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How Effective Are Anti-Depressants?

Many Americans battle depression. How do anti-depressant drugs work, and are how effective are they?
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Nearly 50 million adults in America experienced at least one mental illness in 2019. That’s according to the nonprofit Mental Health America’s most recent findings. More than half of adults with mental illness are going untreated. Among those mental illnesses is depression. 

Dr. Mark Rasenick, a distinguished professor of psychiatry at the University of Illinois College of Medicine, says the mood disorder is a mix of social, psychological and physical health problems. 

"It's the leading cause of disability in the world," he said. 

Depression can sometimes manifest in terrible ways. 

"The human costs are just incalculable," said Rasenick. 

And when it comes to seeking treatment the opinions can feel endless. 

But here’s the thing — doctors don’t actually have a solid understanding about what causes depression or how anti-depressants work. 

"If I could answer that question easily, then we'd be a lot further ahead than we are right now," Rasenick said. 

What doctors can say for certain is there is no single cause of depression.

"It's in your head, but it's in your blood, too. This is a biological problem and it needs a biological treatment," Rasenick continued. 

Another theory points to low serotonin levels. That’s where SSRIs – or selective serotonin re-uptake inhibitors — come in. Serotonin is usually reabsorbed by the nerve cells in a process known as "re-uptake." And SSRIs like Lexapro, Prozac or Citalopram block (or inhibit) that reabsorption so more serotonin is available to pass between cells. Doctors agree more serotonin does improve your mood. But Rasenick says the function of anti-depressants is more complicated than just bumping up serotonin levels. 

"The fact is that these drugs also work on anxiety and some other things as well. So even the term anti-depressant may be an oversimplification," he said. 

Clinicians say the medications aren't an overnight cure as the drugs can take weeks or even months to take effect. And studies show people get different benefits from them depending on the severity of depression. They were least effective in people with mild symptoms. But a 2020 study in the National Library of Medicine found 20% of people saw an improvement in their symptoms if they were on anti-depressants compared to those who weren’t. 

But some researchers like Joanna Moncrieff at University of College London question the efficacy of anti-depressants. In an umbrella study reviewing 50 years of research, Moncrieff concluded low serotonin is not the main cause of depression. While much of the medical community agreed with her findings, some criticized the paper for seemingly dismissing the efficacy of anti-depressants.  

"Though that particular paper basically said, 'well, see, SSRIs don't work well.' That's simply not true. I mean, you know, a third of the people who are taking these drugs get relief from the first drug they take," said Rasenick. 

It’s true that in many cases of depression people don’t find success with the first SSRI they try. A study funded by the National Institutes of Health found about one third of depressed patients don’t respond to several attempts and are deemed treatment-resistant. 

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But Rasenick makes this caveat: "one size never fits all. What we call depression may be a different entity in different individuals. So in effect, it's really remarkable that a third of the people respond on the first try."

In recent years doctors have discovered new potential treatments. Some of those struggling with the most severe cases of depression are trying a new, at-home medical treatment that electrically stimulates a part of the brain. Ketamine or psilocybin, known as "club drugs," are also promising. Several studies found psilocybin eases anxiety and depression, even treating veterans with PTSD. Rasenick says while results differ from patient to patient, the effects can be long-lasting. 

"It lasts. Just like the clinical reports that a single trip with psilocybin can last, can have months long antidepressant effects," said Rasenick. 

But there’s debate about how long those benefits linger. In one study published in the New England Journal of Medicine 29% of patients taking 25 milograms of psilocybin were in remission after three weeks. But effects wore off after three months.  

Regardless of treatment path, psychiatrist Dr. Sue Varma told Newsy she doesn’t believe people should solely depend on anti-depressants to treat mental illness. 

"Do we need better coping mechanisms? I always say that medications are such an important part of a comprehensive treatment program that includes therapy, exercise, meditation, yoga, friendship, connection," said Varma. 

Rasenick is also in the middle of decades of promising research that could one day make a depression diagnosis as simple as a blood test.  

"We would be able to predict whether they're going to get better at two months. Treat them in the dish with anti-depressants, a bunch of different drugs, and say, ah, this one's going to work in you," said Rasenick. 

Deciding whether an anti-depressant is the best path for your recovery is up to you and your doctor. And taking medication now doesn’t mean it’s forever. Rasenick says it’s very common for people to slowly wean off their meds after a depressive episode and pick them back up again when they need to. But he acknowledged that stigma and shame stop many from trying in the first place. 

"Saying, 'well, it's all in my head, I'll get over it or I won't seek treatment because it doesn't, you know, I'm too tough for that—' It's a real problem," said Rasenick. 

It's a problem with the potential for a solution, no matter how hopeless it may feel.