What is Zoloft (sertraline), and how is it used?

Zoloft (sertraline) is a serotonin reuptake inhibitor (SSRI) antidepressant used to treat depression, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD).

Common side effects of Zoloft include

Serious side effects of Zoloft include

Withdrawal symptoms such as abdominal cramps, fatigue, nausea, vomiting, diarrhea, headaches, lightheadedness, dizziness, decreased appetite, flu-like symptoms, sweating, chills, insomnia, and memory impairment may occur if you suddenly stop taking Zoloft.

Drug interactions of Zoloft include monoamine oxidase inhibitors (MAOIs), tryptophan, St. John's wort, meperidine, tramadol, cimetidine, pimozide, and warfarin. Use of Zoloft during the 3rd trimester of pregnancy may lead to adverse effects in the newborn. Use of Zoloft by nursing mothers has not been adequately evaluated.

What are the important side effects of Zoloft (sertraline)?

WARNING

As demonstrated in short-term studies, antidepressants increased the risk of suicidal thinking and behavior (suicidality) in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of Zoloft or any other antidepressant in a child or adolescent must balance this risk with the clinical need for the antidepressant. Patients who are started on therapy should be closely observed for clinical worsening, suicidal thoughts, or unusual changes in behavior.

Zoloft side effects:

The most common side effects of Zoloft are:

Possible serious side effects of Zoloft include:

  • Irregular heartbeats
  • Serious allergic reactions
  • Worsening of depression
  • Serotonin syndrome
  • Hyponatremia
  • Abnormal bleeding
  • Priapism (prolonged erection)
  • Decreased liver function
  • Suicidality
  • Activation of mania in patients with bipolar disorder

Important side effects are irregular heartbeats, allergic reactions and activation of mania in patients with bipolar disorder.

If Zoloft is discontinued abruptly, some patients experience side effects such as:

A gradual dose reduction of Zoloft is recommended when therapy is discontinued.

QUESTION

Depression is a(n) __________ . See Answer

Zoloft (sertraline) side effects list for healthcare professionals

The following adverse reactions are described in more detail in other sections of the prescribing information:

  • Hypersensitivity reactions to sertraline
  • Disulfiram-alcohol reaction when Zoloft oral solution is taken with disulfiram
  • QTc prolongation and ventricular arrhythmias when taken with pimozide
  • Suicidal thoughts and behaviors
  • Serotonin syndrome
  • Increased risk of bleeding
  • Activation of mania/hypomania
  • Discontinuation syndrome
  • Seizures
  • Angle-closure glaucoma
  • Hyponatremia

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below are from randomized, double-blind, placebo-controlled trials of Zoloft (mostly 50 mg to 200 mg per day) in 3066 adults diagnosed with MDD, OCD, PD, PTSD, SAD, and PMDD. These 3066 patients exposed to Zoloft for 8 to12 weeks represent 568 patient-years of exposure. The mean age was 40 years; 57% were females and 43% were males.

The most common adverse reactions (>5% and twice placebo) in all pooled placebo-controlled clinical trials of all Zoloft-treated patients with MDD, OCD, PD, PTSD, SAD and PMDD were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido (see Table 3). The following are the most common adverse reactions in trials of Zoloft (>5% and twice placebo) by indication that were not mentioned previously.

Table 3: Common Adverse Reactions in Pooled Placebo-Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD*
Zoloft
(N=3066)
Placebo
(N=2293)
Cardiac disorders
Palpitations4%2%
Eye disorders
Visual impairment4%2%
Gastrointestinal Disorders
Nausea26%12%
Diarrhea/Loose Stools20%10%
Dry mouth14%9%
Dyspepsia8%4%
Constipation6%4%
Vomiting4%1%
General disorders and administration site conditions
Fatigue12%8%
Metabolism and nutrition disorders
Decreased appetite7%2%
Nervous system disorders
Dizziness12%8%
Somnolence11%6%
Tremor9%2%
Psychiatric Disorders
Insomnia20%13%
Agitation8%5%
Libido Decreased6%2%
Reproductive system and breast disorders
Ejaculation failure (1)8%1%
Erectile dysfunction (1)4%1%
Ejaculation disorder (1)3%0%
Male sexual dysfunction (1)2%0%
Skin and subcutaneous tissue disorders
Hyperhidrosis7%3%
1 Denominator used was for male patients only (n=1316 Zoloft; n=973 placebo).
* Adverse reactions that occurred greater than 2% in Zoloft-treated patients and at least 2% greater in Zoloft-treated patients than placebo-treated patients.
Adverse Reactions Leading To Discontinuation In Placebo-Controlled Clinical Trials

In all placebo-controlled studies in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 368 (12%) of the 3066 patients who received Zoloft discontinued treatment due to an adverse reaction, compared with 93 (4%) of the 2293 placebo-treated patients. In placebo-controlled studies, the following were the common adverse reactions leading to discontinuation in Zoloft-treated patients:

  • MDD, OCD, PD, PTSD, SAD and PMDD: nausea (3%), diarrhea (2%), agitation (2%), and insomnia (2%).
  • MDD (>2% and twice placebo): decreased appetite, dizziness, fatigue, headache, somnolence, tremor, and vomiting.
  • OCD: somnolence.
  • PD: nervousness and somnolence.
Male And Female Sexual Dysfunction

Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment. However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance and satisfaction are difficult to obtain, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence.

Table 4 below displays the incidence of sexual adverse reactions reported by at least 2% of Zoloft-treated patients and twice placebo from pooled placebo-controlled trials. For men and all indications, the most common adverse reactions (>2% and twice placebo) included: ejaculation failure, decreased libido, erectile dysfunction, ejaculation disorder, and male sexual dysfunction. For women, the most common adverse reaction (≥2% and twice placebo) was decreased libido.

Table 4: Most Common Sexual Adverse Reactions (≥2% and twice placebo) in Men or Women from Zoloft Pooled Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD
Men onlyZoloft
(N=1316)
Placebo
(N=973)
Ejaculation failure8%1%
Libido decreased7%2%
Erectile dysfunction4%1%
Ejaculation disorder3%0%
Male sexual dysfunction2%0%
Women only(N=1750)(N=1320)
Libido decreased4%2%
Adverse Reactions In Pediatric Patients

In 281 pediatric patients treated with Zoloft in placebo-controlled studies, the overall profile of adverse reactions was generally similar to that seen in adult studies. Adverse reactions that do not appear in Table 3 (most common adverse reactions in adults) yet were reported in at least 2% of pediatric patients and at a rate of at least twice the placebo rate include fever, hyperkinesia, urinary incontinence, aggression, epistaxis, purpura, arthralgia, decreased weight, muscle twitching, and anxiety.

Other Adverse Reactions Observed During The Premarketing Evaluation Of Zoloft

Other infrequent adverse reactions, not described elsewhere in the prescribing information, occurring at an incidence of < 2% in patients treated with Zoloft were:

Cardiac disorders – tachycardia

Ear and labyrinth disorders – tinnitus

Endocrine disorders - hypothyroidism

Eye disorders - mydriasis, blurred vision

Gastrointestinal disorders - hematochezia, melena, rectal hemorrhage

General disorders and administration site conditions - edema, gait disturbance, irritability, pyrexia

Hepatobiliary disorders - elevated liver enzymes

Immune system disorders - anaphylaxis

Metabolism and nutrition disorders - diabetes mellitus, hypercholesterolemia, hypoglycemia, increased appetite

Musculoskeletal and connective tissue disorders - arthralgia, muscle spasms, tightness, or twitching

Nervous system disorders - ataxia, coma, convulsion, decreased alertness, hypoesthesia, lethargy, psychomotor hyperactivity, syncope

Psychiatric disorders - aggression, bruxism, confusional state, euphoric mood, hallucination

Renal and urinary disorders - hematuria

Reproductive system and breast disorders - galactorrhea, priapism, vaginal hemorrhage

Respiratory, thoracic and mediastinal disorders - bronchospasm, epistaxis, yawning

Skin and subcutaneous tissue disorders - alopecia; cold sweat; dermatitis; dermatitis bullous; pruritus; purpura;erythematous, follicular, or maculopapular rash; urticaria

Vascular disorders – hemorrhage, hypertension, vasodilation

Post-marketing Experience

The following adverse reactions have been identified during postapproval use of Zoloft. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Bleeding or clotting disorders - increased coagulation times (altered platelet function)

Cardiac disorders - AV block, bradycardia, atrial arrhythmias, QTc-interval prolongation, ventricular tachycardia (including Torsade de Pointes)

Endocrine disorders - gynecomastia, hyperprolactinemia, menstrual irregularities, SIADH

Eye disorders - blindness, optic neuritis, cataract

Hepatobiliary disorders - severe liver events (including hepatitis, jaundice, liver failure with some fatal outcomes), pancreatitis

Hemic and lymphatic disorders - agranulocytosis, aplastic anemia and pancytopenia, leukopenia, thrombocytopenia, lupus-like syndrome, serum sickness

Immune system disorders - angioedema

Metabolism and nutrition disorders - hyponatremia, hyperglycemia

Musculoskeletal and connective tissue disorders - rhabdomyolysis, trismus

Nervous system disorders - serotonin syndrome, extrapyramidal symptoms (including akathisia and dystonia), oculogyric crisis

Psychiatric disorders - psychosis, enuresis, paroniria

Renal and urinary disorders - acute renal failure

Respiratory, thoracic and mediastinal disorders - pulmonary hypertension

Skin and subcutaneous tissue disorders - photosensitivity skin reaction and other severe cutaneous reactions, which potentially can be fatal, such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN)

Vascular disorders - cerebrovascular spasm (including reversible cerebral vasoconstriction syndrome and Call-Fleming syndrome), vasculitis

What drugs interact with Zoloft (sertraline)?

Clinically Significant Drug Interactions

Table 5 includes clinically significant drug interactions with Zoloft.

Table 5: Clinically-Significant Drug Interactions with Zoloft
Monoamine Oxidase Inhibitors (MAOIs)
Clinical Impact:The concomitant use of SSRIs including Zoloft and MAOIs increases the risk of serotonin syndrome.
Intervention:Zoloft is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue.
Examples:selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue
Pimozide
Clinical Impact:Increased plasma concentrations of pimozide, a drug with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias.
Intervention:Concomitant use of pimozide and Zoloft is contraindicated.
Other Serotonergic Drugs
Clinical Impact:The concomitant use of serotonergic drugs with Zoloft increases the risk of serotonin syndrome.
Intervention:Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of Zoloft and/or concomitant serotonergic drugs.
Examples:other SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort
Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants)
Clinical Impact:The concurrent use of an antiplatelet agent or anticoagulant with Zoloft may potentiate the risk of bleeding.
Intervention:Inform patients of the increased risk of bleeding associated with the concomitant use of Zoloft and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio.
Examples:aspirin, clopidogrel, heparin, warfarin
Drugs Highly Bound to Plasma Protein
Clinical Impact:Zoloft is highly bound to plasma protein. The concomitant use of Zoloft with another drug that is highly bound to plasma protein may increase free concentrations of Zoloft or other tightly-bound drugs in plasma.
Intervention:Monitor for adverse reactions and reduce dosage of Zoloft or other protein-bound drugs as warranted.
Examples:warfarin
Drugs Metabolized by CYP2D6
Clinical Impact:Zoloft is a CYP2D6 inhibitor. The concomitant use of Zoloft with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate.
Intervention:Decrease the dosage of a CYP2D6 substrate if needed with concomitant Zoloft use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if Zoloft is discontinued.
Examples:propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, thoridazine, tolterodine, venlafaxine
Phenytoin
Clinical Impact:Phenytoin is a narrow therapeutic index drug. Zoloft may increase phenytoin concentrations.
Intervention:Monitor phenytoin levels when initiating or titrating Zoloft. Reduce phenytoin dosage if needed.
Examples:phenytoin, fosphenytoin
Drugs that Prolong the QTc Interval
Clinical Impact:The risk of QTc prolongation and/or ventricular arrhythmias (e.g., TdP) is increased with concomitant use of other drugs which prolong the QTc interval.
Intervention:Pimozide is contraindicated for use with sertraline. Avoid the concomitant use of drugs known to prolong the QTc interval.
Examples:Specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus).

Drugs Having No Clinically Important Interactions With Zoloft

Based on pharmacokinetic studies, no dosage adjustment of Zoloft is necessary when used in combination with cimetidine. Additionally, no dosage adjustment is required for diazepam, lithium, atenolol, tolbutamide, digoxin, and drugs metabolized by CYP3A4, when Zoloft is administered concomitantly.

False-Positive Screening Tests For Benzodiazepines

False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking Zoloft. 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 Zoloft. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish sertraline from benzodiazepines.

SLIDESHOW

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Summary

Zoloft (sertraline) is a serotonin reuptake inhibitor (SSRI) antidepressant used to treat depression, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD). Common side effects of Zoloft include sleepiness, nervousness, difficulty sleeping (insomnia), dizziness, nausea, tremor, skin rash, constipation, upset stomach, loss of appetite, headache, diarrhea, abnormal ejaculation, decreased sex drive, dry mouth, increased sweating, and weight loss.

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Medically Reviewed on 10/16/2019
References
FDA Prescribing Information

Professional side effects list and drug interactions section courtesy of the U.S. Food and Drug Administration
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