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Depression
24 min read
Written by Klarity Editorial Team
Published: Oct 31, 2022
Medically Reviewed by Dr. Zoe Russell
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—
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.
Amoxapine | Trimipramine | |
Drug Class | Tricyclic antidepressant | Tricyclic antidepressant |
Brand / Generic Status | Generic (Brand name: Asendin) | Generic (Brand name: Surmontil) |
Form(s) of the Drug | Immediate-release color-coded tablets | Immediate-release color-coded tablets |
Standard Dosage | Immediate-release color-coded tablets: • 25mg: white • 50mg: orange • 100mg: blue • 150mg: light orange | Immediate-release capsules: • 25 mg • 50 mg • 100 mg |
Conditions Treated | FDA-approved: • Depression with psychotic features • Nerve pain Off-label: • Difficulty sleeping | FDA-approved: • Major depressive disorder Off-label: • Difficulty sleeping |
Cost | Generic (amoxapine): • $20 to $36 for a 30-day supply Brand name: • Brand name formula not available for Rx | Generic (trimipramine): • $30 to $78 for a 30-day supply Brand name: • $160 to $171 for a 30-day supply |
Side-Effects | Common side effects: • 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 Serious side effects • Signs of Neuroleptic • Malignant Syndrome (NMS) • Serotonin syndrome • Increased suicidal thoughts or self-harm behaviors | Common side effects: • 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 Serious side effects: • Suicidal thoughts or self-harm behaviors • Serotonin syndrome • Signs of heart attack • Signs of stroke |
Warnings For Use | Drug interactions • Other anticholinergic medications • Blood pressure medication • Alcohol and barbiturates • MAOIs • SSRIs • Thyroid supplements | Drug interactions • Anticholinergic medications • MAOIs • Certain medications for high blood pressure • Drugs that may increase the level of the medication • Protease inhibitors • Drugs that affect heart rhythm • Motion sickness medication • SSRIs • MDMA • St. John’s wort • Thyroid medications |
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.
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 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.
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.
Trimipramine has been used off-label for treating several conditions in addition to its FDA-approved uses for treating depression. Some include
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.
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
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.
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:
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
some rare but serious conditions may occur and if you experience any of the following, contact your healthcare provider immediately:
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:
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.
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.
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:
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:
There are several rare but serious side effects associated with trimipramine, and you should contact your healthcare provider immediately if you experience the following:
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:
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.
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.
As described above, the most common side effects associated with TCAs include the following:
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:
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.
Tricyclic antidepressants, including amoxapine, trimipramine, and other tricyclic antidepressants, are typically avoided during pregnancy due to the following complications:
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.
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:
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.
Comparing different medications can be challenging, especially if they come from the same class.
Here are some commonly asked questions regarding amoxapine and trimipramine:
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.
Amoxapine is considered an off-label treatment for anxiety because other medications are safer and more effective in treating anxiety, like SSRIs, for example.
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.
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.
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.
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.
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.
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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