Amoxapine vs Trimipramine: Two Tricyclic Antidepressants

If you are researching tricyclic antidepressants, chances are you’ve tried first-line depression treatments, and they haven’t worked for you. Tricyclic antidepressants are often prescribed for people who have treatment-resistant depression. 

Amoxapine and trimipramine are two tricyclic antidepressants that can be prescribed to treat treatment-resistant depression and other mental health conditions. Though these medications work similarly, there are key differences between them that might make one a better choice over the other.

That’s exactly what we’ll explore in this post. We’ll cover—

• What tricyclic antidepressants are and how they work
• Important side effects for each medication
• Drug warnings for each antidepressant
• Potential drug interactions for each antidepressant
• How much each costs
• Plus, some FAQs to help answer any questions you may have!

Not sure which tricyclic medication is best for treating your treatment-resistant depression? The best way to find out is to speak with a board-certified medical provider about your specific situation. Don’t want to wait weeks to meet with an in-person provider? Now you no longer have to!

When you book an appointment on Klarity, we’ll connect you with a depression-trained mental health provider in 48 hours or less. Schedule an appointment now. 

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 (Tricyclic Antidepressants)

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 named for their chemical structure and used to treat depression and occasionally anxiety. They act on several different chemical neurotransmitter pathways in the brain and work to improve mood. 

Specifically, tricyclic antidepressants block serotonin and norepinephrine reuptake, resulting in increased levels of these neurotransmitters in the brain. These two neurotransmitters are decreased in depressed patients, and TCAs help to increase the levels of these two neurotransmitters to restore balance.

Trimipramine and Amoxapine are Both Used To Treat Major Depressive Disorder

Trimipramine and amoxapine are two different tricyclic medications commonly used to treat depression and various anxiety disorders. Although these medications have a similar mechanism of action, important differences between the two should be considered. 

What Else Does Trimipramine Treat?

Aside from being prescribed to treat depression, 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  

Trimipramine has been used off-label for treating several conditions in addition to its FDA-approved uses for treating depression. Some include

• Anxiety disorders: Trimipramine has been used off-label to treat anxiety disorders, including GAD and panic disorder.
• Obsessive-compulsive disorder (OCD): Trimipramine has been used off-label to treat OCD, which is characterized by repetitive, intrusive thoughts and behaviors.
• Chronic pain: Trimipramine has been used off-label to treat chronic pain conditions, such as fibromyalgia and neuropathic pain.
• Migraines: Trimipramine has been used off-label to prevent migraines, a type of headache that is often accompanied by nausea, vomiting, and sensitivity to light and sound.
• Sleep disorders: Trimipramine has been used off-label to treat sleep disorders, including insomnia.

What Else Does Amoxapine Treat?

Amoxapine is unique compared to other antidepressants due to its effect on norepinephrine, serotonin, and dopamine. Therefore, this medication can be useful for treating depression with psychotic features. 

In addition to treating major depressive disorder, amoxapine is commonly prescribed for nerve pain. Because of its sedating effects, it may be a better choice for patients with agitation associated with depression. 

Off-label Uses for Amoxapine  

In addition to its FDA-approved indications for the treatment of depression, Amoxapine, like Trimipramine, has been used off-label for the treatment of several other conditions. Some of these include

• Anxiety disorders: Amoxapine can treat anxiety disorders, including generalized anxiety disorder (GAD) and panic disorder.
• Obsessive-compulsive disorder (OCD): Amoxapine has been used off-label to treat OCD.
• Post-traumatic stress disorder (PTSD): Amoxapine has been used off-label to treat PTSD, which can occur after exposure to a traumatic event.
• Attention deficit hyperactivity disorder (ADHD): Amoxapine has been used off-label to treat ADHD, characterized by hyperactivity, impulsivity, and inattention.
• Sleep disorders: Amoxapine can be prescribed to treat sleep disorders, including insomnia and sleep apnea.

Doses, Dosage Form, and Side Effects of Amoxapine  

Amoxapine is available as a tablet and has generic equivalents in the US. Four different dosage forms are available, and the medication is typically prescribed for multiple daily doses. As with most TCA medications, several side effects are associated with the drug, which 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 should start at 25 mg, 2-3 times a day. 

The medication can be titrated over 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 several side effects associated with amoxapine. Of note, amoxapine is considered a high-risk medication in elderly patients over 65 due to its potential for sedation, lowering blood pressure, and lowering sodium levels in the blood. 

Therefore, this medication should be used cautiously 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 

some rare but serious conditions 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 several 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. Before starting this medication, you should discuss all your current prescriptions with your healthcare provider, 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 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?

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 serotonin levels 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

Tricyclic antidepressants, including amoxapine, trimipramine, and other tricyclic antidepressants, 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 tricyclic antidepressants is generally viewed to be safe for the infant due to the relatively low levels of the drug found in breast milk. 

Increased Bleeding Risk With Tricyclics

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

Increased bleeding risk should be considered in patients 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 increased bleeding risk. 

Signs and symptoms of internal bleeding include: 

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

Black Box Warning For Antidepressants

Antidepressants, including amoxapine, trimipramine, and other tricyclic antidepressants, carry a black box warning from the US Food and Drug Administration (FDA) due to the potential for increased risk of suicidal thoughts and behavior in children, adolescents, and young adults under the age of 24. 

This warning is based on clinical studies that found an increased risk of suicidal ideation and behavior in this age group, particularly in the first few months of treatment or during dosage changes.

The black box warning advises that close monitoring of patients, particularly those new to antidepressant therapy or who have experienced dosage changes, is necessary to identify signs of suicidal ideation or behavior. 

It also recommends that patients and their families be educated about the risks associated with antidepressant therapy and advised to report any unusual changes in behavior or mood to their healthcare provider.

It is important to note that while the black box warning applies to all antidepressants, the risk of suicidal ideation and behavior is generally considered low in adults over 24. Additionally, the benefits of antidepressant therapy in treating depression and other mental health disorders can outweigh the risks when used appropriately and under close medical supervision.

Amoxapine and Trimipramine Frequently Asked Questions

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

Here are some commonly asked questions regarding amoxapine and trimipramine:

Are amoxapine, trimipramine, and other tricyclic antidepressants the same drug?

No, although amoxapine, trimipramine, and other tricyclic antidepressants belong to the same class of medications and act similarly on your brain’s neurochemistry, they all are different 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 and have key differences. 

Why is Amoxapine an off-label treatment for anxiety?

Amoxapine is considered an off-label treatment for anxiety because other medications are safer and more effective in treating 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 because other medications, such as SSRIs, are more effective and have fewer side effects. 

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

What’s better for depression? Amoxapine or Trimipramine?

Trimipramine is typically better for treating 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 Treatment-Resistant Depression with Healthcare Providers on Klarity

With so many medications for depression, finding what treatment plan is best for you can be overwhelming, especially if you’ve tried treatment before and didn’t have success. 

Let Klarity help. 

Klarity offers access to quality online care at your convenience. Skip the traditional visit to the psychiatrist and connect with a board-certified mental health provider online from the comfort of home instead.

Schedule an appointment, and we’ll connect you with a licensed healthcare provider in your state so you can start depression treatment as soon as possible—even in as little as 48 hours!

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