Reviewed by Kristin Hall, FNP
Written by Our Editorial Team
An estimated 21 million American adults suffer from depression every year -- about 8.4 percent of the entire US adult population. Many of these people are prescribed antidepressants to treat their symptoms and assist with the recovery process.
Amitriptyline is a medication for depression. It belongs to an older class of medications referred to as tricyclic antidepressants. Although it’s rarely used as a first-line treatment for depression, you may be prescribed amitriptyline if other forms of antidepressant therapy don’t work for you.
Amitriptyline can cause side effects. In fact, as an older type of antidepressant, amitriptyline has a more considerable risk of causing side effects than modern antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
Below, we’ve explained how amitriptyline works, as well as the side effects you may experience if you’re prescribed this medication.
We’ve also discussed amitriptyline drug interactions, potential safety risks and other issues you should be aware of before using amitriptyline to treat depression or any other condition.
What is amitriptyline used for? Amitriptyline is a tricyclic antidepressant, or TCA. It’s an FDA-approved medication for treating major depressive disorder (MDD). It’s also used off-label to treat a variety of common medical conditions, such as chronic pain, anxiety, insomnia and irritable bowel syndrome.
Amitriptyline works by increasing levels of the neurotransmitters serotonin and norepinephrine, which are involved in regulating certain aspects of your moods, thoughts and feelings.
Experts theorize that by increasing the levels of these neurotransmitters in the brain and body, medications like amitriptyline can help to treat mood disorders such as depression.
Like other antidepressants, the effects of amitriptyline aren’t immediate. For most people, it can take two to four weeks before amitriptyline produces noticeable improvements in the symptoms of depression.
Amitriptyline is one of many medications for treating depression. Our full list of antidepressants provides more information about how it and similar tricyclic antidepressants function.
Like all antidepressants, amitriptyline can cause side effects. In fact, experts regard amitriptyline as having a considerable side effect profile — one reason it’s no longer widely used as a first-line treatment for depression.
Common side effects of amitriptyline include changes in body weight, dizziness, headaches, dry mouth, somnolence (drowsiness) and gastrointestinal issues. These may improve over time as your body adjusts to the effects of the medication.
Changes in body weight, including weight gain, are common effects of tricyclic antidepressants such as amitriptyline. While using amitriptyline, you may develop a stronger appetite than usual and make changes in your eating habits, resulting in weight gain.
These effects may occur due to amitriptyline’s effects on histamine (H1) receptors. It’s best to talk to your healthcare provider if you notice a significant change in your appetite, eating habits and/or weight after starting treatment with amitriptyline.
Dizziness is a common side effect of amitriptyline. Feelings of dizziness and unsteadiness are known side effects of many antidepressants and are likely related to the effects of these drugs on your brain.
You may feel dizzy shortly after taking amitriptyline. If you have persistent or severe dizziness, it’s important to inform your healthcare provider.
Headaches are a frequently reported side effect of amitriptyline. Like dizziness, headaches are common with antidepressants and may occur as a result of the effects of this type of medication on your brain. Headaches related to amitriptyline use may improve over time.
Interestingly, amitriptyline and other antidepressants are occasionally prescribed off-label to stop migraine headaches.
If you develop a headache after your dose of amitriptyline, try to rest and take in plenty of fluids to keep yourself hydrated. Over-the-counter pain relief drugs such as acetaminophen (Tylenol®) may help to provide relief.
Amitriptyline can cause xerostomia, or dry mouth. This is a common side effect of medications used in the treatment of depression. It’s caused by the effects of these drugs on the function of your salivary glands (the glands that produce saliva) and on your perception of oral dryness.
If you develop a dry mouth while using amitriptyline, try increasing your fluid intake, chewing on sugar-free gum or sucking sugar-free candy to stimulate saliva production. Limiting your intake of caffeine, alcohol and other substances that can dry out your mouth may also help.
If this side effect persists or is severe, talk to your healthcare provider. They may suggest using a saliva substitute lozenge, spray or gel to relieve your symptoms.
Somnolence, or sleepiness, is one of the most common side effects of amitriptyline. You may feel more tired than usual after taking amitriptyline and experience symptoms such as daytime sleepiness.
In fact, because of its sedative effects, amitriptyline is sometimes prescribed off-label as a sleep aid for people with insomnia or nighttime anxiety.
If you’re prescribed amitriptyline, do not drive a car or operate any machinery that could cause injury until you’re familiar with how this medication makes you feel.
Amitriptyline may cause or aggravate gastrointestinal health issues, such as nausea, vomiting and constipation. You may feel like you have an upset stomach after using your medication or eating a meal.
If you experience persistent nausea, vomiting or constipation after starting amitriptyline, talk to your healthcare provider before using any over-the-counter or prescription medications to treat these symptoms.
In addition to the common side effects listed above, amitriptyline may cause other side effects, including some that may require medical attention. Your risk of certain adverse events may be higher if you have other medical conditions, including certain forms of mental illness.
More severe adverse effects of amitriptyline include:
Confusion and/or delirium
Orthostatic hypotension (low blood pressure after standing up)
Tachycardia (fast heart rate) or arrhythmia (irregular heartbeat)
Acute angle-closure glaucoma (sudden onset eye pain)
Reduced seizure threshold
Hyperhidrosis (excessive sweating)
Decreased interest in sexual intercourse
Muscle spasms that affect your jaw, back and neck
Slowed speech and/or difficulty speaking
Increased risk of bone injuries
Numbness or weakness in your limbs
Severe chest pain
Although uncommon, amitriptyline may induce mania in people with bipolar disorder or a family history of psychiatric disorders that involve manic symptoms.
Contact your healthcare provider as soon as you can if you experience any severe side effects from amitriptyline.
Amitriptyline is generally safe when used as directed. However, it can interact with several other widely used medications, including some used to treat depression and other mental illnesses.
Like other antidepressants, amitriptyline can cause serotonin syndrome -- a dangerous increase in serotonin levels -- when used with other medications that increase serotonin.
Symptoms of serotonin syndrome include irregular heart rhythms, high blood pressure, unusual or excessive sweating, dilated pupils, muscle stiffness, elevated body temperature, hyperactive bowel sounds, increased alertness and agitation.
When severe, serotonin syndrome can potentially cause seizures, respiratory failure, coma and even death.
To prevent serotonin syndrome, amitriptyline should not be used with other medications that can increase serotonin levels, including other antidepressants and some medications for Parkinson's disease.
It’s especially important to take care when using amitriptyline if you’ve recently used monoamine oxidase inhibitors (MAOIs) — an older class of antidepressants that can cause interactions up to 14 days after their use is discontinued.
Amitriptyline should not be taken with medications that increase QTc (the interval between your heart contracting and relaxing). Many antiarrhythmic medications, antihistamines, beta-blockers, diuretics and other medications can affect your QT interval.
Amitriptyline should also not be used if you have an arrhythmia (heart rate or rhythm issue), any history of QTc prolongation, heart failure or have recently suffered a myocardial infarction (heart attack) or any other medical issue that causes significant cardiovascular symptoms.
To avoid interactions and safety issues, make sure to inform your healthcare provider about any medications you currently use or have recently used, as well as your full medical history, before using amitriptyline.
Amitriptyline may cause your skin to become more sensitive to sunlight, meaning you may get a sunburn faster when you’re exposed to bright, direct sunlight.
Try to limit the amount of time you spend in bright, direct sunlight while using amitriptyline. Wear protective clothing that covers as much of your skin as possible and make sure to apply an SPF 30+, broad-spectrum sunscreen on sunny days.
Like other antidepressants, amitriptyline should not be stopped abruptly. If you suddenly stop using Amitriptyline, you may experience withdrawal symptoms such as nausea, reduced levels of energy and nausea.
These flu-like symptoms are referred to as antidepressant discontinuation syndrome. They can potentially occur with amitriptyline and other medicines for major depression.
If you’re prescribed amitriptyline to treat depression, it’s important to continue using it after you start to feel better. Stopping treatment early may cause your depression to come back.
If you’d like to stop using amitriptyline, your healthcare provider will help you to gradually taper your dosage to reduce your risk of experiencing withdrawal symptoms.
Like other antidepressants, amitriptyline is associated with an increased risk of suicidal ideation and behavior in children, teenagers and adults under 25 years of age. As such, this medication carries a “black box” warning from the FDA.
If you’re under 25 years of age, using amitriptyline or other antidepressants may cause changes in your mental health and an increased risk of suicidality. Your mental health provider may ask to see you frequently for follow-up visits while you’re using this medication.
Although amitriptyline is generally effective at treating depression, it’s rarely used as a first-line treatment due to its significant risk of causing side effects.
Because of this, your healthcare provider will likely recommend a more modern antidepressant medication, such as an SSRI or serotonin-norepinephrine reuptake inhibitor (SNRI) before you use a tricyclic antidepressant such as amitriptyline.
Your healthcare provider may also recommend using a newer antidepressant if you’re prone to side effects or experience an allergic reaction to amitriptyline.
For most people, depression can be managed with SSRIs or SNRIs -- modern antidepressants that work by increasing your serotonin levels. These medications are more selective than older drugs such as amitriptyline and have a lower risk of causing dangerous side effects.
We offer several SSRIs and SNRIs online, including fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), escitalopram (Lexapro®), duloxetine (Cymbalta®) and venlafaxine (Effexor®).
We also offer bupropion (Wellbutrin®), an atypical antidepressant that’s often used when other antidepressant drugs cause unwanted sexual side effects.
Psychotherapy, or talk therapy, often helps to reduce the severity of depression symptoms. In fact, many people with depression benefit from taking part in psychotherapy while they’re also using medication.
Several different forms of talk therapy are commonly used to treat clinical depression, such as cognitive behavioral therapy (CBT) and interpersonal therapy (IPT). Our guide to the different types of therapy covers many common techniques used in depression treatment.
We offer therapy online, allowing you to connect with a licensed counselor and access help from the privacy of your home.
For many people, the symptoms of depression can become less severe and overwhelming with simple habits and lifestyle changes.
Healthy habits for treating depression include getting at least 30 minutes of daily exercise, going to sleep and waking up on a consistent schedule, eating a balanced diet and spending time with close friends and family members.
Many people with depression also benefit from avoiding alcohol, cigarettes and illicit drugs that can interfere with recovery.
Our guide to self-help strategies for depression goes into more detail about habits and lifestyle changes that you can make to improve your wellbeing and make progress as you recover from depression.
Although amitriptyline isn’t commonly used as a first-line treatment for depression, your mental health provider may suggest using it if other medications aren’t fully effective at controlling your symptoms.
If you experience side effects from amitriptyline that are severe or persistent, it’s best to let your healthcare provider know. They may adjust your dosage of amitriptyline or suggest switching to a different medication.
Interested in learning more about treating depression? Our guide to depression treatments goes into more detail about your options, from antidepressants to psychotherapy, lifestyle changes and more.
If you’re feeling depressed and want to seek expert help right away, you can also connect with a licensed psychiatry provider from home using our online psychiatry service.
Kristin Hall is a board-certified Family Nurse Practitioner with decades of experience in clinical practice and leadership.
She has an extensive background in Family Medicine as both a front-line healthcare provider and clinical leader through her work as a primary care provider, retail health clinician and as Principal Investigator with the NIH.
Certified through the American Nurses Credentialing Center, she brings her expertise in Family Medicine into your home by helping people improve their health and actively participate in their own healthcare.
Kristin is a St. Louis native and earned her master’s degree in Nursing from St. Louis University, and is also a member of the American Academy of Nurse Practitioners. You can find Kristin on LinkedIn for more information.