https://www.insider.com/ssris-mark-horowitz-antidepressants-serotonin-chemical-imbalance-false-2022-9
Mark Horowitz in London in August 2022. Daniel Jackont
When Mark Horowitz was 21, he began taking antidepressants.
At the time, he was feeling a "bit miserable" in school — like "a neurotic, Woody Allen kind of guy." His medical provider suggested he start taking a selective serotonin reuptake inhibitor, or SSRI.
He never imagined the debilitating withdrawal symptoms he'd experience 13 years later while trying to come off the drug.
Horowitz recalled waking up in "animal terror," feeling like he'd just been chased off a cliff, or enduring a "state of panic" so pervasive he took to running several miles a day until his feet bled. For the first time in his life, he thought about killing himself.
Shaken, he moved back home to Australia from London, where he'd been getting his Ph.D., to be closer to his family. His doctor prescribed a higher dose of Lexapro, the drug that he'd been taking.
Today, 19 years after he began, Horowitz is determined to stop taking his SSRI for good. He's slowly, methodically undertaking what may be a yearslong process to wean himself off the drug, using a liquid version and decreasing his dose by just a smidgen every few weeks to avoid panic attacks.
Horowitz isn't just any patient, though. He's the psychiatry researcher behind a major new study showing that there's no solid link between low serotonin levels and depression.
Based on his research, Horowitz believes SSRIs like Lexapro aren't really doing what he was once led to believe: correcting a "chemical imbalance" in his brain. In fact, he says it's high time that this conventional wisdom is properly debunked for the general public once and for all, instead of being relegated to watercooler chatter among academics, doctors, and drugmakers.
Like Viagra, modern antidepressants were discovered by accident. In [1952](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9048453/#:~:text=In 1952%2C Selikoff,in social activity.), clinicians at Staten Island's Sea View Hospital began treating tuberculosis patients with a new, experimental neurotransmitter-acting drug.
Many TB patients treated with iproniazid at Sea View likely had severe depression%20patients.) after months or years of hospitalization. But within weeks, they were more alert, sociable, and regaining lost weight.
These drugs were called monoamine oxidase inhibitors, or MAOIs. They prevent enzymes in the brain from breaking down key chemicals, including norepinephrine, serotonin, and dopamine.
Soon, psychiatrists began prescribing MAOIs on a larger population of depressed patients. While some of the results were promising, researchers were cautious to note that there were "varying degrees of improvement" in cases. The drug wasn't working for everyone, and providers didn't fully understand why.
Over the next decade or so, researchers endeavored to develop even better antidepressant drugs, with fewer undesirable side effects. During the late 1960s, scientists found evidence that the corpses of patients who died by suicide had low serotonin levels. As a result, pharmaceutical companies raced to develop antidepressant drugs targeting serotonin. The very first SSRI, Prozac, was born at Eli Lilly in the early 1970s — though it didn't hit pharmacy shelves in the US until 1988.
Though SSRIs were chemically different from MAOIs, the thinking behind these new drugs remained largely the same. If you can make chemicals like serotonin, dopamine, and norepinephrine more available to the brain, you may be able to keep mild, moderate, and severe depression at bay.