Sertraline (Zoloft) is an antidepressant. It belongs to the class of drugs called selective serotonin reuptake inhibitors. It is used in the treatment of patients with depression, anxiety, obsessive compulsive disorder, and post-traumatic stress disorder.

Sertraline (Zoloft) Uses:

• Major depressive disorder (unipolar):

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

• Obsessive-compulsive disorder:

  • Treatment of obsessions and compulsions in patients of obsessive-compulsive disorder (OCD).

• Panic disorder:

  • Treatment of panic disorder in adults with or without agoraphobia.

• Posttraumatic stress disorder:

  • Treatment of posttraumatic stress disorder (PTSD) in adults.

• Premenstrual dysphoric disorder:

  • Treatment of premenstrual dysphoric disorder (PMDD) in adults.

• Social anxiety disorder:

  • Treatment of social anxiety disorder (social phobia) in adults.

• Off Label Use of Sertraline in Adults:

  • Binge eating disorder;
  • Body dysmorphic disorder;
  • Bulimia nervosa;
  • Generalized anxiety disorder;
  • Premature ejaculation

Sertraline (Zoloft) Dose in Adults

Note:

• In patients susceptible to side effects, some experts suggest a lower starting dose of 12.5 to 25 mg daily and slow titration in increases of not more than 25 mg, especially in patients with anxiety who are generally susceptibility to overstimulation effects (eg, anxiety, insomnia) with antidepressants.

Sertraline (Zoloft) Dose in the treatment of Binge eating disorder (off-label):

• Oral: Initial: 25 mg once daily post-lunch.
• May increase dose according to response and tolerance in increases of 25 mg every 3 days.
• dose range: 100 to 200 mg daily.
• Maximum dose: 200 mg/day. Based on limited data, some experts suggest doses used for major depressive disorder and slower titrations (eg, ≥1 week).

Sertraline (Zoloft) Dose in the treatment of body dysmorphic disorder (BDD) (off-label): Based on limited data:

• Oral: Some experts advise starting dose of 50 mg once daily; may increase based on response and tolerance in increases of 25 to 50 mg every 2 to 3 weeks to a usual dose of 200 mg/day;
• Doses up to 400 mg/day may be needed in some patients for an adequate response.

Note: An adequate trial for assessment of effect in BDD is 12 to 16 weeks, including maximum tolerated doses for at least 3 to 4 of those weeks.

Sertraline (Zoloft) Dose in the treatment of Bulimia nervosa (alternative agent) (off-label):

• Oral: Initial: 50 mg daily;
• may increase the dose based on response and tolerance in increases of 50 mg every week or more.
• Maximum dose: 300 mg/day.

Sertraline (Zoloft) Dose in the treatment of Generalized anxiety disorder (GAD) (off-label):

• Oral: starting: 25 mg once daily;
• may be increased based on response and tolerability in increases of 25 to 50 mg every 1 to 2 weeks.
• Usual dose: 50 to 150 mg/day.
• Maximum dose: 200 mg/day.

Sertraline (Zoloft) Dose in the treatment of major depressive disorder (MDD) (unipolar):

• Oral: Initial: 50 mg once daily;
• may increase the dose based on response and tolerability in increases of 25 to 50 mg once weekly to a maximum of 200 mg/day (according to manufacturer's labeling); however, doses up to 300 mg/day have been used in clinical practice for MDD and may be of benefit.
• More rapid titrations (every 3 days) combined with an antipsychotic (eg, olanzapine) are used by some experts for patients with psychotic features.

Sertraline (Zoloft) Dose in the treatment of Obsessive-compulsive disorder:

• Oral: starting: 50 mg once daily may increase the dose based on response and tolerability in increments of 25 to 50 mg once weekly to a maximum of 200 mg/day (according to the manufacturer's labeling).
• Doses up to 400 mg/day may be of modest clinical benefit in patients with inadequate response to standard doses, but adverse effects may be more.

Sertraline (Zoloft) Dose in the treatment of Panic disorder:

• Oral: Initial: 25 mg once daily for 3 to 7 days, then increase to 50 mg/day;
• The dose maybe up titrated based on response and tolerance in increases of 25 to 50 mg every week to a maximum of 200 mg/day.

Sertraline (Zoloft) Dose in the treatment of Posttraumatic stress disorder (PTSD):

• Oral: starting: 25 to 50 mg once daily;
• may increase the dose based on response and tolerance in increases of 25 to 50 mg every week to a maximum of 200 mg/day; however, doses up to 250 mg/day have been used and may be beneficial..

Sertraline (Zoloft) Dose in the treatment of Premature ejaculation (off-label):

• Oral: starting: 50 mg once daily;
• may increase the dose based on response and tolerability every 3 to 4 weeks in 50 mg increases up to 200 mg/day.

Sertraline (Zoloft) Dose in the treatment of Premenstrual dysphoric disorder (PMDD):

• Continuous daily dosing regimen:

  • Oral: starting: 25 mg once daily;
  • Over the first month, increase to the usual effective dose of 50 mg once daily;
  • In subsequent menstrual cycles, further increases in dose (eg, in 50 mg increments per menstrual cycle) up to 200 mg/day may be required in few patients for an adequate response.

• Intermittent regimens:

  • Luteal phase dosing regimen:
    • Oral: Initial: 25 mg once daily during the luteal phase of the menstrual cycle only (ie, starting therapy 14 days prior to the anticipated onset of menstruation and continue until the onset of menses);
    • over the first month, increase to the usual effective dose of 50 mg/day;
    • in next menstrual cycles, further increases in dose (eg, in 50 mg increases per menstrual cycle) up to 150 mg/day during the luteal phase may be needed in some patients for complete response.

• Symptom-onset dosing regimen (off-label dosing):

  • Oral: starting: 25 mg once daily from the day of symptom onset until a few days after the beginning of menstruation;
  • Over the first month, increase to the usual effective dose of 50 mg/day;
  • In the next menstrual cycles, further increases in dose (eg, in 50 mg increases per menstrual cycle) up to 150 mg/day may be needed for some patients for an adequate response.

Note: If a daily dose ≥ 100 mg was achieved in prior cycles, may begin with 50 mg once daily for 2 to 3 days in subsequent cycles, then increase to the previous dose.

Sertraline (Zoloft) Dose in the treatment of Social anxiety disorder:

• Oral: Initial: 25 to 50 mg once daily.
• After about 6 weeks, may increase the dose according to response and tolerance in increments of 25 to 50 mg at intervals ≥1 week to a maximum of 200 mg/day

• Discontinuation of therapy:

  • Stop taking antidepressant medication after it has been in effect for more than 3 weeks. Slowly reduce the dose, eg over 2 to 4 week, to reduce withdrawal symptoms.
  • Gradual titration (eg over 4 weeks) is preferred when the drug has a half-life of 24 hours (eg paroxetine or venlafaxine), or if there are previous antidepressant withdrawal symptoms.
  • If withdrawal symptoms become unbearable, you can restart the previous dose or decrease the dose at an earlier rate.
  • Tapering over 3 months may be beneficial for some patients, e.g. those who have had discontinuation syndrome in the past.
  • There is not much evidence to support ideal taper rates.

• Change to antidepressants

  • There is limited evidence to support the ideal antidepressant switch strategy. Strategies include cross-titration, which allows you to slowly decrease the antidepressant dose while simultaneously increasing the antidepressant slowly. And direct switching, whereby the antidepressant is abruptly discontinued and the new one started at a lower dose or at the same dose.
  • Cross-titration is a standard procedure for most switches, but it is contraindicated for switching to or from a MAOI.
  • Direct switching may be a better option when switching to an agent of the same or similar type (eg when switching between two SSRIs). This is especially true if the antidepressant has been in use for less than one week or if the discontinuation is due to side effects.
  • Consider the possibility of drug interactions and other antidepressant properties.

• Switching to an MAOI or switching from an MAOI:

  • Between discontinuing an MAOI treatment and initiating sertraline, allow 14 days.
  • Between the time you stop taking sertraline and when you start an MAOI, allow 14 days.

Sertraline (Zoloft) Dose in Children

Sertraline (Zoloft) Dose in the treatment of Depression in Children: Oral:

• Children 6 to 12 years:

  • Initial: 12.5 to 25 mg once daily;
  • Titrate the dose upwards if clinically needed;
  • May increase by 25 to 50 mg/day increments at intervals of at least 1 week;
  • Range: 25 to 200 mg/day;
  • Maximum daily dose: 200 mg/day
  • Avoid excessive dosing

• Adolescents 13 to 17 years:

  • Initial: 25 to 50 mg once daily;
  • Titrate the dose upwards if clinically needed;
  • The dose may be increased by 50 mg/day increments at intervals of at least 1 week;
  • Range: 25 to 200 mg/day;
  • The maximum daily dose: 200 mg/day.

Sertraline (Zoloft) Dose in the treatment of Obsessive-compulsive disorder: Oral:

• Children 6 to 12 years:

  • Initial: 25 mg once daily;
  • Titrate the dose upwards if clinically needed;
  • Increase the dose by 25 to 50 mg/day increments at intervals of at least 1 week; range: 25 to 200 mg/day;
  • The maximum daily dose: 200 mg/day;
  • Avoid excessive dosing

• Adolescents 13 to 17 years:

  • Initial: 50 mg once daily;
  • Titrate the dose upwards if clinically necessary;
  • Increase the dose by 50 mg/day increments at intervals of at least 1 week;
  • Range: 25 to 200 mg/day;
  • The maximum daily dose: 200 mg/day

• Discontinuation of therapy:

• • Consider discontinuing antidepressants for lower-stress times, recognizing non-illness-associated factors could cause stress or anxiety and be misattributed to antidepressant discontinuation.
  • Stop antidepressant therapy and slowly reduce the dosage to avoid discontinuation syndromes (withdrawal). Also, monitor for signs of relapse.
  • There is not much evidence to support the ideal taper rate after illness remission.
  • NICE and APA guidelines recommend tapering therapy for at least a few weeks, taking into account the half-life of antidepressants; antidepressants that have a shorter half life may need to be tapered slower.
  • WFSBP guidelines recommend that antidepressant treatment for long periods (years) be stopped. They should be tapered over 4 to 6 month, and closely monitored for the 6 months after discontinuation.
  • Consider restarting the previous dose or decreasing the dose at a slower pace if you experience severe discontinuation symptoms.

• Recommendations for MAO inhibitors:

  • The ability to switch to an MAO inhibitor to treat psychiatric disorders

    • Between stopping a MAO inhibitor to treat psychiatric disorders (or starting sertraline) take 14 days.
    • Allow 14 days between the time you stop taking sertraline or start an MAO inhibitor to treat psychiatric disorders.

Sertraline (Zoloft) Pregnancy Risk Category: C

• Sertraline passes the human placental boundary.
• Studies that evaluated the teratogenic effects of maternal sertraline use in the first trimester of pregnancy have not found an increase in major birth defects.
• Different birth defects are not always identified in studies.
• The newborn may experience nonteratogenic effects from SSRI/SNRI late in the third trimester.
• These include respiratory distress, seizures, temperature instability and feeding difficulties, as well as hypoglycemia or hypotonia, hypo-, hypertonia, hyperreflexia and jitteriness.
• Symptoms could be due to toxicity of SSRIs/SNRIs, or a discontinuation syndrome.
• This may also be consistent with serotonin syndrome that is associated with SSRI treatment.
• SSRIs have also been shown to cause persistent pulmonary hypertension in the newborn (PPHN).
• It is not known what long-term effects in utero SSRIs have on infant behavior and development.
• Women who are pregnant might need to adjust the dose of sertraline in order to attain euthymia due to pregnancy-induced physiological changes.
• ACOG recommends that treatment with SSRIs and SNRIs during pregnancy is individualized.
• Treatment of depression during pregnancy should include clinical expertise from the mental health provider, obstetrician, and pediatrician.
• The American Psychiatric Association states that medication treatment has risks, but should be considered in conjunction with other treatments and untreated depression.
• Women who have stopped antidepressant medication during pregnancy or who are at high risk of postpartum depression can resume the medication after birth.
• The ACOG and APA have developed treatment algorithms for women with depression before and during pregnancy.
• Pregnant women who have been exposed to antidepressants during pregnancy should enroll in the National Pregnancy Registry for Antidepressants.

Use of sertraline while breastfeeding

• Breast milk contains desmethyl sertraline and its active metabolite.
• Pooled data showed that the relative infant dose of sertraline (RID) was 0.5% to 3.0% of weight-adjusted mother dose. One review noted a RID at 3.7%.
• You can continue to breastfeed if your RID is less than 10%. However, some sources suggest that breastfeeding should be restricted if psychotropic drugs are more than 5%.
• Breastfeeding should be avoided if the RID is greater than 25%
• Desmethyl sertraline milk concentrations were higher than those of sertraline when they were analyzed.
• After the maternal dose, peak milk concentrations were observed in 5 to 8 hours for sertraline and 5 to 11 hours for desmethyl sertraline.
• Avoiding breastfeeding at peak concentrations of antidepressants will not reduce infant exposure.
• The majority of studies that have been done evaluated the serum concentrations in breastmilk and not in infants who were breastfeeding, showed no difference in their results.
• The manufacturer analyzed data from 53 mothers-infant pairs and found that sertraline concentrations in breastfed infants was 2%. This is within the range of 0% to 15%.
• Some studies have shown adverse reactions in breastfed infants after maternal use of sertraline.
• Mothers who use psychotropic medication should monitor their infants daily for any changes in sleep, feeding, behavior, or neurodevelopment.
• Pregnancy may be delayed if a mother uses an SSRI.
• Sertraline is the first antidepressant to be started in a nursing woman.
• If there are no contraindications, women who have been successfully treated with sertraline in pregnancy can continue to use it while breastfeeding if they are not experiencing any other side effects.
• According to the manufacturer breastfeeding during therapy is a decision that should be based on the risks to infants, the benefits to the mother and the benefits to the infant.

Dose in Kidney Disease:

No dosage adjustment needed.

Sertraline (Zoloft) dose in Liver disease:

• Mild impairment (Child-Pugh class A):
  • Reduce dose to 50% of usual dose.
• Moderate to severe impairment (Child-Pugh class B or C):
  • Use not recommended.

Common Side Effects of Sertraline (Zoloft):

• Central Nervous System:

  • Insomnia
  • Dizziness
  • Fatigue
  • Drowsiness

• Gastrointestinal:

  • Nausea
  • Diarrhea
  • Xerostomia

Less Common Side Effects of Sertraline (Zoloft):

• Cardiovascular:

  • Palpitations
  • Edema
  • Hypertension
  • Syncope
  • Tachycardia
  • Vasodilation

• Central Nervous System:

  • Agitation
  • Malaise
  • Anxiety
  • Abnormal Gait
  • Ataxia
  • Coma
  • Confusion
  • Euphoria
  • Hallucination
  • Hypertonia
  • Hypoesthesia
  • Impaired Consciousness
  • Irritability
  • Lethargy
  • Psychomotor Agitation
  • Seizure
  • Yawning

• Dermatologic:

  • Hyperhidrosis
  • Alopecia
  • Bullous Dermatitis
  • Dermatitis
  • Diaphoresis
  • Erythematous Rash
  • Follicular Rash
  • Maculopapular Rash
  • Pruritus
  • Urticaria

• Endocrine & Metabolic:

  • Decreased Libido
  • Weight Loss
  • Diabetes Mellitus
  • Galactorrhea
  • Hypercholesterolemia
  • Hypoglycemia
  • Hypothyroidism

• Gastrointestinal:

  • Dyspepsia
  • Decreased Appetite
  • Constipation
  • Abdominal Pain
  • Vomiting
  • Bruxism
  • Hematochezia
  • Increased Appetite
  • Melena

• Genitourinary:

  • Ejaculation Failure
  • Erectile Dysfunction
  • Ejaculatory Disorder
  • Urinary Incontinence
  • Sexual Disorder
  • Hematuria
  • Priapism
  • Vaginal Hemorrhage

• Hematologic & Oncologic:

  • Hemorrhage
  • Rectal Hemorrhage

• Hepatic:

  • Increased Liver Enzymes

• Hypersensitivity:

  • Anaphylaxis

• Neuromuscular & Skeletal:

  • Tremor
  • Hyperkinesia
  • Muscle Spasm

• Ophthalmic:

  • Visual Disturbance
  • Blurred Vision
  • Mydriasis

• Otic:

  • Tinnitus

• Respiratory:

  • Bronchospasm

Sertraline Side effects (Frequency Not Defined):

• Central Nervous System:

  • Aggressive Behavior

• Hematologic & Oncologic:

  • Purpura

• Neuromuscular & Skeletal:

  • Arthralgia
  • Muscle Twitching

• Respiratory:

  • Epistaxis

• Miscellaneous:

  • Fever

Contraindications to Sertraline (Zoloft):

• Use of MAOIs, including linezolid and methylene blue (concurrently or within fourteen days of stopping an MAOI/sertraline);
• Use of pimozide concurrently
• Hypersensitivity to sertraline and any other component of the formulation (eg anaphylaxis or angioedema);
• Use of disulfiram concurrently (oral solution only).

There are limited data on allergenic cross-reactivity of SSRIs. Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Bleeding Risk:

  • Use of aspirin, NSAIDs, or warfarin together may cause platelet aggregation to be impaired, which can increase the risk of bleeding events.
  • There have been reports of bleeding due to SSRI usage, from minor bruising to epistaxis to life-threatening hemorrhage.

• Depression in the CNS:

  • There is a low chance of cognitive impairment or impaired motor function. Use caution when operating hazardous machinery or driving.

• Fractures

  • Antidepressant treatment has been shown to be associated with bone fractures.
  • If an antidepressant-treated person presents with unresolved bone pain or tenderness, swelling, or bruising, there may be a fragility fracture.

• Ocular effects

  • Mild pupillary dilation may occur, which can in some cases lead to narrow-angle glaucoma.
  • Patients who have not undergone an iridectomy to reduce the risk of narrow-angle glaucoma should be evaluated. Patients with anatomically narrow angles should be avoided.

• Extension of QT

  • Sertraline has been shown to prolong QTc and cause torsades de pointes.
  • Many reports included other risk factors. Patients with QTc prolongation risk factors should be cautious. Studies have shown correlations between serum sertraline levels and other risk factors.

• Serotonin syndrome

  • Serotonin syndrome (SS), which can be life-threatening, has been reported to occur when serotonergic drugs (eg SSRIs, SNRIs) are combined with other serotonergic agents (eg triptans TCAs, fentanyl and buspirone, lithium, tramadol or buspirone, tryptophan, St John's wort, and tryptophan), or agents that impair serotonin metabolic processes (eg MAO inhibitors for psychid, intravenous methylene blue blue, linezolid, intravenous methylene, methylene blue)
  • SS symptoms include mental changes such as agitation, hallucinations and delirium; autonomic instability (eg tachycardia or labile blood pressure, diaphoresis); neuromuscular disorders (eg tremors, rigidity, myoclonus); GI symptoms like nausea, vomiting, diarrhea; and/or seizures.
  • If you notice any symptoms or signs of serotonin syndrome, stop taking any serotonergic agents and any other serotonergic drugs immediately.

• Sexual dysfunction

  • It can lead to or exacerbate sexual dysfunction.

• SIADH and Hyponatremia

  • SSRIs, SNRIs, and SIADH have been linked to the development of hyponatremia. Hyponatremia is a rare condition (including severe cases of serum sodium 110 mmol/L), which has been most common in the elderly.
  • Risk is increased by volume depletion and/or concurrent diuretics use.
  • If hyponatremia is symptomatic, discontinue use.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious as the drug clearance is decreased, which can lead to an increase in plasma levels.
  • In mild hepatic impairment, use a lower dose
  • Avoid using it if you have a severe or moderate impairment.

• Hypomania and mania:

  • Patients at high risk of developing bipolar disorder may experience a manic episode or mixed-manic episode.
  • Patients with a family history or bipolar disorder, hypomania, or mania should be screened. Patients with depressive symptoms should be screened for bipolar disorder.
  • Sertraline has not been approved by the FDA for the treatment of bipolar disorder.

• Seizure disorder

  • Patients with a history of seizures or a condition that predisposes to seizures, such as brain damage or alcoholism, should be cautious.

Sertraline: Drug Interaction

Monitoring parameters:

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

How to administer Sertraline (Zoloft)?

Oral solution:

• Dilute immediately prior to use to make the preparation more palatable.
• Direct administration of the pure solution is astringent and may numb the tongue/mouth for at least a day, even if the mouth is rinsed.
• Note: Use cautiously in patients with latex sensitivity (the dropper dispenser contains dry natural rubber).

Mechanism of action of Sertraline (Zoloft):

Antidepressants that have selective inhibitory effects upon presynaptic Serotonin (5 HT) reuptake but very little effect on dopamine and norepinephrine neuronal uptake In vitro studies have not shown any remarkable affinity for GABA, GABA or dopaminergic receptors.

The beginning of action:

• Depression: The first signs of depression usually appear within one week.
• However, each person's response is different and complete results may not be seen until 8 to 12 months after treatment has begun.

Protein binding:

• 98%

Metabolism:

• It is metabolized by the liver. Metabolism could involve CYP2C19 or CYP2D6.
• It goes through extensive first-pass metabolism and forms N-desmethylsertraline.
• Notification:
  • Children aged 6-17 years may be able to metabolize sertraline slightly more efficiently than adults. However, lower doses of the drug are advised for children younger than this age.

Bioavailability:

• Bioavailability of tablets and solution are equivalent

Half-life elimination:

• Sertraline: Mean: 26 hours; N-desmethylsertraline: 62 to 104 hours
• Children 6 to 12 years: Mean: 26.2 hours
• Children 13 to 17 years: Mean: 27.8 hours
• Adults 18 to 45 years: Mean: 27.2 hours

Time to peak, plasma:

• 4.5 to 8.4 hours

Excretion:

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

International Brand Names of Sertraline:

• Zoloft
• ACT Sertraline
• AG-Sertraline
• APO-Sertraline
• Auro-Sertraline
• BIO-Sertraline
• DOM Sertraline
• GD-Sertraline
• JAMP-Sertraline
• Mar-Sertraline
• MINT-Sertraline
• MYLAN-Sertraline
• PHL-Sertraline
• PMS-Sertraline
• Priva-Sertraline
• RAN-Sertraline
• RIVA-Sertraline
• SANDOZ Sertraline
• TEVA-Sertraline
• VAN-Sertraline
• Adjuvin
• Agrelocit
• Aleval
• Altisben
• Altruline
• Aluprex
• Andep
• Aremis
• Asentra
• Aserin
• Aurasert
• Besiran
• Chear
• Conexine
• Deprax
• Depreger
• Deprine
• Deptral
• Dominum
• Doxime
• Eleva
• Emergen
• Fatral
• Freedep
• Fridep
• Gladem
• Iglodep
• Inosert
• J Zoloft
• Lesefer
• Lustral
• Lustraline
• Prosertin
• Purtraline
• Selrotine
• Seltra
• Serdep
• Serenada
• Serenorm
• Seretral
• Serimel
• Serlain
• Serlife
• Serlift
• Serlin
• Sernade
• Serolox
• Serolux
• Sertex
• Sertra
• Sertral
• Sertram
• Sertranex
• Sertranquil
• Setaloft
• Setra
• Setrax
• Setrof
• Setrona
• Solotik
• Sosser
• Starin
• Startline-50
• Stimuloton
• Suprisec
• Syche
• Tatig
• Xydep
• You-Jet
• Zerlin
• Zolodin
• Zolotral
• Zosert
• Zotaline

Sertraline Brand Names in Pakistan: