How long does it take for Zoloft to work?

Why would an antidepressant make you feel more depressed?
Why would an antidepressant make you feel more depressed?

Shawn McGrath didn't make it to the big time.

An up-and-coming professional wrestler, McGrath -- known as "Badseed Shawn Osborne" -- spent years trying to secure a spot with World Wrestling Entertainment. In 2006, after penning his signature on a development contract with the company, his dream seemed within reach.


But despite a few promising matches, McGrath was released from his contract in 2008. He fizzled out of the spotlight and on Jan. 26, 2011, at age 34, killed himself. McGrath's suicide note insisted the only drug in his system was Zoloft, a medication prescribed for depression and anxiety [source: Clark].

Was it McGrath's disappointment over his career, a frayed safety net of family and friends, or an antidepressant that hadn't taken hold in time that was to blame for his suicide? For those seeking answers on the efficacy – and timeliness -- of one of the U.S.'s most popular antidepressants, McGrath's death raised important questions.

Just how long does Zoloft take to work? And, in the interim between first dose and full power, can it actually make symptoms worse?

Symptoms such as excessive sleepiness, lack of energy or dull appetite may improve within the first two weeks of taking Zoloft. Other critical symptoms however, such as depressed mood, make take eight weeks before showing a marked turnaround [source: National Alliance on Mental Illness].

And therein lies the concern.

In 2004, the U.S. Food and Drug Administration issued a public warning about the increased risk of suicide for children and teens taking selective serotonin reuptake inhibitor (SSRI) antidepressants. In 2006, the warning was extended to users up to age 25. And in 2007, the FDA asked all antidepressant manufacturers to update the medication's warning label, warning consumers -- particularly young adults aged 18 to 24 -- about the increased risks in suicidal thinking and behavior during the first one to two months of use.

Although there are differing opinions as to why the risk increases, one prevailing theory is that taking an SSRI initially causes the body's naturally occurring serotonin levels to drop -- even as they are being replaced by an antidepressant pill. This occurs when the brain's autoreceptors sense higher levels of serotonin and signal the brain to make even less of the chemical. After a few weeks, these receptors are joined by new receptors built to handle the increase in serotonin, and the body begins to allow more serotonin to enter the bloodstream.

Nevertheless, a study published in the April 18, 2007, Journal of the American Medical Association reported the benefits of antidepressants outweighed the risks to children and teens with serious depression and anxiety. The study was based on a review of pediatric trials between 1988 and 2006 [sources: FDA, National Institute of Mental Health].

What Is Zoloft?

Zoloft is classified as a Selective Serotonin Reuptake Inhibitor. This class of antidepressants affects receptors in the brain that absorb the neurotransmitter serotonin.
Zoloft is classified as a Selective Serotonin Reuptake Inhibitor. This class of antidepressants affects receptors in the brain that absorb the neurotransmitter serotonin.
Joe Raedle/Getty Images

For a small amber or blue oval pill, Zoloft sure generates a lot of buzz -- and so do other members of its family of antidepressants.

A study released in 2011 by the National Center for Health Statistics reports that from 2005 to 2008, one in 10 Americans age 12 and older took antidepressant medication, making antidepressants the third most commonly prescribed drug taken by Americans of all ages during and the No. 1 medication of adults age 18 to 44. Overall, the rate of antidepressant usage in the U.S. -- among all ages -- skyrocketed 400 percent between 1988 and 2008 [source: NCHS].


Zoloft -- also known by its generic name sertraline hydrochloride -- is a prescription antidepressant classified as a selective serotonin reuptake inhibitor (SSRI), as we mentioned. This class of antidepressants affects receptors in the brain that absorb serotonin.

Serotonin -- 5-Hydroxytryptamine or 5-HT -- is a naturally occurring chemical found in intestines, blood platelets, certain cells and the brain. Serotonin is a derivative of tryptophan, a natural amino acid, and is concentrated in the midbrain and hypothalamus -- two areas responsible for mood, sleep and aggression. When there isn't enough serotonin, either because it is absorbed too quickly or in too great a quantity by the brain's neurons, depression can occur.

An SSRI antidepressant like Zoloft acts as an air traffic controller in the brain. It commands serotonin to circle the runway before landing, causing a critical delay that allows the brain's neurons to more effectively absorb the optimal amount of mood-boosting serotonin. The air traffic controller opens more runways, in this case receptors in the brain, so more serotonin can reach its intended destination. And, because (as its name suggests) an SSRI is "selective," it targets only serotonin and allows other chemicals to continue their normal flight pattern in the brain. In effect, it inhibits the reabsorption or reuptake of serotonin from happening too quickly [source: Bussing, Crowe].

The first generation of antidepressants in the 1950s boosted the levels of several brain neurotransmitters or chemicals. Later scientists concentrated on drugs that could improve the uptake of just one chemical. In 1987, the first SSRI -- Prozac -- was approved by the FDA, followed by fluvoxamine maleate (Luvox), paroxetine (Paxil), Zoloft and, in 1998, citalopram (Celexa) [source: Bussing].

The newest class of antidepressants is serotonin norepinephrine reuptake inhibitors (SNRIs), called dual-action antidepressants because they increase levels of serotonin and norepinephrine (both neurotransmitters). This class includes duloxetine (Cymbalta), venlafaxine (Effexor) and desvenlafaxine (Pristiq). For some people, this combination works better than an SSRI [source: Medicine Net].

How Will You Know if Zoloft Is Working?

Zoloft isn't only for major depression. It's also used to treat obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder (PMDD) and social anxiety disorder.

Zoloft, an oral antidepressant pill made of compressed crystalline powder, is usually prescribed to first-time users in a 50-milligram-per-day dose for depression and PMDD and 25 milligrams per day for other disorders. Dosages can be increased with time and medical supervision up to 200 milligrams per day. It's also available in liquid form [source: RX List].


Within just a few hours of taking an SSRI for the first time, the levels of serotonin in the brain and bloodstream increase. Yet, we don't feel immediate results. Zoloft takes weeks to work. Why?

The answer is us. Our bodies need time to adapt to the new normal created by taking a pill laced with sertraline that is designed to increase serotonin levels in the brain. Not only does this SSRI medication help the brain absorb serotonin into the blood stream more effectively, but it may actually change the makeup of the brain. The brain needs new receptors to help absorb the additional serotonin; it builds and installs additional receptors -- a biological process that can take up to eight weeks. So, even though Zoloft increases the levels of serotonin in our bodies nearly immediately, our brains aren't immediately equipped to absorb it [source: Crowe].

If, however, after six to eight weeks, Zoloft doesn't seem to be positively affecting your mood, anxiety -- or other condition for which it was prescribed -- it's time to alert your physician. Not every antidepressant will work the same for every person, and an estimated 50 percent of people who try an antidepressant will need to take a different brand or class before finding one that works for them. Or, it could just be that your dosage needs to be increased [source: Grohol].

Your physician will help determine your type and dosage of antidepressant by considering your symptoms, other medications you are taking, health conditions, potential side effects, and whether you are pregnant or breastfeeding. In addition, she may inquire as to whether a particular antidepressant has been taken by a close relative, and what the results were. If your brother's depression, for example, lifted after taking Zoloft, yours probably will, too [source: Mayo Clinic].

Lots More Information

Author's Note: How long does it take for Zoloft to work?

Zoloft and other antidepressants take a few weeks to work. This is information I've heard before. What I'd never heard, however, was "why." The idea that Zoloft increases the levels of serotonin -- a mood-boosting chemical in the brain -- almost immediately after taking the first few doses was a new one to me. But what really astounded me was the idea that in response, the brain is physically changing. Growing new receptors. Absorbing serotonin in greater amounts. And, in turn, affecting mood and behavior. The human body is amazing.

Related Articles

  • Bussing, Regina. "Choosing the Best SSRI." Psych Central. Jan. 30, 2013. (Sept. 15, 2013)
  • Clark, Ryan. "Ex-WWE Developmental Star Commits Suicide." Wrestling Inc. Jan. 27, 2011. (Sept. 15, 2013)
  • Crowe, Jonathan. "Why Do Antidepressants Take So Long to Work?" Oxford Mental Health Forum. March 18, 2012. (Sept. 15, 2013)
  • Grohol, John. "How Long Do Antidepressants Take to Work?" 2011. (Sept. 15, 2013)
  • Mayo Clinic. "Antidepressants: Selecting One That's Right For You." Nov. 8, 2011. (Sept. 15, 2013)
  • Mayo Clinic. "Depression (Major Depression)." July 9, 2013. (Sept. 15, 2013)
  • Medicine Net. "Antidepressants." May 31, 2013. (Sept. 15, 2013)
  • National Alliance on Mental Illness. "Zoloft (Sertraline)." (Sept. 15, 2013)
  • National Center for Health Statistics. "Antidepressant Use in Persons Aged 12 and Over: United States, 2005-2008." October 2011. (Sept. 15, 2013)
  • National Institute of Mental Health. "Antidepressant Medications for Children and Adolescents: Information for Parents and Caregivers." (Sept. 15, 2013)
  • RX List. "Zoloft." (Sept. 15, 2013)
  • U.S. Food and Drug Administration. "Antidepressant Use in Children, Adolescents and Adults." (Sept. 15, 2013)