Continuing Education Activity

Sertraline is a medication used to manage and treat major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, and social anxiety disorder. It is in the SSRI class of medications. This activity outlines the indications, action, and contraindications for sertraline as a valuable agent in the treatment of major depressive disorder and other disorders. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, monitoring, relevant interactions) pertinent for members of the interprofessional healthcare team in treating patients with major depressive disorder and related conditions.


  • Identify the mechanism of action of sertraline.
  • Describe the adverse effects of sertraline.
  • Review the appropriate monitoring for sertraline.
  • Summarize interprofessional team strategies for improving care coordination and communication to advance sertraline and improve outcomes.


Sertraline is an antidepressant used as a first-line treatment of major depressive disorder. The Food and Drug Administration (FDA) has also approved other indications for sertraline, including the treatment of obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, and social anxiety disorder.

There are many off-label, non-FDA-approved uses for sertraline. Sertraline has been used to treat many psychiatric conditions, including binge eating disorder, body dysmorphic disorder, bulimia nervosa, generalized anxiety disorder, and premature ejaculation.[1][2][3]

Mechanism of Action

Sertraline is an antidepressant medication within the selective serotonin reuptake inhibitors (SSRIs) class. Sertraline is an antidepressant with primarily inhibitory effects on presynaptic serotonin reuptake. This inhibition of serotonin reuptake results in an accumulation of serotonin. Serotonin in the central nervous system plays a role in regulating mood, personality, and wakefulness, which is why blocking serotonin reuptake is thought to be beneficial in disorders such as major depression. Sertraline also has minimal effects on norepinephrine and dopamine uptake, and research has shown that it has more dopaminergic activity than other medications in the same SSRI class. Sertraline's mechanism of action makes it highly efficacious when used in the treatment of various psychiatric conditions.[4][5][2]


Sertraline is orally administered once daily in the morning or evening. If the patient experiences somnolence with sertraline, administer it in the evening. Available dosages in the oral tablet form are 25 mg, 50 mg, 100 mg, and solution form 20mg/ml. The absorption of sertraline may be improved when taken with food.[6]

Per FDA recommendation, the starting dose for major depressive disorder is 50 mg/day, but for PTSD, PD and ASD are 25mg/day. The sertraline dose increase in 50 mg/day increments at weekly intervals up to a maximum of 200 mg/day. Sertraline dosing is generally once daily, and administration may be at any time of the day.[7]

Adverse Effects

SSRIs, considered a newer class of antidepressants, are better tolerated than tricyclic antidepressants or monoamine oxidase inhibitors. The primary side effects of sertraline include syncope, lightheadedness, diarrhea, nausea, sweating, dizziness, xerostomia, confusion, hallucinations, tremor, somnolence, impotence, a disorder of ejaculation, fatigue, rhinitis, and female sexual disorder.

There is a bleeding risk associated with sertraline, as it may inhibit platelet aggregation. 

Sertraline can prolong the QT interval; however, the prolongation is dose-dependent and is very modest. Furthermore, this risk is higher in citalopram rather than sertraline or other SSRIs.

Sertraline may rarely produce symptoms of serotonin syndrome, though this generally happens when combining it with another serotonergic medication. These symptoms include myoclonus, muscle rigidity, diaphoresis, tremor, hyperreflexia, agitated delirium, and hyperthermia.

Sertraline, like other antidepressants, may increase the risk of suicidal ideation and behavior in children, adolescents, and young adults with major depression.

Sertraline use requires caution in patients 65 years and older. It is identified in the Beers Criteria as a high-risk medication in geriatric patients, as it may induce a syndrome of inappropriate antidiuretic hormone or hyponatremia.[5][8][9][10]

Sertraline use in the first trimester of pregnancy increased the risk of cardiovascular-related malformations such as atrial and/or ventricular septal defects in infants.[11]


Sertraline is contraindicated in patients with documented hypersensitivity to the drug or its components. The coadministration of sertraline with thioridazine, pimozide, or monoamine oxidase inhibitors, including linezolid or methylene blue, is also contraindicated. Patients who are taking other serotonergic medications should receive education regarding the risks of coadministration with sertraline. Sertraline is contraindicated with disulfiram only in solution form as it contains 12% alcohol, and it may cause an alcohol-disulfiram reaction.

Sertraline therapy should not start within two weeks of discontinuing any monoamine oxidase inhibitor to prevent toxicity with serotonin syndrome.

There is a US black box warning for use in pediatric patients and young adults. Use with caution in patients who are ages 18 to 24 years old due to the risk of an increase in suicidal ideation.[12]


It is essential to monitor patients for unusual changes in behavior, anxiety, suicidality, or any other clinical signs of worsening illness. Regularly evaluate for depression and suicidality, especially when changing the dose of sertraline. Sertraline may also precipitate mania in patients who are at risk for bipolar disorder. Monitor for symptoms of mania in patients who are started on sertraline, especially if they have a family history of mania or bipolar disorder.

Monitor for abnormal bleeding, adverse effects of medication use, or withdrawal symptoms from abrupt discontinuation in patients taking sertraline. The abnormal bleeding may primarily occur if used concurrently with aspirin, NSAIDs, warfarin, or other anticoagulants, as sertraline may impair platelet aggregation and cause bruising, epistaxis, or hemorrhage.

For geriatric patients, monitor for changes in mental status, and check their sodium concentration regularly due to the risk of SIADH or hyponatremia.

Sertraline is considered safe in patients with a history of myocardial infarction, heart failure, and other cardiac conditions. However, due to the minor effect of QT prolongation, it may benefit the provider to monitor the QT interval with electrocardiograms. 

Sertraline is also considered safe in pregnancy and with breastfeeding. Although not mandatory, therapeutic drug monitoring may be a consideration to ensure the safety of pregnant patients and infants who may have exposure to the medication.[13][14][15][16][17]


The overdose of sertraline is generally well-tolerated. Sertraline toxicity may result in serotonin syndrome, resulting in myoclonus, muscle rigidity, diaphoresis, tremor, hyperreflexia, agitated delirium, and hyperthermia. Treatment of serotonin syndrome requires discontinuing the medication and supportive care. Consider antiemetics (non-serotonergic), benzodiazepines, and standard cooling measures for symptom relief. The patient can also receive serotonin antagonists such as cyproheptadine. If there is severe toxicity and the patient develops muscular rigidity and hyperthermia with body temperatures higher than 41 degrees C, consider sedation, endotracheal intubation, external cooling, and neuromuscular paralysis. It is important to note that antipyretics are likely not beneficial to patients experiencing hyperthermia due to serotonin syndrome.[18]

Enhancing Healthcare Team Outcomes

Healthcare providers who often prescribe sertraline include primary care physicians, psychiatrists, nurse practitioners, and others, functioning as an interprofessional team. All healthcare team members must follow the patient regularly to monitor for the reduction of symptoms or any adverse effects. All providers should know the medication's contraindications, adverse effects, and interactions with other drugs. It is also essential to educate all patients who are prescribed sertraline on the possible adverse effects and the prevention and recognition of toxicity due to sertraline (in combination with other serotonergic drugs). Patient education regarding medication use and compliance will improve outcomes and ensure patient safety.

Patient safety can also be improved when dosing adjustments are considered by health care professionals who are a part of a patient's care team. Elderly patients may need dosing adjustments, as they may tolerate lower doses better. Patients with medical conditions affecting their liver may also need decreased doses for better tolerability. 

Clinicians require vigilance regarding the toxic effects of serotonergic medications and ensure not to prescribe multiple medications that can cause serotonin syndrome, which is possible by preventing polypharmacy and minimizing unnecessary use of these drugs; this is one of the areas where the pharmacist can provide valuable input to the team as they monitor and verify the patient's medication regimen as well as monitor dosing of sertraline and other drugs. Furthermore, should a patient need to be switched to a different serotonergic medication, physicians and other healthcare team members must ensure that no new medication starts until at least two weeks after the discontinuation of sertraline.[18] Nursing can play a significant role in this type of monitoring, ensuring patient compliance, providing counsel, assessing therapeutic effectiveness, being aware of potential adverse drug reactions, and alerting the team of any concerns. Only with this type of cohesive interprofessional team coordination can sertraline therapy provide an optimal therapeutic benefit while minimizing adverse events. [Level 5]

Article Details

Article Author

Hardeep Singh

Article Editor:

Abdolreza Saadabadi


11/22/2020 9:33:55 AM

PubMed Link:




Fenske JN,Schwenk TL, Obsessive compulsive disorder: diagnosis and management. American family physician. 2009 Aug 1;     [PubMed PMID: 19621834]


Cipriani A,La Ferla T,Furukawa TA,Signoretti A,Nakagawa A,Churchill R,McGuire H,Barbui C, Sertraline versus other antidepressive agents for depression. The Cochrane database of systematic reviews. 2010 Apr 14;     [PubMed PMID: 20393946]


Aigner M,Treasure J,Kaye W,Kasper S, World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. 2011 Sep;     [PubMed PMID: 21961502]


Kitaichi Y,Inoue T,Nakagawa S,Boku S,Kakuta A,Izumi T,Koyama T, Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats. European journal of pharmacology. 2010 Nov 25     [PubMed PMID: 20816814]


Sanchez C,Reines EH,Montgomery SA, A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike? International clinical psychopharmacology. 2014 Jul;     [PubMed PMID: 24424469]


Hicks JK,Bishop JR,Sangkuhl K,Müller DJ,Ji Y,Leckband SG,Leeder JS,Graham RL,Chiulli DL,LLerena A,Skaar TC,Scott SA,Stingl JC,Klein TE,Caudle KE,Gaedigk A, Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors. Clinical pharmacology and therapeutics. 2015 Aug;     [PubMed PMID: 25974703]


Preskorn SH,Lane RM, Sertraline 50 mg daily: the optimal dose in the treatment of depression. International clinical psychopharmacology. 1995 Sep     [PubMed PMID: 8675965]


Beach SR,Kostis WJ,Celano CM,Januzzi JL,Ruskin JN,Noseworthy PA,Huffman JC, Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation. The Journal of clinical psychiatry. 2014 May;     [PubMed PMID: 24922496]


American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society. 2019 Apr;     [PubMed PMID: 30693946]


Selective Serotonin Reuptake Inhibitor-Induced Hyponatremia: Clinical Implications and Therapeutic Alternatives., Varela Piñón M,Adán-Manes J,, Clinical neuropharmacology, 2017 Jun 16     [PubMed PMID: 28622213]


Shen ZQ,Gao SY,Li SX,Zhang TN,Liu CX,Lv HC,Zhang Y,Gong TT,Xu X,Ji C,Wu QJ,Li D, Sertraline use in the first trimester and risk of congenital anomalies: a systemic review and meta-analysis of cohort studies. British journal of clinical pharmacology. 2017 Apr     [PubMed PMID: 27770542]


DeVane CL,Liston HL,Markowitz JS, Clinical pharmacokinetics of sertraline. Clinical pharmacokinetics. 2002;     [PubMed PMID: 12452737]


Glassman AH,O'Connor CM,Califf RM,Swedberg K,Schwartz P,Bigger JT Jr,Krishnan KR,van Zyl LT,Swenson JR,Finkel MS,Landau C,Shapiro PA,Pepine CJ,Mardekian J,Harrison WM,Barton D,Mclvor M, Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002 Aug 14;     [PubMed PMID: 12169073]


O'Connor CM,Jiang W,Kuchibhatla M,Silva SG,Cuffe MS,Callwood DD,Zakhary B,Stough WG,Arias RM,Rivelli SK,Krishnan R, Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial. Journal of the American College of Cardiology. 2010 Aug 24;     [PubMed PMID: 20723799]


Paulzen M,Goecke TW,Stickeler E,Gründer G,Schoretsanitis G, Sertraline in pregnancy - Therapeutic drug monitoring in maternal blood, amniotic fluid and cord blood. Journal of affective disorders. 2017 Apr 1;     [PubMed PMID: 28129551]


Pinheiro E,Bogen DL,Hoxha D,Ciolino JD,Wisner KL, Sertraline and breastfeeding: review and meta-analysis. Archives of women's mental health. 2015 Apr;     [PubMed PMID: 25589155]


Leverich GS,Altshuler LL,Frye MA,Suppes T,McElroy SL,Keck PE Jr,Kupka RW,Denicoff KD,Nolen WA,Grunze H,Martinez MI,Post RM, Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. The American journal of psychiatry. 2006 Feb     [PubMed PMID: 16449476]


Wang RZ,Vashistha V,Kaur S,Houchens NW, Serotonin syndrome: Preventing, recognizing, and treating it. Cleveland Clinic journal of medicine. 2016 Nov;     [PubMed PMID: 27824534]