Article: Sertraline

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Image:Zoloft.jpg
Sertraline
Systematic (IUPAC) name
(1S)-cis-4-(3,4-dichlorophenyl)-
1,2,3,4-tetrahydro-
N-methyl-
1-naphthalenamine
Identifiers
CAS number 79617-96-2
ATC code N06AB06
PubChem 68617
DrugBank APRD00175
Chemical data
Formula C17H17NCl2 
Mol. weight 342.7
Pharmacokinetic data
Bioavailability 95%
Metabolism N-demethylation (liver)
Half life ~26 hours
Excretion Urine
Therapeutic considerations
Pregnancy cat.

C

Legal status

â„ž Prescription only

Routes oral


Sertraline hydrochloride (Zoloft®, Sertralin®, Lustral®, Apo-Sertral®, Asentra®, Gladem®, Serlift®, Stimuloton®, Xydep®, Serlain®, Concorz®) is an orally administered antidepressant of the selective serotonin reuptake inhibitor (SSRI) type. It was first approved by the Food and Drug Administration (FDA) in 1991.

Indications

Approved

Sertraline is used medically mainly to treat the symptoms of depression and anxiety. It is also prescribed for the treatment of obsessive-compulsive disorder (OCD)[1], post-traumatic stress disorder (PTSD)[2], premenstrual dysphoric disorder (PMDD)[3], panic disorder[4]and social phobia/social anxiety disorder[5].

Unapproved/Off-label/Investigational

Sertraline can also be used in the treatment of generalized anxiety disorder[6], binge eating disorder [7], premature ejaculation [8]

There is also evidence that sertraline may be effective in the treatment of refractory neurocardiogenic syncope in children and adolescents[9].

A study has shown that sertraline is an effective treatment for impulsive aggressive behavior in personality disordered patients.[10]

Side effects

Sertraline can have a number of adverse effects, including insomnia, asthenia, gastrointestinal complaints, tremors, confusion, dizziness, anorgasmia, and decreased libido; it can induce mania or hypomania in around 0.5% of patients. It has also been known to cause minor weight loss. It is contraindicated in individuals taking MAOIs or undergoing electroconvulsive therapy.

Until 2003 Zoloft 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. In June, 2004, Britain banned the use of Zoloft by minors and in February, 2005, Pfizer was forced to change the labeling of Zoloft to include information regarding increased incidences of suicidal behavior and depression in adolescent users of the drug. According to mentalhealth.com, Zoloft is not currently recommended or advised for use in individuals under the age of 18. After these changes, multiple incidences and at least one medical study showed an increased risk of suicide in seniors who were taking Zoloft. In response to these findings, the FDA released a public health warning. This warning indicates that anyone currently using Zoloft for any reason has a greater chance of exhibiting suicidal thoughts or behaviors regardless of age. This warning is questionable, however, due to the types of illnesses Zoloft is used to treat, it is impossible to determine if these tendencies are a side effect of the drug or the illness the drug is meant to treat.

Zoloft has long been seen as the best option for breastfeeding mothers who wish to continue breastfeeding and be able to take their antidepressants. Despite its apparent safety and effectiveness during the breastfeeding period, recent studies and consumer complaints have seen a need to alter Zoloft's labeling regarding use during the third trimester of pregnancy. Though there are no teratogenetic defects associated with Zoloft, there is reason to be concerned about its effects on infants who were exposed to sertraline during the third trimester in utero. It seems that Zoloft use in late pregnancy significantly increases the potential need for hospitalization and breathing assistance in the newborn period and has also been shown to cause an increased risk of neonatal death. In light of this increased risk it is still being used due to the greater potential risk of a seriously depressed mother to herself and her unborn child. Like all other medications Zoloft's use must be decided only after carefully weighing out all potential risks and benefits.

Formulations

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Zoloft logo

Sertraline is manufactured by Pfizer and sold as Zoloft in the United States as small green 25 mg tablets, blue 50 mg tablets, and yellow 100 mg tablets (Generic 100mg sertraline tablets are also yellow), each of which is scored to allow easy halving. In the UK, the brand name is Lustral and is available in white 50mg or 100mg tablets, according to the British National Formulary (BNF). In Australia, only the 50 mg and 100 mg strengths are available, both as white tablets. Sertraline is an odorless, white, sparingly soluble crystalline solid. The minimum effective dose is 50 mg per day, but lower doses may be used in the initial weeks of treatment to acclimate the patient's body, especially the liver, to the drug and to minimize the severity of any side effects. Patients who do not experience relief of symptoms at 50 mg a day may have their dose increased, up to 200 mg a day.

The patent for this brand-name drug expired in December 2005. It is anticipated that the generic drug will be available in the United States in June of 2006, manufactured by Andrx, Aurobindo, Genpharm, Ivax, Mylan, and Roxane. In Scandinavia a generic drug called Sertralin, manufactured by HEXAL is available. The price differences between Zoloft® and Sertralin® are as high as 1.50 dollars per pill.

Precautions

Because of its metabolism, liver impairment can affect the elimination of this drug from the body. If someone with liver impairment is treated with sertraline, lower or less frequent dosage should be used. Similarly, patients should limit their alcohol intake while on sertraline (or any antidepressant). Because the liver is doubly taxed with processing both substances (in addition to any other drugs the patient may be taking), alcohol remains in the bloodstream longer, so the effects of alcohol may be more strongly and quickly felt by people taking sertraline or other antidepressants. According to some studies grapefruit juice might interfere with the metabolisation of sertraline, increasing its concentration in the blood.

Dopamine

One property of sertraline is that it appears to be also a minor inhibitor of dopamine reuptake. At higher dosages (300 mg/day), sertraline inhibits the reuptake of dopamine as well as serotonin.

Controversy

In June 2003, Britain banned the use of sertraline for children under 18 after studies showed a link to increasing suicidal rates. Similar concern has prevailed in the United States, where only the anti-depressant fluoxetine (another SSRI) was officially banned by the FDA for the treatment of depression in minors. However, because the antidepressant-suicide link is correlational, scientists do not know whether the increased suicide risk for people taking antidepressants occurs because the drugs make people suicidal, whether suicide occurs because the drugs un-depress the people enough to motivate the energy required to commit suicide (a popular theory), or because of a third, unknown factor.

Evidence against Effectiveness

A major study funded by the NIH in the United States, found a sertraline product to be ineffective in treating major depression of moderate severity. (Hypericum Depression Trial Study Group, 2002) This study involved 340 patients, diagnosed with Major Depressive Disorder based on DSM-IV criteria and assessed using Hamilton Depression Rating Scale (HAM-D) and Clinical Global Impression (CGI) scores. The trial was a multi-centre randomised double-blind placebo-controlled trial, comparing one preparation of St John's wort (Li 160) to sertraline and placebo. Li 160 proved no more effective than placebo in alleviating moderately severe major depression. Sertraline was also no better than placebo in this study, based on the primary outcome measure (HAM-D).

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