Antidepressants May Not Be All They’re Cracked Up to Be

In his new book, ‘Lost Connections,’ author Johann Hari argues that antidepressants aren’t the miracle cure-all we’ve made them out to be.

depression anxiety antidepressant anti depressant paxil prozac ssri serotonin johann hari do they work

Photo Illustration by The Daily Beast

In a new book called Lost Connections: Uncovering the Real Causes of Depression and the Unexpected Solutions, writer Johann Hari questions whether antidepressants used to treat depression and anxiety actually work.

“We need to have a much more nuanced conversation about chemical antidepressants and their effectiveness,” he told The Daily Beast. While he believes they should remain on the menu of treatment options—certainly they are helpful for many—he maintains that society has developed an over-reliance on them. Hari argues there is no one-size-fits-all approach to depression, a complex condition that can be created by many factors, including genetic vulnerability, stressful life events, bad working conditions, and medical problems.

The debut of his book coincides with a major study published this month in The Lancet showing that antidepressants are more effective at treating major and moderate depression than placebo pills, at least for the first eight weeks of use. Researchers analyzed data from 522 trials, which included nearly 120,000 subjects. They found that some antidepressants are one-third more effective in relieving the symptoms of depression than placebos; others are more than twice as effective.

The drugs found to be more effective include agomelatine (not available in the U.S.) amitriptyline, escitalopram, mirtazapine, and paroxetine. (The last four, under the brand names Elavil, Lexapro, Remeron, and Paxil, respectively, have been approved by the FDA.) The least effective include fluoxetine (Prozac), fluvomaxine (Luvox), and trazedone.

That Prozac—perhaps the most popular of the antidepressants—isn’t as effective is striking.

Since the data covered only two months of treatment, it is difficult to conclude what the drugs’ long-term benefits might be. The lead researcher of the study, University of Oxford psychiatrist Andrea Cipriani, told the BBC: “Medication should be considered alongside other options, such as psychological therapies, where these are available.”

However, a six-year study of subjects with major depressive disorders found that the drugs offered only modest long-term benefits. Hari himself was on antidepressants for 13 years. And while it worked for him for brief periods of time—he shared Cipriani’s theory, too: What if the roots of depression are not solely chemical?

Lost Connections is a followup to Hari’s 2015 bestseller Chasing the Scream, about the century-old “war on drugs.” His new book explores the antidepressant industry and whether the drugs help ease the anxiety and depression that they purport to treat.

Hari bases his book on his own experiences with depression. When Hari was a teenager, he fell into a deep, painful despair. He went to his family physician, who diagnosed him with depression.

This didn’t surprise Hari; his mother, too, suffered from the illness, and he’d seen her take medication to ease her condition.

The doctor pulled out a picture of the brain and explained Hari’s problem as simply as an orthopedist might identify a broken leg on an X-ray: His brain wasn’t making enough of the neurotransmitter serotonin, which has been linked to emotional regulation.

It was as simple as that, and Hari felt relieved. The doctor prescribed the antidepressant Paxil and told him he’d feel better soon.

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To Hari, now 39 and baby-faced, it all made sense. He’d grown up amidst turbulence: His mother and father divorced when he was young, and he experienced extreme violence at the hands of another adult, whom he prefers not to name. Meanwhile, Margaret Thatcher had told his fellow citizens of the U.K. that it was not up to society to provide a social safety net, but rather on families or themselves for help.

He saw the chemical antidepressants as his only hope. His brain, after all, was broken. And he’s not the only one to think that upping his antidepressant intake would help mend his broken brain.

At about the same time, scientists came forward with a seemingly magical treatment for depression, the first of a new class of antidepressants called selective serotonin reuptake inhibitor, or SSRIs. Though their exact mechanism is unknown and side effects remain unclear, SSRIs seem to work by increasing serotonin by inhibiting its reabsorption. That means there’s more serotonin left to bind to the postsynaptic receptor and therefore regulate the neurological chemicals that might be putting a person into depression. SSRIs led to the development of the blockbuster drug Prozac, which made its American debut in 1987. 

Hari believed Paxil could solve everything. And initially, it did, as even The Lancet noted regarding the drug’s effectiveness. But soon, he fell despondent again. His doctor increased his drug’s dosage, and his symptoms improved.

This pattern continued for 13 years. Hari would take more medication, only to feel his psychic pain roaring back. Still, he saw the chemical antidepressants as his only hope. His brain, after all, was broken. And he’s not the only one to think that upping his antidepressant intake would help mend his broken brain. According to a 2017 report from the World Health Organization, an estimated 300 million people suffer from depression, and another 264 million have anxiety disorders, figures that have been steadily rising (PDF). Meanwhile, the prescription rates of antidepressants have soared. (Antidepressants are often prescribed to treat both disorders.)

Hari stopped taking antidepressants when he was 31. To be sure, it’s not a decision he recommends for everyone. But Hari said he found relief, substituting medication with social connections and talk therapy.

Hari’s book explores whether patients and doctors have been bamboozled into thinking depression is caused by spontaneously malfunctioning brains, despite the fact that research has long showed that depression and anxiety have psychological and social sources that may not be easily fixed with antidepressants. Neither he nor his sources argue that drugs aren’t helpful for some—as many as 17 percent of people in the U.S. take medicine for psychiatric issues, and for many, they can be life-saving. Yet those drugs, prescribed at similarly high rates in other developed countries aren’t without larger side effects: insomnia, nausea, blurred vision, weight gain, sexual problems, and more, according to the Mayo Clinic. Even our filtered water supply is laced with the antidepressants our bodies excrete.

In Lost Connections, Hari reports that pharmaceutical companies of the biggest-selling selective SSRIs cherry-picked the findings of their drug trials in order to gain FDA approval. Despite its widespread use, for example, a 2014 meta-analysis of antidepressants found it difficult to ascertain the effects of antidepressants, because up to 40 percent of drug trials aren’t made public by pharmaceuticals—which can lead to bias and overblowing drug efficacy. And a 2015 BMJ study showed that antidepressant use among teens can lead to worrisome consequences like suicide ideation and cardiovascular problems.

Hari points to the measurement of depression on something called the Hamilton Scale (PDF), which runs from a 1, in which you’re joyful, to a 59, where you feel suicidal. Typically, movement on the scale is incremental: Improving sleep patterns, for example, can bump you up six points. And according to a leading researcher at Harvard Medical School, Irving Kirsch, chemical antidepressants give an average boost of 1.8 points.

Many of Hari’s sources, including Kirsch, were initially convinced that chemicals provided the best answer to a major global health crisis. But Kirsch and others have increasingly become antidepressant skeptics, suggesting wider societal pressure might be to blame.

“We think in individualistic and materialistic terms, and believed antidepressants were the answer to our problems,” he said. “But the truth is, many of us feel this way because we’re living in a way that’s incompatible with human nature.” What people crave but don’t get in modern life, Hari firmly believes, is for someone to pay attention to them. To be sure, this is a controversial way of thought in approaching depression, to think that medication can be replaced by social networks. But Hari stands by this thought, as he recounts that never during his run on antidepressants did anyone, even his therapist, ask him, “Is there any reason you might feel so distressed? Is there anything hurting you we might want to change?”

Hari thinks the conversation surrounding depression is taking a turn, and the solutions some experts have found to ease it are less drug-oriented. One of his favorite examples came from a South African psychiatrist named Derek Summerfield, who specializes in treating trauma patients. Hari writes about how Summerfield had visited Cambodia in the early 2000s and met a rice farmer whose leg was blown off by a landmine. The farmer returned to the fields with a prosthesis, but cried every day about his psychic and physical pain. His Cambodian doctors devised a drug-free way to help him: They bought him a cow. It achieved many things: Because he could sit during the day, his leg didn’t hurt him. He was away from the site of his carnage, and as a local milk provider, his community valued him.

We need to have a much more nuanced conversation about chemical antidepressants and their effectiveness.
Johann Hari, author of ‘Lost Connections’

Hari recognizes that his own life is worlds away from the Cambodian man’s. His 2015 bestseller on addiction, Chasing the Scream, catapulted him into a life of privilege. And he’s the first to say that he has a great therapist.

But he points to social factors that have been shown to be helpful in boosting mood elsewhere. For example, a 1970s experiment in Manitoba gave people a universal basic income, and was shown to significantly reduce depression in the town.

And when researchers at the University of Toronto compared subjects in the U.S., Russia, and East Asia they found that when Americans are unhappy, they tend to focus on external things—buying something, aiming for a promotion, posting vacation pictures on Instagram—that they think will make them feel better. Elsewhere, people invest time in their communities and friends—and report feeling greater contentment than Americans.

To Hari, depression and anxiety don’t have to mean popping a pill. It can certainly help some people, but Hari thinks that a critical eye is necessary. When he got depressed before, he’d buy something for himself. Now, when he feels his pain returning, he leaves his phone at home, shows up at the homes of his family and friends, and listens.