, guanethidine
  • Drugs that may increase the level of the medication: cimetidine, haloperidol
  • Protease inhibitors: fosamprenavir, ritonavir
  • Drugs that affect heart rhythm: flecainide, quinidine, propafenone
  • Motion sickness medication: meclizine, scopolamine 
  • Drugs that increase serotonin: SSRIs, MDMA, St. John’s wort
  • Thyroid medications 

How Much Does Trimipramine Cost?

Surmontil or trimipramine is available in both name-brand and generic forms and is slightly more expensive than amoxapine. These medications are generally covered by most health insurance policies but average around $35 for a monthly supply with a coupon code. Coupon codes are widely available and easy to use at most commercial pharmacies.

Do I Need A Prescription for Trimipramine or Amoxapine?

Yes, you will need a prescription from a licensed healthcare provider to receive either medication. You can schedule an appointment with a provider on Klarity today and be seen within 48 hours.  

Other Tricyclic Side Effects

As described above, the most common side effects associated with TCAs include the following: 

  • Drowsiness or dizziness 
  • Dry mouth 
  • Constipation
  • Blurred vision 
  • Weight pain
  • Excessive sweating 
  • Palpitations or irregular heartbeat, increased heart rate 

What is Serotonin Syndrome?

Serotonin syndrome is a rare but serious side effect of antidepressants, specifically linked to SSRIs or SNRIs. This condition occurs when there are elevated levels of serotonin in the brain, likely caused by a medication, such as another antidepressant, ADHD medications, opioids, St. John’s wort, or recreational drugs like MDMA. 

Signs and symptoms of serotonin syndrome include: 

  • Altered mental status or confusion 
  • Agitation or restlessness 
  • Muscle twitching or rigidity 
  • Fever and increased sweating or shivering 
  • Nausea, vomiting, or diarrhea 
  • Rapid heart rate and high blood pressure 
  • Dilated pupils 
  • Insomnia or difficulty sleeping 
  • Dilated pupils 

Severe symptoms include seizures, irregular heartbeat, and unconsciousness. It is important to contact your healthcare provider or report to the emergency department immediately if you begin to experience these symptoms. 

Pregnancy and Breastfeeding on Tricyclics

TCAs, including amoxapine and trimipramine, are typically avoided during pregnancy due to the following complications: 

  • Spontaneous abortion 
  • High blood pressure, leading to preeclampsia or eclampsia 
  • Postpartum hemorrhage 
  • Preterm birth 
  • Postnatal effects, including withdrawal symptoms, hypoglycemia, respiratory illness, or jaundice 

Breastfeeding while on TCAs is generally viewed to be safe for the infant due to the relatively low levels of the drug found in breastmilk. 

Increased Bleeding Risk With Tricyclics

When used alone, TCAs do not appear to increase the patient’s bleeding risk. This is unlike other antidepressants, such as SSRIs, which have a significantly increased bleeding risk, especially when used with over-the-counter pain relievers.  

Increased bleeding risk should be considered in patients who are simultaneously taking Warfarin with TCAs, as TCAs prevent Warfarin metabolism and breakdown in the body. With increased levels of Warfarin in the body, there is potential for an increased bleeding risk. 

Signs and symptoms of internal bleeding include: 

  • Black or tarry stools 
  • Severe abdominal pain 
  • Easy bruising 
  • Bleeding gums without trauma

Amoxapine and Trimipramine Frequently Asked Questions

Comparing different medications can be challenging, especially if they come from the same class of medications. 

Here are some commonly asked questions regarding amoxapine and trimipramine:

Are Amoxapine, Trimipramine, and other Tricyclics the same drug?

No, although amoxapine, trimipramine, and other TCAs belong to the same class of medications and act in a similar manner on your brain’s neurochemistry, they all are separate medications. 

Since they are from the same family of drugs, they tend to have similar side effect profiles and drug interactions, but these medications are not identical to one another and have key differences. 

Why is Amoxapine an off-label treatment for anxiety?

Amoxapine is considered an off-label treatment for anxiety because there are other medications that have been shown to be safer and more effective in the treatment of anxiety, like SSRIs, for example. 

What’s better for anxiety? Amoxapine or Trimipramine?

Either medication, amoxapine or trimipramine, are not considered first-line treatments for anxiety due to the fact that other medications, such as SSRIs, have been shown to be more effective and have fewer side effects. 

But, when comparing these two TCA drugs, amoxapine is better than trimipramine for the treatment of anxiety due to its unique effects on serotonin and norepinephrine. 

What’s better for depression? Amoxapine or Trimipramine?

Trimipramine is typically better for the treatment of depression than amoxapine due to its side effect profile and efficacy. With more side effects, amoxapine is commonly used to treat more severe depression in patients who have failed other medications. 

Can I drive on antidepressants like Amoxapine or Trimipramine?

Due to the sedative effects of TCAs, they are typically prescribed to take at night before bedtime. Patients should be instructed by their prescribing physician not to drive or operate heavy machinery after taking a TCA antidepressant. 

Can I drink alcohol on Amoxapine or Trimipramine?

No, you should avoid consuming alcohol while taking a TCA medication due to the sedating effects of both substances. There is a risk for safety and health concerns when taking TCA medications with alcohol, such as falls and central nervous system depression, which can be lethal. 

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

Yes, it does matter what time of day you take amoxapine or trimipramine. Due to the sedating effects of these medications, they should be taken at night before bed. 

Find the Right Medication for Your Anxiety with Healthcare Providers on Klarity

With so many medications for depression, finding what treatment plan is best for you can be overwhelming. Let Klarity help. 

Klarity offers access to quality online care at your convenience. Skip the traditional visit to the psych clinic and the associated hassles, including long wait times and expensive copays. Klarity offers affordable care with no insurance, no subscriptions, or hidden fees. 

Schedule an appointment or start by taking a brief 2-minute self-assessment today. You can be seen in as little as 48 hours by a licensed healthcare provider in your state so you can start your depression treatment as soon as possible, if applicable. 


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