Synopsis: While antidepressants often save lives, they can also result in very serious emotional and physical side effects from missed doses, reduced doses, or abrupt stopping. This article talks about the rarely discussed risk of acute depressive symptoms and the more widely known physical symptoms of serotonin withdrawal from switching or stopping your antidepressant medication.

BY LEN LANTZ, MD / 7.31.22; No. 59 / 7 min read

Disclaimer: Yes, I am a physician, but I’m not your doctor, and this article does not create a doctor-patient relationship. This article is for educational purposes and should not be seen as medical advice. You should consult with your physician before you rely on this information. This post might also contain affiliate links. Please click this LINK for the full disclaimer.

The good and the bad of antidepressant medications

I’ve been hesitant in writing about this subject because I’m worried about how it could be misused by the antipsychiatry movement in the US and Europe. This small group of people believes it is their duty to “expose” the limitations of psychiatric diagnoses and treatments as they often have had bad experiences themselves. Unfortunately, this group’s actions primarily involve misrepresentations of the research (and the researchers), and this results in distrust of psychiatric care and increased stigma. Stigma toward psychiatric care is exceedingly harmful, and it results in people suffering unnecessarily and dying from suicide. So, please reach out to me if you learn that this article is being misused, and I’ll archive it in a heartbeat.

Antidepressants can be very effective at treating depression and anxiety. While these medications do not help everyone, they can and do save lives. For some background information on antidepressant medications, please check out my article “A Stepwise Approach to Medications for Depression.” Most people sort out for themselves whether or not an antidepressant medication works for them. If they stay on their medication over the long term, they have usually made some sort of calculation that the benefits from the medication outweigh any lingering side effects.

However, a smaller percentage of people remain on antidepressant medications not because they are seeing a benefit but because they feel stuck on the medication. They may have experienced significant physical or emotional side effects from missing one or more doses of the medication or trying to wean themselves off. This can leave them feeling fearful about changing or stopping their antidepressant. These serotonin withdrawal symptoms have received several labels over time, including “antidepressant discontinuation syndrome” and “antidepressant withdrawal,” which are simply new names for the same condition. It’s worth noting that the antidepressant Wellbutrin (bupropion) is uncommonly associated with emotional withdrawal symptoms even though it has virtually no effect on serotonin.

Serotonin withdrawal symptoms

Serotonin withdrawal symptoms have been studied and reported for decades. In 1988, Rosenbaum and colleagues studied the effects of abruptly stopping the antidepressants of patients who were on Paxil (paroxetine), Zoloft (sertraline), and Prozac (fluoxetine) for 5-8 days. (Rosenbaum, et. al. Biological Psychiatry. 1988). From this study, the researchers developed the Discontinuation-Emergent Signs and Symptoms (DESS), which outlines over 40 possible emotional and physical symptoms a person could experience from abruptly stopping their antidepressant. To learn more about the DESS, click this LINK.

While many people never experience serotonin withdrawal symptoms, other sensitive individuals might start feeling sick if they are an hour or two late in taking their daily dose of their antidepressant. It’s worth noting that genetics might play a role in sensitivity to serotonin withdrawal symptoms. For example, people who rapidly metabolize certain medications might be at increased risk if they miss doses or abruptly stop their medication. For more information, please see my article, “Genetic Testing for Psychiatric Medications.”

There is a wide variety of physical and emotional symptoms that range in severity from minimal to extreme. Here are some examples of serotonin withdrawal symptoms that I see most often in my clinic:

• Flu-like symptoms: headache, nausea, dizziness, and muscle aches

• Zapping sensations: feeling buzzing, jolting, or electrical sensations in the head (“brain zaps”) or body ranging from mild to severe, such as feeling like lightning is shooting up or down your spine

• Muscle twitching: feeling and sometimes observing the same small surface muscles twitching

• Increased anxiety, tearfulness, fatigue

It is relatively easy to fix these symptoms of serotonin withdrawal by restarting the antidepressant that was stopped, increasing back to the previous dose if it was recently lowered, or switching back to the old medication if you recently switched meds. When you do this under the supervision of your prescriber, your symptoms of serotonin withdrawal often go away in a matter of hours to days.

The rare risk of rapid-onset depression and suicidality from missed antidepressant doses

I’m going to explain an emotional aspect of serotonin withdrawal that is listed above in the DESS but which seems completely different from the other – mostly physical – symptoms of serotonin withdrawal. Psychiatrists might be unhappy with me for highlighting and separating it from the other serotonin withdrawal symptoms because antipsychiatry folks might use this information to further their misguided mission.

So, here is what concerns me greatly: there is a possible but uncommon risk of having rapid depressive symptoms and new onset suicidal symptoms from lowering/stopping antidepressants. This can occur in any of the following scenarios:

• Rapidly lowering and stopping an antidepressant

• Running out of an antidepressant over a weekend or on vacation

• Abruptly switching (rather than gradually cross-tapering) from a short-acting antidepressant, such as Paxil (paroxetine) or Effexor (venlafaxine) to a long-acting antidepressant, such as Prozac (fluoxetine)

• Switching from any antidepressant to Wellbutrin (bupropion), which has virtually no serotonin effects

• Switching from an antidepressant to a non-antidepressant, such as an anticonvulsant or antipsychotic medication

Why highlight the depressive mood effects of serotonin withdrawal?

It’s worthwhile to point out that there are several possible emotional side effects of serotonin withdrawal. People can experience anxiety, irritability, panic attacks, and agitation. The reason why I’m pointing out the small percentage of people who experience depression is that these folks can find themselves in a sort of medication-withdrawal depression which, at its extreme, involves a rapid switch into severe sadness, uncontrolled crying, and new-onset suicidality. You can feel almost as though a switch got flipped and that you have been thrown into depression. For more information on dealing effectively with suicidal thoughts, please read my article, “Your Safety Plan for Suicide Prevention.”

Unlike the relatively rapid improvement in physical symptoms after restarting your antidepressant, it can take days to weeks to recover from a rapid switch to depression and suicidal thoughts caused by serotonin withdrawal. Knowing about this risk can help you plan to avoid running out of medication and take the necessary steps to obtain your medication if you run out.

What you can do when you are out of your antidepressant and unable to get a refill quickly

Currently, 18 states allow for an emergency 3-day prescription to continue medication that can be dispensed by a pharmacist if the patient’s prescriber cannot be reached. The legislation that gives pharmacists the authority to dispense the medication –  often called “Kevin’s Law” – needs to be adopted by all states.

What can a person do if they are out of medication but in a state without a version of Kevin’s Law or cannot convince the pharmacist to dispense them 3 days of medication?

• Go to a local urgent care

• Call your doctor’s office and ask to speak with your provider or the doctor/nurse covering for your provider

• If you are visiting another town or state and have a prescription available at your hometown pharmacy, talk to the pharmacist where you are located and see if they can transfer your prescription from your hometown pharmacy to them (offer to pay out of pocket for a small supply of the generic version of your prescription if your insurance won’t pay for this).

Dealing with serotonin withdrawal when your goal is to stop your antidepressant

For people who are particularly sensitive to serotonin withdrawal, there are a few strategies for tapering off antidepressants. There is limited recent information from medical research on managing serotonin withdrawal symptoms. In 1997, there was a Discontinuation Consensus Panel meeting of experts to address the management and treatment of serotonin withdrawal from antidepressants. Here is a summary of their findings:

“Following the 1997 panel meeting, Rosenbaum and Zajecka published clinical management strategies for the treatment of SRI discontinuation syndrome. This included (1) reassuring patients that the symptoms associated with SRI discontinuation syndrome are likely to be short-lived and mild; (2) for severe and distressing symptoms, the dosage of the drug prescribed immediately before the dose decrease that led to the onset of discontinuation symptoms should be reinstituted and the rate of taper should be slowed; (3) all SRIs, with the exception of fluoxetine, should be gradually tapered; and (4) using or switching to agents with an extended half-life, such as fluoxetine, can help reduce the incidence of SRI discontinuation syndrome.” (Schatzberg, et al. Journal of Clinical Psychiatry. 2006)

A 2004 panel then met to update those recommendations with newer research, but they offered no new advice regarding the treatment and management of serotonin withdrawal. Here is a summary of the 2004 panel recommendations:

“The panel reviewed the 1997 treatment recommendations and agreed that slow tapering and drug substitution with longer-acting drugs, such as fluoxetine, were still among the best management strategies for minimizing and/or preventing SRI discontinuation syndrome.” (Schatzberg, et al. Journal of Clinical Psychiatry. 2006)

The fluoxetine strategy

Note: This is not a recipe or a recommendation. All antidepressant management should be supervised by a psychiatrist, other skilled mental health prescriber, or primary care provider.

The reality is that gradual tapers of antidepressants do not work for some people, because they can feel incredibly sick even with a very slow taper of their antidepressant. In rare cases, people can even struggle with a very slow taper of long-acting fluoxetine. Some psychiatrists use the fluoxetine strategy. This involves first adding fluoxetine (usually 20 mg daily for 2-4 weeks) to a person’s current antidepressant (as long as fluoxetine is not contraindicated for them), then gradually lowering and stopping the old antidepressant. If serotonin withdrawal symptoms flare up when decreasing the old antidepressant, then fluoxetine is increased accordingly. After a month off the old antidepressant, the psychiatrist starts slowly decreasing fluoxetine (going especially slowly in the final month of the taper) until it is gone. This works very well for most people, however, a small number of people still have some serotonin withdrawal symptoms even with this strategy. One more benefit of the fluoxetine strategy is that the medication is available in liquid form, so it can be dispensed in very small doses at the end of the medication taper for particularly sensitive individuals.

Regaining a sense of control over antidepressants and withdrawal side effects

Antidepressants can and do save lives, but these medications need to be taken consistently, and there can be some challenges in tapering off them. If antidepressants are ineffective for some individuals, there is no need for them to remain on their antidepressant simply due to the fear of side effects from tapering and stopping the medication. Knowledge about serotonin withdrawal can also improve people’s motivation to avoid skipping their antidepressant unnecessarily and throwing themselves into a crisis. There is no need to have a ruined weekend or vacation due to serotonin withdrawal symptoms. If you find that you are out of your antidepressant for more than a day, there are several steps that you can take to obtain your medication and feel your best.

For further reading, check out:

• Len’s Article, “A Stepwise Approach to Medications for Depression”

• Len’s Article, “Genetic Testing for Psychiatric Medications”

• Len’s Article, “Your Safety Plan for Suicide Prevention”

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