A Short History of SSRIs

By Dr.Prater

In 1987, the first selective serotonin reuptake inhibitor (SSRI), fluoxetine, hit the market as an antidepressant. Other SSRIs include paroxetine, setraline, escitalopram, citalopram, and nefazodone, which are all also known by popular brand names – Prozac, Paxil, Zoloft, Lexapro, Celexa, and Serzone. More than 20 years later, the mechanism by which this popular class of drugs treats depression is still being determined even while many use them to alleviate their psychological symptoms.


SSRIs work on the basis of a concept of depression in which the neurochemical serotonin is inappropriately taken up by neurons, blocking neurotransmission and lowering mood. However, this is likely not the mechanism at play in every person suffering from depression. Other types of antidepressants include MAOIs and tricyclics, which also benefit some patients and, together with SSRIs, made up a $10.9 billion market in the U.S. in 2004. However, what follows is a short history of SSRIs, specifically.

As SSRIs hit the market, side effects became more apparent, including sexual dysfunction in many patients. Paroxetine has a disturbing effect of withdrawal symptoms in 25% of those receiving it, and a 40% relapse rate, making it a candidate for abuse. The market became troubled for SSRIs in 2004 when Serzone (generic: nefazodone) was recalled due to hepatitis and liver failure fears along with the death of 20 patients taking the drug, which was made by Squibb.

Childhood SSRI prescriptions were banned in Britain in 2003, and in 2004, the U.S. Food and Drug Administration issued a black box warning against prescribing SSRIs to children. The reason for the concern was confirmed by a 2007 study that found that SSRIs increase suicidal tendencies in individuals under the age of 24. This information, in conjunction with previous studies showing that the SSRIs, with the exception of fluoxetine, offer no additional benefit over placebos in children, reinforced the bans and warnings.

Many studies have shown that psychotherapy over 12-16 sessions (with or without medication) is as beneficial as medication for minor depression symptoms. Minor and major depression appear to be two different disorders when considering how beneficial medication is for treating the symptoms. Medication, including SSRIs, appears to be better suited for major depression, and psychotherapy better suited for minor depression. In fact, SSRIs are approved by the FDA for the treatment of major depressive disorder specifically.

A study published in Archives of General Psychiatry in December 2009 and funded by GlaxoSmithKline found that SSRIs may work in major depression by affecting the patient’s personality, as opposed to changing their mood which then affects their personality as previously thought. What this means for those undergoing antidepressant treatment is yet to be seen.

Antidepressants were the most prescribed drugs in the U.S. in 2005 according to the Centers for Disease Control and Prevention, with a total of 118 million prescriptions. From the period 1988-1994 (6 years) to the period 1999-2000 (1 year), the use of antidepressants nearly tripled. Between 1995 and 2002, the use of antidepressants increased 48 percent, and SSRIs are the most commonly prescribed antidepressants drugs. Some have questioned whether antidepressants, including SSRIs, have surpassed their historical context of treating a disease.


Please note: SSRIs should not be taken with MAOIs or supplements that affect serotonin, including St John’s Wort. The interaction could result in serotonin syndrome, a life-threatening disorder. Also, the American College of Obstetricians and Gynecologists warns that SSRIs should be avoided during pregnancy due to potential birth defects.

The copyright of the article, "A short history of SSRIs," in "Interesting Health Articles & Facts " is owned by Alicia M Prater, PhD. Permission to republish this article in print or online must be granted by the author in writing.
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