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Sertraline hydrochloride (Zoloft, Lustral) is an antidepressant
of the selective serotonin reuptake inhibitor (SSRI) class. It was
introduced to the market by Pfizer in 1991. Sertraline is primarily
used to treat clinical depression in adult outpatients as well as
obsessive-compulsive, panic and social anxiety disorders in both
adults and children. Sertraline shares the common side effects and
contraindications with other members of SSRI class; however, it
does not cause weight gain. Controversy and legal actions have resulted
from the suspicion that sertraline, similarly to other antidepressants,
may increase the risk of suicide. In 2006 it was the most prescribed
antidepressant on the U.S. retail market with 28,060,000 prescriptions.
The history of sertraline goes back to the beginning of 1970s
when Pfizer chemist Reinhard Sarges synthesized a norepinephrine
reuptake inhibitor tametraline. Tametraline's development was
soon stopped because of undesired stimulant effects observed in
animals. Several years later, biochemist Kenneth Koe and chemist
Willard Welch generated and tested derivatives of tametraline
in vitro for the serotonin reuptake inhibition. Welch then prepared
stereoisomers of the most promising candidate, which were tested
in vivo by animal behavioral scientist Albert Weissman. The most
active (+)-cis-isomer was taken into further development and eventually
became sertraline. During the development, the group had to overcome
the initial reluctance of Pfizer bureaucracy to pursue sertraline,
as Pfizer was considering licensing an antidepressant candidate
from another company.
Sertraline was approved by the Food and Drug Administration (FDA)
in 1991 based on the recommendation of the Psychopharmacological
Drugs Advisory Committee. The committee achieved a consensus that
sertraline is safe and efficient for the treatment of depression.
During the discussion, Paul Leber, Director of the FDA Division
of the Neuropharmacological Drug Products noted that it was a
"tough decision", since the treatment effect on outpatients
with depression is "modest to minimal". Other experts
emphasized that the drug's effect on inpatients is not different
from placebo and criticized poor design of the trials by the drug's
manufacturer Pfizer. For example, 40% of the participants dropped
out of the trials, significantly decreasing their validity.
Until 2003, sertraline was only approved for use in adults ages
18 and over; that year it was approved by the FDA for use in treating
children ages 6 to 17 with extreme obsessive compulsive disorder
(OCD). In 2003 the UK Medicines and Healthcare Products Regulatory
Agency issued a guidance that SSRIs, except fluoxetine (Prozac)
are not suitable for the treatment of depression in minors. However,
sertraline still can be used for the treatment of OCD in children
and adolescents. In 2005 the FDA, changed the labeling of antidepressants,
including sertraline, adding a black box warning pertaining to
pediatric suicidality, followed in 2007 by the warning regarding
the suicidality in young adults.
The patent for Zoloft brand of sertraline expired in 2006, and
the drug is now available in generic form.
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