“Sertraline blocks the serotonin transporter (SERT)” as do all SSRIs. Sertraline (Zoloft) is the #1 prescribed antidepressant and the #14 overall prescribed medication in the United States. It is a reasonable first-line treatment for any of its FDA-approved conditions. Sertraline has no real advantage over escitalopram (Lexapro), which has a slight advantage over sertraline in terms of side effects.
Among SSRIs, sertraline is the most likely to cause diarrhea—“Zoloft makes your stools So Soft”. “So soft” also refers to sertraline’s potential to cause erectile dysfunction, which is a side effect of all SSRIs. In terms of antidepressant-associated sexual dysfunction, sertraline is slightly better than paroxetine (Paxil) and slightly worse than escitalopram.
For any SSRI, treatment of obsessive-compulsive disorder (OCD) may require significantly higher doses than used for depression. Although the FDA max for Zoloft is 200 mg, it may be necessary to go as high as 400 mg for treatment of OCD (titrated gradually).
On drug screens, Zoloft can cause a false positive result for benzodiazepines.
Risk of mortality with single-drug overdose on sertraline is about 1 in 10,000 (Nelson & Spyker, 2017), which is similar to mortality risk of escitalopram.
Zoloft combines well with bupropion (Wellbutrin) for depression with prominent fatigue (“Well-off”). Trazodone (Desyrel) is a common add-on for insomnia. For anxiety, sertraline combines well with buspirone (Buspar) or any benzodiazepine. For bipolar depression or refractory unipolar depression, sertraline can be combined with any mood stabilizer or antipsychotic. Buspirone can counter SSRI-induced sexual dysfunction and bruxism.
Dosing: 50 mg is the starting dose for most indications; FDA max is 200 mg; For treatment of OCD the dose may need to go as high as 400 mg (Stahl, 2016). Taper gradually to avoid unpleasant serotonin discontinuation symptoms.
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