Why Is Antidepressant Withdrawal So Hard?

A few years ago it was estimated that one out of eight Americans took an antidepressant medication (JAMA Internal Medicine, Feb. 2017) daily. According to my current calculations, 46 million people now take drugs like sertraline, escitalopram, bupropion, trazodone,  fluoxetine, citalopram, duloxetine, venlafaxine or paroxetine annually. That’s closer to one out of seven Americans. Some of these antidepressants are also prescribed for anxiety, panic, neuropathy, fibromyalgia, back pain, osteoarthritis, OCD and hot flashes. Are patients adequately warned that antidepressant withdrawal can be devastating?

Waking Up To Antidepressant Withdrawal Symptoms:

The mainstream media have suddenly discovered that stopping antidepressants can lead to disastrous symptoms. An article in the New York Times carried the headline, “Many People Taking Antidepressants Discover They Cannot Quit” (April 7, 2018).

A patient who had been on sertraline (Zoloft) described symptoms of antidepressant withdrawal: dizziness, confusion and fatigue. They persisted far longer than most health professionals would imagine.

According to the NYT account:

“It took nine months to wean herself from the drug, Zoloft [sertraline], by taking increasingly smaller doses.

“‘I couldn’t finish my college degree,’ she said. ‘Only now am I feeling well enough to try to re-enter society and go back to work.’”

Medical Researchers Reporting “Discontinuation Symptoms”

An article in Lancet Psychiatry, July, 2024, is now reporting on something the FDA calls “discontinuation syndrome:”

“Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified.”

Do you find that somewhat disquieting? Antidepressants have been on the market for many decades. And yet here are psychiatrists admitting that health professionals have not “quantified” the incidence of this problem. The authors reviewed 79 studies of people discontinuing their antidepressants. Of these, 44 were randomized controlled trials, allowing for comparison between placebo and antidepressant.

The findings:

“Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication.”

“Our study yielded four main results. First, across all studies and antidepressants, we found that approximately every third patient discontinuing antidepressants will have antidepressant discontinuation symptoms of any kind…”

We cannot verify those stats, though we suspect the likelihood of antidepressant withdrawal symptoms may be even higher. The authors of the Lancet Psychiatry article list these symptoms:

• Dizziness
• Headache
• Insomnia
• Nausea
• Irritability

The medicines that were most frequently associated with discontinuation problems included desvenlafaxine, venlafaxine, imipramine and escitalopram. The most severe symptoms were linked to imipramine, paroxetine, desvenlafaxine and venlafaxine. That does mean, however, that people taking other antidepressants are home free. As you will read shortly, people can experience severe symptoms after stopping duloxetine or some other SSRI or SNRI antidepressant.

The authors discuss tapering the dose of antidepressant medication to reduce the likelihood of developing withdrawal symptoms. The trouble is that there are no clear instructions on how to do that. Each clinician is on her own when it comes to developing a dose reduction plan. Neither drug companies nor the FDA seem inclined to provide much guidance.

Antidepressant Withdrawal an Old Story:

Readers of this column have been reporting the same kind of problem for decades.

In August, 1995, we heard from one person:

“I’m having trouble with rather severe withdrawal effects caused by abrupt discontinuation of paroxetine [Paxil] nearly two months ago. I took 20 mg daily for about two years for depression. When I felt less depressed and realized my inability to have orgasms was a side effect of the drug, I asked my shrink about discontinuation. He said to stop cold, so I did.

“Two days later, I saw sparkling zig-zag colored lights and had tunnel vision. Diarrhea, shakiness, horrible insomnia, wildly brittle emotions, and overwhelming crankiness set in. I was completely unable to concentrate or to do normal mental tasks, such as subtracting one four-digit number from another. I kept saying there was something wrong inside my head! I fell down, ran into things, and got covered with bruises. I was nauseated.

“I called the psychiatrist, who told me to take more Paxil. Instead, I asked him to do a literature search about withdrawal from Paxil, so he would know more about the drug he was prescribing. Two days later I received a letter from him, firing me as a patient.

“I am still emotionally volatile, really mad at the shrink and wondering if my depression is back. Was this doctor out of line, or was I?”

Our 1995 People’s Pharmacy Response:

In our answer, we pointed to a growing recognition that sudden discontinuation of antidepressants like paroxetine (Paxil) can sometimes cause withdrawal symptoms. The manufacturer told us that dizziness, sensory disturbances, nausea, agitation and anxiety had all been reported.

We were disappointed that the psychiatrist wasn’t more understanding and sympathetic about the symptoms this person was experiencing. We weren’t that surprised, however. In the mid 1990s, there still wasn’t widespread realization that stopping drugs like sertraline or paroxetine could lead to long-lasting and severe adverse reactions.

The Official Paxil (Paroxetine) Prescribing Information:

In our 1994 edition of the Physicians’ Desk Reference (PDR), the only mention we could locate about Paxil withdrawal was this:

Physical and Psychological Dependence

“Paxil has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence.”

Another SSRI-type antidepressant, sertraline (Zoloft) had equally reassuring prescribing information in 1994:

Physical and Psychological Dependence

“ZOLOFT has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. However, premarketing clinical experience with ZOLOFT did not reveal any tendency for a withdrawal syndrome or any drug-seeking behavior.”

It’s hardly any wonder that physicians did not think there was such a thing as antidepressant discontinuation symptoms. The official prescribing information for paroxetine and sertraline was reassuring. The FDA did not require studies and drug companies did not feel motivated to investigate this issue. See no evil, hear no evil, speak no evil.

Antidepressant Withdrawal Is Now “Discontinuation Syndrome”:

Fast-forward to 2024. There is much more awareness about antidepressant withdrawal symptoms. The FDA has given this kind of reaction a scientific name: “discontinuation syndrome.” It may seem less scary than antidepressant withdrawal.

Today, the official prescribing information for Zoloft (sertraline) is quite different from the 1994 PDR:

Discontinuation Syndrome

“Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.”

The FDA requires this for generic Zoloft (sertraline):

After a long list of antidepressant withdrawal symptoms comes:

“During marketing of sertraline and other SSRIs and SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs…While these events are generally self-limiting, there have been reports of serious discontinuation symptoms.

“Patients should be monitored for these symptoms when discontinuing treatment with sertraline. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.”

The current prescribing information for paroxetine (Paxil) is quite similar and differs dramatically from the official line of the mid 1990s.

What Does “Gradual Reduction” in Dose Mean?

Neither the FDA nor the drug companies that make antidepressant medications spell out in detail what they mean by gradual reduction. For some physicians that could be interpreted as a week or two. For others it might be several weeks.

We suspect that many health professionals have very little idea what their patients go through when they try to stop antidepressant medications. Just listing symptoms such as brain zaps, dizzy spells, nausea, headaches, sweating, anxiety, fatigue, insomnia and digestive problems does not do antidepressant withdrawal justice.

Some of the other antidepressant drugs that can produce the discontinuation syndrome include citalopram (Celexa), desvenlafaxine (Pristiq), duloxetine (Cymbalta), escitalopram (Lexapro) and venlafaxine (Effexor).

Stories from Readers:

You can find over 1,900 reader comments associated with this article:

Duloxetine (Cymbalta) Side Effects & Withdrawal

If you would prefer to just read just a few case reports, here are some:

Carl in Brisbee, Arizona, is going through hell:

“I was prescribed Cymbalta [duloxetine] and Provigil [modafinil] for PTSD (post-traumatic stress disorder) and narcolepsy.

“In the fall of 2017 my insurance company suddenly decided to not pay for my prescriptions. This lasted for 5 1/2 months. My Provigil alone is $4,500.00 a month! I could not afford to buy anything for 3 1/2 months.

“I had no idea about the side effects of stopping CYMBALTA suddenly! I was going crazy! I was suicidal. It was the most horrible I have ever felt in my life!

“It has been nearly seven months since the onset of withdrawal symptoms. I have been in bed for 3 3/4 months. Just a few steps make me exhausted. I am dizzy. I cannot walk a straight line. I bounce off the walls and hit the sides of doorways. It is as if I have very little control over my upright body.

“I know it is from the suddenly stopping Cymbalta! I took this drug for more than a decade. I just got used to it. I kept taking it for years, until insurance refused to pay in Sept. 2017. My life has been a wreck ever since. It still is going on. I am in a living hell and am unable to find a solution!”

Diane in Texas reduced her dose very gradually:

“I took Cymbalta for years and got off of it a few years ago. It was very difficult. I ended up opening the capsules and counting beads. I made very gradual adjustments and it took months to get off it. I felt withdrawal symptoms from the slightest decrease.”

Cindy in Seattle, Washington, offers an insider’s perspective:

“I worked in psych for 30 years (inpatient units), and one of the main reasons for an admission was to ‘wean’ the patient off SSRI’s. The withdrawal symptoms were that horrible and dangerous.”

Dagny offers an interesting taper tip:

“Antidepressants can quit working and result in withdrawal symptoms that are the same as they would be if the person quit the drug cold turkey. You might want to ask your doctor about switching to a different SSRI and see if that helps.

“I’ve gone through antidepressant withdrawal cold turkey. It was three and a half years of misery. The discomfort slowly decreased over that time period.

“If you want to get off antidepressants, your doctor may be able to prescribe a liquid version. As you get close to reducing the dose in smaller increments this will make it easier to titrate the dose. You can taper very gradually during the last months. That is when it begins to get most difficult. A compounding pharmacy can make up the prescription for you.

“It will no doubt be more expensive than an ordinary prescription, but it would be well worth it. I wish I had known about this when I was suffering. Whatever you do, don’t just stop the drug. After a month or so of going off cold turkey, going back on the drug to stop withdrawal symptoms may not work. Take it slow and easy.”

How to Stop Duloxetine (Cymbalta) from “Hopeful” in Indiana:

Patients who have been through the hell of antidepressant withdrawal often try to help their fellow sufferers. Here is an article we wrote about a year ago with some thoughtful suggestions from “Hopeful” in Indiana. Remember to always check with a health professional about any withdrawal strategy:

How to Stop Duloxetine (Cymbalta) Without Withdrawal Symptoms

Why Is It So Hard to Stop Antidepressants?

To our surprise there has not been a large amount of research devoted to this crucial question. We now know that antidepressants affect a number of important neurochemicals: serotonin, norepinephrine and dopamine for starters. It is likely that other systems are also impacted, including GABA and “neurotrophic factors” (Frontiers in Pharmacology, April 16, 2013).

When drug-induced modifications occur within the body, there are frequently cellular adaptations. Receptor sites on neurons change. This is the way the body attempts to deal with changes in neurochemistry. Because neuroscientists have not devoted a lot of research to this issue, we do not yet have a good explanation for the underlying causes of discontinuation syndrome.

We suspect that withdrawal symptoms occur as the body tries to reestablish homeostasis. Some people are super sensitive to this challenge. It may take them months or years to achieve balance. Others may overcome the challenge over several weeks.

People’s Pharmacy Perspective:

We are glad to learn that the medical profession and the media are starting to wake up to the seriousness of antidepressant withdrawal. This is not the depression returning. That has sometimes been used as an explanation for why people suffer symptoms after stopping an antidepressant. It is much easier to blame the patient than the drug.

We believe this because symptoms are different and people report the discontinuation syndrome even when they were taking the medication for other reasons than depression:

Jan was taking duloxetine for the pain of fibromyalgia:

“I was on Cymbalta for over 10 years for fibromyalgia. I just didn’t feel good on the medication. I asked myself, why I am I taking it? My symptoms were actually worse.

“I decided I need to get off this drug. At my annual checkup my doctor said fine, but let me give you 30 mg for a month (I was on 60 mg.) Then you should be fine.

“NO. I am on my 3rd day and as everyone else has said on this website, I am going a bit crazy. I threw up the first day. I had the brain zaps, crying and the shakes to name a few! I have been drinking tons of water and trying to eat lots of fruits and veggies. I took a long Epson Salt bath with peppermint oil to try and sooth my pain.

“Thank You so much for sharing the idea of opening the capsule and removing the small white balls and weaning that way…who knew?”

Occasionally, patients may need to stay on antidepressant medication for many years. Others may need to be on such drugs indefinitely. But for those who wish to get off their medicine, there are no good guidelines for gradual tapering.

You may be interested in our podcast “Are We Medicating Normal Emotions?” in which we speak with a psychiatrist about the withdrawal phenomenon. And our Show 1389: Getting Off the Medication Treadmill may also be helpful.

It is long past time for the FDA to require drug makers to develop evidence-based strategies to help people discontinue antidepressants safely.

Share Your Own Antidepressant Withdrawal Story

If you needed to stop an antidepressant medication for any reason, please share your experience in the comment section below.