Amitriptyline Withdrawal and How Long Does Elavil Stay in Your System

Last Updated: June 29, 2021

Authored by Sharon Levy, MD, MPH

Reviewed by Michael Espelin APRN

Amitriptyline, under the brand name Elavil, is a tricyclic antidepressant that has been approved for use in the United States since 1961 for the treatment of depression. Similar to other antidepressants, Amitriptyline withdrawal symptoms are quite common upon cessation of drug use. According to a study, 56 out of 100 users of antidepressant drugs, including Elavil, experience withdrawal symptoms after discontinuing the drug. Additionally, 46 of those 56 individuals reported that the withdrawal symptoms they have experienced are severe. While the severity of symptoms is not as bad compared to other drugs, they can still be discomforting. It is normal to ask: how long will this discomfort from Amitriptyline withdrawal last? 

To determine the duration of Elavil in one’s circulation, the Amitriptyline half-life must be understood, and the average half-life of Amitriptyline is 15 hours. In this article, information about Elavil’s mechanism of action, symptoms of Amitriptyline withdrawal, Amitriptyline half-life, including how long it stays in the blood, saliva, urine, and hair, the factors that influence how long it stays in the system, and tips on stopping Amitriptyline properly and safely will be provided.

Amitriptyline Mechanism of Action

In the brain, there are two hormones that are responsible for regulating mood and communication between nerves: norepinephrine and serotonin. When the levels of these two are low, depressive symptoms occur because there is an imbalance of these chemicals or hormones. This is the reason why Elavil is used to manage these symptoms. Similar to other TCAs, this antidepressant increases and balances the levels of these two hormones. But, how does this happen? Amitriptyline inhibits the reuptake of norepinephrine and serotonin by the presynaptic neuronal membrane in the central nervous system, thereby increasing the synaptic concentrations of these two.

Aside from its antidepressant properties, Amitriptyline modulates the histamine system in the brain and inhibits sodium, calcium, and potassium channels. Because of this ability, this drug is effective for the treatment of other medical health conditions such as anxiety, migraines, neuropathic pain, and insomnia.

A woman is sitting on the sofa and experiences a headache due to Amitriptyline withdrawal.

Amitriptyline Withdrawal Symptoms

Withdrawal is a group of symptoms that occur upon the abrupt cessation or decrease in dosage of medications. Amitriptyline withdrawal symptoms are often caused by changes in neurochemistry after drug cessation. When someone starts taking this drug, the brain and the central nervous system (CNS) adjust to its effects. Soon after, they rely upon Elavil’s regular presence to balance neurotransmitter concentrations and receptor activities. In other words, the body may develop a dependence on Elavil, which normally is a result of long-term use, and this is dangerous to the health. According to a study, aside from distended bladder caused by Elavil toxicity, Amitriptyline withdrawal also causes cholinergic hyperactivity such as paralysis.

Other Withdrawal Symptoms After Stopping Amitriptyline Can Manifest As Follows:

  • Dizziness
  • Headaches
  • Nausea
  • Vomiting
  • Diarrhea
  • Sweating
  • Fever
  • Chills
  • Appetite loss
  • Muscle aches
  • Aching joints
  • Mild Psychological Symptoms
  • Anxiety
  • Fatigue
  • Restlessness
  • Irritability
  • Insomnia
  • Problems with concentration
  • Memory problems
  • Hypersensitivity to lights or sound
  • Mood swings
  • Severe Psychological Symptoms
  • Severe depression
  • Feelings of depersonalization
  • Panic attacks
  • Suicidal thoughts

Stopping Amitriptyline will require both the brain and the CNS to transit back to functioning without the drug. During this phase, neurotransmission can become unstable or erratic, provoking Elavil adverse effects related to stopping the drug. Additionally, some of the common side effects of this drug may aggravate during the stopping period. The severity of withdrawal is dependent on the dosage and the physiology of the individual taking the drug.

If anyone is experiencing the withdrawal symptoms above, immediately tell a doctor or seek medical help to get a proper treatment of the symptoms.

How Long Do Amitriptyline Withdrawal Symptoms Last?

Withdrawal symptoms appear when the brain and body are trying to recalibrate themselves from their normal functioning without the presence of the drug which was recently used. This medicine falls under tricyclic antidepressants, which are known to affect serotonin. Evidence showed that all antidepressants have the potential to cause withdrawal symptoms, especially if abruptly stopped or reduced after using them for more than 6-8 weeks. Normally, Amitriptyline withdrawal symptoms may last for up to three weeks after the last dose. However, the withdrawal timeline may vary greatly. Some people may require a longer time to eliminate this drug from their bodies, while others experience a delay in the onset of symptoms.

Though Individual Variability May Be Involved, the General Pattern of Amitriptyline Withdrawal Duration Can Be as Follows:

  • The symptoms will start to appear within 3-7 days after the last dose.
  • They are often mild and should resolve quickly.
  • Patients undergoing Elavil withdrawal often complain of flu-like symptoms.
  • Patients presenting with severe psychological side effects may require further treatment.

Two important factors that affect the duration of Amitriptyline withdrawal symptoms include the length of use and the dosage. In general, patients who took high doses of this medicine for an extended period of time will often take longer to feel normal again. If the negative reactions last longer, it is best to speak to a doctor to get quality medical help.

A pen and a paper with the words half-life on it.

Half-Life of Amitriptyline

Half-life means the time for a drug’s concentration to decrease by half. The reported half-life of Amitriptyline is 15 hours and the reported time for healthy adults to eliminate the drug from the body is around 3.44 days following the final dose. However, this does not mean that the metabolites of Elavil are cleared completely from the blood, saliva, urine, and hair. The information below will explain how long this drug stays in the blood, saliva, urine, and hair:

Blood up to 3 days
Saliva up to 2 days
Urine up to 1 month
Hair up to 3 months

The information about Amitriptyline half-life is important, especially when the prescriber and the patient are considering the possible occurrence of withdrawal symptoms. A patient who uses a drug with a shorter half-life has the tendency to experience more withdrawal problems. On the other hand, a patient who uses a drug with a longer half-life has the tendency to experience fewer withdrawal problems.

Factors That Influence How Long  Amitriptyline Stays In The Body

It is important to understand that the person’s ability to metabolize and eliminate Elavil and its metabolites from the body is dictated by different factors. Some of these variables are liver enzymes, personal factors, dosage, term of administration, and other drugs which were used together with Elavil. To understand more about these factors, take a good read about the information below:

CYP2D6 / CYP2C19 Metabolism

In the body, there are enzymes called cytochrome P450 (CYP450), and these enzymes determine the elimination speed of Elavil. Additionally, these enzymes are associated with alleles called CYP2D6 and CYP2C19, which influence the speed of elimination as well. If a person using this drug has one reduced or non-functioning enzyme (either CYP2D6 or CYP2C19 or both), what will happen is that there will be an inadequate metabolism of Elavil and this will make the drug stay longer in the body because plasma concentration of the drug will increase and its elimination half-life will be prolonged. According to a study, only 10% of the users of Elavil have decreased enzyme function.

Age and Other Health Conditions

The elimination half-life of Amitriptyline may last longer in elderly patients (65 years old and above). Prolonged elimination of Elavil could be due to age-related physiological changes such as decreased concentrations of plasma proteins, declining hepatic function, and diminishing renal function. Additionally, elderly patients are more at risk of having other health conditions which may interfere with the drug’s metabolism. According to a study, the elimination half-life of Amitriptyline in elderly patients is 21.7 hours, while in younger adults, it is only 16.2 hours.

Body Mass and Fat Percentage

A person’s body mass and fat percentage influence the circulation and duration of Elavil in the body. Obese users of this drug with a high percentage of body fat have altered levels of plasma proteins, and this causes Amitripyline’s volume of distribution in the body to be altered as well. A person with a higher body mass and fat percentage happens to have a greater quantity of fat stores. Since this drug has lipophilic properties, the tendency is that it will be accumulated in the fats of a person and this will prolong its elimination time.

Hepatic Function

Elavil must be taken with caution in patients with impaired hepatic functions. The more hepatically impaired a patient is, the longer will be the retainment of the drug in the system because there is more unmetabolized Elavil. This happens because health conditions, including hepatic impairment, interfere with the enzymes CYP2D6 and CYP2C19.

Renal Function

Just like with hepatic function, renal function also affects the circulation and elimination of Elavil in the system. According to a study, individuals who are renally impaired may experience fluctuations in the elimination half-life of Amitriptyline.

Metabolic Rate

The basal metabolic rate of a person also influences the elimination of Amitriptyline in the body as it indicates how much energy the body is burning even at a resting stage. Individuals with higher basal metabolic rates tend to burn more energy even at a resting stage and this allows them to eliminate the drug faster from the body.

A medical worker stands near the window.

Urinary pH

What the body does to the drug (pharmacokinetics) depends on a patient’s urinary pH. When the urinary pH of a patient is more acidic, renal excretion of Elavil is increased. According to a study, a urine pH level of 4 (very acidic) increases the excretion of Elavil by up to 1000-fold.

Drug Dosage

The dosage of Elavil taken affects how long it stays in the system. For example, a patient who took 75mg of this drug will take less time for elimination compared to a patient who took 300mg of this drug. Additionally, this is related to metabolism. So, a patient who took a smaller dose will not require the enzymes in the body to work harder and eliminate the drug faster. On the other hand, a patient who took a larger dose of this drug has to wait a longer period for its enzymes to work on the elimination and is at risk of overdose.

Term or Duration of Administration

The term of administration also affects how long it stays in the system. Patients who have used Elavil for 1 to 2 days will be able to eliminate the drug faster compared to those who have used the drug for 3 to 8 days. This happens because those who just used the drug for 1-2 days have not yet attained a stable plasma concentration of the drug since there is an insufficient amount of the drug to be accumulated in the plasma.

Co-administered Drugs

If a patient has taken other drugs or supplements together with Elavil, there is a possibility for the alteration of metabolism. Co-administered medications with this drug may either make the elimination faster or slower. Since Elavil is metabolized by the enzymes CYP2D6 and CYP2C19, medications that inhibit or induce these enzymes will alter the metabolism of Elavil. Examples of drugs that may inhibit these enzymes are Chloramphenicol and Fluoxetine. If these medicines are taken, the tendency is that Elavil will stay longer in the system. Examples of drugs that may induce these enzymes are Rifampicin and Dexamethasone. If these medicines are taken, the tendency is that Elavil will be eliminated faster.

How To Stop Taking Amitriptyline Safely?

While there are several other factors that may influence the severity of Amitriptyline withdrawal symptoms, how quickly one tapers is extremely important. Tapering can help the body adjust to sobriety, allowing patients to find relief from several severe withdrawal adverse effects. According to a study, tapering the dose of this drug over a four-week period is recommended. To safely manage Elavil withdrawal symptoms, one has to gradually reduce the drug dose as recommended by a doctor or other healthcare professionals. This will help relieve the discomfort and allows the body to accept lower doses.

Below Are Some Other Tips on How to Take Care Of One’s Health and Get Through After Discontinuing Elavil:

  • It is important to keep a healthy and active lifestyle, as this drug may cause weight gain. Regular physical activities, eating well, meditating, and socializing – these things can help a person get through Amitriptyline withdrawal physically and mentally.
  • It is essential to keep into account various Elavil drug interactions, which may exacerbate adverse effects.
  • Supplements like probiotics, N-acetyl-cysteine, L-Tryptophan, Krill oil, etc. can also be used to help minimize the severities of Amitriptyline withdrawal symptoms or expedite recovery. However, it is recommended to consult a doctor before trying any of these supplements to prevent allergy.

Take note that stopping Amitriptyline should be done gradually with the help and supervision of an experienced medical professional. Additionally, a safe and quality treatment should always be the priority over a fast one.

Take-Home Advice On Amitriptyline Withdrawal and Addiction

Elavil uses include treatment of depression and chronic pain. While the medication has been proven to be very effective, misuse of Elavil can be dangerous and may cause drug addiction. If someone is abusing Elavil, there are substance abuse treatment programs available across counties to help addicts. Dedicated specialists from different rehabilitation centers can help one get started on recovery in a safe way. Additionally, if someone is experiencing Amitriptyline withdrawal symptoms, it is important to consider getting help from a doctor or other professionals as these people will help in managing the symptoms safely and effectively.

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Published on: February 7th, 2020

Updated on: June 29th, 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.