Initial: 50 mg q Day PO given continuously throughout menstrual cycle or given during luteal phase only May increase by 50 mg at the onset of each new menstrual cycle; no more than 150 mg q Day when administered continuously or 100 mg q Day when administered during luteal phase only 25 mg PO q Day initially; may increase by 25 mg every 2-3 days; not to exceed 200 mg q Day Alzheimer dementia related depression: Start at 12.5 mg/day and titrate every 1-2 weeks to response; not to exceed 150-200 mg Renal impairment: Dose adjustment not necessary Mild hepatic impairment (Child-Pugh 5-6): Decrease recommended starting dose and therapeutic dose by 50% Moderate-to-severe hepatic impairment (Child-Pugh 7-15): Not recommended; sertraline is extensively metabolized, and the effects in patients with moderate and severe hepatic impairment have not been studied Clinical worsening and suicide ideation may occur despite medication Use caution in patients with seizure disorders May worsen mania symptoms or precipitate mania in patients with bipolar disorder Increases risk of hyponatremia and impairment of cognitive/motor functions in the elderly Increases risk of bleeding in patients taking anticoagulants/antiplatelets concomitantly Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy Pregnancy: Conflicting evidence regarding use of SSRIs during pregnancy and increased risk of persistent pulmonary hypertension of the newborn (see Pregnancy) In neonates exposed to SNRIs/SSRIs late in third trimester: Risk of complications such as feeding difficulties, irritability, and respiratory problems Avoid abrupt withdrawal Bone fractures reported with antidepressant therapy; consider the possibility if patient presents with bone pain, bruising, or point of tenderness Coadministration with other drugs that enhance the effects of serotonergic neurotransmission (eg, tryptophan, fenfluramine, fentanyl, 5-HT agonists, St. John’s Wort) should be undertaken with caution and avoided whenever possible due to the potential for pharmacodynamic interaction (see Contraindications) May cause false-positive urine immunoassay screening tests for benzodiazepines SSRIs and SNRIs are associated with development of SIADH; hyponatremia reported Several SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline) are metabolized by CYP2D6 CYP2D6 is involved in the metabolism of approximately 20% of drugs in clinical use and displays large individual-to-individual variability in activity due to genetic polymorphisms More than 80 CYP2D6 variant alleles have been identified; however, 4 of the most prevalent alleles, CYP2D6*3, *4, *5, and *6, account for 93-97% of CYP2D6 poor metabolizers CYP2D6*4, the most common variant (~25% frequency in whites), causes a splicing defect; CYP2D6*3 (2.7% frequency) causes a frameshift mutation; and CYP3D6*5 (2.6%) is an entire deletion of the CYP2D6 gene; individuals homozygous for these alleles have no CYP2D6 activity The impact of CYP2D6 activity is further complicated in some SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline) because in addition to being substrates for CYP2D6, they are also known to moderately inhibit CYP2D6 activity The above information is provided for general informational and educational purposes only. 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