Amitriptyline for sleep: a common off-label use

Amitriptyline, also sold under the brand name Elavil, is a tricyclic antidepressant (TCA) drug developed in the 1960s. It works by stopping nerve cells from reabsorbing norepinephrine and serotonin, two neurotransmitters. This leaves more of them available in the brain.

In recent years, healthcare providers have favored selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for treating many types of depression. But amitriptyline is still one of the 100 most prescribed medications in the United States (AHRQ, n.d.).

While the FDA approves amitriptyline for the treatment of depression, it has other off-label uses as well, including chronic pain management and the treatment of insomnia (Pagel, 2001).

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Getting a good night's sleep isn't so easy for many people. Insomnia afflicts an estimated 10–30% of people worldwide. It crosses all socio-economic barriers. It appears to be more likely in people over the age of 36 and is somewhat more common in women than men (Bhaskar, 2016). Because many people with sleep problems never seek treatment, the number could be much higher (Léger, 2008). 

Mental health issues and sleep disorders are all too familiar bedfellows. Insomnia is one of the most common symptoms of depression. Research estimates that over 90% of patients diagnosed with clinical depression will have insomnia (Khurshid, 2018). 

It goes both ways, as well. An analysis of thirty years' worth of data found people with insomnia and no depression were twice as likely to have depression later in life than those without sleep issues (Baglioni, 2011).

For patients being treated for depression that have insomnia, drugs can be a double-edged sword. Just as depression goes hand-in-hand with sleep issues, most medications for it can affect sleep as well. 

One of the most common side effects of SSRIs is insomnia. Sometimes this is short-term and goes away after a few weeks. Some patients may supplement their prescription with a sleeping pill such as zolpidem (brand name Ambien) or another hypnotic drug. 

If a patient is already having trouble sleeping, they may be better with a different antidepressant entirely. While amitriptyline does carry a greater risk of side effects, it could be a preferable treatment option for combined depression and insomnia patients.

Healthcare providers often prescribe amitriptyline to fibromyalgia patients with insomnia. Studies found it more effective than SNRIs duloxetine (brand name Cymbalta) and milnacipran (brand name Savella) for sleep management. Researchers suspect this is because SNRIs do not have the antihistamine properties of amitriptyline. For patients with sleep and pain disorders, it can potentially treat both (Roizenblatt, 2011).

There have been no clinical trials to date studying amitriptyline as a sleep aid for patients who have chronic insomnia without depression, neuropathic pain, or other conditions. But over the decades, observing patients' experiences has given healthcare providers confidence in prescribing amitriptyline for it. It remains one of the most commonly prescribed medications for insomnia, even for patients without depression (Nazarian, 2014). Because it is not habit-forming, many healthcare providers find it a better solution for patients with substance abuse issues than benzodiazepines or non-benzodiazepines (Z drugs).

Amitriptyline is generally well-tolerated in low doses. The most common side effects reported by amitriptyline users include (MedlinePlus, 2017):

• Drowsiness/sleepiness

• Dizziness

• Nausea or vomiting

• Headaches

• Dry mouth

• Difficulty urinating

• Constipation

• Blurred vision

• Confusion

• Changes in libido

• Nightmares

Because it can make you drowsy, you should not drive a car or operate machinery when first taking amitriptyline until you know its effect on you. 

Amitriptyline, like nearly all antidepressants, can cause appetite changes or weight gain in some patients. A large study found such effects from amitriptyline to be significantly lower than those from SSRIs (Blumenthal, 2014).

Serious side effects can include (MedlinePlus, 2017):

• Heart attack

• Stroke

• Irregular heartbeat

• Chest pain

• Numbness in the arms or legs

• Slurred or difficult speech

• Skin rash or hives

• Swelling of the face or tongue

• Yellowing of the skin or eyes

• Orthostatic hypotension (sudden drop in blood pressure when you stand up)

• Spasms in the jaw, neck, or back

• Fainting

• Seizures

• Hallucinations

If any of these occur, contact your healthcare provider immediately or call 911. They could be signs of an allergic reaction or overdose.

Do not take more than your prescribed dose of any medication. While rare, there are anecdotes of patients misusing large amounts to achieve euphoric feelings (Sullivan, 2014). However, amitriptyline overdose can result in seizures, coma, and death (DailyMed, 2016). If you believe you have overdosed, call 911 or the poison control helpline at 1-800-222-1222.

While some adverse effects may tempt you to stop taking this medication, it's essential to consult with your healthcare provider before doing so. Some people can experience withdrawal symptoms, including nausea, fatigue, and headaches, when abruptly stopping amitriptyline (DailyMed, 2016). Your prescriber may prefer to lower your dose gradually. 

Tell your healthcare provider about all medications—prescription and nonprescription—including any herbal supplements you are already taking. Amitriptyline can cause potentially dangerous drug interactions. These include but are not limited to (MedlinePlus, 2017):

• Monoamine oxidase inhibitors (MAOIs). Do not take amitriptyline if you are taking or have recently taken MAOIs. At least 14 days should pass between the end of MAOI therapy and starting amitriptyline, or vice-versa. 

• Selective serotonin reuptake inhibitors (SSRIs) or any other antidepressants

• Sedatives, sleeping pills, or tranquilizers

• Thyroid medications

• Cisapride (brand name Propulsid) for nighttime heartburn

• Guanethidine (brand name Ismelin) for high blood pressure

• Quinidine (brand name Quinidex) for irregular heartbeats or malaria

Combining medications or supplements that affect serotonin levels can cause serotonin syndrome, a potentially serious condition. Serotonin syndrome symptoms include increased heart rate, shivering, abnormal sweating, spasms, and twitching. Severe cases can result in seizures, muscle breakdown, high blood acid, kidney failure, and death (Boyer, 2005).

Your healthcare provider will want to know if any of the following conditions apply to you, as they may increase the risk of some side effects (MedlinePlus, 2017):

• If you have a heart problem or have suffered a heart attack recently 

• If you have any liver or kidney disease

• If you are a heavy drinker of alcohol

• If you have diabetes

• If you have had glaucoma

• If you have ever had a seizure

Tell your prescriber if you are pregnant, could become pregnant, or are nursing before taking amitriptyline. While many studies have found no ill effects, there have been case reports of infants being sedated by amitriptyline in breast milk (LactMed, 2020).

Do not consume alcohol while taking amitriptyline. Amitriptyline may exaggerate the effects of alcohol (DailyMed, 2016). 

Patients with bipolar disorder should not take amitriptyline. Your healthcare provider may wish to screen you for risks associated with bipolar disorder before prescribing it. 

Amitriptyline is available in doses from 10–150 mg. Patients taking amitriptyline for insomnia alone might take one low dose at bedtime. Those treating insomnia with other conditions such as depression or chronic pain might take smaller doses throughout the day with a higher dose at bedtime.

Generic amitriptyline is inexpensive, with prices ranging from $4 to $25 for a 30-day supply, depending on the dose (GoodRx, n.d.). 

Keep amitriptyline out of sight and reach of children. Do not store in areas with excess heat or moisture, such as a bathroom.