Video: Antidepressants work, but some better than others

Study seeks to end antidepressant debate: the drugs do work

Video: Antidepressants work, but some better than others

LONDON (Reuters) – A vast research study that sought to settle a long-standing debate about whether or not anti-depressant drugs really work has found they are indeed effective in relieving acute depression in adults.

The international study – a meta-analysis pooling results of 522 trials covering 21 commonly-used antidepressants and almost 120,000 patients – uncovered a range of outcomes, with some drugs proving more effective than others and some having fewer side effects.

But all 21 drugs – including both off-patent generic and newer, patented drugs – were more effective than placebos, or dummy pills, the results showed.

“Antidepressants are routinely used worldwide yet there remains considerable debate about their effectiveness and tolerability,” said John Ioannidis of Stanford University in the United States, who worked on a team of researchers led by Andrea Cipriani of Britain’s Oxford University.

Cipriani said these findings now offered “the best available evidence to inform and guide doctors and patients” and should reassure people with depression that drugs can help.

“Antidepressants can be an effective tool to treat major depression, but this does not necessarily mean antidepressants should always be the first line of treatment,” he told a briefing in London.

According to the World Health Organization, some 300 million people worldwide have depression. While both pharmacological and psychological treatments are available, only one in six people with depression in rich countries gets effective treatment. That drops to one in 27 patients in poor and middle-income countries.

EFFECTIVENESS VARIES

The study, published in The Lancet medical journal, found some differences in the effectiveness of the 21 drugs.

In general, newer antidepressants tended to be better tolerated due to fewer side effects, while the most effective drug in terms of reducing depressive symptoms was amitriptyline – a drug first discovered in the 1950s.

Some well-known medicines – such as the selective serotonin reuptake inhibitor (SSRI) fluoxetine, sold under the Prozac brand – were slightly less effective but better tolerated.

The scientists noted that their study could only look at average effects, so should not be interpreted as showing that antidepressants work in every patient. Only around 60 percent of people prescribed depression medication improve, Cipriani said.

“Unfortunately, we know that about one third of patients with depression will not respond to them,” he said. “It’s clear there is still a need to improve treatments further.”

Several experts not directly involved in the study said its results gave a clear message.

“This meta-analysis finally puts to bed the controversy on antidepressants,” said Carmine Pariante, a professor at Britain’s Institute of Psychiatry, Psychology and Neuroscience.

James Warner, a psychiatrist at Imperial College London, added: “Depression causes misery to countless thousands every year and this study adds to the existing evidence that effective treatments are available.”

Reporting by Kate Kelland; Editing by Gareth Jones

Our Standards:The Thomson Reuters Trust Principles.

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Source: https://www.reuters.com/article/us-health-antidepressants/study-seeks-to-end-antidepressant-debate-the-drugs-do-work-idUSKCN1G52XX

Some antidepressants work better than others – now we know why

Video: Antidepressants work, but some better than others

Three million Australians are currently living with depression or anxiety, and antidepressants are now the third most commonly prescribed class of medication in Australia, after antibiotics and cholesterol-lowering drugs.

Doctors have up to nine different types of antidepressant medications at their disposal, each of which produces different changes in chemical levels in the brain and downstream changes.

Although we’ve long known that some antidepressants are more effective than others, we haven’t been clear about why. A study we recently published in the journal Neuroscience & Behaviours Review shows the answer might come down to changes in the activity of the amygdala, an almond- region responsible for automatic vigilance.

Getting the right fit

For people with depression or anxiety, finding an effective medication is a difficult task, often requiring lengthy periods of trial and error.

During these periods, patients are prescribed a particular medication and dose, with the hope that it will be effective. If it’s ineffective, the dose may be changed or the patient will have to try a different medication altogether.

The longer these trial-and-error periods are, the longer the patient remains unwell. This may result in everyday struggles with work and family or, in more serious cases, the risk of suicide or other harmful behaviours.

Serotonin is involved in mood and emotion and noradrenaline is involved in stress and attention. Both are thought to be involved in depression and anxiety.

The more commonly prescribed medications increase levels of serotonin (serotonin selective reuptake inhibitors or SSRI) or noradrenaline (noradrenaline reuptake inhibitors or NRIs), and some produce increases in both (serotonin and noradrenaline reupatake inhibitors or SNRIs).

For the average patient, antidepressants that cause increases in serotonin (SSRIs) have been shown to be more effective than those that only increase levels of noradrenaline (NRIs).

However, NRIs are still prescribed as they may be effective in some patients, and they are sometimes used in combination with other medications.

SSRIs vs NRIs

Our research suggests that the varying effectiveness of SSRIs and NRIs may be underpinned by their different impacts on brain activity, which can be seen after just one dose.

We took brain activity data from nine different international studies. Five studies looked exclusively at SSRIs, two looked exclusively at NRIs, and the other two looked at both SSRIs and NRIs. A total of 152 patients participated in these studies: 103 received SSRIs while the other 81 received NRIs.

When participants were given an SSRI, the amygdala became less active. This indicates that our brains become less emotionally reactive after a single dose of an antidepressant.

SSRI treatment also increased activity in frontal regions of the brain, including a region of the prefrontal cortex involved in regulating emotions, suggesting that SSRIs may increase capacity to regulate our emotions.

In contrast, when participants were given an NRI, only frontal regions increased in activity, while amygdala activity did not change.

So, SSRIs may be more effective than NRIs for treating mood and anxiety disorders because SSRIs impacted the emotionally reactive amygdala, while NRIs did not.

Next steps

These findings are important because patients only begin to display observable changes in symptoms after six weeks of ongoing treatment. But if the increases in frontal lobe activity and decreases in amygdala activity follow a single dose of an SSRI, this could act as an early indicator of the effectiveness of treatment over the longer term.

The next steps in our research are to further investigate how these changes occur, and whether genetic differences play a role. More research is also needed on both healthy people and patient samples to better understand how antidepressant treatments work and to predict outcomes with different treatments.

Though we don’t yet have the answers or tests to predict whether a treatment will work for a particular patient, it’s important that we increase our understanding about why some antidepressants are more effective than others.

The authors acknowledge the assistance of Rachel Martin in the preparation of this article.

Source: http://theconversation.com/some-antidepressants-work-better-than-others-now-we-know-why-17850

Major Study Finds Antidepressants Work, But May Have Limitations

Video: Antidepressants work, but some better than others

For years, researchers have been debating the efficacy of antidepressants, which are used by around 13 percent of Americans over the age of 12.  As Aaron E. Carroll reports for the New York Times, a comprehensive new study has shown that the drugs do work, but their benefits may be modest.

The study, published late last month in The Lancet, analyzed 522 double-blind studies that included 116,477 patients and 21 commonly prescribed antidepressants. The paper marks the most comprehensive study on antidepressants to date, and, according to its authors, includes “the largest amount of unpublished data” of any study on the medications.

Using a network meta-analysis technique, which allows scientists to simultaneously compare multiple treatments, the researchers sought to determine antidepressants’ efficacy and their acceptability, or how many patients stuck to taking the drugs at prescribed intervals. The results of the study showed that all 21 of the antidepressants were more effective than placebos in reducing depressive symptoms during the first eight weeks of treatment. Large and small trials did not vary significantly in their results.

The new analysis suggests, however, that the efficacy of the drugs may be limited. For one thing, the benefits applied in the short term, and only to patients who are suffering from acute major depression.

“[W]e still do not know how well antidepressants work for those with milder symptoms that fall short of major depression, especially if patients have been on the drugs for months or even years,” Carroll writes.

“Many people probably fall into that category, yet are still regularly prescribed antidepressants for extended periods.”

The researchers also found evidence of the “novelty effect:” Antidepressants worked better when they first came onto the market, but were shown to lose efficacy and acceptability as the years went on. Additionally, not all of the drugs were shown to be equally effective.

“Some antidepressants were more effective than others, with agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine proving most effective, and fluoxetine, fluvoxamine, reboxetine, and trazodone being the least effective,” the study authors write.

(These are the generic names for antidepressants commonly sold in the U.S., including Prozac, Elavil and Paxil.)

As Olivia Goldhill of Quartz points out, much of the past evidence showing that antidepressants may be no more effective than placebos derives from a 2008 meta-analysis led by Irving Kirsch, associate director of the Program in Placebo Studies at Harvard Medical School.

Kircsh used the Freedom of Information Act to obtain data that was sent to the Food and Drug Administration by pharmaceutical companies seeking approval for antidepressants. (Un peer-reviewed literature, pharmaceutical companies must submit the results of their trials regardless of the result.) They found 74 trials covering more than 12,500 patients.

The researchers showed that around half of those trials showed antidepressants were more effective than a placebo. But as Carroll notes, the published literature did not reflect these results.

While all of the “positive” studies were published, only three of the “negative” studies, or studies that did not show statistically significant benefits for antidepressants, had been published in journals. Eleven had been presented to appear positive, and 22 never appeared in medical literature.

In an effort to gain a more accurate picture of the drugs’ effectiveness, the new study analyzed 86 unpublished trials found on trial registries and pharmaceutical company websites. The new analysis includes an additional 15 unpublished studies discovered through “personal communication or [by] hand-searching other review articles,” the study authors write.

Researchers also asked for and received unpublished data from more than half of the trials included in the study, in order to account for potentially misleading representations of trial outcomes in published journal articles. But lingering questions of bias remain. Of the 522 trials included in the new analysis, 409 were funded by pharmaceutical companies.

So while the new study suggests that antidepressants are more effective than a placebo, at least in some cases, media reports claiming that the research shows “antidepressants do work, and many more people should take them” are not entirely accurate.

“The clinical (as opposed to statistical) significance of the treatment effects that we detected will continue to be contested,” John Ioannidis, a co-author of the study who has previously argued that the benefits of antidepressants have been inflated, tells Carroll. “[I]t is still important to find ways that one can identify the specific patients who get the maximum benefit.”

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Source: https://www.smithsonianmag.com/smart-news/major-study-finds-antidepressants-work-may-have-limitations-180968452/

Antidepressants really work, major new study confirms; some are better than others

Video: Antidepressants work, but some better than others

Antidepressant drugs actually do help ease depression, countering debate over whether the medications do what they're supposed to, a large research review has found.

Some antidepressants, though, are more effective and better tolerated than others, the findings showed.

The researchers analyzed data from 522 trials — published and unpublished — that included more than 116,000 participants. Of the 21 antidepressants studied, all of them worked better than a placebo.

  • Antidepressant use in U.S. soars by 65 percent in 15 years

“In the short-term, for acute depression, antidepressants seem to work modestly,” said study author Dr. John Ioannidis. He's a professor of disease prevention at Stanford University in California. “They do have some benefit, on average, but they are not a panacea. Clearly, we need more effective interventions.”

Antidepressants sold in the United States that the study found to be most effective included:

  • Amitriptyline
  • Effexor (venlafaxine)
  • Lexapro (escitalopram)
  • Paxil (paroxetine)
  • Remeron (mirtazapine)
  • Trintellix (vortioxetine)

Those that made the least-effective list of antidepressant drugs sold in the United States included:

  • Luvox (fluvoxamine)
  • Oleptro (trazodone)
  • Prozac (fluoxetine)

When the researchers checked which depression drugs were tolerated the best, these topped the list:

  • Celexa (citalopram)
  • Lexapro (escitalopram)
  • Prozac (fluoxetine)
  • Trintellix (vortioxetine)
  • Zoloft (sertraline)

The drugs that were found to be less well-tolerated included:

  • Amitriptyline
  • Anafranil (clomipramine)
  • Cymbalta (duloxetine)
  • Effexor (venlafaxine)
  • Luvox (fluvoxamine)
  • Oleptro (trazadone)

The study authors wrote that there's been “a long-lasting debate and concern about [antidepressants'] efficacy and effectiveness, because short-term benefits are, on average, modest and because long-term balance of benefits and harms is often understudied.”

However, Dr. Richard Catanzaro, chairman of psychiatry at Northern Westchester Hospital in Mount Kisco, N.Y., said this review shows that “all of these medications can be effective in treating depression.”

He explained that “all distinguish themselves from placebo, but there's no hands-down winner.”

  • Most antidepressants ineffective in teens, study finds

And, Catanzaro said, if you're looking for the most tolerable and the most effective, you're left with Lexapro and Trintellix.

Are antidepressants ineffective for teens?

In addition, Catanzaro noted that while amitriptyline was on the most-effective list, it was also on the least-tolerated list, and he said it's generally not considered a first-line drug for depression treatment.

Ioannidis said that the differences between the medications were small, so even medications on the less-effective list might work very well for some people.

That's another issue with antidepressant medications, Catanzaro explained: What works well for one person doesn't always work well for another, so there may be some trial and error involved in finding the right medication for you.

It's also important to be sure you're getting the right dose of medicine and that you take the drug long enough to give it time to work well, Catanzaro said. That can be as long as four to six weeks.

Both Ioannidis and Catanzaro said that people with depression shouldn't rely on medications alone, whenever possible.

“I would never advocate that antidepressants are the only way to approach this major problem,” Ioannidis said, recommending psychotherapy with medications.

Study finds antidepressants during pregnancy do not cause autism

Catanzaro said that he, too, recommends therapy along with medication. “But in many areas it can be hard to get good-quality therapy. Medications are often the only treatment people have access to, and if the alternative is nothing, then that's certainly preferable,” he advised.

Both experts noted that this study looked only at responses after eight weeks of treatment. How these medications might work for people taking them for years was not assessed.

The study was published online Feb. 21 in The Lancet.

First published on February 22, 2018 / 12:11 PM

© 2018 HealthDay. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

Source: https://www.cbsnews.com/news/antidepressants-really-work-study-confirms-some-better-than-others/

Antidepressants Do Work, Some Better Than Others

Video: Antidepressants work, but some better than others

From the WebMD Archives

By Serena Gordon

HealthDay Reporter

THURSDAY, Feb. 22, 2018 (HealthDay News) — Antidepressant drugs actually do help ease depression, countering debate over whether the medications do what they're supposed to, a large research review has found.

Some antidepressants, though, are more effective and better tolerated than others, the findings showed.

The researchers analyzed data from 522 trials — published and unpublished — that included more than 116,000 participants. Of the 21 antidepressants studied, all of them worked better than a placebo.

“In the short-term, for acute depression, antidepressants seem to work modestly,” said study author Dr. John Ioannidis. He's a professor of disease prevention at Stanford University in California. “They do have some benefit, on average, but they are not a panacea. Clearly, we need more effective interventions.”

Antidepressants sold in the United States that the study found to be most effective included:

  • Amitriptyline
  • Effexor (venlafaxine)
  • Lexapro (escitalopram)
  • Paxil (paroxetine)
  • Remeron (mirtazapine)
  • Trintellix (vortioxetine)

Those that made the least-effective list of antidepressant drugs sold in the United States included:

  • Luvox (fluvoxamine)
  • Oleptro (trazodone)
  • Prozac (fluoxetine)

When the researchers checked which depression drugs were tolerated the best, these topped the list:

  • Celexa (citalopram)
  • Lexapro (escitalopram)
  • Prozac (fluoxetine)
  • Trintellix (vortioxetine)
  • Zoloft (sertraline)

The drugs that were found to be less well-tolerated included:

  • Amitriptyline
  • Anafranil (clomipramine)
  • Cymbalta (duloxetine)
  • Effexor (venlafaxine)
  • Luvox (fluvoxamine)
  • Oleptro (trazadone)

The study authors wrote that there's been “a long-lasting debate and concern about [antidepressants'] efficacy and effectiveness, because short-term benefits are, on average, modest and because long-term balance of benefits and harms is often understudied.”

However, Dr. Richard Catanzaro, chairman of psychiatry at Northern Westchester Hospital in Mount Kisco, N.Y., said this review shows that “all of these medications can be effective in treating depression.”

He explained that “all distinguish themselves from placebo, but there's no hands-down winner.”

And, Catanzaro said, if you're looking for the most tolerable and the most effective, you're left with Lexapro and Trintellix.

In addition, Catanzaro noted that while amitriptyline was on the most-effective list, it was also on the least-tolerated list, and he said it's generally not considered a first-line drug for depression treatment.

Ioannidis said that the differences between the medications were small, so even medications on the less-effective list might work very well for some people.

That's another issue with antidepressant medications, Catanzaro explained: What works well for one person doesn't always work well for another, so there may be some trial and error involved in finding the right medication for you.

It's also important to be sure you're getting the right dose of medicine and that you take the drug long enough to give it time to work well, Catanzaro said. That can be as long as four to six weeks.

Both Ioannidis and Catanzaro said that people with depression shouldn't rely on medications alone, whenever possible.

“I would never advocate that antidepressants are the only way to approach this major problem,” Ioannidis said, recommending psychotherapy with medications.

Catanzaro said that he, too, recommends therapy along with medication. “But in many areas it can be hard to get good-quality therapy. Medications are often the only treatment people have access to, and if the alternative is nothing, then that's certainly preferable,” he advised.

Both experts noted that this study looked only at responses after eight weeks of treatment. How these medications might work for people taking them for years was not assessed.

The study was published online Feb. 21 in The Lancet.

SOURCES: John P.A. Ioannidis, M.D., D.Sc., professor, disease prevention,  and professor, statistics and biomedical data science,  Stanford University, Stanford, Calif.; Richard Catanzaro, M.D., chairman of psychiatry, Northern Westchester Hospital, Mount  Kisco, N.Y.; Feb. 21, 2018,The Lancet, online Copyright © 2013-2018 HealthDay. All rights reserved.

Source: https://www.webmd.com/depression/news/20180222/antidepressants-do-work-some-better-than-others

Do Antidepressants Work?

Video: Antidepressants work, but some better than others
Continue reading the main storyImageAntidepressants are widely used, but there are still so many unanswered questions about them.Credit…Jonathan Nourok/Getty Images

More people in the United States are on antidepressants, as a percentage of the population, than any other country in the world. And yet the drugs’ efficacy has been hotly debated.

Some believe that the short-term benefits are much more modest than widely thought, and that harms may outweigh benefits in the long run. Others believe that they work, and that they can be life-changing.

Settling this debate has been much harder than you might think.

It’s not that we lack research. Many, many studies of antidepressants can be found in the peer-reviewed literature. The problem is that this has been a prime example of publication bias: Positive studies are ly to be released, with negative ones more ly to be buried in a drawer.

In 2008, a group of researchers made this point by doing a meta-analysis of antidepressant trials that were registered with the Food and Drug Administration as evidence in support of approvals for marketing or changes in labeling. Companies had to submit the results of registered trials to the F.D.A. regardless of the result. These trials also tend to have less data massaging — such as the cherry-picking of outcomes — than might be possible in journals.

The researchers found 74 studies, with more than 12,500 patients, for drugs approved between 1987 and 2004. About half of these trials had “positive” results, in that the antidepressant performed better than a placebo; the other half were “negative.

” But if you looked only in the published literature, you’d get a much different picture. Nearly all of the positive studies are there. Only three of the negative studies appear in the literature as negative.

Twenty-two were never published, and 11 were published but repackaged so that they appeared positive.

A second meta-analysis published that year also used F.D.A. data instead of the peer-reviewed literature, but asked a different question.

Researchers wondered if the effectiveness of a study was related to the baseline levels of depression of its participants. The results suggested yes.

The effectiveness of antidepressants was limited for those with moderate depression, and small for those with severe depression.

The take-home message from these two studies was that the effectiveness of antidepressants had been overstated, and that the benefit might be limited to far fewer patients than were actually using the drugs.

These points, and more, were made in a paper written by John Ioannidis in the journal Philosophy, Ethics, and Humanities in Medicine in 2008.

He argued that the study designs and populations selected, especially the short length of many studies, biased them to positive results. He argued that while many studies achieved statistical significance, they failed to achieve clinical significance.

He argued that we knew too little about long-term harms, and that we were being presented with biased information by looking only at published data.

This paper — “Effectiveness of Antidepressants: An Evidence Myth Constructed From a Thousand Randomized Trials?” — sowed lingering doubts about the use of antidepressants and the conduct of medical research. But recently, the most comprehensive antidepressants study to date was published, and it appears to be a thorough effort to overcome the hurdles of the past.

Researchers, including Dr. Ioannidis this time, searched the medical literature, regulatory agency websites and international registers for both published and unpublished double-blind randomized controlled trials, all the way till the beginning of 2016.

They looked for both placebo-controlled and head-to-head trials of 21 antidepressants used to treat adults for major depressive disorder.

They used a “network meta-analysis technique,” which allows multiple treatments to be compared both within individual trials directly and across trials indirectly to a common comparator.

They examined not only how well the drugs worked, but also how tolerated the treatment was — what they called acceptability.

They found 522 trials that included more than 116,000 participants. Of those, 86 were unpublished studies found on trial registries and company websites.

An additional 15 were discovered through personal communication or by hand-searching review articles.

The authors went an extra step and asked for unpublished data on the studies they found, getting it for more than half of the included trials.

The reassuring news is that all of the antidepressants were more effective than placebos. They varied modestly in terms of efficacy and acceptability, so each patient and doctor should discuss potential benefits and harms of individual drugs.

Further good news is that smaller trials did not have substantially different results from larger trials.

It also did not appear that industry sponsoring of trials correlated with significant differences in response or dropout rates. But — and this is a big “but” — the vast majority of trials are funded by industry. As a result, this meta-analysis may not have had enough data on non-industry trials to accurately determine if a difference exists.

There were also signs of “novelty” bias: Antidepressants seemed to perform better when they were newly released in the market but seemed to lose efficacy and acceptability in later years.

The bad news is that even though there were statistically significant differences, the effect sizes were still mostly modest.

The benefits also applied only to people who were suffering from major depression, specifically in the short term.

In other words, this study provides evidence that when people are found to have acute major depression, treatment with antidepressants works to improve outcomes in the first two months of therapy.

Because we lack good data, we still do not know how well antidepressants work for those with milder symptoms that fall short of major depression, especially if patients have been on the drugs for months or even years.

Many people probably fall into that category, yet are still regularly prescribed antidepressants for extended periods. We don’t know how much of the benefit received from such use is a placebo effect versus a biological one.

I asked Dr. Ioannidis if the results of this new study were as radical as many news articles had suggested.

He confirmed that this was a much-larger meta-analysis — with about 10 times more information — than the ones from a decade ago, with more unpublished data and more antidepressants covered.

He’s also hopeful that future studies will be even better at informing individual-level responses, which might help to see if some patients benefit substantially even when others don’t seem to benefit at all.

But he thought that some of the exuberance in the news media might be a little overblown.

“I am afraid that some news stories gave very crude interpretations that may be misleading, especially when their titles were too absolute, ‘the drugs work’, ‘the debate is over’ and so forth,” he said.

“The clinical (as opposed to statistical) significance of the treatment effects that we detected will continue to be contested, and it is still important to find ways that one can identify the specific patients who get the maximum benefit.”

Even with so much research on antidepressants, there are still many unanswered questions. It’s unclear if drug companies would be interested in the results, or indeed why they would be. The drugs are already being widely used, and no regulatory agency is requiring more data. If patients want answers, they will need to demand the research themselves.

“,”author”:”Aaron E. Carroll”,”date_published”:”2018-03-12T09:00:11.000Z”,”lead_image_url”:”https://static01.nyt.com/images/2018/03/13/upshot/up-healthdepress/up-health-Jumbo.jpg”,”dek”:null,”next_page_url”:null,”url”:”https://www.nytimes.com/2018/03/12/upshot/do-antidepressants-work.html”,”domain”:”www.nytimes.com”,”excerpt”:”The most comprehensive study on them has recently been published, showing mostly modest effects.”,”word_count”:1204,”direction”:”ltr”,”total_pages”:1,”rendered_pages”:1}

Source: https://www.nytimes.com/2018/03/12/upshot/do-antidepressants-work.html

I spent half my life on antidepressants. Today, I’m off the medication and feel all right

Video: Antidepressants work, but some better than others

The prescriptions began in the wake of my father’s sudden death when I was 15: Wellbutrin XL and Effexor XR for anxiety and depression, two separate doses of Synthroid to right a low-functioning thyroid, a morning and nighttime dose of tetracycline for acne, birth control to regulate the unpleasant side effects of womanhood, and four doses of Sucralfate to be taken at each meal and before bedtime — all given to me by the time I was old enough to vote.

My general practitioner asked what Sucralfate was after I’d finished rattling off my prescriptive party mix during our first appointment. I was 22 and a recent Manhattan transplant. I had an apartment in Murray Hill and a job waiting tables at a local Italian restaurant.

“It’s for something called bile reflux disease,” I said. “I used to randomly puke up bile all the time.”

“Huh. Never heard of it.” He ripped off a completed prescription slip and scribbled across the new blank page.

“You should really get the prescription for antidepressants from a psychiatrist, but I’ll give it to you along with all the rest since you’ve been on it for so long. And whenever you come back, maybe we should do a physical.”

At the time, it never occurred to me that my medication needed monitoring or that perhaps my doctor should do a physical before sending me to the pharmacy.

Not only was this five-minute exchange routine, but at no point during my years in the American mental health system did a psychiatrist, psychologist, doctor or pharmacist suggest that I consider reevaluating the decision to take antidepressants.

Therefore, I believed that my only choices were to cope with depression or cope with antidepressants, and that depression would always thump inside me with the regularity of my own pulse.

At age 30, I found myself hanging halfway out my Manhattan high-rise window, calculating the time it would take to hit the ground.

Still depressed despite my antidepressants — possibly caused by the possible decrease in antidepressants’ efficacy over time or because I’d never properly dealt with loss and trauma — I regularly considered suicide.

As I looked for breaks in the pedestrian traffic patterns, a thought dawned on me: I’ve spent half my life — and my entire adult life — on antidepressants. Who might I be without them?

The suicidal gears in my mind came to a screeching halt.

I pulled myself back inside my apartment, scheduled an appointment with a new psychiatrist and made the decision to get off all the drugs before deciding whether to take my life. I needed to figure out my true baseline. If I didn’t what I found, well, the window was always open.

Flash forward to today, 3½ years since I took my last antidepressant. I’m all right. Deeply, honestly, joyfully, all right.

I followed my psychiatrist’s advice and went off one drug at a time, beginning with Effexor XR. I was on the lowest dose available — just 37.5 mg per day — so I had no choice but to stop taking the Effexor, cold turkey.

Within 24 hours of missing my usual dose, flu symptoms set in and my emotions went into overdrive; so in between the sweats and the shakes, I resisted the urge to saw off my skin with a box cutter just to get away from myself.

After six days without the drug in my system, my mind began to flood with bloody, homicidal visions. I was too scared to tell my psychiatrist what was flashing through my mind because I feared that she would deem me a danger to myself or others and put me on an involuntary, psychiatric hold.

I called an old family friend, a psychologist who lived across the country. She assured me that I wasn’t going to hurt anyone, but I still didn’t trust myself not to snap. So I locked myself in my apartment for a week.

The visions eventually lifted and were replaced by an intolerable sensitivity to light and sound. I tore the clothes off my back when shirts I’d worn for years suddenly became unbearably itchy. Then, I bent a metal ironing board in half rage.

I am not alone in this experience. In one New Zealand study of 180 long-term antidepressant users, 73 percent of participants reported withdrawal effects, with 33 percent reporting their effects as severe.

Even several clinical trials aimed at discontinuing long-term antidepressant prescriptions “failed to successfully withdraw a majority of patients from the drugs despite slow and gradual tapers,” according to a 2019 article on antidepressant withdrawal published in Epidemiology and Psychiatric Sciences.

For many people, antidepressants can be literal lifesavers. But not everyone wants to stay on them indefinitely, and herein lies the problem: There are few accounts about what it’s to get off and stay off these drugs. For good.

The conversation is beginning to shift about the efficacy of long-term antidepressant use, with articles in the Wall Street Journal and New York Times discussing questions that have long been neglected. But I think an important aspect of the issue remains overlooked: the importance of hope and role models.

I’ve spent the past 3½ unmedicated years wandering back through time, trying to untangle the decisions that led me to calculating the rate of a falling object from my windowsill. I began speaking publicly on the topic in an effort to organize my thoughts and break the shame I felt for letting my 20s slip away into a depressed, robotic haze.

When audience members approached me and told me that I gave them hope for their sons, their daughters, for themselves, I initially brushed these declarations off as niceties given to anyone who stands onstage and bares part of their soul. But as I reach a broader audience, my inbox is filled with messages from strangers specifically asking how I got off antidepressants.

This strikes me as odd. I’m not a medical professional. My bachelor’s degree is in history. I spent most of my career making $7.25 an hour in sweaty Manhattan kitchens, and there’s little I can offer others than to wish them well and send them links to a few books that helped me.

And the people who tend to contact me are not without other resources.

Among the strangers who have reached out to me in the past year: a Google executive, an American Airlines pilot, an audiologist, a physician assistant, a wealthy software developer and more than a few veterans.

They tell me that they’ve taken the drugs, talked to the doctors, practiced yoga, changed their diet and filled out the gratitude journals. And yet, they’re still depressed. What are they missing?

“Objectivity is what makes therapists so effective,” says J.P. Crum, a Reno, Nev., psychologist, “but it also comes with a loss of power. When patients can talk with other people who have had the same experience, who know what it’s , that can sometimes be even more powerful and effective than what a psychologist or psychiatrist can do.”

The people who reach out to me are looking for hope. Hope that they can escape what’s been presented to them as a choice between depression or antidepressants. They want to rewrite their own personal stories, they want role models for how to do that, and few are available.

“The lack of research into patients who have recovered from depression is a great puzzle to me,” says Jonathan Rottenberg, professor of psychology at the University of South Florida.

“The fields of psychology, psychiatry, epidemiology, and public health focus on the causes of people doing poorly — having more depression and more symptoms — rather than the causes of people doing well.

We need to flip that paradigm.”

But hope, much depression itself, can’t be measured in a lab. So what role does it play in the brain?

“Neurotransmitters are activated by more than just medicine,” Crum says. “If you eat something you , chocolate for example, dopamine spikes. It’s a pleasurable activity that has nothing to do with medication. Having hope, being inspired, being encouraged — that’s a pleasurable state. There’s a chemical change because you feel different.”

Fidel Vila-Rodriguez, a clinician-scientist at the University of British Columbia, says he observes the effects of hope in his research on the neurobiology of mental disorders.

“Before the clinical trial begins,” he says, “patients report all these symptoms.

Three days later, when they’ve officially entered the clinical trial but we haven’t begun any treatment, they tell us that they’re doing better. It’s because they have hope. We [as researchers] have done nothing.

There are variables — nonmedication and nontreatment factors — that contribute to people feeling better. Hope is one of them.”

Had I been shown a role model for hope and a life without antidepressants early on, would I have spent so many years struggling to cope? I can’t ever know the answer. That’s part of what was taken from me.

But what I do know is that we rarely speak about depression as a temporary human experience.

So let me introduce myself:

My name is Brooke Siem. I am 33 years old. I spent nearly 15 years on antidepressants. As of today, it’s been 1,368 days without them.

He wanted a new prescription. He ended up in the psych ward instead.

What your psychiatrist may not be telling you about antidepressants

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