Zoloft Does Not Improve Depression, Even in Severe Cases, Study Finds

Despite their finding, the researchers suggest that SSRIs be given to people who do not meet criteria for depression or anxiety.


A new study published in Lancet Psychiatry found that sertraline (Zoloft) was no better than placebo for the treatment of depression. The primary outcome of the study was whether sertraline led to reduced depressive symptoms after six weeks.

According to the researchers:

“We found no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at 6 weeks.”

medical problems

The study recruited real-world participants who reported depressive symptoms to their general practitioners in the UK. This is different from the usual pharmaceutical industry-funded clinical trials, which carefully select participants to avoid common real-world complexities.

They also assessed whether the drug was more effective for people with more severe depression. However, the drug appeared ineffective even for severe depression: “We observed no evidence that treatment response varied with depression severity or duration.”

Another outcome was whether sertraline reduced depressive symptoms after 12 weeks. The researchers found “weak” evidence for this outcome. They found a statistically significant effect, barely better than placebo. As a result, the authors write that their study “does not exclude the possibility of a clinically important effect.”

However, the researchers conclude that the “findings support the prescription of SSRI antidepressants in a wider group of participants than previously thought, including those with mild to moderate symptoms who do not meet diagnostic criteria for depression or generalized anxiety disorder.”

The researchers suggest that SSRIs should be given to more people, including those who do not have a mental health diagnosis.

They justify this conclusion using a controversial reporting process called outcome switching. Although their primary outcome failed, the researchers included a number of secondary measures. Some of these outcomes showed a small statistically significant effect. This procedure is controversial because the more measures you use in a sample, the more likely you are to find at least one positive effect by chance.

In fact, the researchers themselves acknowledge this, writing, “results from secondary analyses should be interpreted with caution.”

Nonetheless, the researchers based their own conclusions solely on these switched, secondary outcomes (since their primary outcome actually found that sertraline was ineffective for depression).

Media reports have also highlighted these secondary outcomes, especially the finding that sertraline had a marginal effect on reducing anxiety. Although the effect on anxiety is likely clinically insignificant the researchers and media reports have used this finding to suggest that sertraline is effective for treating even people “who do not meet diagnostic criteria” for mental health problems.

The BBC’s report that SSRIs “work” by reducing anxiety is contradicted by the actual findings since the researchers write that they found “no evidence” that the drug had a meaningful effect on depression. The BBC article adds: “Psychiatrists say the findings are reassuring for doctors and patients, confirming the benefits of treatment.”

According to the researchers, “SSRIs are among the most commonly prescribed medications in the world and yet we still have an imperfect knowledge of their clinical effectiveness and indications for their use.”



Lewis, G., Duffy, L., Ades, A., Amos, R., Araya, R., Brabyn, S., . . . & Lewis, G. (2019). The clinical effectiveness of sertraline in primary care and the role of depression severity and duration (PANDA): a pragmatic, double-blind, placebo-controlled randomised trial. Lancet Psychiatry. (Link)


  1. For example, anti-scientific communication operations that seek to promote or protect corporations or businesses, and that have the effect of degrading the health of the population, could be punished by real jail time.

    Indeed, this kind of propaganda has the effect of maintaining or increasing the consumption of legal narcotics, and thus of causing harm to society, which can be measured in financial losses, in losses of years of life in good health and losses of human lifes.

    These losses should be measured concretely and the people involved should be punished in the same way as other criminals.

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  2. I took the old tricylics and they made no difference to my mood, and it looks like the SSRI s don’t work for most people either.

    I’ve experienced melancholoy, but I don’t think I have ever been clinically depressed, and I don’t know what I would do if I was.

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    • My SSRI drugs made me feel guilty for not improving.
      I believed what I had been told. That I was being helped with these safe and effective medications. Yet I couldn’t find work or get along with people. The constant exhaustion and inability to think straight or process human emotions (which hadn’t existed prior to the cocktail) were all my fault according to my counselor and other folks running the mental illness system.

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  3. EileenLL
    A friend said to a doctor regarding one of these drugs: “but I am not depressed” the doctor answered: “it doesn’t matters, take it anyway.”
    That night, an ambulance had to pick her up. She was suffering from insomnia and low blood pressure.
    After I recommended a doctor trained in functional medicine and integrative nutrition, she is a lot better now.
    No drugs. Nutrition, supplements, and energy medicine only.

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  4. It’s not “controversial” to rely on secondary outcomes, it’s a violation of basic scientific principles and any study relying on secondary outcomes should never be published. So much for “peer review!” And even their sketchy “Secondary outcomes” did not support their conclusions.

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  5. Spin, spin, spin, spin, spin, spin. The antidepressants are mind altering, neurotoxic drugs that make people manic and psychotic, which is very profitable for the psychiatrists. And why the “Psychiatrists say the findings are reassuring for doctors …, confirming the benefits of treatment” for the psychiatrists.

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  6. I must make a confession. In the late 90’s I became a disciple of the “mental health” system in that I believed the lies of my GP when I went to him for help about feeling down and unhappy. He immediately gave me a prescription for Zoloft. I got it filled and faithfully took the devil’s tic tacs. I went home to visit my mom one weekend and she seemed down and low so I suggested that she ask her doctor for some good old Zoloft. She did so and began taking it. A few months later I went back to visit and she was much better, back to her old self. I stated that the Zoloft must have helped her. She laughed and said that she threw the damned pills down the commode and flushed them and never filled the prescription again. When I asked why she said that she realized what a crock of bull the so-called “antidepressants” were when she looked at her kitchen floor one day and realized that it was a filthy mess. She said that she sat there wondering how she’d ever let her floor get like that because she was a meticulous housekeeper, even though she worked ten hours a day in a plant. She said that she realized that the pills did nothing but make her numb to everything going on around her. My mother had only a third grade education but was brilliant in so many ways! It took me many more years and numerous “antidepressants” to finally understand how wise she truly was that day that she threw the damned pills in the commode. I ended up on the Devil’s Tic Tacs of devil’s tic tacs , good ol’ Effexor XR. I tried killing myself while taking those pills.

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