Sertraline

Sertraline is an Antidepressant agent belonging to the Serotonin Reuptake Inhibitor class.

Sertraline is a selective serotonin reuptake inhibitor (SSRI) indicated to treat major depressive disorder, social anxiety disorder and many other psychiatric conditions.

Sertraline is Slowly absorbed from the gastrointestinal tract. Time taken to reach peak plasma concentration is Approximately 4.5-8.4 hours. Sertraline is widely distributed, and its volume of distribution is estimated to be more than 20L/kg. It is Approximately 98% bound to plasma proteins. Sertraline is heavily metabolized in the liver mainly via N-demethylation by CYP2C19 and CYP2D6 to less active metabolite, N-desmethyl sertraline; further metabolized via oxidative deamination and subsequent reduction, hydroxylation and glucuronide conjugation. Undergoes extensive first-pass metabolism. It is excreted mainly via urine (40-45% as metabolites) and (12-14% as unchanged drug) via faeces.

Sertraline shows side effects like Nausea, diarrhea, constipation, vomiting, difficulty falling asleep or staying asleep, dry mouth, heartburn, loss of appetite, weight changes, etc.

Sertraline is available in the form of Oral Tablets and oral capsule and oral solution.

Sertraline is available in India, US, Germany, Australia, China, France, Italy, Vietnam, Canada and Japan.

Sertraline belongs to the Serotonin Reuptake Inhibitor class and acts as Antidepressant Agent.

Sertraline selectively inhibits the reuptake of serotonin (5-HT) at the presynaptic neuronal membrane, thereby increasing serotonergic activity. This results in an increased synaptic concentration of serotonin in the CNS, which leads to numerous functional changes associated with enhanced serotonergic neurotransmission. These changes are believed to be responsible for the antidepressant action and beneficial effects in obsessive-compulsive (and other anxiety related disorders). It has been hypothesized that obsessive-compulsive disorder, like depression, is also caused by the disregulation of serotonin.

The Onset of action of Sertraline is not clinically established.

The Time to peak plasma concentration of Sertraline is approximately 4.5 to 8.4 hours.

Sertraline is available in the form of Oral Tablets and oral capsule and oral solution.

Sertraline tablet and capsule are swallowed whole with water once daily dosage.

Sertraline oral solution must be diluted immediately before use to make the preparation more palatable.

Sertraline is used to treat mental conditions such as depression, obsessive-compulsive disorder (repetitive thoughts that do not go away causing the need to perform certain actions over and over), panic attacks (sudden or unexpected attacks of extreme fear and worry), posttraumatic stress disorder (disturbing psychological symptoms that develop after a frightening experience), and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life).

Sertraline is an Antidepressant agent belonging to the Serotonin Reuptake Inhibitor class.

Sertraline, a naphthalenamine-derivative antidepressant, selectively inhibits presynaptic serotonin (5-HT) reuptake. It has very weak effects on norepinephrine and dopamine neuronal uptake.

Sertraline is approved for use in the following clinical indications

• Major depressive disorder (MDD)
• Obsessive-compulsive disorder (OCD)
• Panic disorder (PD)
• Posttraumatic stress disorder (PTSD)
• Social anxiety disorder (SAD)
• Premenstrual dysphoric disorder (PMDD)

• Major depressive disorder (MDD)

Adult:

Starting Dose: 50 mg

Therapeutic Range: A dosage of 25 mg or 50 mg per day is the initial therapeutic dosage or 50-200 mg.

• Obsessive-compulsive disorder (OCD)

Adult:

Starting Dose: 50 mg

Therapeutic Range: A dosage of 25 mg or 50 mg per day is the initial therapeutic dosage or 50-200 mg.

Pediatric (ages 6-12 years old):

Starting Dose: 25 mg

Therapeutic Range: A dosage of 25 mg or 50 mg per day is the initial therapeutic dosage or 50-200 mg.

Pediatric (ages 13-17 years old):

Starting Dose: 25 mg

Therapeutic Range: A dosage of 25 mg or 50 mg per day is the initial therapeutic dosage or 50-200 mg.

• Panic disorder (PD)

Adult:

Starting Dose: 25 mg

Therapeutic Range: A dosage of 25 mg or 50 mg per day is the initial therapeutic dosage or 50-200 mg.

• Posttraumatic stress disorder (PTSD)

Adult:

Starting Dose: 25 mg

Therapeutic Range: A dosage of 25 mg or 50 mg per day is the initial therapeutic dosage or 50-200 mg.

• Social anxiety disorder (SAD)

Adult:

Starting Dose: 25 mg

Therapeutic Range: A dosage of 25 mg or 50 mg per day is the initial therapeutic dosage or 50-200 mg.

• Premenstrual dysphoric disorder (PMDD)

The recommended starting Sertraline dosage in adult women with PMDD is 50 mg per day. Sertraline may be administered either continuously (every day throughout the menstrual cycle) or intermittently (only during the luteal phase of the menstrual cycle, i.e., starting the daily dosage 14 days prior to the anticipated onset of menstruation and continuing through the onset of menses). Intermittent dosing would be repeated with each new cycle.

When dosing continuously, patients not responding to a 50 mg dosage may benefit from dosage increases at 50 mg increments per menstrual cycle up to 150 mg per day.

When dosing intermittently, patients not responding to a 50 mg dosage may benefit from increasing the dosage up to a maximum of 100 mg per day during the next menstrual cycle (and subsequent cycles) as follows: 50 mg per day during the first 3 days of dosing followed by 100 mg per day during the remaining days in the dosing cycle.

Sertraline is available in various strengths as 50 mg; 100 mg; 25 mg; 150 mg; 200 mg, 20 mg/mL.

Sertraline is available in the form of Oral Tablets and oral capsule and oral solution.

• Dosage Adjustment in Kidney Patient

Mild to severe impairment: No dosage adjustment necessary.

• Dosage Adjustment in Hepatic impairment Patient

Mild impairment (Child-Pugh class A): Reduce dose to 50% of usual dose; some experts recommend a maximum dose of 100 mg/day.

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

Avoid consumption of St. John's Wort.

Sertraline is contraindicated in patients with

• Taking, or within 14 days of stopping, MAOIs, (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome
• Taking pimozide
• With known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema)
• In addition to the contraindications for all Sertraline formulations listed above, Sertraline oral solution is contraindicated in patients:
• Taking disulfiram. Sertraline oral solution contains alcohol, and concomitant use of Sertraline and disulfiram may result in a disulfiram-alcohol reaction.

• Serotonin Syndrome

Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including Sertraline, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs . Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of Sertraline with MAOIs is contraindicated. In addition, do not initiate Sertraline in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Sertraline, discontinue Sertraline before initiating treatment with the MAOI. Monitor all patients taking Sertraline for the emergence of serotonin syndrome. Discontinue treatment with Sertraline and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Sertraline with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

• Increased Risk of Bleeding

Drugs that interfere with serotonin reuptake inhibition, including Sertraline, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients of the increased risk of bleeding associated with the concomitant use of Sertraline and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio.

• Activation of Mania or Hypomania

In patients with bipolar disorder, treating a depressive episode with Sertraline or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were generally excluded; however, symptoms of mania or hypomania were reported in 0.4% of patients treated with Sertraline. Prior to initiating treatment with Sertraline, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.

• Discontinuation Syndrome

Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.

• Seizures

Sertraline has not been systematically evaluated in patients with seizure disorders. Patients with a history of seizures were excluded from clinical studies. Sertraline should be prescribed with caution in patients with a seizure disorder.

• Angle-Closure Glaucoma

The pupillary dilation that occurs following use of many antidepressant drugs including Sertraline may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including Sertraline, in patients with untreated anatomically narrow angles.

• Hyponatremia

Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including Sertraline. Cases with serum sodium lower than 110 mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In patients with symptomatic hyponatremia, discontinue Sertraline and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs and SNRIs.

• False-Positive Effects on Screening Tests for Benzodiazepines

False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking Sertraline. This finding is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of Sertraline. Confirmatory tests, such as gas chromatography/mass spectrometry, will help distinguish Sertraline from benzodiazepines.

Avoid consumption of alcohol if you are taking Sertraline as it may increase the risk of side effects such as dizziness, drowsiness, difficulty concentrating, etc. Avoid performing activities that require mental alertness, like driving vehicles or operating machines.

There is no data on the effects of sertraline on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Sertraline and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Sertraline is not recommended for use during pregnancy unless necessary. If you are pregnant, consult your doctor before taking this medicine.

Avoid consumption of St. John's Wort.

• Common

Diarrhea, nausea, xerostomia, Dizziness, drowsiness, fatigue, insomnia, Edema, hypertension, palpitations, syncope, tachycardia , vasodilation, Alopecia, bullous dermatitis, dermatitis, diaphoresis, erythematous rash , follicular rash , hyperhidrosis, maculopapular rash , pruritus, urticaria, Decreased libido, diabetes mellitus, galactorrhea not associated with childbirth, hypercholesterolemia , hypoglycemia, hypothyroidism, weight loss, Abdominal pain, bruxism, constipation, decreased appetite, dyspepsia, hematochezia, increased appetite, melena, rectal hemorrhage, vomiting, Ejaculation failure, ejaculatory disorder, erectile dysfunction, hematuria, priapism, sexual disorder, urinary incontinence, vaginal hemorrhage Hemorrhage, Increased liver enzymes, Anaphylaxis, agitation, anxiety, ataxia , coma , confusion , euphoria , hallucination , hypertonia , hypoesthesia , impaired consciousness , irritability , lethargy , malaise, psychomotor agitation , seizure , tremor, yawning, Hyperkinetic muscle activity, muscle spasm, Blurred vision , mydriasis , visual disturbance, Tinnitus, Bronchospasm, Aggressive behavior, Arthralgia, muscle twitching, Epistaxis, Fever.

• Rare

Suicidal thoughts and behavior, serotonin syndrome or neuroleptic malignant syndrome (NMS), hemorrhage (e.g., gastrointestinal, or gynaecological bleeding), anaphylactoid reaction, angioedema, Stevens-Johnson syndrome, erythema multiforme, vasculitis, syndrome of inappropriate antidiuretic hormone secretion (SIADH), hyponatremia.

• Monoamine Oxidase Inhibitors (MAOIs): The concomitant use of SSRIs including Sertraline and MAOIs increases the risk of serotonin syndrome.
• Pimozide: Increased plasma concentrations of pimozide, a drug with a narrow therapeutic index, may increase the risk of QT prolongation and ventricular arrhythmias.
• Other Serotonergic Drugs: The concomitant use of serotonergic drugs with Sertraline increases the risk of serotonin syndrome.
• Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants): The concurrent use of an antiplatelet agent or anticoagulant with Sertraline may potentiate the risk of bleeding.
• Drugs Highly Bound to Plasma Protein: Sertraline is highly bound to plasma protein. The concomitant use of Sertraline with another drug that is highly bound to plasma protein may increase free concentrations of Sertraline or other tightly bound drugs in plasma.
• Drugs Metabolized by CYP2D6: Sertraline is a CYP2D6 inhibitor. The concomitant use of Sertraline with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate.
• Phenytoin: Phenytoin is a narrow therapeutic index drug. Sertraline may increase phenytoin concentrations.

The common side effects of Sertraline include the following

• Common side effects

Nausea, diarrhea, constipation, vomiting, difficulty falling asleep or staying asleep, dry mouth, heartburn, loss of appetite, weight changes, dizziness, excessive tiredness, headache, nervousness, uncontrollable shaking of a part of the body, sexual problems in males; decreased sex drive, inability to get or keep an erection, or delayed or absent ejaculation, sexual problems in females; decreased sex drive, or delayed orgasm or unable to have an orgasm, excessive sweating.

• Rare side effects

Seizures, abnormal bleeding or bruising, agitation, hallucinations, fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea, headache, weakness, unsteadiness, confusion, or memory problems, rash, hives, swelling, difficulty breathing.

• Pregnancy

Pregnancy Category

The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Advise a pregnant woman of possible risks to the fetus when prescribing Sertraline. Sertraline oral solution contains 12% alcohol and is not recommended during pregnancy because there is no known safe level of alcohol exposure during pregnancy.

• Nursing Mothers

There are no data on the effects of sertraline on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Sertraline and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

• Pediatric Use

The safety and efficacy of Sertraline has been established in the treatment of OCD in pediatric patients aged 6 to 17. Safety and effectiveness have not been established in pediatric patients for indications other than OCD.

• Geriatric Use

Of the total number of patients in clinical studies of Sertraline in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 797 (17%) were ≥ 65 years old, while 197 (4%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Symptoms: Somnolence, dizziness, gastrointestinal disturbances (e.g. nausea, vomiting), tachycardia, tremor, agitation, QTc prolongation or Torsade de pointes, and coma. Management: Symptomatic and supportive treatment. Establish and maintain airway and ensure adequate oxygenation or ventilation if necessary. Administration of activated charcoal with a cathartic may be considered. Monitor cardiac and vital signs.

• Pharmacodynamic

Sertraline improves or relieves the symptoms of depression, OCD, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder via the inhibition of serotonin reuptake. Clinical studies have shown that it improves cognition in depressed patients. It has less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because it does not exert significant anticholinergic, antihistamine, or adrenergic (alpha1, alpha2, beta) blocking activity.

• Pharmacokinetics

Absorption

Sertraline is Slowly absorbed from the gastrointestinal tract. Time taken to reach peak plasma concentration is Approximately 4.5-8.4 hours

Distribution

Sertraline is widely distributed, and its volume of distribution is estimated to be more than 20L/kg. It is Approximately 98% bound to plasma proteins.

Metabolism and Excretion

Sertraline is heavily metabolized in the liver mainly via N-demethylation by CYP2C19 and CYP2D6 to less active metabolite, N-desmethyl sertraline; further metabolised via oxidative deamination and subsequent reduction, hydroxylation and glucuronide conjugation. Undergoes extensive first-pass metabolism. It is excreted mainly via urine (40-45% as metabolites) and (12-14% as unchanged drug) via faeces.

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• https://www.uptodate.com/contents/sertraline-drug-information?search=sertaline&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1
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• https://go.drugbank.com/drugs/DB01104
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