Amitriptyline Side Effects: Common And Rare Risks

Last Updated: July 5, 2021

Authored by Sharon Levy, MD, MPH

Reviewed by Michael Espelin APRN

Amitriptyline, marketed as Elavil, is a tricyclic antidepressant (TCA) medication. TCAs were the dominant class of antidepressant drugs on the market until the 1980s-1990s but were quickly supplanted by a newer generation of drugs. The reasons behind their loss of popularity derived mainly from their poor tolerability due to a wide spectrum of Amitriptyline adverse effects, the difficulty of their use, and the high risk of lethality in overdose. Regardless, Amitriptyline is among the nine TCAs that are available on the U.S. market today, but due to its tendency to exhibit serious side effects, it is no longer used as a first-line drug for the treatment of depression. Today, Amitriptyline along with other TCAs is reserved for the treatment of depression that is unresponsive to more commonly used antidepressants. Also, alternative, non-FDA approved uses of Amitriptyline include management of Neuropathic pain of diabetes, fibromyalgia, and postherpetic neuralgia; Prevention of migraine headaches; Treatment of anxiety and PTSD; as well as Management of Inflammatory Bowel Disease (IBD) and Cystitis.  This article endeavors to discuss those Amitriptyline side effects, warnings, and precautions that individuals should be aware of before and during their treatment with Amitriptyline.

What Are Amitriptyline Side Effects?

As mentioned above, Amitriptyline is a Tricyclic Antidepressant (TCA) that primarily works by inhibiting the reuptake of Serotonin and Norepinephrine. In addition, it also has potent effects on alpha-adrenergic, histamine (H1), and muscarinic (M1) receptors within the central nervous system.

The Most Frequently Encountered Amitriptyline Side Effects Are Primarily Related to Its Anticholinergic/Antimuscarinic and Anti-Histaminergic Effects. These Include:

  • Headache and Dizziness
  • Drowsiness and Somnolence
  • Xerostomia/Dry mouth
  • Nausea and vomiting
  • Gastrointestinal upset
  • Constipation
  • Difficulty urinating
  • Weight gain
  • Changes in sexual drive or performance

In addition to the aforementioned Amitriptyline adverse effects, there can be numerous others. Below Are Offered Some of These Side Effects of Amitriptyline Broken Down by Body System and in the Order of Increasing Severity.

  • Cardiovascular: Palpitation, Tachycardia, Orthostatic Hypotension, Syncope, Arrhythmias and non-specific ECG changes, Stroke, Heart Attack
  • CNS: tinnitus, nightmares, restlessness, insomnia, anxiety, excitement, difficulty with concentration, acral paresthesias, tingling, and numbness, peripheral neuropathy,  confusion, delirium, delusion, hallucinations, dose-dependent seizures, coma
  • Neuromuscular: weakness, fatigue, dysarthria, involuntary movements, tremors, ataxia, incoordination
  • Ocular: mydriasis, blurred vision, increased intraocular pressure, disturbance of visual accommodation.
  • Gastrointestinal: dilation of urinary tracts, the elevation of hepatic enzymes and hepatitis, paralytic ileus
  • Allergic: skin rash, urticaria, photosensitivity, angioedema
  • Hematologic: rarely bone marrow suppression with pancytopenia
  • Endocrine: Testicular swelling and gynecomastia in males, galactorrhea and breast enlargement in females, decreased libido and impotence
  • Other: increase in appetite and weight gain, increased perspiration, hyperpyrexia

As always, there can always be other adverse reactions than the ones listed above as side effects of Amitriptyline can be idiosyncratic, as previously mentioned. Therefore it is important that patients seek medical help from a doctor if they experience any of the aforementioned Amitriptyline adverse effects.

Amitriptyline side effects.

Factors That Impact Side Effect Emergence

Drug side effects are also known as Adverse Drug Reactions (ADRs). ADRs are defined as undesirable effects, reasonably associated with the use of a drug that may occur as a part of the pharmacological action of a drug or may be unpredictable/idiosyncratic in their occurrence (Edwards and Aronson, 2000). It is ubiquitously accepted that ADRs are multifactorial in origin, being affected by various genetic and environmental factors. Below are offered some of the factors that could affect the emergence of the side effect of Amitriptyline or any other medication:

  • Age: The hepatic and renal function gradually decreases with age. As such, older individuals are less able to metabolize and excrete many drugs, causing them to stay in an older person’s body for much longer, prolonging their effects and increasing the risk of ADRs. Furthermore, older individuals are statistically more prone to suffer from many health problems for which they take multiple medications, also known as
  • Polypharmacy. This also increases the probability of adverse drug-to-drug interactions, one of the important sources of ADRs, that may even result in overdose.
  • Gender: Differences in body weight, body composition, gastrointestinal tract factors, liver metabolism, and renal function between males and females can affect the way in which the body absorbs, distributes, metabolizes, and eliminates drugs. All of these pharmacokinetic and pharmacodynamic factors can produce variability in the emergence of ADRs.
  • Kidney Disease: Renal function is important for the excretion of drugs and their metabolites. Any disease which compromises renal function can potentially prevent the elimination of drugs and their metabolites, increasing the possibility of ADR emergence.
  • Allergy: Hypersensitivity reactions are also one of the factors that can impact the emergence of ADRs.
  • Body Fat Distribution: Amitriptyline is a highly fat-soluble drug and individuals with large amounts of fat tissue may accumulate and store this drug in adipose tissues, preventing its rapid clearance. This can prolong the side effects of Amitriptyline.
  • Alcohol consumption: Alcohol affects the metabolism of many drugs and is one of the important factors that promote the development of ADRs. Chronic alcohol consumption can have negative effects on the liver, further affecting drug metabolism and the emergence of ADRs.
  • Race: Genetic polymorphisms in genes that govern drug-metabolizing enzymes, transporters, and receptors all impact emergence of ADRs.

These are just some of the numerous factors that can affect the emergence of drug-related, and specifically Amitriptyline side effects. However, more complicated factors such as dose, drug formulation, route of administration, and drug-to-drug interactions due to polypharmacy all play important roles. As such, it is important to consult a medical doctor for information about specific risk factors that one may have that predisposes them to the emergence of various ADRs or specifically, the side effects of Amitriptyline.

Sexual Dysfunction as a Side Effect of Amitriptyline

Sexual dysfunction is among the commonly reported Amitriptyline side effects. The sexual act is very complex, involving emotional and psychological aspects. It is comprised of five successive stages: Desire, Excitement, Plateau, Orgasm, and Resolution. Each of which is governed by a complex interaction between neurotransmitters, hormones, and peptides. It is assumed that antidepressants, by altering the levels of neurotransmitters, impact the various stages of the sexual response cycle and cause various types of dysfunctions. To pinpoint the prevalence of antidepressant-associated sexual dysfunction is quite difficult due to variability between studies, and underreporting as well as lack of discussion and assessment in the past. However, it is purported that around 40% of individuals taking antidepressants will develop some type of symptoms related to sexual dysfunction. With regard to Amitriptyline, it seems to have a lesser propensity for causing sexual dysfunction, at around ~30%, when compared to newer drugs used for depression such as SSRIs and SNRIs.

What exactly are the symptoms of sexual dysfunction? These can include dysfunction in any of the five aforementioned stages of the sexual response cycle. However, the Most Frequently Reported Symptoms Include:

  • Men: Decreased libido, Delayed ejaculation, Erectile dysfunction
  • Women: Breast enlargement, Decreased orgasm

Furthermore, a six-fold disparity exists between the emergence of sexual dysfunction in men when compared to women.

Coping Strategies: Managing Amitriptyline Sexual Side Effects

Managing the sexual side effects of Amitriptyline is very important, as it can be a source of distress to the patient, impacting their social life, self-esteem, and most importantly adherence to antidepressant therapy. The following approaches can be taken to cope with the aforementioned symptoms of sexual dysfunction:

  • The “Wait and See” approach can be used in a small subset of patients. This approach rests upon the assumption that the body needs time to adapt to antidepressants, and once adaptation has occurred the sexual dysfunction will spontaneously remit.
  • If the sexual dysfunction is thought to be dose-related, then the dose of the antidepressant can be lowered to the minimum effective dose. However, this has to be carefully balanced with the risk that a dose-reduction will have on an individual’s mental health, and as such is best done under the supervision of a medical doctor.
  • Switching to another medication with less risk for sexual dysfunction is also another option.
  • Adding an adjunct medication to treat the antidepressant-associated sexual dysfunction is also an option. However, with polypharmacy, there is a risk of developing further ADRs associated with the added medications which can themselves be more intolerable than the sexual dysfunction.
  • A more risky option is a “drug holiday” in which the antidepressant can be omitted prior to planned sexual intercourse.

It is important to remember that managing antidepressant-associated sexual dysfunction should not compromise the mental health and wellbeing of an individual. Whatsmore untreated depression itself can cause worse sexual dysfunction. Thus, before taking any steps, it is important to seek information from a doctor to choose the best option that will help treat the associated sexual dysfunction.

High angle view of doctor writing prescription at table in clinic.

Amitriptyline Weight Gain

Alteration in weight can be caused by depression itself. Certain types of depression are characterized by an increased appetite with polyphagia whereas others as characterized by a decreased appetite and anorexia. On the other hand, Amitriptyline weight gain can occur with use, resulting from an increased appetite produced by an alteration of those neurotransmitters that are involved in the regulation of satiety. In others, however, Amitriptyline weight loss can be experienced. Therefore, it is important to identify the true cause of the weight alterations that one may be experiencing before making any changes.

Amitriptyline And Pregnancy & Breastfeeding

Information regarding Amitriptyline and pregnancy is lacking. Currently, Amitriptyline is classified as Category C medication, and it has been known to be excreted in breast milk. As such, there may be some associated risk to the fetus, but this risk is currently unquantified. Thus, the use of Amitriptyline in pregnancy and postpartum is warranted under the supervision of a medical professional and only when the potential benefits of its use outweigh the potential risk it may pose to the fetus or the breastfeeding infant. Therefore, it is important to provide a prescribing physician with information on whether you are pregnant or plan on becoming pregnant before taking Elavil.

Amitriptyline Warnings, Dangers, and Contraindications

The following Amitriptyline Warnings and precautions should be taken into account before beginning treatment with Elavil. These considerations are critical and may result in life-threatening complications if not adhered to.

  • In adolescents and young adults(<24), Elavil has rarely been shown to increase the risk of suicidal thoughts and behavior.
  • In individuals with a history of Bipolar disorders, past history of mania, or pharmacologically induced hypomania, Elavil can induce mania with rapid cycling.
  • Elavil should not be used if there is a history of arrhythmias, recent history of Acute Coronary Syndromes or Heart Failure, or if there is a history of QTc prolongation.
  • Elavil should not be used in conjunction with those medications that can prolong QT intervals and induce arrhythmias. These medications include but are not limited to terfenadine, sotalol, quinidine, procainamide, pimozide, pentamidine,  indapamide, ibutilide, disopyramide, cisapride, and astemizole.
  • Elavil should be used with caution in those individuals who have a past history of angle-closure glaucoma, urinary retention, and seizures. As its use may worsen these conditions.
  • It should also not be used in those individuals who are taking or have taken MAOIs in the last 2 weeks.
  • As this medication inhibits the reuptake of Serotonin, combination with other drugs that also increase levels of serotonin can lead to potentially life-threatening Serotonin Syndrome.

Although the aforementioned Amitriptyline Warnings and precautions are the ones that are most frequently encountered, it should be remembered that this is not an exhaustive list and there may be other warnings and precautions that are specifically applicable to a particular individual. As such, before beginning treatment, consider possible withdrawal symptoms of Elavil, all past and present medical conditions, all medications, and allergies should be disclosed to the prescribing physician.

Know Elavil Side Effects For Their Timely Management

Using Amitriptyline to treat depression has become uncommon. However, in those special circumstances, such as neuropathic pain or prophylaxis of migraine headaches, where it has to be used, and its side effects do emerge, dealing with them is very important to users and doctors alike. As uncomfortable adverse reactions are one of the major barriers to treatment adherence. Managing these side effects is not all that different from those steps listed above for the management of sexual dysfunction. After all, sexual dysfunction is an uncomfortable side effect of Elavil. Generally, watchful waiting is often a reasonable option, since our bodies adapt to Elavil over time with which adverse effects diminish. If ineffective, reducing or adjusting the dose are reasonable options. And lastly, switching to another antidepressant or adding another medication, but first consider Amitriptilyne drug interactions, to manage the uncomfortable side effects should be done. However, it is always important to remember that these decisions should be made under the guidance and supervision of a healthcare professional.

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Published on: February 7th, 2020

Updated on: July 5th, 2021

About Author

Sharon Levy, MD, MPH

After successful graduation from Boston University, MA, Sharon gained a Master’s degree in Public Health. Since then, Sharon devoted herself entirely to the medical niche. Sharon Levy is also a certified addiction recovery coach.

Medically Reviewed by

Michael Espelin APRN

8 years of nursing experience in wide variety of behavioral and addition settings that include adult inpatient and outpatient mental health services with substance use disorders, and geriatric long-term care and hospice care.  He has a particular interest in psychopharmacology, nutritional psychiatry, and alternative treatment options involving particular vitamins, dietary supplements, and administering auricular acupuncture.