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Sertraline

Medically reviewed on August 12, 2018

Pronunciation

(SER tra leen)

Index Terms

  • Sertraline HCl
  • Sertraline Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Concentrate, Oral:

Zoloft: 20 mg/mL (60 mL) [contains alcohol, usp, menthol]

Generic: 20 mg/mL (60 mL)

Tablet, Oral:

Zoloft: 25 mg [scored; contains fd&c blue #1 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #10 aluminum lake, polysorbate 80]

Zoloft: 50 mg [scored; contains fd&c blue #2 aluminum lake]

Zoloft: 100 mg [scored; contains polysorbate 80]

Generic: 25 mg, 50 mg, 100 mg

Brand Names: U.S.

  • Zoloft

Pharmacologic Category

  • Antidepressant, Selective Serotonin Reuptake Inhibitor

Pharmacology

Antidepressant with selective inhibitory effects on presynaptic serotonin (5-HT) reuptake and only very weak effects on norepinephrine and dopamine neuronal uptake. In vitro studies demonstrate no significant affinity for adrenergic, cholinergic, GABA, dopaminergic, histaminergic, serotonergic, or benzodiazepine receptors.

Metabolism

Hepatic; may involve CYP2C19 and CYP2D6; extensive first pass metabolism; forms metabolite N-desmethylsertraline (APA [Gelenberg 2010]); Note: Children 6 to 17 years may metabolize sertraline slightly better than adults, as pediatric AUCs and peak concentrations were 22% lower than adults when adjusted for weight; however, lower doses are recommended for younger pediatric patients to avoid excessive drug levels)

Excretion

Urine (40% to 45% as metabolites); feces (40% to 45%; 12% to 14% as unchanged drug)

Onset of Action

Depression: The onset of action is within a week, however, individual response varies greatly and full response may not be seen until 8 to 12 weeks after initiation of treatment (APA [Gelenberg 2010]).

Time to Peak

Plasma: Sertraline: 4.5 to 8.4 hours

Half-Life Elimination

Sertraline: Mean: 26 hours; N-desmethylsertraline: 62 to 104 hours

Children 6 to 12 years: Mean: 26.2 hours (Alderman 1998)

Children 13 to 17 years: Mean: 27.8 hours (Alderman 1998)

Adults 18 to 45 years: Mean: 27.2 hours (Alderman 1998)

Protein Binding

98%

Special Populations: Hepatic Function Impairment

Sertraline clearance was reduced in patients with chronic mild liver impairment resulting in a 3-fold greater exposure.

Special Populations: Elderly

Plasma clearance 40% lower; steady state achieved after 2 to 3 weeks

Special Populations: Children

Children 6 to 17 years may metabolize sertraline slightly better than adults, as pediatric AUCs and peak concentrations were 22% lower than adults when adjusted for weight; however, lower doses are recommended for younger pediatric patients to avoid excessive drug levels)

Use: Labeled Indications

Major depressive disorder (unipolar): Treatment of unipolar major depressive disorder (MDD) in adults.

Obsessive-compulsive disorder: Treatment of obsessions and compulsions in patients with obsessive-compulsive disorder (OCD).

Panic disorder: Treatment of panic disorder in adults with or without agoraphobia.

Posttraumatic stress disorder: Treatment of posttraumatic stress disorder (PTSD) in adults.

Premenstrual dysphoric disorder: Treatment of premenstrual dysphoric disorder (PMDD) in adults.

Social anxiety disorder: Treatment of social anxiety disorder (social phobia) in adults.

Off Label Uses

Binge eating disorder

Data from two small, double-blind, randomized, controlled trials support the use of sertraline to improve weight loss, binge frequency, and binge behaviors in patients with binge eating disorder [Leombruni 2008], [McElroy 2000].

Based on the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of eating disorders, sertraline may be effective and is recommended in the management of binge eating disorder [WFSBP [Aigner 2011]].

Body dysmorphic disorder

Based on the National Institute for Health and Care Excellence (NICE) guidelines for treatment of obsessive-compulsive disorder and body dysmorphic disorder, SSRIs given as monotherapy or in combination with cognitive behavior therapy are recommended in the management of body dysmorphic disorder in adults with moderate or severe functional impairment, respectively. SSRIs may be considered in children or adolescents if they decline, are unable to engage in, or have an inadequate response to psychological treatment and are able to be monitored closely for adverse effects.

Bulimia nervosa

Data from one small, randomized, controlled trial and another study of lower quality (open-label, flexible-dose study) in patients with bulimia nervosa support the use of sertraline to reduce the number of binge eating crises and purging in these patients [Milano 2004], [Sloan 2004].

Generalized anxiety disorder

Data from several double-blind, randomized, controlled trials in patients with generalized anxiety disorder, support the use of sertraline to reduce anxiety symptoms in these patients [Ball 2005], [Brawman-Mintzer 2006], [Dahl 2005].

Based on the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of anxiety disorders, sertraline is effective and recommended in the management of generalized anxiety disorder [WFSBP [Bandelow 2008]], [WFSBP [Bandelow 2012]].

Premature ejaculation

Data from randomized controlled trials suggest that sertraline may be beneficial for the treatment of premature ejaculation [Arafa 2006], [McMahon 1998a], [Mendels 1995].

According to the International Society for Sexual Medicine guidelines, sertraline is effective and recommended in the management of premature ejaculation; however, paroxetine may have a more robust effect.

Contraindications

Use of MAOIs including linezolid or methylene blue (concurrently or within 14 days of stopping an MAOI or sertraline); concurrent use with pimozide; hypersensitivity (eg, anaphylaxis, angioedema) to sertraline or any component of the formulation; concurrent use with disulfiram (oral solution only).

Documentation of allergenic cross-reactivity for SSRIs is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Binge eating disorder (off-label use): Limited data available: Oral: Initial: 25 mg daily after lunch for 3 days; may increase dose based on response and tolerability in increments of 25 mg every 3 days. Usual dose range: 100 to 200 mg daily. Maximum dose: 200 mg/day (Leombruni 2008). Based on limited data, some experts recommend doses used for major depressive disorder and slower titrations (eg, ≥1 week) (Sysko 2018).

Body dysmorphic disorder (off-label use): Limited data available: Oral: Some experts suggest an initial dose of 50 mg once daily; may increase dose gradually based on response and tolerability in increments of 25 to 50 mg over 6 to 10 weeks to a usual dose of 200 mg/day; doses up to 400 mg/day may be necessary in some patients for optimal response (Phillips 2018).

Bulimia nervosa (alternative agent) (off-label use): Oral: Initial: 50 mg daily; may increase dose based on response and tolerability in increments of 50 mg at intervals ≥1 week. Maximum dose: 200 mg/day (Milano 2004; Sloan 2004).

Generalized anxiety disorder (GAD) (off-label use): Oral: Initial: 25 mg once daily; may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 to 2 weeks. Usual dose: 50 to 150 mg/day. Maximum dose: 200 mg/day (Ball 2005; Brawman-Mintzer 2006; Dahl 2005).

Major depressive disorder (MDD) (unipolar): Oral: Initial: 50 mg once daily; may increase dose based on response and tolerability in increments of 25 to 50 mg once weekly to a maximum of 200 mg/day (according to manufacturer's labeling); however, doses up to 300 mg/day have been used in clinical practice for MDD and may provide further benefit (Simon 2018). More rapid titrations (every 3 days) in combination with an antipsychotic (eg, olanzapine) are used by some experts for patients with psychotic features (Meyers 2009; Rothschild 2018).

Obsessive-compulsive disorder: Oral: Initial: 50 mg once daily; may increase dose based on response and tolerability in increments of 25 to 50 mg once weekly to a maximum of 200 mg/day (according to the manufacturer's labeling). Doses up to 400 mg/day may have modest clinical benefit in patients with inadequate response to standard doses (Ninan 2006), but adverse effects may be increased.

Panic disorder: Oral: Initial: 25 mg once daily for 3 to 7 days, then increase to 50 mg/day (APA 2009); thereafter, may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 week to a maximum of 200 mg/day

Posttraumatic stress disorder (PTSD): Oral: Initial: 25 to 50 mg once daily (VA/DoD 2017); may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 week to a maximum of 200 mg/day (according to the manufacturer's labeling); however, doses up to 250 mg/day have been used in clinical practice and may provide further benefit (Stein 2018).

Premature ejaculation (off-label use): Oral: Initial: 50 mg once daily; may increase dose based on response and tolerability at intervals of ~3 to 4 weeks in 50 mg increments up to 200 mg/day (McMahon 1998b; Mendels 1995)

Premenstrual dysphoric disorder (PMDD):

Continuous daily dosing regimen: Oral: 50 mg once daily; may increase dose based on response and tolerability in 50 mg increments per menstrual cycle up to 150 mg/day.

Luteal phase dosing regimen: Oral: 50 mg once daily during the luteal phase of menstrual cycle only (beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); may increase dose based on response and tolerability in 50 mg increments per menstrual cycle up to 100 mg/day. If a 100 mg daily dose has been established with luteal phase dosing, begin with 50 mg once daily for 3 days at the beginning of each subsequent luteal phase dosing period, then increase to 100 mg once daily.

Symptom-triggered dosing regimen (off-label dosing): Oral: 50 mg once daily from the day of symptom onset until a few days after the start of menses; may increase dose based on response and tolerability in 50 mg increments per menstrual cycle up to 100 mg/day. If a 100 mg daily dose has been established in previous cycles, begin with 50 mg once daily for 2 days at the beginning of each subsequent luteal phase dosing period, then increase to 100 mg once daily (Yonkers 2015).

Social anxiety disorder: Oral: Initial: 25 to 50 mg once daily (WFSBP [Bandelow 2012]); after ~6 weeks, may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 week to a maximum of 200 mg/day

Discontinuation of therapy: When discontinuing antidepressants, gradually taper the dose (eg, over 2 to 4 weeks) to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms (APA 2010; WFSBP [Bauer 2015]); antidepressants with a shorter half-life may need to be tapered more slowly (APA 2010) (eg, over 4 weeks [Hirsch 2018a]). If intolerable withdrawal symptoms occur following a dose reduction, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, and pharmacodynamics), and the degree of symptom control desired (Hirsch 2018c; Ogle 2013; WFSBP [Bauer 2013]).

Switching to or from an MAOI:

Allow 14 days to elapse between discontinuing an MAOI and initiation of sertraline.

Allow 14 days to elapse between discontinuing sertraline and initiation of an MAOI.

Dosing: Geriatric

Use with caution (Beers Criteria [AGS 2015]). Refer to adult dosing; however, lower initial doses (25 mg once daily) may be better tolerated in older adults (Hirsch 2018b).

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Pediatric

Major depressive disorder (off-label use):

Children ≥6 years of age: Oral: Initial: 12.5 to 25 mg once daily; titrate dose upward if clinically needed; may increase dose in increments of 25 to 50 mg daily at intervals of at least 1 week; mean final dose in 21 children (8 to 18 years of age) was 100±53 mg or 1.6 mg/kg/day (n=11); range: 25 to 200 mg/day; maximum dose: 200 mg/day (Dopheide 2006; Tierney 1995); avoid excessive dosing.

Adolescents: Oral: Initial 25 to 50 mg once daily; titrate dose upward if clinically needed; may increase dose in increments of 50 mg daily at intervals of at least 1 week; mean final dose in 13 adolescents was 110±50 mg or about 2 mg/kg/day (McConville 1996); in another study using a slower titration, the mean dose at week 6 was 93 mg (n=41) and at week 10 was 127 mg (n=34) (Ambrosini 1999); range: 25 to 200 mg/day; maximum dose: 200 mg/day (Dopheide 2006).

Obsessive-compulsive disorder:

Children 6 to 12 years of age: Oral: Initial: 25 mg once daily; may increase dose in increments of 25 to 50 mg once weekly to a maximum of 200 mg/day

Adolescents: Oral: Initial: 50 mg once daily; may increase dose in increments of 25 to 50 mg once weekly to a maximum of 200 mg/day

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

Mild impairment (Child-Pugh class A): Reduce dose to 50% of usual dose.

Moderate to severe impairment (Child-Pugh class B or C): Use is not recommended.

Reconstitution

Oral solution: Must be diluted before use. Immediately before administration, use the dropper provided to measure the required amount of solution; mix with 4 ounces (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade, or orange juice only. Do not mix with any other liquids than these. The dose should be taken immediately after mixing; do not mix in advance. A slight haze may appear after mixing; this is normal.

Administration

Oral solution: Must be diluted immediately before use to make the preparation more palatable. Direct administration of the pure solution is astringent and may numb the tongue/mouth for at least a day, even if the mouth is rinsed extensively (Pfizer Medical Information, written communication, February 2, 2016). Note: Use with caution in patients with latex sensitivity; dropper dispenser contains dry natural rubber.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Consider therapy modification

Amifampridine: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, both drugs have the potential to decrease the seizure threshold, possibly increasing the risk for seizures. Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Monitor therapy

ARIPiprazole: Sertraline may enhance the adverse/toxic effect of ARIPiprazole. Sertraline may increase the serum concentration of ARIPiprazole. Monitor therapy

Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Monitor therapy

Beta-Blockers: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Beta-Blockers. Exceptions: Acebutolol; Atenolol; Betaxolol (Ophthalmic); Betaxolol (Systemic); Bisoprolol; Carteolol (Ophthalmic); Esmolol; Labetalol; Levobunolol; Metipranolol; Nadolol; Penbutolol; Sotalol. Monitor therapy

Blood Glucose Lowering Agents: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Avoid combination

BusPIRone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Management: The combination of a selective serotonin reuptake inhibitor and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Sertraline. Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy

Cimetidine: May decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Sertraline. Monitor therapy

Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Darunavir: May decrease the serum concentration of Sertraline. Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Desmopressin: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dextromethorphan: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine. Consider therapy modification

Disulfiram: May enhance the adverse/toxic effect of Sertraline. This is specifically related to sertraline oral concentrate due to its alcohol content (12%). Management: Sertraline Oral Concentrate contains 12% alcohol, and its use should be avoided with disulfiram. Avoid combination

Dosulepin: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dosulepin. Avoid combination

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy

Efavirenz: May decrease the serum concentration of Sertraline. Monitor therapy

Erythromycin (Systemic): May enhance the adverse/toxic effect of Sertraline. Monitor therapy

Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Fosphenytoin: May decrease the serum concentration of Sertraline. Sertraline may increase the serum concentration of Fosphenytoin. Monitor therapy

Galantamine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Galantamine. Monitor therapy

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Grapefruit Juice: May increase the serum concentration of Sertraline. Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Iobenguane I 123: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Avoid combination

Lithium: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could increase the risk of serotonin toxicity/serotonin syndrome. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Consider therapy modification

MetyroSINE: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Mivacurium: Sertraline may increase the serum concentration of Mivacurium. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Consider therapy modification

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Opioid Analgesics: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Monitor therapy

Phenytoin: Sertraline may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Sertraline. Monitor therapy

Pimozide: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Pimozide. Avoid combination

Propafenone: Sertraline may enhance the QTc-prolonging effect of Propafenone. Sertraline may increase the serum concentration of Propafenone. Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

QTc-Prolonging Agents (Highest Risk): QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

QTc-Prolonging Agents (Moderate Risk): QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

RisperiDONE: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of RisperiDONE. Monitor therapy

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

Serotonin Reuptake Inhibitor/Antagonists: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin Reuptake Inhibitor/Antagonists. This may cause serotonin syndrome. Management: Consider alternatives, and use conservative initial dosing. Monitor patients receiving these combinations for signs/symptoms of serotonin toxicity. Consider therapy modification

Succinylcholine: Sertraline may increase the serum concentration of Succinylcholine. Monitor therapy

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Tricyclic Antidepressants: Sertraline may enhance the adverse/toxic effect of Tricyclic Antidepressants. Sertraline may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with sertraline. Consider therapy modification

Tryptophan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

May interfere with urine detection of benzodiazepines (false-positive)

Adverse Reactions

>10%:

Central nervous system: Insomnia (20%), dizziness (12%), fatigue (12%), drowsiness (11%)

Gastrointestinal: Nausea (26%), diarrhea (20%), xerostomia (14%)

1% to 10%:

Cardiovascular: Palpitations (4%), edema (<2%), hypertension (<2%), syncope (<2%), tachycardia (<2%), vasodilation (<2%)

Central nervous system: Agitation (8%), malaise (≥5%), anxiety (children and adolescents: ≥2%), abnormal gait (<2%), ataxia (<2%), coma (<2%), confusion (<2%), euphoria (<2%), hallucination (<2%), hypertonia (<2%), hypoesthesia (<2%), impaired consciousness (<2%), irritability (<2%), lethargy (<2%), psychomotor agitation (<2%), seizure (<2%), yawning (<2%)

Dermatologic: Hyperhidrosis (7%), alopecia (<2%), bullous dermatitis (<2%), dermatitis (<2%), diaphoresis (<2%), erythematous rash (<2%), follicular rash (<2%), maculopapular rash (<2%), pruritus (<2%), urticaria (<2%)

Endocrine & metabolic: Decreased libido (4% to 7%), weight loss (>7% of body weight; children: 7%; adolescents: 2%), diabetes mellitus (<2%), galactorrhea (<2%), hypercholesterolemia (<2%), hypoglycemia (<2%), hypothyroidism (<2%)

Gastrointestinal: Dyspepsia (8%), decreased appetite (7%), constipation (6%), abdominal pain (≥5%), vomiting (4%), bruxism (<2%), hematochezia (<2%), increased appetite (<2%), melena (<2%)

Genitourinary: Ejaculation failure (8%), erectile dysfunction (4%), ejaculatory disorder (3%), urinary incontinence (≥2%), sexual disorder (males: 2%), hematuria (<2%), priapism (<2%), vaginal hemorrhage (<2%)

Hematologic & oncologic: Hemorrhage (<2%), rectal hemorrhage (<2%)

Hepatic: Increased liver enzymes (<2%)

Hypersensitivity: Anaphylaxis (<2%)

Neuromuscular & skeletal: Tremor (9%), hyperkinesia (children and adolescents: ≥2%), muscle spasm (<2%)

Ophthalmic: Visual disturbance (4%), blurred vision (<2%), mydriasis (<2%)

Otic: Tinnitus (<2%)

Respiratory: Bronchospasm (<2%)

Frequency not defined:

Central nervous system: Aggressive behavior

Hematologic & oncologic: Purpura

Neuromuscular & skeletal: Arthralgia, muscle twitching

Respiratory: Epistaxis

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Acute renal failure, agranulocytosis, angioedema, angle-closure glaucoma, aplastic anemia, atrial arrhythmia, atrioventricular block, blindness, bradycardia, cataract, cerebrovascular spasm (including Call-Fleming syndrome, reversible cerebral vasoconstriction syndrome), coagulation time increased (altered platelet function), diabetes mellitus, edema, extrapyramidal reaction (including akathisia, dystonia), gynecomastia, hepatic failure, hepatitis, hyperglycemia, hyperprolactinemia, hypersensitivity reaction, hypomania, hyponatremia, jaundice, leukopenia, lupus-like syndrome, mania, menstrual disease, neuroleptic malignant syndrome (Stevens 2008), nightmares, oculogyric crisis, optic neuritis, pancreatitis, pancytopenia, prolonged Q-T interval on ECG, psychosis, pulmonary hypertension, rhabdomyolysis, serotonin syndrome, serum sickness, SIADH, skin photosensitivity, Stevens-Johnson syndrome, thrombocytopenia, torsades de pointes, toxic epidermal necrolysis, trismus, vasculitis, ventricular tachycardia, withdrawal syndrome

ALERT: U.S. Boxed Warning

Suicidality and antidepressant drugs:

Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors.

Warnings/Precautions

Major psychiatric warnings:

• [US Boxed Warning]: Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription.

• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their health care provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• Bleeding risk: May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin, NSAIDs, warfarin or other anticoagulants. Bleeding related to SSRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.

• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.

• Fractures: Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda 2013; Rizzoli 2012).

• Ocular effects: May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors. Avoid use in patients with untreated anatomically narrow angles.

• QT prolongation: QTc prolongation and torsades de pointes have been reported with sertraline use. Most reports involved other risk factors; use with caution in patients with risk factors for QTc prolongation. Studies have shown correlations with serum sertraline concentrations.

• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John's wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

• Sexual dysfunction: May cause or exacerbate sexual dysfunction.

• SIADH and hyponatremia: SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium <110 mmol/L), predominately in the elderly. Volume depletion and/or concurrent use of diuretics likely increases risk. Discontinue use if symptomatic hyponatremia occurs.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; use reduced dose in mild impairment; use is not recommended in moderate or severe impairment.

• Mania/hypomania: May precipitate a mixed/manic episode in patients at risk for bipolar disorder. Use with caution in patients with a family history of bipolar disorder, mania, or hypomania. Patients presenting with depressive symptoms should be screened for bipolar disorder. Sertraline is not FDA approved for the treatment of bipolar depression.

• Seizure disorder: Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: Monitor growth in pediatric patients. Given their lower body weight, lower doses are advisable in pediatric patients in order to avoid excessive plasma levels, despite slightly greater metabolism efficiency than adults.

Dosage form specific issues:

• Latex sensitivity: Use oral solution formulation with caution in patients with latex sensitivity; dropper dispenser contains dry, natural rubber.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, lightheadedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).

Monitoring Parameters

Weight, height, BMI (longitudinal monitoring); mental status for depression, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks, or other unusual changes in behavior; signs/symptoms of serotonin syndrome; serum sodium in at-risk populations.

Pregnancy Considerations

Sertraline crosses the human placenta. Available studies evaluating teratogenic effects following maternal use of sertraline in the first trimester have not shown an overall increased risk of major birth defects. Studies evaluating specific birth defects have provided inconsistent results. Nonteratogenic effects in the newborn following SSRI/SNRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. Symptoms may be due to the toxicity of the SSRIs/SNRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn (PPHN) has also been reported with SSRI exposure. The long-term effects of in utero SSRI exposure on infant development and behavior are not known.

Due to pregnancy-induced physiologic changes, women who are pregnant may require adjusted doses of sertraline to achieve euthymia. The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 2008; APA 2010; Yonkers 2009).

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, fatigue, loss of strength and energy, anxiety, nausea, dry mouth, diarrhea, constipation, insomnia, sweating a lot, tremors, abdominal pain, or lack of appetite. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), abnormal heartbeat, tachycardia, passing out, vision changes, eye pain, eye irritation, eye edema, eye redness, agitation, panic attacks, irritability, behavioral changes, angina, seizures, urinary incontinence, severe headache, excessive weight gain or loss, decreased libido, menstrual changes, sexual dysfunction, or priapism (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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