Sertraline - Zoloft®

Sertraline Zoloft®
Classification:

Psychotropic Agents

• Antidepressants
  
  • Selective serotonin reuptake inhibitors (SSRIs)

Description: Sertraline is an oral antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type. It is similar to citalopram, fluoxetine, and paroxetine. Sertraline has one active metabolite and a lower potential for drug interactions involving CYP2D6 (hepatic cytochrome P-450 isoenzyme 2D6) than fluoxetine or paroxetine. Sertraline was approved by the FDA in December 1991 for the treatment of major depression in adults; followed by approval in October 1997 for treatment of obsessive-compulsive disorder (OCD) and panic disorder. Sertraline received FDA approval for the treatment of OCD in children >= 6 years old in 1998. Sertraline was first FDA-approved for initial therapy of post-traumatic stress disorder (PTSD) in December 1999, and a FDA-approval for long term treatment of PTSD was granted in November 2001. The drug was subsequently approved for the treatment of premenstrual dysphoric disorder (PMDD) in May 2002. In February 2003, sertraline received FDA-approval for acute and long-term treatment of social anxiety disorder (also known as social phobia). Sertraline has also been studied for the treatment of postpsychotic depression of schizophrenia, behavioral problems due to brain injury, and for premature ejaculation. Phase III trials are in progress for the treatment of depression in pediatric patients 6—17 years of age. On March 22, 2004 the FDA issued a Public Health Advisory for several antidepressants, including sertraline, warning of increased risk of worsening depression or suicidal tendency in adults and children. British regulators have banned the use of some SSRIs in the UK.

On October 15, 2004 the FDA directed manufacturers of all antidepressants to include a Black Box warning, expanded warning statements, and clinical trial results detailing the increased risk of suicidality in children and adolescents. A Patient Medication Guide (MedGuide) will also accompany all prescriptions for antidepressants. The FDA is currently assessing the risk of suicidality in adults taking antidepressants and a final report is expected by mid- to late 2006.

Mechanism of Action: Sertraline potentiates serotonin (5-HT) in the CNS. Sertraline does not significantly affect the reuptake of norepinephrine as do many tricyclic antidepressants. However, chronic administration of sertraline was found in animals to downregulate brain norepinephrine receptors, as has been observed with other clinically effective antidepressants. Although the precise action of SSRIs is not fully understood, it is believed that sertraline and related agents inhibit reuptake of serotonin at the neuronal membrane. SSRIs have less sedative, anticholinergic, and cardiovascular effects than do the tricyclic antidepressant drugs due to dramatically decreased binding to histamine, acetylcholine, and norepinephrine receptors. Monoamine oxidase is not inhibited by any of the SSRIs. Anticholinergic activity is virtually absent.

Pharmacokinetics: Sertraline is administered orally and is well absorbed following oral administration. The extent of absorption may be somewhat increased by administration with food; the peak concentration may be increased by 25%, and the time taken to attain peak concentration decreased from about 8 hours to 5.5 hours, if administered with food. In young adults, steady-state levels are achieved after about 1 week. Sertraline appears to be highly protein-bound (98%), but it does not compete with warfarin or propranolol for binding sites, possibly because its presumed binding site is alpha1-acid glycoprotein and not albumin.

Sertraline undergoes extensive first pass metabolism. The primary metabolite is N-desmethylsertraline, which is substantially less active than sertraline. Both sertraline and N-desmethylsertraline undergo oxidative deamination and subsequent reduction, hydroxylation, and glucuronide conjugation. Unchanged sertraline is not detected in the urine; however, 12—14% of unchanged sertraline is recovered in feces. The elimination half-life of sertraline is approximately 24 hours.