Amitriptyline, Doxepin, and More: The Essential Facts About 9 Tricyclic Antidepressants
Key takeaways:
Tricyclic antidepressants (TCAs) are prescription medications that are most often used to treat depression. Several of them can treat other health conditions, too, such as nerve pain, insomnia, and obsessive-compulsive disorder.
Amitriptyline, amoxapine, and imipramine are a few TCA examples. Others include clomipramine (Anafranil), desipramine (Norpramin), and doxepin (Silenor, Zonalon, Prudoxin).
Drowsiness, dizziness, and dry mouth are common TCA side effects. TCAs can also cause more serious side effects, such as seizures and heart problems. Other antidepressants are typically prescribed before TCAs due to their risk of side effects.
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Table of contents
Tricyclic antidepressants (TCAs) are unique, prescription-only medications that have been around for over 60 years. They affect the balance of several chemicals — such as norepinephrine and serotonin — throughout the brain and body to help boost mood and relieve pain, among other effects.
TCAs aren’t the right choice for everyone, though. Your prescriber may recommend trying a different medication first. TCAs are typically used when other antidepressants don’t work well for your symptoms. This is because they have a number of risks and can cause various side effects.
Knowing more about your medication options can help you or a loved one make the best decision. Below, we’ve provided a full list of TCAs and the top features to know about each one.
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1. Amitriptyline
Amitriptyline is FDA-approved to treat depression in adults. Kids as young as 12 may receive prescriptions for it, too. It’s one of the most commonly prescribed TCAs, likely for its off-label uses. Nerve pain, insomnia, and migraine prevention are a few examples. In fact, amitriptyline is a possible first-choice medication for nerve pain.
Amitriptyline comes as an oral tablet in a variety of strengths. There are different options for how you take it. You can divide up your daily dose throughout the day in a few smaller amounts. Or you can conveniently take one dose at bedtime. This may help prevent daytime drowsiness, because amitriptyline can make you sleepy. Keep in mind that it can take up to 30 days to feel the full benefits of amitriptyline.
Like other TCAs, amitriptyline may cause QT prolongation (heart rate changes). While very rare, it’s also possible for amitriptyline to cause a dangerous arrhythmia (abnormal heartbeat) known as Torsade de Pointes. Watch for symptoms such as heart palpitations and dizziness while taking amitriptyline. Reach out to your prescriber right away if you experience these symptoms.
Good to know: Taking amitriptyline with other medications that increase the risk of QT prolongation — such as risperidone (Risperdal) or quetiapine (Seroquel, Seroquel XR) — further raises your risk of heart problems. Keep a list of your current medications handy. Your pharmacist can check for any potential interactions before starting you on amitriptyline.
Mixing medications: Amitriptyline, one of the most popular tricyclic antidepressants (TCAs), can interact with certain medications. Learn more about the top amitriptyline interactions here.
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2. Amoxapine
Amoxapine is approved to treat adults who are experiencing depression with added symptoms of anxiety or agitation. It’s also used off-label for health conditions such as nerve pain.
Like amitriptyline, amoxapine comes as an oral tablet. You can take it 1 to 3 times daily, but many people opt to take it once a day at bedtime. Amoxapine tends to kick in faster than amitriptyline. After starting amoxapine, you may start to notice improvement in your symptoms within 7 days. You’ll likely experience the full benefits in about 2 weeks (14 days).
People taking amoxapine have a higher risk of experiencing seizures than with other TCAs — especially if you take too much. Let your prescriber know if you’ve ever experienced a seizure before. They may steer clear of amoxapine in this case. If you have a seizure while taking amoxapine, reach out to your prescriber right away.
Good to know: All TCAs may increase the risk for seizures — not just amoxapine. If you or a loved one are living with epilepsy, a healthcare professional can tell you if a TCA is safe for you to take.
3. Clomipramine
Clomipramine (Anafranil) is approved to treat obsessive-compulsive disorder (OCD) in adults and kids ages 10 and older. It can also be prescribed off-label for depression, anxiety, and more.
Clomipramine comes as an oral capsule in three strengths. You typically take it once daily at bedtime after you’ve found the dosage that works for you. Since clomipramine can upset your stomach, though, it’s best to take it with food to lower the chances of this happening.
4. Desipramine
Like amitriptyline and amoxapine, desipramine (Norpramin) is approved to manage depression. Nerve pain, bulimia (an eating disorder), and overactive bladder are a few examples of despiramine’s off-label uses. Desipramine is considered a possible first-choice treatment for managing nerve pain from shingles.
Adults and adolescents can take desipramine. It comes as an oral tablet in a variety of strengths. You can take it once daily or in smaller doses spread out over the day.
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5. Doxepin
Doxepin (Silenor, Zonalon, Prudoxin) is approved for a variety of health conditions. The reason you’re taking doxepin will likely dictate your ideal dosage form.
Doxepin capsules and oral solution can manage depression and anxiety in adults and kids ages 12 and older. Your doxepin dosage for these purposes will depend on your symptoms.
Doxepin tablets are used for insomnia. Research shows doxepin is an effective treatment for insomnia, too. Doxepin doses for insomnia are typically lower than those used for anxiety and depression. It doesn’t carry the same potential risk of misuse as Z-drugs or benzodiazepines, either, making it a safer option for insomnia.
A topical version is available, too. Doxepin cream can treat itchy skin and neuropathic pain in adults. You can apply it 4 times a day for up to 8 days at a time.
Good to know: If you take doxepin for insomnia, it’s important to take it within 30 minutes of your bedtime. You should also separate doxepin by about 3 hours from your meals. Food can slow doxepin’s absorption in your body.
6. Imipramine
Imipramine gave TCAs their start in 1959. It was the first to be approved. It’s available as two different salt forms: imipramine hydrochloride and imipramine pamoate. The pamoate form is released more slowly in your body, but it also lasts longer than imipramine hydrochloride.
Imipramine hydrochloride is an oral tablet that can treat depression in adults and adolescents. It’s also approved to manage bed-wetting in kids ages 6 and older. Imipramine pamoate is an oral capsule that treats depression in adults.
7. Nortriptyline
Nortriptyline (Pamelor) sounds very similar to amitriptyline. That’s because amitriptyline is metabolized (broken down) to nortriptyline. But nortriptyline side effects tend to be milder.
Nortriptyline is used to manage depression in adults and adolescents. It’s also prescribed off-label to treat health conditions such as nerve pain and migraines. Nortriptyline comes as an oral capsule or oral solution. You can take it once daily or in smaller divided doses throughout the day.
8. Protriptyline
Protriptyline is used to treat depression in adults and adolescents. But it’s more “activating” than other TCAs, so it doesn’t make you quite as tired. This makes it helpful for managing narcolepsy off-label. Sleep apnea and attention-deficit hyperactivity disorder are additional examples of off-label protriptyline uses.
While you can take most TCAs as a single dose at bedtime, this isn’t the case with protriptyline. It comes as an oral tablet that you take 3 to 4 times a day.
9. Trimipramine
Trimipramine is occasionally used to manage depression in adults and adolescents. Like other TCAs, it’s sometimes prescribed off-label for other health conditions. Some studies show trimipramine can manage insomnia, but it likely won’t be as effective as doxepin for this use.
Trimipramine is available as an oral capsule. You can take trimipramine once daily at bedtime or in smaller divided doses throughout the day.
List of tricyclic antidepressant side effects
One of the drawbacks of TCAs is that they can cause a lot of side effects. This is the main reason other antidepressants are usually tried first.
Check out the list below for examples of common TCA side effects:
Eye problems
Trouble peeing
Confusion
Dizziness
Weight gain
Drowsiness
TCAs may also cause more serious side effects, such as QT prolongation. If you’ve recently had a heart attack or other cardiac issue, your prescriber will likely avoid prescribing a TCA for you. Seizures are also possible, so you may be told to avoid TCAs if you have epilepsy.
Like all antidepressants, TCAs also carry a boxed warning — the FDA’s most serious medication warning — about the risk of having suicidal thoughts or self-harming. These risks are more common in people under 25.
Taking too much of a TCA can be especially dangerous, even more than with other antidepressants. That’s because an overdose can cause certain heart and brain complications. If you or a loved one take too much of a TCA, contact Poison Control right away online or at 1-800-222-1222. Seek emergency care immediately if someone is unconscious, has trouble breathing, or experiences a seizure.
Good to know: TCAs can cause several drug interactions, too. It’s important to ensure that your pharmacist and prescriber have a full list of the prescription medications, over-the-counter products, and dietary supplements that you take. This can help them decide if it’s safe for you to take a TCA.
Frequently asked questions
Choosing an antidepressant can be tricky. It typically depends on factors such as convenience, your medical background, and personal preferences. However, if you have insomnia, your prescriber may recommend doxepin or amitriptyline specifically.
Desipramine, nortriptyline, and protriptyline typically have less side effects than other TCAs. This is related to their chemical structure; they each have a secondary amine structure attached. This means they have more of an impact on norepinephrine than serotonin.
Selective serotonin reuptake inhibitors (SSRIs) and TCAs are both effective treatment options for depression. But SSRIs are generally first-choice medications because they have less side effects than TCAs. TCAs could still be an option when other medications don’t help your symptoms. However, adults ages 65 and older are more sensitive to TCA side effects and should be extra cautious with their use. The same goes for kids.
The bottom line
Amitriptyline, doxepin (Silenor, Zonalon, Prudoxin), and amoxapine are a few examples of tricyclic antidepressants (TCAs). They treat a variety of health conditions, such as depression, anxiety, and insomnia. But, because of their side effects, they’re usually not go-to medications. They’re typically only prescribed when other antidepressants aren’t effective. Reach out to your healthcare professional with any questions about TCAs.
Why trust our experts?
For additional resources or to connect with mental health services in your area, call SAMHSA’s National Helpline at 1-800-662-4357. For immediate assistance, call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.
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