Amitriptyline for Depression, Anxiety, and More

If your healthcare provider has prescribed amitriptyline, it’s important to know about possible drug interactions.

Amitriptyline is a prescription oral antidepressant medication that is also sometimes used off-label (for a different purpose outside of its FDA approval) for treating a variety of conditions including anxiety, obsessive-compulsive disorder, and prevention of neuropathic pain. 

This article looks at amitriptyline and why it may be prescribed. It also discusses precautions, dosage, warnings, and side effects.

What Is Amitriptyline Used For?

Amitriptyline is approved by the Food and Drug Administration (FDA) for treating symptoms of depression. According to the manufacturer, amitriptyline is more effective for the treatment of endogenous depression (that which is caused by a genetic or biological factor) than for depression caused by external factors.

This medication is meant to be taken every day for the prevention of depressive symptoms. People usually have to take it for four to six weeks before seeing improvement.

Symptoms of depression can include:

• Sadness or hopelessness
• Loss of interest in activities
• Lack of motivation
• Crying
• Withdrawal from others
• Irritability
• Excessive sleeping or insomnia
• Changes in appetite
• Thinking about suicide
• Unexplained pain

Amitriptyline increases the action of norepinephrine and serotonin, neurotransmitters that play a role in modulating pain and mood. Specifically, amitriptyline prevents the termination of the action of these neurotransmitters by preventing their uptake into membrane receptors.

Amitriptyline is a first-line agent, which means this medication can be prescribed even if you have not tried any other treatments for depression or when it is used off-label.

Amitriptyline for Anxiety

Amitriptyline is sometimes prescribed off-label for generalized anxiety disorder. This means it isn't approved by the FDA for this purpose, but healthcare providers can still prescribe it if they think it might be helpful.

Amitriptyline isn't usually a first-line treatment for anxiety. Your healthcare provider will probably want to try other medications before prescribing amitriptyline.  

Other Off-Label Uses

Amitriptyline is commonly prescribed off-label for several other uses, such as chronic conditions that require consistent, long-term management and palliative care.

Conditions that are often treated with amitriptyline include:

• Pain associated with neuropathy, fibromyalgia, postherpetic neuralgia, or central nervous system disorders
• Migraine prevention
• Insomnia
• Panic attacks
• Obsessive-compulsive disorder
• Post-traumatic stress disorder (PTSD)
• Bulimia
• Sialorrhea (excessive drooling)

As with the treatment of depression, amitriptyline is not expected to alleviate any of these conditions immediately when it is used off label. It may take weeks for symptoms to begin to improve.

What to Know Before Taking Amitriptyline

Amitriptyline drug interactions, as well as certain medical conditions, need to be taken into account when considering treatment with this drug.

Precautions and Contraindications

Amitriptyline can cause sleepiness. As you are adjusting to the medication, it's important that you avoid driving or using dangerous equipment until you can assess the effect it is having on you during the day.

Amitriptyline is not FDA-approved for children under age 12.

Amitriptyline should not be used if you:

• Have had an adverse reaction to it in the past
• Are recovering from a heart attack
• Have cardiac arrhythmia or QT prolongation on your electrocardiogram (EKG)
• Have bipolar disorder (the drug increases the risk of manic episodes)

Your healthcare provider will weigh the pros and cons of this medication before prescribing it to you if you:

• Are pregnant, plan to be pregnant, or are nursing
• Have wide-angle glaucoma
• Have a history of suicidal ideation or a suicide attempt, as amitriptyline has been associated with a risk of suicide
• Have schizophrenia (due to the potential effect of worsening symptoms)
• Have recurrent seizures
• Are at risk of a heart attack or stroke

Other Tricyclic Antidepressants

Due to its molecular structure, amitriptyline is described as a tricyclic antidepressant.

Some other tricyclic antidepressants include:

• Nortriptyline
• Imipramine
• Desipramine
• Doxepin
• Amoxapine

Other Antidepressants

Other antidepressant classes include monoamine oxidase inhibitors (MAOIs), such as selegiline and rasagiline, and selective serotonin reuptake inhibitors (SSRIs), such as sertraline, fluoxetine, and paroxetine.

Warnings and Interactions

Withdrawal from this drug can cause nausea, headaches, irritability, and sleep disturbances. Rarely, mania can occur after abruptly stopping this medication. If you are going to stop taking amitriptyline, it's important that you discuss a tapering schedule with your healthcare provider.

Amitriptyline can interact with a number of prescription medications. This medication is especially dangerous when combined with other antidepressants, such as other tricyclic antidepressants or MAOIs. If you are replacing one antidepressant with another, your healthcare provider will give you detailed instructions regarding decreasing or stopping the medication you are already taking before you start the other.

Some common medications that interact with amitriptyline include medications that increase serotonin:

• Celexa (citalopram)
• Cymbalta (duloxetine)
• Prozac (fluoxetine)
• Zoloft (sertraline)

Opioid-based medications should also be avoided, such as:

• Ultram (tramadol)
• OxyContin (oxycodone)
• Vicodin (hydrocodone)
• Codeine
• Morphine
  

Dangerous interactions can occur with sedatives and muscle relaxants, such as:

• Flexeril (cyclobenzaprine)
• Desyrel (trazodone)
• Xanax (alprazolam)
• Cyclobenzaprine

Other common medications that interact with amitriptyline include:

• Lyrica (pregabalin)
  
• Synthroid (levothyroxine)
• Topamax (topiramate)
  

Alcohol and antihistamines like Benadryl have a depressant effect and shouldn't be consumed when taking amitriptyline. Combining the two may make side effects more severe.

When you are taking amitriptyline, it's also important that you tell your healthcare provider and pharmacist about any other medications you are taking to prevent interactions between medications. 

Dosage

Amitriptyline comes in tablet form and is available in doses of 10 milligrams (mg), 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg. For treatment of depression, the medication is usually started at a dose between 50 mg and 100 mg per day.

If necessary, your dose may be increased by 25 mg every three to seven days to a total of 150 mg per day.

The standard maintenance dose of amitriptyline for the treatment of depression is 75 mg per day, either once at bedtime, or divided into two doses per day.

Modifications

According to the package label, hospitalized patients may require 100 mg a day initially. This can be increased gradually to 200 mg or 300 mg per day if necessary.

Adolescents between the ages of 12 and 18 and elderly adults should start at a lower dose of approximately 30 mg per day, with a target dose of 60 mg per day.

If you have liver disease, your healthcare provider may prescribe a lower dose of amitriptyline for you.

Follow your prescriber's instructions and never alter your dose on your own.

Off-Label Dose

When used off-label, amitriptyline is started at a lower dose than when it is used as an antidepressant—typically at a dose of 10 mg or 20 mg per day. If needed, this dose can be slowly increased under the guidance of your healthcare provider.

The amitriptyline dosage for anxiety may also be modified in light of amitriptyline drug interactions.

Sometimes amitriptyline is used when you have depression and pain. In these situations, the dosing would follow the recommendations for treatment of depression, rather than treatment of pain.

How to Take and Store

Amitriptyline is taken by mouth, initially in divided doses, but can be taken once per day when the target dose is established. If you are taking your entire dose of amitriptyline at once, it should be at bedtime, and if you are taking it in divided doses, one of the doses should be taken at bedtime.

Amitriptyline should be stored in the original container at 68 to 77 degrees. If necessary, you can place your medication in a pillbox to help you manage your medication schedule.

Side Effects

Amitriptyline can cause side effects when it is used for the treatment of depression or for an off-label indication. Sometimes the side effects are temporary and may resolve after a few weeks, but you might continue to have side effects even after months of using it. Rarely, side effects emerge after months or even years of using this drug without side effects.

Some side effects are dose-related and might improve if your healthcare provider reduces your dose.

Common

Common side effects of amitriptyline include:

• Headaches
• Lightheadedness, dizziness, or orthostatic hypotension (low blood pressure when standing)
• Increased appetite and weight gain (the weight gain can be more than what you would expect from the increased appetite)
• Dry mouth or mouth sores
• Diminished sex drive or impotence
• Sleepiness or drowsiness

Using amitriptyline at night may alleviate sleepiness, but some people continue to feel drowsy during the day, even after a full night's sleep.

Severe

Amitriptyline may cause severe adverse effects. If you experience serious side effects, your healthcare provider will likely give you instructions to discontinue taking amitriptyline.

Severe side effects of amitriptyline include:

• Suicidal thinking, especially among adolescents
• Mood changes
• Sleep disturbances
• Anxiety
• Agitation
• Seizures
• Acute angle-closure glaucoma
• Increased risk of bleeding

Rare Side Effects

Amitriptyline has also been associated with severe side effects that occur very infrequently.

Rare side effects include:

• Allergic reaction: skin rash, swelling, and/or trouble breathing
• Neuroleptic malignant syndrome: fever, muscle rigidity, confusion, severe constipation, increased heart rate, and sweating

Summary

Amitriptyline is a prescription medication approved by the FDA for treating depression. It is also prescribed off-label to treat many other conditions, including anxiety and chronic pain.

Amitriptyline can cause drug interactions and side effects, some of them severe. Make sure you tell your healthcare provider about any other medications you are taking and keep them informed if you experience side effects like suicidal thoughts, seizures, or sleep disturbances.