Key takeaways:
Antidepressant discontinuation syndrome (antidepressant withdrawal) can happen when people suddenly stop antidepressant medications. It’s thought to be due to a drop in certain chemicals in the brain.
Common discontinuation symptoms include flu-like symptoms, problems sleeping, upset stomach, and physical sensations like electric shocks or “pins and needles.”
Antidepressant withdrawal symptoms are usually mild and short-lived — lasting 1 to 2 weeks. Severe symptoms, such as extreme behavior changes, are rare. If they happen, they may need immediate medical attention.
Antidepressant discontinuation syndrome is best avoided by lowering medication doses slowly. Always discuss any changes to your medication with your healthcare provider first.
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If you’ve ever missed a few doses of a selective serotonin reuptake inhibitor (SSRI) or other antidepressant, you may have noticed some uncomfortable symptoms. People in this situation can experience sleep changes, muscle aches, and even flu-like symptoms. This is known as antidepressant discontinuation syndrome.
Antidepressant discontinuation syndrome happens to about half of those who suddenly stop taking antidepressants. It’s sometimes also called SSRI discontinuation syndrome or antidepressant withdrawal. And while not a life-threatening condition, its symptoms can be bothersome. And it can make getting off antidepressants a bit tricky.
What causes SSRI discontinuation syndrome?
Antidepressant discontinuation syndrome can happen when people suddenly stop their antidepressants, or lower their dose. And it can occur with more than just SSRIs. Antidepressant withdrawal likely happens because of a sudden drop in serotonin. Serotonin is a chemical in the brain that experts believe plays a role in mood and anxiety. Many antidepressants raise serotonin levels.
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If you plan to lower your antidepressant dose, your brain needs time to adjust to the serotonin changes. Stopping too fast may not allow your brain enough time to adjust.
Experts think that the chemicals norepinephrine and acetylcholine also play a role in antidepressant withdrawal. Some antidepressants affect these chemicals along with serotonin. But serotonin seems to play the biggest role in causing symptoms.
Examples of antidepressants include:
SSRIs like sertraline (Zoloft), paroxetine (Paxil), and fluoxetine (Prozac)
Serotonin and norepinephrine reuptake inhibitors (SNRIs) like duloxetine (Cymbalta) and venlafaxine
Monoamine oxidase inhibitors (MAOIs) like phenelzine (Nardil) and isocarboxazid (Marplan)
Tricyclic antidepressants (TCAs) like amitriptyline and clomipramine (Anafranil)
Atypical antidepressants like trazodone, mirtazapine (Remeron), and bupropion
What are the symptoms of antidepressant discontinuation syndrome?
When your brain senses this drop in serotonin and other chemicals, the following symptoms may happen:
Flu-like symptoms (such as tiredness, muscle aches, diarrhea)
Headache
Dizziness
Trouble with balance
Upset stomach
Nausea
Vomiting
Trouble sleeping
Electric shock sensations
“Pins and needles” sensations
Anxiety
Irritation or feeling on edge
Restlessness
Everyone’s experience is unique. You could feel some or all of the above symptoms.
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Some antidepressants have unique withdrawal symptoms. For instance, stopping TCAs too quickly may cause movement problems, like stiff muscles and tremors. Stopping MAOIs too fast can cause muscle spasms or psychosis (losing touch with reality).
Severe cases of discontinuation syndrome are rare but possible. Serious symptoms can include:
Extreme mental health changes
Unusual movements or behaviors
Confusion
Contact your healthcare provider right away if you experience any severe symptoms. You may need medical attention to help resolve them.
How long do antidepressant withdrawal symptoms last?
For the most part, antidepressant withdrawal symptoms are mild and short-lived. Symptoms usually resolve on their own within 1 to 2 weeks.
Antidepressant discontinuation symptoms usually appear within 3 days after stopping an antidepressant. But this can vary based on how long the antidepressant lasts in the body. The faster a medication leaves the body, the sooner you may experience symptoms.
What raises the risk of experiencing antidepressant discontinuation syndrome?
These factors may raise your risk of withdrawal symptoms:
Taking antidepressants for 6 weeks or longer
Stopping an antidepressant that leaves the body in a shorter amount of time
Stopping an antidepressant without a healthcare provider’s guidance
Antidepressants that stay in the body for a long time have a lower risk of withdrawal symptoms. This is because it may take longer for your body to notice a drop in serotonin after initially stopping them. An example of a longer-lasting antidepressant is fluoxetine (Prozac).
Experts consider fluoxetine to have a lower risk of antidepressant discontinuation syndrome. Some even suggest switching from other antidepressants to fluoxetine before trying to come off these medications.
What antidepressants are the hardest to stop?
Everyone’s experience stopping antidepressants is different. But a 2022 literature review found the following antidepressants have high or very high risks of withdrawal symptoms upon stopping:
Phenelzine
Tranylcypromine (Parnate)
Paroxetine
Venlafaxine
Desvenlafaxine (Pristiq)
Amitriptyline
Are there any treatments available for antidepressant withdrawal?
There are no medications that are specifically intended to treat antidepressant withdrawal. But there are options your healthcare provider may suggest to help relieve symptoms.
Temporarily restarting your antidepressant may help. Doing this helps restore serotonin levels in the brain and ease symptoms. If symptoms appear while lowering your dose, your provider may raise your dose. Once symptoms let up, they will likely lower your dose more slowly.
Your provider may also switch you to an antidepressant that lasts longer in the body, such as fluoxetine. These antidepressants may be easier to stop and have lower risks for withdrawal. You may have more success by switching antidepressants first before trying to come off it.
Healthcare providers may also prescribe medications to treat specific symptoms. As mentioned above, stopping TCAs too fast can cause movement problems. Your provider may temporarily prescribe a medication, like benztropine (Cogentin), to help with this.
Keep in mind this condition is temporary. The worst symptoms usually happen during the first few days.
How can I come off antidepressants safely?
Slowly lowering (tapering) your antidepressant dose can help prevent withdrawal. But there isn’t one “best” way of coming off an antidepressant. Some experts suggest lowering the dose by 25% to 50% and waiting a few weeks to see how you feel. If this is successful, the dose can be lowered again. Completely coming off antidepressants may take several weeks.
Talk to your healthcare provider before stopping your antidepressant. They’ll help you find a schedule for stopping your medication. During this time, tell your provider if you have any bothersome symptoms. This will help them know if they should change your taper schedule.
The bottom line
Antidepressant discontinuation syndrome can happen when antidepressants are suddenly stopped. It’s believed that a drop in serotonin causes this temporary condition. Antidepressant withdrawal symptoms are more likely to happen if you take an antidepressant for more than 6 weeks. Certain antidepressants, like phenelzine and paroxetine, may also be more likely to cause these issues.
The best way to avoid withdrawal symptoms is to lower your dose slowly with a healthcare provider’s guidance. Your provider can help suggest a taper schedule for you. Talk to your provider first before stopping an antidepressant on your own.
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References
Endocrine Society. (2022). Adrenal hormones.
Henssler, J., et al. (2019). Antidepressant withdrawal and rebound phenomena. Deutsches Ärzteblatt international.
National Center for Biotechnology Information (2023). PubChem compound summary for CID 3386, fluoxetine.
Purves, D., et al. (2001). Acetylcholine.
Rizkalla, M., et al. (2020). Antidepressant discontinuation syndrome: A common but underappreciated clinical problem. Journal of Osteopathic Medicine.
Sørensen, A., et al. (2022). Clinical practice guideline recommendations on tapering and discontinuing antidepressants for depression: A systematic review. Therapeutic Advances in Psychopharmacology.
Warner, C. H., et al. (2006). Antidepressant discontinuation syndrome. American Family Physician.
Wilson, E., et al. (2015). A review of the management of antidepressant discontinuation symptoms. Therapeutic Advances in Psychopharmacology.
