Sertraline (Zoloft)

Sertraline (Tradename: Zoloft) is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of psychiatric disorders such as major depressive disorder and generalized anxiety disorder.

See also article: Introduction to Pharmacology

See also article: Cytochrome (CYP) P450 Metabolism

* = Sertraline has dose-dependent inhibition of 2D6, at doses less than 75 mg there is less inhibition.

Selective and potent inhibition of serotonin reuptake, through inhibition of the serotonin transporter (SERT)
- Selectively inhibit the reuptake of serotonin at the presynaptic membrane
- Results in increased synaptic concentration of serotonin in the CNS, and leads to functional changes associated with enhanced serotonergic neurotransmission.
Dopamine transporter (DAT) inhibition (controversial since they are weaker than the SERT inhibition)
Sigma-1 (σ1) receptor binding
It is suggested that these modifications are responsible for the antidepressant action observed during long term administration of antidepressants.
It has also been hypothesized that obsessive-compulsive disorder is caused by the dysregulation of serotonin, and that sertraline plays a role my modulation of serotonin

Starting	25 or 50mg PO x 2 weeks
Titration	25-50mg PO q1 week
Maximum	200mg
Taper	> 8 week treatment: taper by 25% q4-6 weeks < 8 week treatment: taper over 1-2 weeks^[1]

DA reuptake inhibition may help with anhedonia & amotivation
σ1 antagonism may have some anxiolytic effects
More sedating than other SSRIs, therefore consider qHS dosing
Starting at 50mg might cause anxiety symptoms. In fact, historically, it was co-prescribed with a benzodiazepine sometimes to mitigate the anxiety symptoms
- Starting at 25mg reduces the risk of developing these anxiety symptoms.
The only SSRI to also modulate dopamine levels
Good SSRI for use in pregnancy and lactation (sertraline is the one SSRI that generally does not elevate prolactin)
More GI side effects (diarrhea) than other SSRIs
Can be anxiogenic and can be activating in panic disorder
Good first-line choice for medically complex or ill patients
Individuals taking sertraline may falsely screen positive for LSD or benzodiazepines on urine drug screen (up to 26.5% false positive).^[3]
New research has shown that it is not effective for patients with non-dialysis CKD!^[4]

See main article: Geriatric Pharmacology

See main article: Obstetric and Fetal Pharmacology

Sertraline has been the most extensively studied of the SSRI.^[5]
Small increased risk of spontaneous abortions, prematurity, and low birth weight
SSRIs have been associated with a very slight risk of cardiac defects (incidence 2%, general expected 1%)
Neonatal Abstinence Syndrome (NAS) (withdrawal) may occur in up to 30% of infants.
Small risk of PPHN for all SSRIs (incidence 0.3%; expected 0.1 – 0.2%), approximately double the background risk.^[6]