Sertraline (Zoloft)


Brandname Zoloft
Class Selective Serotonin Reuptake Inhibitors (SSRI)
Target Sodium-dependent serotonin transporter (SERT), Sodium-dependent dopamine transporter (DAT)
  • 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.

Cytochrome P450 Metabolism

Metabolized by 2C19, 2D6
Induces -
Inhibits 2D6, 3A4


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]
½ Life 26 hours, metabolite = 3-6 days
  • DA reuptake inhibition may help with anhedonia & amotivation
  • σ1 antagonism may have some anxiolytic effects
  • Dose range: 50-200mg

Clinical Pearls

  • 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.
  • Commonly used in child psychiatry
  • Can be used in atypical depression
  • The only SSRI to affect 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![2]

Side Effects

  • Sexual dysfunction (up to 30%)
  • Gastrointestinal (poor appetite, nausea, diarrhea, constipation, dry mouth)
  • CNS effects (insomnia or sedation, depending on the patient)
  • Hyponatremia (rare)[3]
  • Hypotension (rare)
  • Weight gain is unusual, some patients may actually experience weight loss
  • Syndrome of inappropriate ADH secretion (SIADH)

Drug-Drug Interactions

  • Tramadol (increased risk of seizures)
  • Tricyclics (increased TCA levels)
  • Warfarin (increased bleeding)
  • Triptans (weakness, hyper-reflexia)


  • MAO inhibitors (serotonin syndrome)
  • Thioridazine (arrythmias)
  • Pimozide (QTc prolongation, arrythmias)

Treatment for

First line Notes
Major Depressive Disorder (MDD) -
Generalized Anxiety Disorder (GAD) -
Premenstrual Dysphoric Disorder (PMDD) -
Obsessive-Compulsive Disorder (OCD) -
Indicated Notes
Panic Disorder -
Posttraumatic Stress Disorder (PTSD) -
Social Anxiety Disorder (Social Phobia) Titrate up to 250mg, as social anxiety typically responds only partially to antidepressants and usually requires the upper end of the dose range.
Bulimia Nervosa -