Hippocrates’ descriptions of depression, written 2,400 years ago, mirror those of modern times, UCHealth psychiatrist Dr. Christopher Schneck reminds his University of Colorado Anschutz School of Medicine students.
Metaphors of being in a hole you can’t climb out of or stuck in a dark cave appear to be timeless. Depression is “a deeply biological illness,” Schneck said.
Hippocrates attributed what he called “melancholia” to an excess of black bile. His treatments included donkey milk and a plant called hellbore. Today, we have proven therapies that work much better than Hippocrates’ go-to cures: antidepressants. These consist mainly of selective serotonin-reuptake inhibitors, or SSRIs, such as Prozac and Zoloft; and serotonin-norepinephrine reuptake inhibitors, or SNRIs, including Cymbalta and Effexor.
Roughly 16% of U.S. adults use an antidepressant. They help millions of people, though exactly how remains unknown.
There can be side effects, and, when someone goes off an antidepressant, they may experience unpleasant withdrawal symptoms.
A May 4 “Mental Health and Overmedicalization Summit” kicked off recent federal efforts encouraging patients to taper off or stop using antidepressants. And some health activists are calling on medical providers to “deprescribe” antidepressants. Efforts to reduce the use of antidepressants or to encourage people who have been taking them for long periods of time to stop using them have gotten a lot of recent attention.
These new trends raise many questions. Do antidepressants work? If people who are coping with depression don’t use antidepressants, then what drugs or therapies will help them? What are the risks of tapering off antidepressants or deprescribing them? Where do major medical societies stand on those topics? How common is antidepressant withdrawal? What are the symptoms? To answer these and other questions, we talked with Schneck and reviewed relevant research.
Do antidepressants work?
Yes, antidepressants work, although it often takes some trial and error to find the right medication and dosage, Schneck said.
A big study found that half of participants’ depression symptoms had improved after either the first or second antidepressant they tried, and nearly 70% of patients who continued trying up to four different medications eventually became symptom-free.
Do antidepressants address a ‘chemical imbalance?’
No one knows precisely how antidepressants work. The early theory behind SSRIs, prevalent in the 1990s into the 2000s, rested on the now discredited idea of a “chemical imbalance.” That imbalance had to do with having too little serotonin, a mood-regulating chemical messenger, in the brain. The body constantly produces and then breaks down serotonin; an SSRI’s reuptake inhibitor slows that process, the idea being that more serotonin stays in the brain and improves depression symptoms. The same would hold for norepinephrine, another chemical messenger, in an SNRI.
But research has shown that, while SSRIs and SNRIs do work, there’s more going on than just a simple chemical imbalance. The complexity of the brain so far has defied scientists’ ongoing attempts to figure out how antidepressants actually work.
Why is antidepressant tapering and deprescribing in the news?
U.S. Department of Health and Human Services Secretary Robert F. Kennedy Jr. presided over a Mental Health and Overmedicalization Summit on May 4. Leaning harder into alternatives to antidepressants and curbing antidepressant overprescribing and deprescribing were key themes at the event. A series of meetings through the summer may lead to new formal clinical guidance on “the appropriate use of psychiatric medications and tapering and discontinuation.”
The nature of that guidance already has emerged. The day of the summit, the Department of Health and Human Services’ Substance Abuse and Mental Health Services Administration, or SAMHSA, issued a public “dear colleague” letter to providers as well as guidance on billing information for alternatives to antidepressants.
What are alternatives to antidepressants in managing depression?
The “dear colleague” letter mentions “psychotherapy, social connection, behavioral approaches, sleep-focused treatments, physical activity interventions, and dietary and nutrition-related strategies.” These are, the letter continues, not to be viewed as “interchangeable with medication in every circumstance, nor should they be presented as sufficient for all individuals,” but rather made available as part of a bigger depression-care picture.
Medical experts already rely on a variety of types of medications, therapies and interventions to help patients, Schneck said.
“We have many proven psychotherapies that help treat depression, although we also have studies showing that the best treatment for severe depression is a combination of medications and psychotherapy, or now other neuromodulation techniques like transcranial magnetic stimulation, esketamine or ketamine, and ECT,” referring to electroconvulsive therapy, first developed nearly a century ago but “still an incredibly effective treatment,” said Schneck, who is also a professor of psychiatry at the University of Colorado Anschutz School of Medicine.
Are there barriers to accessing antidepressant alternatives?
Yes. There are many barriers to accessing some alternative antidepressant therapies. The American Psychiatric Association put it this way:
“Too many patients cannot access timely, comprehensive care, while care remains unevenly distributed across our health system,” psychiatric experts wrote.
Other challenges include: “persistent workforce shortages, limited psychiatric beds, inadequate visit time, barriers to psychotherapy and social supports, insufficient integration of psychiatric expertise in primary care through the Collaborative Care model and the lack of a true continuum of care.”
Schneck encounters these issues often. When he suggests psychotherapy, some patients tell him they can’t find a therapist, their insurance won’t cover sessions with a therapist or their copays are too high, he said.
“It’s not just a matter of there being lots of alternatives to medications,” he said. “It’s also about accessibility.”
What are the risks if patients decide to stop antidepressants?
The principal risk of going off antidepressants is falling into depression — a risk that itself depends on a patient’s history with depression. The data show that, if you have a single episode of depression, your lifetime chance of recurrence is 50%. With two episodes, it’s about 65%, and it rises to 90% with three or more episodes. In that case, “You’re virtually guaranteed that you’re going to have a relapse of depression,” Schneck said.
Another risk, though a far less likely one, is antidepressant withdrawal.
What is antidepressant withdrawal?
Withdrawal is the body’s reaction to withholding a drug it’s gotten used to. Antidepressant withdrawal (technically, antidepressant discontinuation symptoms) can include irritability, anxiety, low mood, insomnia, problems concentrating, dizziness, and numbness, among others symptoms.
“Patients sometimes feel like they have the flu. Sometimes, patients say they get these weird electric-shock sensations, either up the back of the neck or in the brain. Dizziness, lightheadedness, vertigo, nausea — those are fairly common,” Schneck said.
His experience has been that patients generally experience antidepressant withdrawal in the first two to four weeks, but withdrawal symptoms sometimes can last for months.
How common is antidepressant withdrawal?
A 2024 study concluded that at least one symptom of antidepressant withdrawal happens in about 15% of patients, so roughly one in six to seven patients who stop using an antidepressant may experience antidepressant withdrawal. The placebo effect played an interesting role: 17% of patients who had been on a placebo also reported withdrawal symptoms.
The study found that about 3% of patients dealt with severe withdrawal symptoms.
“The vast majority of patients can get off these medications successfully, and fairly easily,” Schneck said.
Are there ways to minimize antidepressant withdrawal?
Yes. It’s called hyperbolic dose reduction, which means tapering the antidepressant dose over time to help the body acclimate to its progressive absence.
Those doses can get truly tiny, Schneck said.
“As you get to lower and lower doses, you have to go smaller and smaller in terms of the milligrams you’re giving patients. Because pills don’t come in those sizes, you need to use things like compounding pharmacies or liquid formulations or liquid films, which not every doctor knows how to do,” Schneck said.
He has even had patients who open Effexor extended-release caplets and carefully count specific, ever-declining numbers of the microspheres inside as they continue to taper off the drug.
How do providers and patients decide whether antidepressants are the right choice?
“I think what a good doc does is say, ‘You know, I think you have depression, and here are the treatment options,’ just like if you had some other condition,” Schneck said. “It’s a shared decision.”
Part of that decision is about how long the patient might expect to be on antidepressants, he said, and that estimation will depend on the severity of the patient’s depression.
What should patients and providers discuss before tapering off or stopping an antidepressant?
This is another shared decision, Schneck said.
“You talk about the risks and benefits if you go off this drug, and, certainly with depression, the risk is getting depressed again,” he said.
Patients should keep doctors informed about how they’re doing after they’ve stopped using antidepressants, Schneck said. Part of the deprescribing conversation should be about signs of recurring depression that patients should look for, and, if they happen, the importance of immediately reaching out to get help.
What are doctors and some major medical societies saying about deprescribing antidepressants and the federal push for it?
Deprescribing and antidepressant withdrawal risk has been a serious topic in psychiatry for years, Schneck said. Just as he and colleagues have for years referred to the mainstay “Maudsley Prescribing Guidelines in Psychiatry,” they now do the same with the “Maudsley Deprescribing Guidelines, which came out in early 2024, he said.
In a statement timed for the May 4 summit, medical experts at the American Psychiatric Association said they welcomed attention placed on the country’s mental health crisis and federal health officials’ plans for more investment on research and training in prescribing and deprescribing. But the 40,000-member association strongly objected to “framing the nation’s mental health crisis as primarily a problem of ‘overmedicalization’ or ‘overprescribing.’”
“In psychiatry, as in all areas of medicine, prescribing and deprescribing occur every day as part of an individualized evidence-based treatment planning between physicians and patients,” association officials said.