Brand name: Zoloft
Drug class: Selective Serotonin-reuptake Inhibitors
- Selective Serotonin-reuptake Inhibitors
- Serotonin-reuptake Inhibitors
- SSRIs
VA class: CN609
Molecular formula: C₁₇H₁₇C₁₂N•ClH
CAS number: 79559-97-0

Medically reviewed by Drugs.com on Feb 5, 2024. Written by ASHP.

Introduction

Antidepressant; selective serotonin-reuptake inhibitor (SSRI).

Uses for Sertraline

Major Depressive Disorder

Management of major depressive disorder.

Efficacy in hospital settings not established.

APA states that effectiveness of antidepressants is generally comparable between and within classes of medications, including SSRIs, SNRIs, TCAs, MAOIs, and other antidepressants (e.g., bupropion, mirtazapine, trazodone). Choose antidepressant based mainly on patient preference; nature of prior response to medication; safety, tolerability, and anticipated adverse effects; concurrent psychiatric and medical conditions; and specific properties of the medication (e.g., half-life, actions on CYP450 enzymes, other drug interactions). For most patients, an SSRI, SNRI, mirtazapine, or bupropion is considered optimal. Consult APA’s Practice Guidelines for the Treatment of Patients with Major Depressive Disorder for additional information.

Obsessive-Compulsive Disorder (OCD)

Management of OCD; reduces but does not completely eliminate obsessions and compulsions.

Panic Disorder

Management of panic disorder with or without agoraphobia.

Posttraumatic Stress Disorder (PTSD)

Management of PTSD; more effective in women than in men.

Not effective for combat- or war-related PTSD.

Premenstrual Dysphoric Disorder (PMDD)

Management of PMDD; improves symptoms (e.g., depressed mood, premenstrual anger/irritability) and functional impairment (e.g., difficulty in concentrating, lethargy) associated with this disorder.

Efficacy when used in conjunction with oral contraceptives for the treatment of PMDD is unknown.

Social Phobia

Management of social phobia (social anxiety disorder).

Premature Ejaculation

Has been used in the management of premature ejaculation^{† [off-label]}.

Vascular Headaches

Has been used in the management of vascular headaches^{† [off-label]} with equivocal efficacy.

Sertraline Dosage and Administration

General

• Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor and initiation of sertraline and vice versa. A washout period also is advisable when transferring from another antidepressant (e.g., fluoxetine) to sertraline. (See Contraindicationsand Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Cautions and see also Interactions.)

• Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments. (See Worsening of Depression and Suicidality Risk under Cautions.)

• Sustained therapy may be required; monitor periodically for need for continued therapy.

• Avoid abrupt discontinuance. Taper dosage gradually and monitor for withdrawal symptoms. If intolerable symptoms occur following dosage reduction or discontinuance, consider reinstituting previously prescribed dosage, then resume more gradual dosage reductions. (See Withdrawal of Therapy under Cautions.)

• Consider cautiously tapering dosage during third trimester of pregnancy prior to delivery. (See Pregnancy under Cautions.)

Administration

Oral Administration

Administer orally once daily (morning or evening).

With oral concentrate solution, measure doses carefully using the calibrated dropper provided by the manufacturer. (See Sensitivity Reactions under Cautions.) Oral concentrate solution must be diluted just prior to administration. Dilute in 120 mL of water, ginger ale, lemon/lime soda, lemonade, or orange juice just prior to administration; do not mix in advance or use anything other than these liquids.

Dosage

Available as sertraline hydrochloride; dosage is expressed in terms of sertraline.

Pediatric Patients

OCD

Oral

Children 6–12 years of age: Initially, 25 mg once daily.

Adolescents 13–17 years of age: Initially, 50 mg once daily.

Dosage may be increased at weekly intervals according to clinical response.

Avoid excessive dosages in children.

Optimum duration not established; may require several months of therapy or longer.

Adults

Major Depressive Disorder

Oral

Initially, 50–100 mg once daily. Dosage may be increased at weekly intervals according to clinical response.

Optimum duration not established; may require several months of therapy or longer.

OCD

Oral

Initially, 50 mg once daily. Dosage may be increased at weekly intervals according to clinical response.

Optimum duration not established; may require several months of therapy or longer.

Panic Disorder

Oral

Initially, 25 mg once daily. After 1 week, increase to 50 mg once daily. Dosage may be increased at weekly intervals according to clinical response.

Optimum duration not established; may require several months of therapy or longer.

PTSD

Oral

Initially, 25 mg once daily. After 1 week, increase to 50 mg once daily. Dosage may then be increased at weekly intervals according to clinical response.

Optimum duration not established; may require several months of therapy or longer.

PMDD

Oral

Initially, 50 mg once daily given continuously throughout the menstrual cycle or just during the luteal phase (i.e., starting 2 weeks prior to the anticipated onset of menstruation and continuing through the first full day of menses).

Dosage may be increased in 50-mg increments at the onset of each new menstrual cycle.

If a dosage of 100 mg daily has been established with luteal phase dosing, titrate dosage using a 50 mg daily dosage for the first 3 days of each luteal phase dosing period.

Optimum duration not established; periodically assess need for dosage adjustment and continued therapy.

Social Phobia

Oral

Initially, 25 mg once daily. After 1 week, increase to 50 mg once daily. Dosage may be increased at weekly intervals according to clinical response.

Optimum duration not established; may require several months of therapy or longer.

Premature Ejaculation† [off-label]

Oral

25–50 mg daily. Alternatively, 25–50 mg daily on an “as needed” basis.

Prescribing Limits

Pediatric Patients

OCD

Oral

Maximum 200 mg daily.

Adults

Major Depressive Disorder

Oral

Maximum 200 mg daily.

OCD

Oral

Maximum 200 mg daily.

Panic Disorder

Oral

Maximum 200 mg daily.

PTSD

Oral

Maximum 200 mg daily.

PMDD

Oral

Maximum 150 mg daily when administered continuously or 100 mg daily when administered during the luteal phase only.

Social Phobia

Oral

Maximum 200 mg daily.

Special Populations

Hepatic Impairment

Decreased clearance; lower dosages or less frequent administration recommended.

Renal Impairment

No dosage adjustments needed. Not substantially removed by dialysis; supplemental doses may be unnecessary after dialysis.

Cautions for Sertraline

Contraindications

• Concomitant use with pimozide or an MAO inhibitor. (See Contraindications and Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Cautions and see also Interactions.)

• Concomitant use of sertraline oral concentrate solution (contains alcohol 12%) and disulfiram or other agents likely to produce disulfiram-like reactions (e.g., metronidazole).

• Known hypersensitivity to sertraline or any ingredient in the formulation.

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs. However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

Appropriately monitor and closely observe patients receiving sertraline for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments. (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality. Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms. If decision is made to discontinue therapy, taper sertraline dosage as rapidly as is feasible but consider risks of abrupt discontinuance. (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, OCD) and nonpsychiatric disorders.

Bipolar Disorder

May unmask bipolar disorder. (See Activation of Mania/Hypomania under Cautions.) Sertraline is not approved for use in treating bipolar depression.

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.

MAO Inhibitors Interaction

Concomitant use of SSRIs and MAO inhibitors associated with serious, sometimes fatal reactions, including hyperthermia, rigidity, myoclonus, autonomic instability, and mental status changes; these reactions have resembled serotonin syndrome or neuroleptic malignant syndrome (NMS). (See Contraindications and Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Cautions and also see Interactions.)

Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions

Potentially life-threatening serotonin syndrome or NMS-like reactions reported with SSRIs and SNRIs, including sertraline, but particularly with concurrent administration of other serotonergic drugs (e.g., 5-HT₁ receptor agonists [triptans]), drugs that impair serotonin metabolism (e.g., MAO inhibitors), or antipsychotics or other dopamine antagonists. (See Contraindications under Cautions and also see Interactions.)

Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).

Severe serotonin syndrome may resemble NMS, which is characterized by hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuations in vital signs, and mental status changes.

Monitor patients receiving sertraline for the development of serotonin syndrome or NMS-like signs and symptoms. If such signs and symptoms occur, immediately discontinue treatment with sertraline and any concurrently administered serotonergic or antidopaminergic agents, including antipsychotic agents, and initiate supportive and symptomatic treatment.

Sensitivity Reactions

Latex Sensitivity

Dropper dispenser provided with Zoloft oral concentrate solution contains natural latex proteins in the form of dry natural rubber; possible sensitivity reactions in susceptible individuals.

General Precautions

Activation of Mania/Hypomania

Possible activation of mania or hypomania. Use with caution in patients with history of mania or hypomania. (See Bipolar Disorder under Cautions.)

Weight Loss

Possible anorexia and weight loss. Use with caution in patients who may be adversely affected (e.g., underweight patients).

Seizures

Limited experience in patients with a history of seizures; use with caution in such patients.

Withdrawal of Therapy

Withdrawal effects (e.g., dysphoric mood, irritability, agitation, dizziness, sensory disturbances [e.g., paresthesias, such as electric shock sensations], anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania) reported following discontinuance of serotonergic antidepressants, particularly when discontinuance was abrupt. Events generally self-limiting, but serious cases reported.

Taper dosage gradually; monitor patients for withdrawal symptoms when discontinuing therapy. If intolerable symptoms occur following dosage reduction or discontinuance, consider reinstituting previously prescribed dosage then resume more gradual dosage reductions.

Abnormal Bleeding

Possible increased risk of bleeding with SSRIs, including sertraline, and SNRIs; events ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Concomitant use of aspirin, NSAIAs, warfarin, or other anticoagulants may increase risk. (See Drugs Affecting Hemostasis and Specific Drugs under Interactions.)

Uricosuric Effect

Decrease in serum uric acid concentrations possible. Use with caution in patients who may be adversely affected (e.g., those at risk for acute renal failure).

Concomitant Illnesses

Experience in patients with concomitant diseases is limited. Patients with recent history of MI or unstable heart disease generally were excluded from premarketing clinical studies, but a postmarketing controlled study suggests that sertraline therapy is well tolerated in these patients.

Use with caution in patients with altered metabolism or hemodynamics.

Hyponatremia or SIADH

Possible hyponatremia during treatment with SSRIs, including sertraline, and SNRIs; in many cases, hyponatremia appears to be due to SIADH. Increased risk in patients who are volume depleted, elderly, or taking diuretics. Initiate appropriate medical intervention and consider drug discontinuance in patients with symptomatic hyponatremia.

Angle-Closure Glaucoma

SSRIs, including sertraline, may affect pupil size resulting in mydriasis; this effect may narrow the eye angle resulting in increased IOP and angle-closure glaucoma. Use with caution in patients with angle-closure glaucoma or history of glaucoma.

Endocrine Effects

Possible hypothyroidism, elevated serum thyrotropin, and/or reduced serum thyroxine concentrations. Monitor thyroid function periodically in patients with thyroid disease.

Electroconvulsive Therapy (ECT)

Effects of concomitant use with ECT have not been systematically evaluated.

Specific Populations

Pregnancy

Category C.

Possible complications, sometimes severe and requiring prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care, reported in neonates exposed to sertraline, other SSRIs, or SNRIs late in the third trimester; may arise immediately upon delivery. (See General under Dosage and Administration.)

Conflicting findings from available studies evaluating possible risk of persistent pulmonary hypertension of the newborn (PPHN) following in utero exposure to SSRIs; currently unclear whether SSRI use during pregnancy can cause PPHN.

Consult joint APA and ACOG guidelines (at [Web]) for additional information on management of depression in women prior to conception and during pregnancy, including treatment algorithms.

Effect on labor and delivery unknown.

Lactation

Distributed into milk; use with caution.

Pediatric Use

Safety and efficacy for OCD not established in children <6 years of age.

Safety and efficacy for other disorders (e.g., major depressive disorder, panic disorder, PTSD, PMDD, social phobia) not established in pediatric patients. Results of 2 placebo-controlled trials in children and adolescents with major depressive disorder did not support a claim of efficacy for use of sertraline in pediatric patients with this condition.

Adverse effect profile generally similar to that seen in adults. Decreased appetite and weight loss observed with use of SSRIs; monitor weight and growth regularly during long-term sertraline therapy.

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, OCD, or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others). However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials.

Carefully consider these findings when assessing potential benefits and risks of sertraline for any clinical use. (See Suicidality in the Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Clinically important hyponatremia reported in geriatric patients, who may be at increased risk for this adverse effect. Some clinicians recommend periodic monitoring (especially during the first several months) of serum sodium concentrations in geriatric patients receiving SSRIs. (See Hyponatremia or SIADH under Cautions.)

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo. (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Hepatic Impairment

Decreased clearance; use with caution. (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

Nausea, diarrhea/loose stools, dyspepsia, dry mouth, somnolence, dizziness, insomnia, tremor, ejaculatory delay, sweating.

Adverse effects in children are similar to those reported in adults. (See Pediatric Use under Cautions.)

Drug Interactions

Apparently metabolized by multiple CYP isoenzymes, with none contributing more than 40% to overall metabolism. Inhibits CYP2D6 and 3A4, but less potent as an inhibitor than many other drugs.

Drugs Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interactions (increased plasma concentrations of CYP2D6 substrates).

Clinically important pharmacokinetic interactions with substrates of 3A4 unlikely.

Drugs Affecting Hepatic Microsomal Enzymes

Clinically important pharmacokinetic interactions with inhibitors or inducers of CYP2D6 or 3A4 unlikely.

Drugs Affecting Hemostasis

Potential pharmacologic interaction (increased risk of bleeding) with concomitant use of drugs that affect hemostasis. Use with caution. (See Abnormal Bleeding under Cautions.)

Protein-bound Drugs

Potential for displacement of sertraline or other protein-bound drugs from binding sites. Monitor patients for potential adverse effects.

Drugs Associated with Serotonin Syndrome

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) with serotonergic agents. Avoid such use, or use with caution. (See Contraindications and see Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Cautions.) If serotonin syndrome or NMS occurs, immediately discontinue sertraline and any concurrently administered serotonergic or antidopaminergic agents and initiate supportive and symptomatic treatment.

Specific Drugs

Sertraline Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability in humans has not been fully elucidated to date, but ranges from 22–36% in animals.

Commercially available tablets and oral concentrate solution are bioequivalent.

Food

Food increases the extent of absorption.

Distribution

Extent

Crosses the blood-brain barrier.

Distributes into breast milk.

Plasma Protein Binding

Approximately 98% bound to plasma proteins, principally to albumin and α₁-acid glycoprotein.

Elimination

Metabolism

Extensively metabolized, probably in the liver to N-desmethylsertraline and several other metabolites. Apparently metabolized by multiple CYP isoenzymes, with none contributing more than 40% to overall metabolism.

N-Desmethylsertraline is approximately 5–10 times less potent an inhibitor of serotonin reuptake than sertraline.

Elimination Route

Excreted in both urine and feces.

Half-life

Averages approximately 25–26 hours for sertraline and 62–104 hours for N-desmethylsertraline.

Special Populations

Because sertraline is extensively metabolized by the liver, hepatic impairment can affect the elimination of the drug.

No clinically important decreases in sertraline clearance observed in patients with renal impairment.

Geriatric patients may have reduced sertraline plasma clearance.

Stability

Storage

Oral

Concentrate Solution or Tablets

25°C (may be exposed to 15–30°C).

Actions

• Mechanism of action as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the CNS resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT).

• Has very weak effects on the reuptake of norepinephrine or dopamine and does not exhibit clinically important anticholinergic, antihistaminic, or adrenergic (α₁, α₂, β) blocking activity at usual therapeutic dosages.

Advice to Patients

• Importance of providing copy of written patient information (medication guide) each time sertraline is dispensed. Importance of advising patients to read the patient information before taking sertraline and each time the prescription is filled.

• Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment. (See Worsening of Depression and Suicidality Risk under Cautions.)

• Importance of instructing patients not to take sertraline with an MAO inhibitor or within 14 days of stopping the drug, and vice versa.

• Importance of informing patients of potential risk of serotonin syndrome and neuroleptic malignant syndrome (NMS)-like reactions, particularly with concurrent use of sertraline and 5-HT₁ receptor agonists (also called triptans), tramadol, tryptophan, other serotonergic agents, or antipsychotic agents. Importance of immediately contacting clinician if signs and symptoms of these syndromes develop (e.g., agitation, hallucinations, coma, mental status changes, loss of coordination, muscle twitching, fast heart beat, increased or decreased BP, sweating, increased body temperature, muscle rigidity, diarrhea, nausea, vomiting, confusion).

• Risk of cognitive and motor impairment, importance of exercising caution while operating hazardous machinery, including automobile driving, until patients gain experience with the drug’s effects.

• Importance of patients being aware that withdrawal effects may occur when stopping sertraline, especially with abrupt discontinuance of the drug.

• Importance of informing patients that if they receive diuretics, or are otherwise volume-depleted, or are elderly, that they may be at greater risk of developing hyponatremia during sertraline therapy.

• Risks associated with concomitant use with alcohol; concomitant use not recommended.

• Importance of continuing sertraline therapy even if improvement is evident within 1–4 weeks, unless directed otherwise by their clinician.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of advising patients, their families, and caregivers to observe sertraline-treated patients for signs of activation of mania/hypomania.

• Importance of diluting oral concentrate solution with appropriate liquid just prior to administration.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., pimozide, MAO inhibitors) and OTC drugs or herbal supplements, as well as any concomitant illnesses or personal or family history of suicidality or bipolar disorder. Importance of advising patients about the risk of bleeding associated with concomitant use of sertraline with aspirin or other NSAIAs, warfarin, or other drugs that affect coagulation.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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