Brand name: Remeron
Drug class: Serotonin Modulators

Medically reviewed by Drugs.com on Mar 10, 2025. Written by ASHP.

Introduction

Tetracyclic antidepressant; a piperazinoazepine-derivative.

Uses for Mirtazapine

Major Depressive Disorder

Treatment of major depressive disorder in adults.

The manufacturer states that mirtazapine is not approved for use in pediatric patients.

Guidelines from the American Psychiatric Association (APA) and the Department of Veterans Affairs/Department of Defense state that there is no evidence to suggest superiority of one first-line antidepressant over another. Recommended first-line agents for initial treatment of major depressive disorder include bupropion, mirtazapine, an SSRI, an SNRI, trazodone, vilazodone, or vortioxetine. Select an initial antidepressant for treatment based on the following factors: patient preference; nature of prior response to medication; safety, tolerability, and anticipated adverse effects; concurrent psychiatric and medical conditions; specific properties of the medication; and cost.

Panic Disorder

Has been used for the treatment of panic disorder^{† [off-label]} .

APA guidelines state that mirtazapine may be considered in patients who have failed to respond to other therapy or based on other patient-specific factors (e.g., cost, prior treatment history, comorbid conditions). International experts state that no recommendation is possible for or against use of mirtazapine in panic disorder due to limited available evidence.

Social Anxiety Disorder

Has been used for the treatment of social anxiety disorder^{† [off-label]} .

International experts provide a limited recommendation for use of mirtazapine in social anxiety disorder based on evidence from a single study.

Post-Traumatic Stress Disorder

Has been used for the treatment of post-traumatic stress disorder (PTSD)^{† [off-label]} .

Guidelines from the Department of Veterans Affairs/Department of Defense state that there is insufficient evidence to recommend for or against use of mirtazapine for PTSD. International experts provide a limited recommendation for use of mirtazapine in PTSD based on evidence from a single study.

Obsessive-Compulsive Disorder

Has been used for the treatment of obsessive-compulsive disorder (OCD)^{† [off-label]}.

APA guidelines state that patients may switch to another SSRI or mirtazapine as a second-line treatment if they fail to respond to initial treatment with an SSRI. International experts provide a limited recommendation for the use of mirtazapine in OCD.

Generalized Anxiety Disorder

Has been used for the treatment of generalized anxiety disorder (GAD)^{† [off-label]} .

Amphetamine-type Stimulant Use Disorder

Has been used for the treatment of amphetamine-type stimulant use disorder^† .

American Society of Addiction Medicine (ASAM) and American Academy of Addiction Psychiatry (AAAP) guidelines state that mirtazapine may be considered as a treatment option to promote reduced use of amphetamine-type stimulants.

Cancer Cachexia

Has been used for the treatment of cancer cachexia^† .

American Society of Clinical Oncology (ASCO) guidelines state that mirtazapine improves appetite and weight in about one-third of patients across different cancer types. However, ASCO also noted a lack of information on the impact of cancer treatment on mirtazapine use.

Mirtazapine Dosage and Administration

General

Pretreatment Screening

• Screen for a personal or family history of bipolar disorder, mania, or hypomania.

Patient Monitoring

• Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment.

• Monitor for the emergence of serotonin syndrome during therapy.

• Monitor patient weight, liver enzymes, and lipids.

• Monitor for signs of infection and low WBC count.

• Monitor for withdrawal symptoms when discontinuing mirtazapine.

• Monitor for signs of hyponatremia.

Dispensing and Administration Precautions

• The Institute for Safe Medication Practices (ISMP) includes Remeron (mirtazapine) and Rozerem (ramelteon) on the ISMP List of Confused Drug Names, and recommends special safeguards to reduce the risk of errors when prescribing mirtazapine (Remeron); these may include strategies such as using both brand and generic names on prescriptions/labels and including the purpose of the medication on prescriptions.

Other General Considerations

• If a patient is being transitioned to mirtazapine therapy from a monoamine oxidase (MAO) inhibitor, allow at least 14 days to elapse between discontinuation of the MAO inhibitor and initiation of mirtazapine. Conversely, if switching from mirtazapine to an MAO inhibitor, allow at least 14 days to elapse between discontinuation of mirtazapine and initiation of the MAO inhibitor.

• When discontinuing therapy, reduce dosage gradually and monitor for possible withdrawal symptoms; avoid abrupt discontinuation whenever possible.

Administration

Oral Administration

Administer orally as conventional tablets and orally disintegrating tablets once daily (at bedtime) without regard to meals.

Do not break orally disintegrating tablets.

Just prior to administration of orally disintegrating tablet (ODT), remove tablet from blister package; peel open blister package, place tablet on tongue to dissolve without chewing or crushing, and swallow with saliva; administration with liquid is not necessary.

Dosage

Adults

Major Depressive Disorder

Oral

Initially, 15 mg daily. If no improvement, dosage may be increased up to a maximum of 45 mg daily at intervals of not less than 1–2 weeks.

Dosage Adjustment for Drug Interactions

An increase in dosage of mirtazapine may be needed when used concomitantly with a strong CYP3A inducer (e.g., carbamazepine, phenytoin, rifampin). A decrease in dosage of mirtazapine may be needed if the CYP3A inducer is discontinued.

A decrease in dosage of mirtazapine may be needed when used concomitantly with a strong CYP3A4 inhibitor (e.g., ketoconazole, clarithromycin). An increase in dosage of mirtazapine may be needed if the CYP3A4 inhibitor is discontinued.

A decrease in dosage of mirtazapine may be needed when used concomitantly with cimetidine; an increase in dosage of mirtazapine may be needed if cimetidine is discontinued.

Special Populations

Hepatic Impairment

Dosage of mirtazapine may require reduction in patients with moderate to severe hepatic impairment.

Renal Impairment

Dosage of mirtazapine may require reduction in patients with moderate to severe renal impairment.

Geriatric Patients

Use caution when administering mirtazapine to geriatric patients; start at the low end of the dosing range, due to age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Mirtazapine

Contraindications

• Known hypersensitivity to mirtazapine, or to any ingredient in its formulations.

• Concurrent or recent (i.e., within 14 days) therapy with monoamine oxidase (MAO) inhibitors, including linezolid and IV methylene blue.

Warnings/Precautions

Warnings

Suicidal Thoughts and Behaviors

Increased risk of suicidal thoughts and behavior in adolescent and young adult patients taking antidepressants. (See Boxed Warning.) Depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all patients treated with antidepressants for any indication of clinical worsening or emergence of suicidal thoughts and behaviors, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments. Counsel families and caregivers to monitor for changes in the patient’s behavior, and to report such symptoms to a clinician. Consider changing the therapeutic regimen or discontinuing mirtazapine in patients whose depression is persistently worse or in patients experiencing emergent suicidal thoughts or behaviors.

Other Warnings and Precautions

Agranulocytosis

Agranulocytosis or severe neutropenia (with or without infection) reported rarely. Monitor for signs and symptoms of agranulocytosis; if signs of infection (e.g., sore throat, fever, stomatitis) and low WBC counts occur, discontinue therapy and monitor patient closely.

Serotonin Syndrome

Serotonergic antidepressants can precipitate serotonin syndrome; potentially life-threatening. Increased risk with concurrent use of other serotonergic drugs (e.g., serotonin [5-hydroxytryptamine; 5-HT] type 1 receptor agonists [“triptans”], tricyclic antidepressants [TCAs], fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s wort [Hypericum perforatum]) and with drugs that impair serotonin metabolism (i.e., MAO inhibitors).

Symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and GI symptoms (e.g., nausea, vomiting, diarrhea).

Concurrent or recent (i.e., within 14 days) use of MAO inhibitors is contraindicated. Do not initiate mirtazapine in patients treated with MAO inhibitors such as linezolid or IV methylene blue. If MAO inhibitor is necessary, discontinue mirtazapine before initiating the MAO inhibitor.

Monitor patients for serotonin syndrome. If manifestations occur, immediately discontinue treatment with mirtazapine and any concurrently administered serotonergic agents, and initiate supportive symptomatic treatment.

Angle-closure Glaucoma

May cause pupillary dilation (mydriasis), which can trigger an angle closure attack in patients without a patent iridectomy with anatomically narrow angles.

QT Prolongation and Torsades de Pointes

Cases of QT prolongation, torsades de pointes, ventricular tachycardia, and sudden death reported. Use with caution in patients with known cardiovascular disease or family history of QT prolongation, and with concomitant use of other drugs that prolong the QTc interval.

Drug Reaction with Eosinophilia and Systemic Symptoms

Drug reaction with eosinophilia and systemic symptoms (DRESS), which is sometimes fatal, reported. Symptoms may include cutaneous reactions (e.g., rash, exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and pericarditis. Immediately discontinue use of mirtazapine if DRESS is suspected and initiate appropriate treatment.

Increased Appetite and Weight Gain

Possible increased appetite and weight gain.

Somnolence

May cause somnolence. Caution patients about engaging in activities that require alertness (e.g., operating heavy machinery and motor vehicles), until reasonably certain that mirtazapine does not affect them adversely.

Avoid concomitant use of benzodiazepines and alcohol.

Activation of Mania and Hypomania

Activation of mania and hypomania reported with mirtazapine and other antidepressants.

Screen patients for any personal or family history of bipolar disorder, mania, or hypomania prior to starting treatment with mirtazapine.

Seizures

Risk of seizures. Not systematically evaluated in patients with seizures; use with caution in patients with a seizure disorder.

Elevated Cholesterol and Triglycerides

Clinically important increases in serum cholesterol (e.g., ≥20% ULN) and serum triglyceride (e.g., ≥500 mg/dL) concentrations reported.

Hyponatremia

Serotonergic antidepressants, including mirtazapine, may cause hyponatremia; in many cases, SIADH is apparent cause. Increased risk in geriatric patients, and in patients taking diuretics or who are otherwise volume depleted.

Discontinue mirtazapine and initiate appropriate medical intervention in patients with symptomatic hyponatremia.

Transaminase Elevations

Potentially clinically important elevations (e.g., 3 times ULN) in serum ALT concentrations; use caution in patients with impaired hepatic function.

Discontinuation Syndrome

Withdrawal effects (dizziness, abnormal dreams, sensory disturbances [e.g., paresthesia, electroshock sensations], agitation, anxiety, fatigue, confusion, headache, tremor, nausea, vomiting, sweating) reported following discontinuation, particularly when abrupt. Gradually reduce dosage (versus abrupt cessation) when discontinuing therapy.

Use in Patients with Concomitant Illness

Not systemically evaluated in patients with a recent history of myocardial infarction (MI) or other significant heart disease. Associated with significant orthostatic hypotension in early clinical trials. Use in caution in patients with known cardiovascular or cerebrovascular disease that could be exacerbated by hypotension (e.g., history of MI, angina, ischemic stroke) and in conditions that predispose patients to hypotension (e.g., dehydration, hypovolemia, treatment with antihypertensive medication.)

Phenylketonuria

Mirtazapine ODT contains phenylalanine, a component of aspartame. Phenylalanine can be harmful to patients with phenylketonuria (PKU).

Mirtazapine ODT contain the following amounts of phenylalanine in each tablet strength: 2.6 mg in 15 mg ODT, 5.2 mg in 30 mg ODT, and 7.8 mg in 45 mg ODT.

Consider the combined daily amount of phenylalanine from all sources, including mirtazapine ODT, before prescribing to patients with PKU.

Specific Populations

Pregnancy

National Pregnancy Registry for Antidepressants available at 1-844-405-6185 or [Web].

Available evidence has not reliably identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks associated with untreated depression in pregnancy.

Consider the risk of untreated depression when discontinuing or changing antidepressants during pregnancy and postpartum.

Lactation

Present at low levels in human milk. No adverse effects on the breast-fed infant reported in most cases of maternal use of mirtazapine. Not known if mirtazapine affects milk production.

Consider the developmental and health benefits of breast-feeding, the mother’s clinical need for mirtazapine, and any potential adverse effects on the breast-fed child from drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established; not approved for use in pediatric patients. Increased risk of suicidal thoughts and behaviors observed in pediatric patients treated with antidepressants. Possible increase in weight gain in pediatric patients.

Geriatric Use

Decreased clearance of mirtazapine in geriatric patients based on pharmacokinetic studies. May cause confusion and over-sedation in geriatric patients; may also be at greater risk of hyponatremia.

Use with caution in geriatric patients; select dosage conservatively, starting at low end of dosing range.

Hepatic Impairment

Decreased clearance in moderate to severe hepatic impairment; a decrease in dosage may be necessary according to the manufacturer.

Renal Impairment

Decreased clearance in patients with moderate to severe renal impairment; a decrease in dosage may be necessary according to the manufacturer.

Common Adverse Effects

Adverse effects (≥5%): somnolence, increased appetite, weight gain, dizziness.

Drug Interactions

Metabolized principally by CYP3A; also metabolized by CYP2D6 and CYP1A2.

Drugs Affecting Hepatic Microsomal Enzymes

Strong CYP3A inducers: Concomitant use with strong CYP3A inducers (e.g., phenytoin, carbamazepine, rifampin) decreases mirtazapine plasma concentrations. Increase dosage of mirtazapine if needed with concomitant use; decrease dosage of mirtazapine if needed when strong CYP3A inducer is discontinued.

Strong CYP3A inhibitors:Concomitant use with strong CYP3A inhibitors (e.g., itraconazole, ketoconazole, ritonavir, nefazodone) may increase mirtazapine plasma concentrations. Decrease dosage of mirtazapine if needed with concomitant use; increase dosage of mirtazapine if needed when strong CYP3A inhibitor is discontinued.

Drugs Associated with QT Prolongation

Concomitant use with other drugs which prolong the QTc interval increases risk of QT prolongation and/or ventricular arrhythmias including torsades de pointes. Use caution with concomitant use.

Serotonergic Drugs

Potential pharmacologic interaction (serotonin syndrome) with serotonergic drugs. Monitor for serotonin syndrome with concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuing mirtazapine and any concurrently administered serotonergic agents.

Specific Drugs

Mirtazapine Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 50% following oral administration.

Peak plasma concentration usually attained within 2 hours.

Plasma levels linear and related to dose over range of 15-80 mg; steady state plasma levels attained within 5 days with about 50% accumulation.

Food

Food does not affect absorption.

Distribution

Extent

Present in human milk at low levels, with relative infant doses 0.6-2.8% of maternal weight-adjusted dose.

Plasma Protein Binding

Approximately 85%.

Elimination

Metabolism

Extensively metabolized by demethylation and hydroxylation, followed by glucuronide conjugation. CYP2D6 and CYP1A2 involved in formation of 8-hydroxy metabolite, and CYP3A4 responsible for formation of N-desmethyl and N-oxide metabolite.

Elimination Route

Excreted in urine (75%) and feces (15%).

Half-life

20–40 hours.

Special Populations

Renal impairment may reduce clearance; patients with GFR of 11-39 mL/minute per 1.73 m² had approximately 30% reduced clearance; patients with GFR ≤10 mL/minute per 1.73 m² had approximately 50% reduced clearance.

In patients with hepatic impairment, oral clearance decreased approximately 30% following a single 15-mg oral dose.

Clearance reduced in geriatric patients. In geriatric males, clearance was 40% lower than younger males; in geriatric females, clearance was 10% lower than younger females.

Females of all ages have significantly longer elimination half-life (37 hours) compared to males (26 hours).

Impact of race on mirtazapine pharmacokinetics not evaluated.

Stability

Storage

Oral

Tablets

20-25°C (excursions permitted between 15-30°C); protect from light and moisture.

Orally Disintegrating Tablets

20-25°C (excursions permitted between 15-30°C); protect from light and moisture. Use immediately after opening individual tablet blister.

Actions

• Mechanism of action as an antidepressant is unclear, but presumed to be linked to potentiation of noradrenergic and serotonergic activity in the CNS resulting from its antagonism at central presynaptic α₂-adrenergic autoreceptors and heteroreceptors.

• Exhibits potent antagonism of serotonin type 2 (5-HT₂) and type 3 (5-HT₃) receptors; does not exhibit high affinity for serotonin type 1A (5-HT_1A) or type 1B (5-HT_1B) receptors.

• Exhibits potent antagonism of histamine H₁ receptors.

• Exhibits moderate peripheral α₁-adrenergic blocking activity and moderate antagonism at muscarinic receptors.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).

• Advise patients and caregivers to monitor for the emergence of suicidal thoughts and behaviors, especially during the first few months of therapy or during periods of dosage adjustment. Instruct patients and caregivers to report such symptoms to their clinician.

• Advise patients to contact their clinicians if they experience fever, chills, sore throat, mucous membrane ulceration, flu-like complaints, or other symptoms that might suggest the patient has an infection.

• Inform patients of the risk of serotonin syndrome with concomitant use of mirtazapine and other serotonergic agents including MAO inhibitors, SSRIs, SNRIs, triptans, TCAs, fentanyl, tramadol, lithium, buspirone, amphetamines, tryptophan, and St. John’s wort (Hypericum perforatum). Stress importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.

• Inform patients of the risk of QT prolongation and torsades de pointes, which can be fatal. Inform patients to consult their clinician immediately if they feel faint, lose consciousness, or have heart palpitations. Advise patients to inform their clinicians that they are taking mirtazapine before any new drug is taken.

• Inform patients of the risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Advise patients to report to their clinicians at the earliest onset of fever, rash, swollen lymph nodes, or other signs and symptoms suggestive of DRESS.

• Advise patients of the risk of cognitive and motor impairment because of the sedative effect of mirtazapine. Advise patients to exercise caution while operating hazardous machinery, including driving a motor vehicle, until they are reasonably certain that mirtazapine therapy does not adversely affect their ability to engage in such activities.

• Advise patients to avoid alcohol consumption during mirtazapine therapy.

• Advise patients and their caregivers to look for signs of activation of mania/hypomania.

• Advise patients not to abruptly stop taking mirtazapine without first talking with their clinician. Inform patients that withdrawal symptoms may occur when suddenly stopping mirtazapine.

• Advise patients to notify their clinician if any sign or symptoms of an allergic reaction develop during mirtazapine therapy (e.g., rash, hives, swelling, difficulty breathing).

• Advise patients that mirtazapine can cause mild pupillary dilation, which can lead to an episode of angle-closure glaucoma in susceptible individuals.

• Inform patients with phenylketonuria that the ODT contains phenylalanine.

• Advise females of child bearing potential to inform their clinicians if they are or plan to become pregnant or plan to breast-feed. Advise females that there is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to mirtazapine during pregnancy.

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as concomitant illnesses.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• Does Remeron help with sleep?

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