Sertraline (Zoloft)

Pharmacokinetics of Sertraline

Sertraline: Cytochrome P450 Metabolism

Metabolized by 2C19, 2D6*
Induces -
Inhibits 2D6, 3A4
  • 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, as it is treated by sertraline, and the drug corrects this imbalance.
  • Major depressive disorder
  • Generalized anxiety disorder
  • Premenstrual dysphoric disorder
  • Obsessive compulsive disorder
  • Panic disorder
  • Posttraumatic disorder
  • Social anxiety disorder
  • Bulimia nervosa

Dosing for Sertraline

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]
  • Sertraline comes in oral (PO) formulation
  • Thioridazine (arrythmias)
  • Tramadol (increased risk of seizures)
  • Tricyclics (increased TCA levels)
  • Warfarin (increased bleeding)
  • Triptans (weakness, hyper-reflexia)
  • Sexual dysfunction (up to 30%)
  • Gastrointestinal (poor appetite, nausea, diarrhea, constipation, dry mouth)
  • CNS effects (insomnia or sedation, depending on the patient)
  • Hyponatremia (rare)[2]
  • Hypotension (rare)
  • Weight gain is unusual, some patients may actually experience weight loss
  • Syndrome of inappropriate ADH secretion (SIADH)
  • 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
  • New research has shown that it is not effective for patients with non-dialysis CKD![3]
  • Sertraline has been the most extensively studied of the SSRI.[4]
  • 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.[5]