Sertraline (Zoloft)

Primer

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.

Pharmacokinetics

See also article: Introduction to Pharmacology

Pharmacokinetics of Sertraline

Absorption
Distribution
Metabolism
Elimination
Half-life

See also article: Cytochrome (CYP) P450 Metabolism

Sertraline: Cytochrome P450 Metabolism

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

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

Pharmacodynamics

Mechanism of Action

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

Toxicity

Indications

Major depressive disorder
Generalized anxiety disorder
Premenstrual dysphoric disorder
Obsessive compulsive disorder
Panic disorder
Posttraumatic disorder
Social anxiety disorder
Bulimia nervosa

Dosing

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]

Formulations

Sertraline comes in oral (PO) formulation

Contraindications

Absolute

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

Relative

Thioridazine (arrythmias)

Drug-Drug Interactions

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

Side Effects

Sexual dysfunction (up to 30%)
Gastrointestinal (poor appetite, nausea, diarrhea, constipation, dry mouth)
CNS effects (insomnia or sedation, depending on the patient)
Bruising/bleeding (rare)
Hyponatremia (rare)^[2]
Hypotension (rare)
Weight gain is unusual, some patients may actually experience weight loss
Syndrome of inappropriate ADH secretion (SIADH)

Adverse Events

Serotonin syndrome

Clinical Pearls

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]

Special Populations

Geriatric

See main article: Geriatric Pharmacology

Obstetric and Fetal

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]

Pediatric

See main article: Pediatric Pharmacology

Medically Ill

See main article: Psychotropic Dosing in the Medically Ill

¹⁾ Royal College of Psychiatrists - Coming off antidepressants

²⁾ Jacob, S., & Spinier, S. A. (2006). Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Annals of Pharmacotherapy, 40(9), 1618-1622.

³⁾ Nasky, K. M., Cowan, G. L., & Knittel, D. R. (2009). False-positive urine screening for benzodiazepines: an association with sertraline?: a two-year retrospective chart analysis. Psychiatry (Edgmont), 6(7), 36.

⁴⁾ Hedayati, S. S., Gregg, L. P., Carmody, T., Jain, N., Toups, M., Rush, A. J., ... & Trivedi, M. H. (2017). Effect of Sertraline on Depressive Symptoms in Patients With Chronic Kidney Disease Without Dialysis Dependence: The CAST Randomized Clinical Trial. JAMA.

⁵⁾ B.C.'s Best Practice Guidelines for Mental Health Disorders in the Perinatal Period (2014)

⁶⁾ B.C.'s Best Practice Guidelines for Mental Health Disorders in the Perinatal Period (2014)

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