Antidepressants And The Symptoms Of Antidepressant Withdrawal

  • Salma Tarabeih Pharm.D. Clinical Pharmacist | Pharmacy Preceptor, Beirut Arab University
  • Bhashwati Deb Barma Bachelor of Physiotherapy,M.S., Ramaiah Medical College, India
  • Ellen Rogers MSc in Advanced Biological Sciences, University of Exeter

Introduction

Antidepressants are a group of medications primarily used for treating depression. However, many of these medications are also used to treat other conditions, such as obsessive-compulsive disorders, generalised anxiety disorders, eating disorders, neuropathic pain syndromes, and chronic pain syndromes.1

Antidepressants are usually classified as either first- or second-generation. The first-generation antidepressants include tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs). Even though they are effective in the management of depression and other conditions, use of the first-generation agents is commonly complicated by adverse effects, toxicity (in overdose situations), and common drug-drug and drug-food interactions. The second generation of antidepressants comprises selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and other medications, including trazodone, bupropion, and mirtazapine. Generally, these agents have better side effect profiles and are far less likely to lead to death in cases of overdose.1

Both first- and second-generation antidepressant medications target certain neurotransmitters (chemicals that help send messages around the brain and nervous system) to modulate your mood and behaviour, but work slightly differently. All currently licensed antidepressants are believed to elevate either serotonin, norepinephrine, or both in the synapse (space between two nerves).2

Antidepressant withdrawal syndrome refers to the physical and psychological symptoms that people may experience when missing or reducing doses of any antidepressant or when they stop taking them completely. Taking any antidepressant regularly can influence the availability and levels of several neurotransmitters within the body, leading to various physiological effects. Upon discontinuation of the medication, the body requires time to adapt and adjust, potentially resulting in symptoms during this period.3 Whilst the precise mechanisms and reactions causing these symptoms have not yet been determined, various explanations have been proposed. 

This article delves into an exploration of these withdrawal symptoms, the factors that shape them, and the strategies you can try to alleviate and treat them. Stay tuned for a deeper understanding of these aspects.

Understanding antidepressant withdrawal symptoms

Antidepressants are not deemed addictive in the conventional sense, as individuals typically use them not to pursue a euphoric sensation but rather to alleviate symptoms associated with significant medical issues. However, prolonged use can encourage a state of physical dependence, which makes antidepressants notoriously hard to quit. Consequently, antidepressant withdrawal can cause a cluster of unpleasant symptoms, often leading patients to restart taking their medication again. The ongoing usage is not driven by a desire for euphoria but rather to alleviate disease symptoms or prevent the discomfort associated with discontinuing antidepressants.1

Approximately 20% of individuals experience antidepressant discontinuation syndrome when abruptly discontinuing or significantly reducing the dosage of an antidepressant that has been consistently taken for a month. Symptoms are generally mild and can manifest after treatment with any category of antidepressant. They usually appear within two to four days of medication cessation and generally last one to two weeks - but they can persist for up to one year. If the same or a similar medication is initiated, the symptoms will resolve within one to three days.4

Failure to identify antidepressant discontinuation syndrome can lead to incorrect medical or psychiatric diagnoses. You can use the helpful mnemonic ‘FINISH’ to recall the symptoms of antidepressant discontinuation syndrome:4

  • Flu-like symptoms (lethargy, fatigue, headache, achiness, sweating)
  • Insomnia (with vivid dreams or nightmares)
  • Nausea (sometimes vomiting)
  • Imbalance (dizziness, vertigo, light-headedness)
  • Sensory disturbances (“burning,” “tingling,” “electric-like” or “shock-like” sensations)
  • Hyperarousal (anxiety, irritability, agitation, aggression, mania, jerkiness)

Stopping antidepressant therapy may raise the risk of relapse of depression or anxiety. Unlike the symptoms of antidepressant discontinuation syndrome, symptoms of relapse usually require more than a few days to appear and disappear following reintroduction of the antidepressant.4

Factors influencing antidepressant withdrawal symptoms

Several factors are thought to increase the severity and longevity of the symptoms of antidepressant withdrawal, such as:

  • Taking antidepressants for a longer time
  • Taking high doses of antidepressants
  • Taking antidepressants with a shorter half-life
  • Taking one of the antidepressants that are thought to have a more significant effect on the brain

It's important to remember that antidepressant withdrawal symptoms will vary between individuals (due to physiological and biochemical differences between patients), as will the likelihood of a given patient experiencing them.5

Managing antidepressant withdrawal

Individualised management is necessary for antidepressant discontinuation syndrome due to the absence of specific treatment data. Each treatment plan must consider:4

  • Gradually decreasing dosage may not be necessary for patients who have taken an antidepressant for less than four weeks or those who are taking fluoxetine
  • Faster reduction in the dose may be possible in cases where doses are low
  • The dose of antidepressants with short half-lives needs to be reduced gradually; however, gradual reduction may not prevent the syndrome in all cases
  • Patients can be comforted by knowing that their symptoms can be reversed, are not life-threatening, and typically go away on their own
  • In certain situations, transitioning to fluoxetine might be beneficial when contemplating discontinuation of another antidepressant
  • If symptoms are severe, the drug should be reinitiated and a slower decrease in the dose should be started

Patient education

When a patient is thinking about coming off of an antidepressant, doctors should be cautious (e.g., during pregnancy). Similarly, changing to a different antidepressant or antidepressant formulation may cause an unintentional decrease in overall dosage since not all formulations of the same medication are bioequivalent

Patients should speak with their doctor before quitting an antidepressant to minimise their risk of withdrawal symptoms. One way to lower the risk could be to prescribe an antidepressant with a longer half-life, or to slowly reduce their dose of the medication over a period of six to eight weeks.4

Summary

  • Antidepressants are commonly used to treat various forms of depression and other conditions such as obsessive-compulsive disorders, generalised anxiety disorders, and chronic pain syndromes.
  • Antidepressants act on neurotransmitters like serotonin and norepinephrine to modulate mood and behaviour.
  • The prolonged use of antidepressants can lead to physical dependence, making discontinuation challenging.
  • Antidepressant withdrawal syndrome refers to the physical and psychological symptoms experienced by patients when they stop or reduce their dose of antidepressants, with symptoms lasting one to two weeks. However, symptoms can sometimes persist for up to one year.
  • The FINISH mnemonic summarises symptoms of antidepressant discontinuation syndrome: Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, and Hyperarousal.
  • Adaptations to the presence of antidepressant medication underlie withdrawal symptoms. As such, taking antidepressants for a longer period of time and/or at a higher dosage is thought to worsen withdrawal symptoms.
  • The treatment and management of antidepressant withdrawal syndrome will vary between individuals. Gradually decreasing antidepressant dosage may not be required in cases of short-term use, whilst faster reduction may be possible for patients on low doses.
  • Patients should consult with their doctor before quitting antidepressants to reduce the risk of withdrawal syndrome. Lowering the risk may involve prescribing an antidepressant with a longer half-life or reducing the dose over six to eight weeks.

References 

  1. Rizkalla M, Kowalkowski B, Prozialeck WC. Antidepressant Discontinuation Syndrome: A Common but Underappreciated Clinical Problem. JOM. [Internet]. 2020 [cited 2024 Jan 30]; 120:174–8. Available from: https://www.degruyter.com/document/doi/10.7556/jaoa.2020.030/html?lang=en.
  2. Sheffler ZM, Patel P, Abdijadid S. Antidepressants. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Jan 30]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK538182/.
  3. Perry T. Antidepressant Withdrawal Syndrome. In: Therapeutics Letter [Internet]. Therapeutics Initiative; 2018 [cited 2024 Jan 30]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK598502/.
  4. Gabriel M, Sharma V. Antidepressant discontinuation syndrome. CMAJ [Internet]. 2017 [cited 2024 Jan 30]; 189:E747. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449237/.
  5. Horowitz MA, Framer A, Hengartner MP, Sørensen A, Taylor D. Estimating Risk of Antidepressant Withdrawal from a Review of Published Data. CNS Drugs [Internet]. 2023 [cited 2024 Jan 30]; 37:143–57. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911477/.
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Salma Tarabeih

Pharm.D. Clinical Pharmacist | Pharmacy Preceptor

Salma is a Doctor of Pharmacy with several years of experience in Pharmacy Management and Patient Consultation. She has a track record of delivering remarkable patient care and optimizing drug therapy outcomes. Her expertise includes guiding students, collaborating with healthcare professionals, and ensuring quality standards. She is passionate about Clinical Research and Pharmacy Practice Education, and she is dedicated to making a positive impact in these areas.

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