Possible Long-Term Side Effects of Amitriptyline

For more than 50 years, amitriptyline has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of depression 12. It is also sometimes prescribed "off-label" for other conditions, such as chronic pain and migraines 127.

Amitriptyline belongs to a class of medications known as tricyclic antidepressants (TCAs) 12. Like all TCAs, amitriptyline increases the levels of two chemicals — serotonin and norepinephrine — around nerves in the brain and other areas of the body 12.

Amitriptyline is a generally safe medication 12. It may initially produce a number of side effects, many of which improve or disappear with continued use. But some potential side effects, such as discontinuation syndrome, weight gain and type 2 diabetes mellitus (T2DM), occur primarily during long-term use.

Discontinuation Syndrome

When TCAs are used on a regular basis for at least 6 to 8 weeks, discontinuation syndrome may occur if they are abruptly stopped or if the dose is suddenly decreased. This syndrome includes a number of possible symptoms, including:

• Headaches
• Lethargy
• Flu-like symptoms
• Abdominal pain
• Nausea
• Vomiting
• Diarrhea
• Insomnia
• Nightmares
• Balance problems
• Restlessness
• Parkinson’s disease-like movements
• Dizziness
• Lightheadedness
• Tremor
• Agitation
• Anxiety
• Low mood

Although disturbing, discontinuation syndrome symptoms are usually mild. They generally begin within 3 days of stopping or suddenly decreasing a TCA and last for up to 2 weeks. Slowly reducing the dose of amitriptyline over at least 2 to 4 weeks will reduce the likelihood of discontinuation syndrome 12.

Weight Gain

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A number of antidepressants can lead to changes in weight during long-term use. In a systematic review published in the “Journal of Clinical Psychiatry” in October 2010, amitriptyline was noted to be one of the antidepressants associated with weight gain 124.

The average increase in weight after 3 months of amitriptyline treatment was approximately 5 pounds 12. Of note, this was an average value, so some people gained more than this. If weight gain cannot be controlled by diet or activity changes, switching to an antidepressant that does not promote weight gain may be considered.

Type 2 Diabetes Mellitus

Several antidepressants, including amitriptyline, may increase the likelihood of developing T2DM with long-term use 12. In a 2018 study published in the British Journal of Clinical Pharmacology, use of amitriptyline was associated with a 30-percent increase in the likelihood of developing T2DM 12. It's currently unclear whether this increased risk is a direct effect of amitriptyline itself or a consequence of weight gain from the medication 126.

Other Side Effects

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Amitriptyline has a number of other potential side effects, which usually appear shortly after beginning treatment and improve or resolve over time 127. The most common of these side effects are 127:

• Tremors
• Dizziness
• Headache
• Dry mouth
• Nausea
• Constipation

Less common — but more serious — side effects include:

• Heart rhythm disturbances
• Low blood pressure upon standing
• Low blood sodium
• Increased pressure in the eye
• Decreased production of blood cells
• Increased risk of suicide in children, adolescents and young adults up to the age of 24

Warnings and Precautions

Amitriptyline interacts with a number of other medications, so contact your doctor before starting all new medications 12. Notify your doctor if you develop any new symptoms while taking amitriptyline 12.

Seek prompt medical care if you experience significant dizziness or lightheadedness, persistent or recurrent heart palpitations, shortness of breath, weakness, confusion, blurred vision or suicidal thoughts.

Reviewed and revised by Mary D. Daley, M.D.