Sertraline

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Sertraline quick reference

Sertraline
Sertraline general drug information
 Pronunciation SER tra leen (.wav file)
 Trade Name(s) Zoloft, Lustral (UK)
 How Supplied Tablets: 25 mg, 50 mg, 100 mg
Oral concentrate solution: 20 mg/mL
 Generic Availability All
 Patent Expiry Date February 7, 2006
 Classification Selective serotonin reuptake inhibitor (SSRI)
 Schedule Rx
 Pregnancy Category C
 Breast-feeding Use with caution. Drug is excreted into breast milk.
Sertraline chemical information
 IUPAC Name (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride
 Empirical Formula C17H17NCl2•HCl
 Molecular Weight 342.7 g/mol
pharmacokinetic information  |  pharmacogenomic information

Description

Sertraline is a selective serotonin reuptake inhibitor (SSRI) originally marketed by Pfizer under the trade name Zoloft®. It was approved by the FDA in 1991 for the treatment of major depression in adults. Further studies led to additional FDA indications including obsessive-compulsive disorder and panic disorder in 1997, post traumatic stress disorder in Novemeber 2001, premenstrual dysphoric disorder in May 2002, and social phobia in Februrary 2003. Sertraline became available generically in early 2006.[1]

The efficacy of sertraline is difficult to objectively determine due to the nature of the conditions it is indicated to treat. Tools that are commonly used to measure depression severity include the Hamilton Depression Rating Scale and the Clinical Global Impression Severity and Improvement scales. The Yale–Brown Obsessive-Compulsive Scale is also commonly used to monitor the efficacy of obsessive-compulsive disorder treatments. Because studies have not conclusively determined superiority of efficacy between members of the SSRI class, selection of an agent is often based on patient specific factors such as perceived efficacy and severity of side effects.[2][3].

Mechanism of Action

Sertraline exerts its actions by inhibiting the CNS presynaptic neuronal reuptake of serotonin. This increases the concentration of serotonin in the synaptic cleft and the potential for serotonergic binding at postsynaptic receptors. Agents that increase serotonin levels have been used for the treatment of depression and anxiety disorders due to the central role serotonin plays in mood regulation. While SSRIs have been shown to weakly inhibit the reuptake of norepinephrine and dopamine, these effects are often considered clinically insignificant. Long-term SSRI use has been associated with downregulation of norepinephrine receptors in the brain. SSRIs have side effect profiles that are generally considered favorable compared to other classes of anti-depressants due to their lack of anticholinergic activity and their lack of monoamine oxidase inhibition.[3]

Time Required for Therapeutic Response

  • Initial: within 2 weeks[1]
  • Maximum: within 8 weeks[1]

Pharmacokinetics

Absorption
Approximately 44% of sertraline is absorbed when the medication is administered on an empty stomach. This value is not significantly different between the tablet and oral solution formulations. Therefore, these two forms can be used interchangably with only minimal changes in plasma drug concentrations[1].

According to the sertraline package insert, administration of sertraline with food has been shown to increase Cmax by 25%. However, data from other studies suggest that the changes in sertraline absorption when coadministered with food may not be significant.[4] Patients should be encouraged to be consistant with the amount of food eaten at the time of sertraline administration.[1][5]

Distribution
Sertraline has a large volume of distribution (318 L), suggesting significant accumulation of the drug into tissues and body fat. Sertraline is also highly bround (98%) to plasma proteins.[1][5]

Metabolism
Multiple CYP 450 enzymes are involved in the metabolism of sertraline. N-demethylation reactions are performed primarily by CYP2B6 with additional contributions by CYP2C19, CYP2C9, CYP3A4, and CYP2D6. Deamination reactions performed by CYP3A4 and CYP2C19 are also involved.[1][5][6]

Excretion
Sertraline has been shown to have a half life of approximately 26 hours. This long half life allows for once-daily dosing. Sertraline's main metabolite, the therapeutically inert molecule N-desmethylsertraline, has a half life of 62-104 hours.[1][5]

The metabolites of sertraline are excreted primarily via renal routes. While no unchanged sertraline is recovered in the urine, 12-14% of the administered dose of sertraline is recovered unchanged in the feces.[1][5]

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Special Population Pharmacokinetics

  • Renal insufficiency: No dosage changes are needed for patients with mild to severe renal impairment.[1] Caution may be warranted in patients with end stage renal disease.[7]
  • Hepatic insufficiency: No dosage changes are needed for patients with hepatic impairment.[1]
  • Hemodialysis: Dialysis patients do not require post-dialysis supplementation with sertraline due to the large volume of distribution. However, smaller doses may be necessary due to decreased renal clearance.[1][7]
  • Geriatric: Clearance of sertraline has been shown to be 40% lower in elderly patients compared to healthy adults. Therefore, lower doses may be effective in elderly patients. The recommended daily maximum dose of 200 mg per day is the same for both healthy adults and geriatric patients.[1]
  • Pediatric: Pharmacokinetic studies of sertraline in pediatric populations have revealed ADME parameters similar to adults. Therefore, pediatric patients should be dosed via adult dosing recommendations.[1][8]
  • Gender: Studies have shown that women are more likely to respond to SSRI treatment than men. However, further research is needed concerning this difference. No gender-specific dosing strategies are currently recommended.[1][9]

Indications and Dosages

FDA Approved Indications

Depression (major)[10][11][12]

  • Starting dose:
    • 50 mg daily
    • 25 mg daily may be used in pediatric patients or adults experiencing significant side effects to the 50 mg daily dose.
  • Maintenance dose:
    • Use the lowest effective dose for maintenance.
    • Sertraline is only effective for one year of continuous therapy for this indication.
  • Titration schedule: titrate up 25-50 mg/day at intervals no shorter than one week until desired response is achieved.

Obsessive-compulsive disorder[13]

  • Starting dose:
    • 50 mg daily for adults
    • 25 mg daily for children older than six years of age (no recommendations for children younger than six)
  • Maintenance dose:
    • Use the lowest effective dose for maintenance.
  • Titration schedule: titrate up 25-50 mg/day at intervals no shorter than one week until desired response is achieved.

Panic disorder[14]

  • Starting dose:
    • 25 mg daily
  • Maintenance dose:
    • Use the lowest effective dose for maintenance.
  • Titration schedule: titrate up to 50 mg/day after one week. Continue increasing the dose by 50 mg/day if needed at intervals no shorter than one week.

Post-traumatic stress disorder[15]

  • Starting dose:
    • 25 mg daily
  • Maintenance dose:
    • Use the lowest effective dose for maintenance.
  • Titration schedule: titrate up to 50 mg/day after one week. Continue increasing the dose by 50 mg/day if needed at intervals no shorter than one week.

Premenstrual dysphoric disorder[16][17]

  • Starting dose:
    • 50 mg daily
  • Maintenance dose:
    • Use the lowest effective dose (usually 100 mg daily)
    • using bullet points
  • Titration schedule: increase the dose by 50 mg/day until effective. Dosing increases are generally performed with each luteal phase of the mensutral cycle if needed.

Non-FDA Approved Indications

  • Bulemia nervosa[18]
  • Premature ejaculation[19]
  • Social phobia[20]

Dosage Adjustment

Hemodialysis: Patients may require lower doses.
Pediatric: No adjustments required. However, pediatric patients may benefit from starting at a lower dose of 25 mg/day.

Dosage Limits

  • Adults: 200 mg/day[1]
  • Elderly: 200 mg/day[1]
  • Adolescents and children: 200 mg/day[1]


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Administration

  • Route: Oral (tablet)
  • Method:
    • Administer with or without food. The amount of food administered with sertraline should be kept consistant.
    • This medication is usually dosed in the morning to prevent insomnia; however, it can be dosed in the evening if drowsiness is the predominant side effect.
    • Do not abruptly discontinue.
  • Route: Oral (concentrated solution)
  • Method:
    • The oral solution must be diluted in 120 mL (4 oz) of water, ginger ale, lemon-lime soda, lemonade, or orange juice.
    • All other directions from tablet dosing considerations apply.

Monitoring Parameters

  • Liver function tests (LFTs) at baseline
  • Thyroid function tests at baseline
  • No routine monitoring is required[1]

Contraindications/Precautions

Black box warning

On October 15, 2004 the FDA mandated the inclusion of a black box warning in the package inserts of all antidepressants outlining the potential for increased suicidal ideations and behavior in children and adolescents who use these medications. A Patient Medication Guide (MedGuide) concerning this risk is also required to be dispensed with each filling of an antidepressant medication (available at the bottom of this page). The regulations have been created due to recent findings in the literature.[21]

Contraindications

  • Monoamine oxidase inhibitor therapy should not be coadministered with sertraline within 14 days of one another[1]
  • Pimozide coadministration[22][1]
  • Concomitant disulfiram therapy with the liquid form of sertraline due to the alcohol contained in the liquid formulation of sertraline.[1]
  • Known allergy or hypersensitivity to sertraline[1]

Precautions

  • Increased risk in suicidal ideations and behavior in adolescents[1][21]
  • Serotonin syndrome: concomitant use of SSRIs and other medications that can potentiate serotonin in the blood has been associated with serotonin syndrome.[1]
  • Seizures: seizures have been reported in 0.2% of patients taking sertraline. Use caution in patients with a history of seizure.[1]

Pregnancy indications

Category C

Studies have shown that sertraline therapy carries no greater risk of teratogenicity than placebo therapy when used at recommended doses.[23]

Breast-feeding indications

Sertraline use in breast-feeding mothers has been shown to confer minimal exposure of the drug to their infants. Caution remains warranted.[24][25]

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Drug-Drug, -Food, -Herb Interactions

Click the link above to go to the drug interactions page.

Adverse Reactions/Side Effects

The most common adverse reactions experienced in clinical trials were gastrointestinal in nature and included nausea, vomiting, and diarrhea.[1]

Sertraline Adverse Reactions Chart
Incidence Body System Adverse Reactions
>10% All Dizziness (13%), fatigue (11%), headache (26%), insomnia (22%), diarrhea (21%), nausea/vomiting (27%), xerostomia (15%), anorgasmia (males) (14%), ejaculatory delay (14%)
1-10% CNS Agitation (6%), agression (pediatric) (2%), anxiety (4%), emotional lability (pediatric) (2%), hot flashes (2%), hyperkinesis (pediatric) (2%), impared cognition (pediatric) (2%), malaise (2%), nervousness (6%), paresthesias (3%), twitching (pediatric) (2%)
Cardiovascular Epistaxis (pediatric) (2%), purpura (pediatric) (2%)
Dermatologic Rash (3%)
GI Anorexia (8%), constipation (7%), dyspepsia (8%), flatulence (4%)
Genitourinary Anorgasmia (women) (2%), decreased libido (5%), urinary incontinence (pediatric) (2%)
Neuromuscular/skeletal Tremor (9%)
Respiratory Sinusitis (pediatric) (2%)
Miscellaneous Blurred vision (4%), fever (pediatric) (2%), weight loss (pediatric) (2%)
<1% All Abdominal pain, acute renal failure, aggressiveness, agranulocytosis, akathisia, allergic reaction, angioedema, aplastic anemia, atrial arrhythmia, AV block, back pain, bilirubin increase, blindness, bradycardia, catatact, chest pain, dystonia, ecchymosis, elevated hepatic enzymes, extrapyramidal symptoms, galactorrhea, gum hyperplasia, gynecomastia, hallucinations, hepatitis, hepatomegaly, hostility, hyperesthesia, hyperglycemia, hyperprolactinemia, hypertonia, hypomania, hyponatremia, hypothyroidism, impulsivity, increased appetite, irritability, jaundice, leukopenia, lupus-like syndrome, malaise, mania, myalgia, neuroleptic malignant syndrome, oculogyric crisis, palpitations, pancreatitis, panic attacks, photosensitivity, platelet dysfunction, priapism, psycosis, pulmonary hypertension, purpura, QT prolongation, rhinitis, serotonin syndrome, serum sickness, SIADH, seizures, suicidal ideation, thrombocytopenia, torsade de pointes, tinnitus, vasculitis, ventricular tachycardia, weakness, weight gain, yawning

Overdosage Measures

Of 634 known patients who have overdosed with sertraline alone, only 8 patients developed fatal complications. Common symptoms of sertraline overdose include alopecia, bradycardia, bundle branch block, coma, delirium, decreased libido, diarrhea, ejaculation disorder, fatigue, hallucinations, hypertension, hypotension, insomnia, manic reaction, pancreatitis, QT-interval prolongation, seizures, serotonin syndrome, somnolence, stupor, and syncope. The literature has examples of cases where ingestion of 13.5 grams of sertraline resulted in complete recovery. However, fatal outcomes have been recorded in patients who ingested as few as 2.5 grams of sertraline. Therefore, the amount of sertraline ingested is not always directly correlated with prognosis.[1]
Treatment:

  • Should be based on symptoms, with special attention given to cardiac rhythm monitoring and the maintenence of adequate respiration.
  • Induction of emesis is not recommended for most cases. Activated charcoal and gastric lavage are recommended after the ingestion of large quantities of sertraline and for patients who have developed potentially life threatening symptoms.
  • Forced diuresis, dialysis, hemoperfusion, and exchange transfusion should not be attempted for sertraline overdose due to the large volume of distribution of this agent.[1]
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Product Information and Distribution

Note: appearance only available for brand-name product
Dose/form Drug color(s) Drug shape Markings or odor/flavor
25 mg tablet green oblong ZOLOFT/25 MG
50 mg tablet blue oblong ZOLOFT/50 MG
100 mg tablet yellow oblong ZOLOFT/100 MG
20 mg/mL concentrate solution clear/colorless - menthol scent
  • Inactive ingredients for tablets: calcium phosphate, dibasic, hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol (PEG), sodium starch glycolate, titanium dioxide, D&C Yellow No. 10 (25 mg tablets), FD&C Blue No. 1 (25 mg tablets), FD&C Red No. 40 (25 mg tablets), FD&C Blue No. 2 (50 mg tablets), yellow iron oxide (100 mg tablets)
  • Inactive ingredients for solution: alcohol 12%, butylated hydroxytoluene, glycerin, menthol

Patient Information

  • Do not discontinue abruptly.
  • Take in the morning to prevent insomnia.
  • Avoid OTC medications and alcohol unless instructed by your physician.
  • Drink 2-3 liters of fluid daily.
  • May cause dizziness, drowsiness, or light headedness. Use caution when driving or operating heavy machinery.
  • May cause nausea, vomiting, dry mouth, or anorexia. Eat smaller meals and use lozenges or chewing gum to prevent these problems.
  • May cause postural hypotension. Use caution when changing position or climbing stairs.
  • May cause male sexual dysfunction. This condition is reversible. Talk to your doctor if these symptoms become bothersome.
  • Report insomnia or significant daytime sedation, agitation, nervousness, muscle pain, changes in gait, check pain, palpitations, swelling of the extremities, ringing in the ears, changes in vision, skin rash, respiratory difficulty, suicidal ideation, or worsening of your condition.
  • Inform your doctor if you are or intend to become pregnant. Breastfeeding is not recommended.
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References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 Pfizer. Zoloft® (sertraline hydrochloride) Package Insert. New York, NY October 2002.
  2. ↑ Solai LK, Mulsant BH, Pollock BG. Selective serotonin reuptake inhibitors for late-life depression: a comparative review. Drugs & aging. 2001;18(5):355-68.
  3. ↑ 3.0 3.1 Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 5th Edition ed. New York, NY: The McGraw-Hill Companies, Inc 2002.
  4. ↑ Ronfeld RA, Wilner KD, Baris BA. Sertraline. Chronopharmacokinetics and the effect of coadministration with food. Clinical pharmacokinetics. 1997;32 Suppl 1:50-5.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 DeVane CL, Liston HL, Markowitz JS. Clinical pharmacokinetics of sertraline. Clinical pharmacokinetics. 2002;41(15):1247-66.
  6. ↑ Obach RS, Cox LM, Tremaine LM. Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug metabolism and disposition: the biological fate of chemicals. 2005 Feb;33(2):262-70.
  7. ↑ 7.0 7.1 Schwenk, M. H., M. A. Verga, et al. (1995). "Hemodialyzability of sertraline." Clin Nephrol 44(2): 121-4.
  8. ↑ Alderman J, Wolkow R, Chung M, Johnston HF. Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression: pharmacokinetics, tolerability, and efficacy. Journal of the American Academy of Child and Adolescent Psychiatry. 1998 Apr;37(4):386-94.
  9. ↑ Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, et al. Gender differences in treatment response to sertraline versus imipramine in chronic depression. The American journal of psychiatry. 2000 Sep;157(9):1445-52.
  10. ↑ McConville BJ, Minnery KL, Sorter MT, West SA, Friedman LM, Christian K. An open study of the effects of sertraline on adolescent major depression. Journal of child and adolescent psychopharmacology. 1996 Spring;6(1):41-51.
  11. ↑ Murray V, von Arbin M, Bartfai A, Berggren AL, Landtblom AM, Lundmark J, et al. Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression. The Journal of clinical psychiatry. 2005 Jun;66(6):708-16.
  12. ↑ Sheikh JI, Cassidy EL, Doraiswamy PM, Salomon RM, Hornig M, Holland PJ, et al. Efficacy, safety, and tolerability of sertraline in patients with late-life depression and comorbid medical illness. Journal of the American Geriatrics Society. 2004 Jan;52(1):86-92.
  13. ↑ Kronig MH, Apter J, Asnis G, Bystritsky A, Curtis G, Ferguson J, et al. Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder. Journal of clinical psychopharmacology. 1999 Apr;19(2):172-6.
  14. ↑ Londborg PD, Wolkow R, Smith WT, DuBoff E, England D, Ferguson J, et al. Sertraline in the treatment of panic disorder. A multi-site, double-blind, placebo-controlled, fixed-dose investigation. Br J Psychiatry. 1998 Jul;173:54-60.
  15. ↑ Brady K, Pearlstein T, Asnis GM, Baker D, Rothbaum B, Sikes CR, et al. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. Jama. 2000 Apr 12;283(14):1837-44.
  16. ↑ Yonkers KA, Halbreich U, Freeman E, Brown C, Endicott J, Frank E, et al. Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group. Jama. 1997 Sep 24;278(12):983-8.
  17. ↑ Halbreich U, Kahn LS. Treatment of premenstrual dysphoric disorder with luteal phase dosing of sertraline. Expert opinion on pharmacotherapy. 2003 Nov;4(11):2065-78.
  18. ↑ McElroy SL, Casuto LS, Nelson EB, Lake KA, Soutullo CA, Keck PE, Jr., et al. Placebo-controlled trial of sertraline in the treatment of binge eating disorder. The American journal of psychiatry. 2000 Jun;157(6):1004-6.
  19. ↑ McMahon CG. Treatment of premature ejaculation with sertraline hydrochloride: a single-blind placebo controlled crossover study. The Journal of urology. 1998 Jun;159(6):1935-8.
  20. ↑ Katzelnick DJ, Kobak KA, Greist JH, Jefferson JW, Mantle JM, Serlin RC. Sertraline for social phobia: a double-blind, placebo-controlled crossover study. The American journal of psychiatry. 1995 Sep;152(9):1368-71.
  21. ↑ 21.0 21.1 Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Tanskanen A, Haukka J. Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort. Archives of general psychiatry. 2006 Dec;63(12):1358-67.
  22. ↑ Alderman J. Coadministration of sertraline with cisapride or pimozide: an open-label, nonrandomized examination of pharmacokinetics and corrected QT intervals in healthy adult volunteers. Clinical therapeutics. 2005 Jul;27(7):1050-63.
  23. ↑ Kulin NA, Pastuszak A, Sage SR, Schick-Boschetto B, Spivey G, Feldkamp M, et al. Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors: a prospective controlled multicenter study. Jama. 1998 Feb 25;279(8):609-10.
  24. ↑ Hendrick V, Fukuchi A, Altshuler L, Widawski M, Wertheimer A, Brunhuber MV. Use of sertraline, paroxetine and fluvoxamine by nursing women. Br J Psychiatry. 2001 Aug;179:163-6.
  25. ↑ Stowe ZN, Hostetter AL, Owens MJ, Ritchie JC, Sternberg K, Cohen LS, et al. The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations. The Journal of clinical psychiatry. 2003 Jan;64(1):73-80.

PUBMED References

Efficacy Trial Articles

  1. Brady K, Pearlstein T, Asnis GM, Baker D, Rothbaum B, Sikes CR, et al. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. Jama. 2000 Apr 12;283(14):1837-44.
  2. Cook EH, Wagner KD, March JS, Biederman J, Landau P, Wolkow R, et al. Long-term sertraline treatment of children and adolescents with obsessive-compulsive disorder. Journal of the American Academy of Child and Adolescent Psychiatry. 2001 Oct;40(10):1175-81.
  3. Greist JH, Jefferson JW, Kobak KA, Chouinard G, DuBoff E, Halaris A, et al. A 1 year double-blind placebo-controlled fixed dose study of sertraline in the treatment of obsessive-compulsive disorder. International clinical psychopharmacology. 1995 Jun;10(2):57-65.
  4. Halbreich U, Kahn LS. Treatment of premenstrual dysphoric disorder with luteal phase dosing of sertraline. Expert opinion on pharmacotherapy. 2003 Nov;4(11):2065-78.
  5. Katzelnick DJ, Kobak KA, Greist JH, Jefferson JW, Mantle JM, Serlin RC. Sertraline for social phobia: a double-blind, placebo-controlled crossover study. The American journal of psychiatry. 1995 Sep;152(9):1368-71.
  6. Londborg PD, Wolkow R, Smith WT, DuBoff E, England D, Ferguson J, et al. Sertraline in the treatment of panic disorder. A multi-site, double-blind, placebo-controlled, fixed-dose investigation. Br J Psychiatry. 1998 Jul;173:54-60.
  7. McConville BJ, Minnery KL, Sorter MT, West SA, Friedman LM, Christian K. An open study of the effects of sertraline on adolescent major depression. Journal of child and adolescent psychopharmacology. 1996 Spring;6(1):41-51.
  8. McElroy SL, Casuto LS, Nelson EB, Lake KA, Soutullo CA, Keck PE, Jr., et al. Placebo-controlled trial of sertraline in the treatment of binge eating disorder. The American journal of psychiatry. 2000 Jun;157(6):1004-6.
  9. McMahon CG. Treatment of premature ejaculation with sertraline hydrochloride: a single-blind placebo controlled crossover study. The Journal of urology. 1998 Jun;159(6):1935-8.
  10. Murray V, von Arbin M, Bartfai A, Berggren AL, Landtblom AM, Lundmark J, et al. Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression. The Journal of clinical psychiatry. 2005 Jun;66(6):708-16.
  11. Sheikh JI, Cassidy EL, Doraiswamy PM, Salomon RM, Hornig M, Holland PJ, et al. Efficacy, safety, and tolerability of sertraline in patients with late-life depression and comorbid medical illness. Journal of the American Geriatrics Society. 2004 Jan;52(1):86-92.
  12. Wagner KD, Ambrosini P, Rynn M, Wohlberg C, Yang R, Greenbaum MS, et al. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. Jama. 2003 Aug 27;290(8):1033-41.
  13. Yonkers KA, Halbreich U, Freeman E, Brown C, Endicott J, Frank E, et al. Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group. Jama. 1997 Sep 24;278(12):983-8.
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Therapeutic Class Comparison Articles

  1. Aberg-Wistedt A, Agren H, Ekselius L, Bengtsson F, Akerblad AC. Sertraline versus paroxetine in major depression: clinical outcome after six months of continuous therapy. Journal of clinical psychopharmacology. 2000 Dec;20(6):645-52.
  2. Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, et al. Gender differences in treatment response to sertraline versus imipramine in chronic depression. The American journal of psychiatry. 2000 Sep;157(9):1445-52.
  3. Rossini D, Serretti A, Franchini L, Mandelli L, Smeraldi E, De Ronchi D, et al. Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial. Journal of clinical psychopharmacology. 2005 Oct;25(5):471-5.
  4. Stahl SM. Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline. Biological psychiatry. 2000 Nov 1;48(9):894-901.
  5. Solai, L. K., B. H. Mulsant, et al. (2001). "Selective serotonin reuptake inhibitors for late-life depression: a comparative review." Drugs Aging 18(5): 355-68.

Pharmacokinetics Articles

  1. Alderman J, Wolkow R, Chung M, Johnston HF. Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression: pharmacokinetics, tolerability, and efficacy. Journal of the American Academy of Child and Adolescent Psychiatry. 1998 Apr;37(4):386-94.
  2. DeVane CL, Liston HL, Markowitz JS. Clinical pharmacokinetics of sertraline. Clinical pharmacokinetics. 2002;41(15):1247-66.
  3. Hong Ng C, Norman TR, Naing KO, Schweitzer I, Kong Wai Ho B, Fan A, et al. A comparative study of sertraline dosages, plasma concentrations, efficacy and adverse reactions in Chinese versus Caucasian patients. International clinical psychopharmacology. 2006 Mar;21(2):87-92.
  4. Obach RS, Cox LM, Tremaine LM. Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug metabolism and disposition: the biological fate of chemicals. 2005 Feb;33(2):262-70.
  5. Reis M, Aberg-Wistedt A, Agren H, Hoglund P, Akerblad AC, Bengtsson F. Serum disposition of sertraline, N-desmethylsertraline and paroxetine: a pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression. Human psychopharmacology. 2004 Jul;19(5):283-91.
  6. Stowe ZN, Hostetter AL, Owens MJ, Ritchie JC, Sternberg K, Cohen LS, et al. The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations. The Journal of clinical psychiatry. 2003 Jan;64(1):73-80.
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Drug Interaction Articles

  1. Bowdle TA. Adverse effects of opioid agonists and agonist-antagonists in anaesthesia. Drug Saf. 1998 Sep;19(3):173-89.
  2. Brannan SK, Talley BJ, Bowden CL. Sertraline and isocarboxazid cause a serotonin syndrome. Journal of clinical psychopharmacology. 1994 Apr;14(2):144-5.
  3. Fisher AA, Davis MW. Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction. The Annals of pharmacotherapy. 2002 Jan;36(1):67-71.
  4. Gordon JB. SSRIs and St.John's Wort: possible toxicity? American family physician. 1998 Mar 1;57(5):950,3.
  5. Hamilton SP, Nunes EV, Janal M, Weber L. The effect of sertraline on methadone plasma levels in methadone-maintenance patients. The American journal on addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2000 Winter;9(1):63-9.
  6. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BC. The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study. Clinical therapeutics. 1999 Nov;21(11):1890-9.
  7. Ronfeld RA, Wilner KD, Baris BA. Sertraline. Chronopharmacokinetics and the effect of coadministration with food. Clinical pharmacokinetics. 1997;32 Suppl 1:50-5.
  8. Tremaine LM, Wilner KD, Preskorn SH. A study of the potential effect of sertraline on the pharmacokinetics and protein binding of tolbutamide. Clinical pharmacokinetics. 1997;32 Suppl 1:31-6.
  9. U.S. Food and Drug Administration (FDA). Combined use of 5-hydroxytryptamine receptor agonists (triptans), selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) may result in life-threatening serotonin syndrome. FDA Public Health Advisory

Adverse Effects Articles

  1. Barbey JT, Roose SP. SSRI safety in overdose. The Journal of clinical psychiatry. 1998;59 Suppl 15:42-8.
  2. Ceylan ME, Alpsan-Omay MH. Bleeding induced by SSRIs. Eur Psychiatry. 2005 Dec;20(8):570-1.
  3. CJ, Burgess JL, Robertson WO. Zolpidem-associated hallucinations and serotonin reuptake inhibition: a possible interaction. Journal of toxicology. 1998;36(3):195-203.
  4. Dalton SO, Johansen C, Mellemkjaer L, Norgard B, Sorensen HT, Olsen JH. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Archives of internal medicine. 2003 Jan 13;163(1):59-64.
  5. Doogan DP. Toleration and safety of sertraline: experience worldwide. International clinical psychopharmacology. 1991 Dec;6 Suppl 2:47-56.
  6. Hendrick V, Fukuchi A, Altshuler L, Widawski M, Wertheimer A, Brunhuber MV. Use of sertraline, paroxetine and fluvoxamine by nursing women. Br J Psychiatry. 2001 Aug;179:163-6.
  7. Klein-Schwartz W, Anderson B. Analysis of sertraline-only overdoses. The American journal of emergency medicine. 1996 Sep;14(5):456-8.
  8. Kulin NA, Pastuszak A, Sage SR, Schick-Boschetto B, Spivey G, Feldkamp M, et al. Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors: a prospective controlled multicenter study. Jama. 1998 Feb 25;279(8):609-10.
  9. Lau GT, Horowitz BZ. Sertraline overdose. Acad Emerg Med. 1996 Feb;3(2):132-6.
  10. Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Tanskanen A, Haukka J. Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort. Archives of general psychiatry. 2006 Dec;63(12):1358-67.
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