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Amitriptyline Withdrawal Symptoms and Timeline

amitriptyline withdrawalAmitriptyline, once most commonly marketed under the trade name Elavil but now only available as a generic drug, is an antidepressant. Antidepressant medications were developed specifically to treat clinical depression, or major depressive disorder (MDD), a mental health disorder where the main feature is depressed mood. Other medications and various activities may help to reduce depression in normal individuals, but antidepressant medications like amitriptyline were developed specifically to address MDD and not the normal variations that people have in their mood from day to day.

Amitriptyline is a tricyclic antidepressant. This class of drugs was developed in the 1950s and 1960s, and it was one of the earlier classes of antidepressant medications. Since the development of this class of drugs, other classes of antidepressants, such as selective serotonin reuptake inhibitors (e.g., Prozac, Zoloft, etc.) and atypical depressants (e.g., Effexor, Cymbalta, Wellbutrin, etc.) have been developed. The preference by most prescribing psychiatrists today is to use SSRIs or atypical antidepressants, as these drugs have fewer side effects than tricyclics like amitriptyline. However, the tricyclic antidepressants are generally as effective as the newer drugs in their overall ability to reduce the symptoms of MDD, and they have also been used for other medical purposes.

Mechanism of Action of Amitriptyline

Because amitriptyline is a tricyclic antidepressant, it shares its mechanism of action with other drugs in its class. These drugs typically work by blocking the reuptake of several different neurotransmitters in the brain, particularly serotonin, norepinephrine, and, to some extent, dopamine.

When the drug works by blocking the reuptake of the neurotransmitter, it basically doesn’t allow neurons in the brain to reabsorb the neurotransmitter once it has been released. This means that more of these neurotransmitters are available in the brain and spinal cord. Early theories of depression developed the idea that the cause of clinical depression was a lack of certain neurotransmitters in the brain, and it is believed that drugs like amitriptyline relieve the symptoms of MDD by allowing the brain to have more of these neurotransmitters available. However, despite this hypothesis, the specific mechanism of action for most of these drugs has not been definitely confirmed.

Because antidepressant drugs are believed to increase the availability of certain neurotransmitters in the brain, they are often used for other medicinal purposes. The World Health Organization (WHO) has classified amitriptyline as one of the essential medicines, meaning it is a drug that should be a part of a basic pharmacological storeroom.

Although it is only approved by the Food and Drug Administration (FDA) for the treatment of clinical depression, the drug is also used by physicians for several other medical reasons, including:

  • The treatment of chronic pain
  • To assist in the treatment of fibromyalgia
  • As a treatment for migraine headache
  • As a treatment for nocturnal bedwetting in children

 Tricyclic antidepressants are no longer considered to be primary approaches to the treatment of MDD, although they still may be used. Certain individuals may have better success with drugs like amitriptyline than they do with newer antidepressants.

Withdrawal from Amitriptyline

All antidepressants have an extremely low potential to become drugs of abuse. Some people are under the mistaken impression that since these drugs are used to treat severe depression, they must produce euphoria in individuals who are not depressed. This is not the case.

Antidepressants do not produce the opposite effects of depression (e.g., mania, extreme happiness, etc.); instead, they are believed to restore a neurochemical balance to the brain that helps people with depression experience relief from their symptoms and eases the symptoms of MDD. Taking large amounts of amitriptyline will not make you extremely happy, euphoric, giddy, etc. In fact, taking large doses of amitriptyline or chronically using amitriptyline recreationally is far more likely to result in emotional blunting, feelings of nervousness or irritability, mild nausea, etc.

When the use of antidepressant medications like amitriptyline first became a popular medical practice, they were believed to have very few serious side effects, and they were not believed to produce physical dependence. The drugs are often used and then discontinued in individuals without using a tapering strategy. A small proportion of individuals who used these drugs for more than 4-6 weeks complained of withdrawal symptoms once they were discontinued abruptly. The notion that antidepressants could produce withdrawal syndromes when abruptly discontinued became quite controversial in medical circles; however, research eventually uncovered a mild withdrawal syndrome associated with the continued use and abrupt discontinuation of antidepressant medications.

The withdrawal syndrome associated with amitriptyline and other antidepressant medications is not referred to as antidepressant withdrawal as one may expect. Instead, it has been given the rather technical-sounding name antidepressant discontinuation syndrome (ADS).

The risk of developing ADS as a result of using amitriptyline is increased for individuals who:

  • Have used amitriptyline on a continual basis for six weeks or longer, with the risk increasing the longer the drug is taken
  • Are prescribed higher doses of the drug
  • Suddenly stop using amitriptyline

Other factors, such as individual differences in metabolism, emotional makeup, etc., can influence whether or not a person develops ADS. The withdrawal symptoms associated with discontinuing antidepressant medications are relatively rare compared to other types of prescription medications (e.g., benzodiazepines like Valium or opiate drugs like OxyContin).

Overall, it appears that approximately 20 percent of people who have been using antidepressant medications for more than eight weeks and suddenly stop using the medication develop some symptoms of withdrawal, and most of these symptoms are very mild. Reliable figures for withdrawal associated with the use of amitriptyline are not available.

The symptom profile associated with ADS can be quite variable. Some people will display very mild symptoms; others may display numerous symptoms or just one or two serious symptoms.

Symptoms that have been reported in individuals who are believed to be undergoing withdrawal associated with discontinuing amitriptyline include:

  • Dizziness and headaches
  • Other physical symptoms, such as nausea, vomiting, appetite loss, diarrhea, muscle aches, aching joints, fever, chills, and sweating
  • Psychological symptoms, such as appetite loss, an increase in anxiety, irritability, fatigue, insomnia, problems with concentration, restlessness, issues with memory, hypersensitivity to environmental stimulation such as lights or sound, and crying spells (mood swings)
  • More serious psychological symptoms, including feelings of depersonalization (feeling as if one is not real), severe depression, panic attacks, and even suicidality (very rare)
  • Feeling as if one has the flu during withdrawal (e.g., headaches, fatigue, nausea, etc.).
  • Weight gain or weight loss

 Individuals who experience hallucinations during withdrawal, which is very rare, most often have a more severe manifestation of some other mental health disorder, such as bipolar disorder or psychotic disorder. These individuals should be followed closely by a psychiatrist.


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Withdrawal Timeline

Antidepressants like amitriptyline have variable half-lives. The individual’s metabolism often dictates how long the drug remains in their system, but in general, the drug can remain in the system from a few days up to three weeks. The withdrawal timeline for antidepressants like amitriptyline is nearly as variable as the list of withdrawal symptoms that can occur.

It is known that antidepressant medications that affect the neurotransmitter serotonin, such as amitriptyline, are more likely to be associated with ADS if a person is abruptly taken off the drug after using it for more than 6-8 weeks. The general pattern of withdrawal from amitriptyline could be expected to progress according to the timeline below, but again, there is quite a bit of variability involved.

  • Withdrawal symptoms will typically last 1-3 weeks overall.
  • Symptoms will most often peak within three days to one week and then begin to decline, although this can be quite variable.
  • The majority of cases appear to be very mild, are associated with very little discomfort, and most often resolve rather quickly.
  • The majority of individuals undergoing withdrawal from amitriptyline describe it as feeling as if they have a cold or the flu.
  • If a person begins to develop severe psychological symptoms, such as anxiety and depression, it may be a sign that the individual’s MDD is returning and further treatment is needed.
  • The symptoms of withdrawal will most resolve very quickly (most often within 24 hours) if the person begins taking amitriptyline again.

How Is the Withdrawal Syndrome Treated?

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Withdrawal from amitriptyline is not considered to be significantly dangerous unless the person begins to feel suicidal or has hallucinations as a result of some other disorder. Anyone who is undergoing any withdrawal syndrome may have issues with concentration, judgment, and memory that may lead to functional issues that could potentially be dangerous. In addition, individuals who experience vomiting and diarrhea may be at risk for dehydration, which can lead to significant health issues. Anyone who is been taking amitriptyline and wishes to discontinue the drug should only do so under the supervision of a physician.

The standard procedure to address any potential withdrawal symptoms associated with discontinuing amitriptyline is for the physician to place the patient on a tapering schedule over the course of several weeks. This tapering schedule is performed under the supervision and monitoring of the physician.

The physician begins with the dose of the drug that results in the patient not experiencing any withdrawal symptoms. Then, at specified times, the physician attempts to slowly reduce the dosage. The patient’s responses are monitored, and the physician ensures that the patient does not experience any significant withdrawal symptoms at this lower dosage. This process continues until the person can be weaned off amitriptyline.

In some cases, physicians may use other medications to treat specific symptoms, such as headaches, nausea, etc.; however, there is no specific medication designed to address withdrawal from amitriptyline currently. Since the withdrawal process is mild for most individuals, use of a tapering approach appears to be sufficient in nearly every case.


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