What is mirtazapine

Mirtazapine is a prescription noradrenergic and specific serotonergic antidepressant (NaSSA) used to treat depression. Mirtazapine is marketed as Remeron and Remeron Soltab. The way mirtazapine works is still not fully understood. It is thought to positively affect communication between nerve cells in the central nervous system and/or restore chemical balance in the brain. Evidence gathered in preclinical studies suggests that mirtazapine enhances central noradrenergic (noradrenaline or norepinephrine) and serotonergic (serotonin) activity. These studies have shown that mirtazapine acts as an antagonist (blocker) at central presynaptic α2-adrenergic inhibitory autoreceptors and heteroreceptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity.

Mirtazapine is a potent blocker of serotonin-2 (5-HT2) and serotonin-3 (5-HT3) receptors. Mirtazapine has no significant affinity for the serotonin-1A (5-HT1A) and serotonin-1B (5-HT1B) receptors.

Mirtazapine is a potent blocker of histamine (H1) receptors. This antihistamine effect is linked to sedation and weight gain.

The blockade of histamine 1 receptors is linked to sedation, increased appetite, weight gain and dry mouth.

• Sedation: this side effect can appear in up to 50% of patients during the first of treatment.
• Increased appetite and weight gain: this can occur in 15-25% of patients.

Mirtazapine is a moderate peripheral α1-adrenergic blocker, a property that may explain the occasional orthostatic hypotension reported in association with its use.

Mirtazapine is a moderate antagonist at muscarinic receptors, a property that may explain the relatively low incidence of anticholinergic side effects associated with its use.

Mirtazapine is commonly used in the elderly population. In this group of patients insomnia and low weight might benefit from sedation and weight gain.

Mirtazapine has no significant drug-drug interactions, this makes it attractive for use in combination with other antidepressants as augmenting option.

Mirtazapine is approved only for depression. There are studies supporting its use in anxiety disorders such as panic disorder, generalized anxiety disorder and social anxiety disorder.

Small size randomized controlled trials support the use of mirtazapine as add-on to antipsychotics for the treatment of negative symptoms in schizophrenia.

The mechanism of action of antiemetic drugs involves 5HT3 antagonism. Mirtazapine is an interesting option for depressed patients suffering from chemotherapy induced nausea and vomiting.

Because of its histamine 1 antagonist properties mirtazapine is sometimes used for the treatment of insomnia. We should keep in mind that mirtazapine can be useful in depressed patients with insomnia, but shouldn’t be used as primary treatment for insomnia without depression.

Pharmacokinetics

Mirtazapine tablets are rapidly and completely absorbed following oral administration and have a half-life of about 20 to 40 hours. Peak plasma concentrations are reached within about 2 hours following an oral dose. The presence of food in the stomach has a minimal effect on both the rate and extent of absorption and does not require a dosage adjustment.

Mirtazapine is extensively metabolized after oral administration. Major pathways of biotransformation are demethylation and hydroxylation followed by glucuronide conjugation. In vitro data from human liver microsomes indicate that cytochrome 2D6 and 1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine, whereas cytochrome 3A is considered to be responsible for the formation of the N-desmethyl and N-oxide metabolite. Mirtazapine has an absolute bioavailability of about 50%. It is eliminated predominantly via urine (75%) with 15% in feces. Several unconjugated metabolites possess pharmacological activity but are present in the plasma at very low levels. The (–) enantiomer has an elimination half-life that is approximately twice as long as the (+) enantiomer and therefore achieves plasma levels that are about three times as high as that of the (+) enantiomer.

Plasma levels are linearly related to dose over a dose range of 15 to 80 mg. The mean elimination half-life of mirtazapine after oral administration ranges from approximately 20 to 40 hours across age and gender subgroups, with females of all ages exhibiting significantly longer elimination half-lives than males (mean half-life of 37 hours for females vs. 26 hours for males). Steady state plasma levels of mirtazapine are attained within 5 days, with about 50% accumulation (accumulation ratio = 1.5).

Mirtazapine is approximately 85% bound to plasma proteins over a concentration range of 0.01 to 10 mcg/mL.

Mirtazapine special precautions

You should not take mirtazapine if you are also taking tryptophan (sometimes called L-tryptophan).

Do not use mirtazapine if you have used a monoamine oxidase (MAO) inhibitor in the past 14 days. A dangerous drug interaction could occur. Monoamine oxidase (MAO) inhibitors include isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others.

Some young people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using mirtazapine. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Do not give this medicine to anyone younger than 18 years old without the advice of a doctor. mirtazapine is not approved for use in children.

It may take up to several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after 4 weeks of treatment.

Drinking alcohol can increase certain side effects of mirtazapine.

Mirtazapine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Some young people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using mirtazapine. Your family or other caregivers should also be alert to changes in your mood or symptoms.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether mirtazapine passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

The orally disintegrating tablet may contain phenylalanine. Talk to your doctor before using this form of mirtazapine if you have phenylketonuria (PKU).

Before taking mirtazapine:

• tell your doctor and pharmacist if you are allergic to mirtazapine, any other medications, or any of the ingredients in mirtazapine tablets or disintegrating tablets. Ask your doctor or pharmacist for a list of the ingredients.
• tell your doctor if you are taking a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate) or if you have stopped taking an MAO inhibitor within the past 14 days. Your doctor will probably tell you not to take mirtazapine. If you stop taking mirtazapine, you should wait at least 14 days before you start to take an MAO inhibitor.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin, Jantoven); antidepressants such as amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin, imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); certain antifungals such as ketoconazole (Nizoral); buspirone; carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, other); cimetidine (Tagamet); diazepam (Valium); erythromycin (E.E.S., E-mycin, Erythrocin); fentanyl (Abstral, Actiq, Fentora, Onsolis, others); lithium (Eskalith, Lithobid); medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex), and zolmitriptan (Zomig); certain medications to treat HIV; medications for anxiety and seizures; nefazodone; phenytoin (Dilantin); rifampin (Rimactane, Rifadin, in Rifater, in Rifamate); sedatives; selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil, Pexeva), and sertraline (Zoloft); selective serotonin and norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Pristiq), duloxetine (Cymbalta), and venlafaxine (Effexor); sleeping pills; tramadol (Ultram); and tranquilizers. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• tell your doctor if you have or have ever had a heart attack, low blood pressure, heart, kidney, or liver disease, or high cholesterol.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking mirtazapine, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking mirtazapine.
• you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• remember that alcohol can add to the drowsiness caused by mirtazapine.
• if you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent mental retardation), you should know that the orally disintegrating tablets contain aspartame that forms phenylalanine.
• you should know that mirtazapine may cause angle-closure glaucoma (a condition where the fluid is suddenly blocked and unable to flow out of the eye causing a quick, severe increase in eye pressure which may lead to a loss of vision). Talk to your doctor about having an eye examination before you start taking this medication. If you have nausea, eye pain, changes in vision, such as seeing colored rings around lights, and swelling or redness in or around the eye, call your doctor or get emergency medical treatment right away.

Mirtazapine and alcohol

Alcohol can add to the drowsiness caused by mirtazapine.

What is mirtazapine used for?

Mirtazapine is used to treat depression. Mirtazapine is in a class of medications called antidepressants. It works by increasing certain types of activity in the brain to maintain mental balance. Mirtazapine is commonly used in the elderly population. In this group of patients insomnia and low weight might benefit from sedation and weight gain. Mirtazapine was approved by the FDA in 1996 for major depressive disorder in a dosage range going from 15-45 mg/day.

Mirtazapine is also used as augmenting agent.

It is relatively easy to combine with other antidepressants, the venlafaxine + mirtazapine combination has been called “California Rocket Fuel” . Since it has no activity on monoamine reuptake it has a complementary mechanism of action with SSRIs and SNRIs.

So what’s the evidence supporting its use as augmenting agent? The STAR*D trial showed that the mirtazapine + venlafaxine combination outperformed tranylcypromine. However, this finding was not statistically significant.

Case series of 32 patients studied the venlafaxine mirtazapine combination, measuring response rate based on the CGI scale. 44% of patients responded at 4 weeks, while 50% responded at 8 weeks.

So, as a conclusion even though the combination of mirtazapine with venlafaxine makes pharmacological sense, the evidence is limited to case reports. Its use can be considered according to clinical judgment of the prescriber.

How should mirtazapine be used?

Mirtazapine comes as a tablet and as a disintegrating tablet to take by mouth. It usually is taken once a day at bedtime. It may be taken with or without food. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take mirtazapine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

To take a mirtazapine disintegrating tablet, open the blister pack with dry hands and place the tablet on your tongue. The tablet will disintegrate on the tongue and can be swallowed with saliva. No water is needed to swallow disintegrating tablets. Once the tablet is removed from the blister pack, it cannot be stored. Do not split mirtazapine disintegrating tablets.

It may take several weeks or longer for you to feel the full benefit of mirtazapine. Continue to take mirtazapine even if you feel well. Do not stop taking mirtazapine without talking to your doctor. Your doctor probably will decrease your dose gradually.

Mirtazapine dosage

Mirtazapine is usually taken once a day at bedtime. Follow your doctor’s instructions.

Take the regular tablet form of mirtazapine with water.

To take the orally disintegrating tablet (Remeron SolTab):

• Keep the tablet in its blister pack until you are ready to take it. Open the package and peel back the foil. Do not push a tablet through the foil or you may damage the tablet.
• Use dry hands to remove the tablet and place it in your mouth.

Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing. If desired, you may drink liquid to help swallow the dissolved tablet.

It may take up to several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after 4 weeks of treatment.

Do not stop using mirtazapine suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using this medicine.

Store at room temperature away from moisture, heat, and light.

Adult Dose for Depression

Use: Treatment of major depressive disorder

• Initial dose: 15 mg orally once a day at bedtime
• Maintenance dose: 15 to 45 mg orally once a day
• Maximum dose: 45 mg/day

Comments:

• May increase the dose every 1 to 2 weeks to a maximum 45 mg/day according to patient response.
• Patients should be periodically reassessed to determine the need for continued use of this drug.

Dose Adjustments

Switching from:

• Monoamine oxidase (MAO) inhibitor to this drug: At least 14 days should elapse
• Mirtazapine to monoamine oxidase (MAO) inhibitor therapy: At least 14 days should elapse
• Immediate treatment with linezolid or IV methylene blue: Stop this drug during treatment and resume after the last dose of linezolid or methylene blue

Treatment withdrawal:

• A gradual dose reduction is recommended instead of abrupt cessation when possible.
• If intolerable symptoms occur, consider resuming the previously prescribed dose and decreasing the dose at a more gradual rate.

Renal Dose Adjustments

• Moderate to severe renal impairment (creatinine clearance less than 40 mL/min): Use with caution

Liver Dose Adjustments

• Use with caution.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Mirtazapine side effects

Mirtazapine may cause side effects.

Common mirtazapine side effects include:

• drowsiness, dizziness;
• strange dreams;
• vision changes;
• dry mouth;
• constipation;
• increased appetite; or
• weight gain.

Tell your doctor if any of these symptoms are severe or do not go away:

• drowsiness
• dizziness
• anxiousness
• confusion
• increased weight and appetite
• dry mouth
• constipation
• nausea
• vomiting

Rare side effects:

• change in menstrual cycle (periods)
• convulsions (seizures)
• decreased sexual ability
• menstrual pain
• mood or mental changes, including anger, feelings of being outside the body, hallucinations (seeing, hearing, or feeling things that are not there), mood
• swings, and unusual excitement
• mouth sores
• sore throat, chills, or fever

Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS section, call your doctor immediately or get emergency medical treatment:

• flu-like symptoms, fever, chills, sore throat, mouth sores, or other signs of infection
• chest pain
• fast heartbeat
• seizures

Get emergency medical help if you have any signs of an allergic reaction to mirtazapine: skin rash or hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

• racing thoughts, decreased need for sleep, unusual risk-taking behavior, feelings of extreme happiness or sadness, being more talkative than usual;
• blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• a light-headed feeling, like you might pass out;
• changes in weight or appetite;
• sudden weakness or ill feeling, fever, chills, sore throat, mouth sores, red or swollen gums, trouble swallowing;
• rash, blisters, oozing, or severe pain in the palms of your hands or the soles of your feet;
• high levels of serotonin in the body – agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting;
• low levels of sodium in the body – headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady; or
• severe nervous system reaction – very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out.

This is not a complete list of side effects and others may occur. Mirtazapine may cause other side effects. Call your doctor if you have any unusual problems while you are taking mirtazapine.

Nervous system

• Very common (10% or more): Somnolence (up to 54%)
• Common (1% to 10%): Dizziness, tremor, headache, sedation/drowsiness
• Uncommon (0.1% to 1%): Hypesthesia, hypokinesia, vertigo, amnesia, hyperkinesia, paresthesia, lethargy
• Rare (0.01% to 0.1%): Syncope, migraine, ataxia, dyskinesia, extrapyramidal syndrome, coordination abnormal, dysarthria, dystonia, reflexes increased, restless legs, akathisia (psychomotor restlessness)
• Very rare (less than 0.01%): Vascular headache, cerebral ischemia, aphasia, nystagmus, stupor, dementia, paralysis, grand mal convulsion, hypotonia, taste loss, myoclonus, parosmia
• Frequency not reported: Hypertonia, taste perversion, convulsions (insults)
• Postmarketing reports: Impaired concentration, cerebrovascular disorder, movement disorders

Gastrointestinal

• Very common (10% or more): Dry mouth (up to 25%), constipation (up to 13%)
• Common (1% to 10%): Nausea
• Uncommon (0.1% to 1%): Abdominal pain, abdominal syndrome acute, vomiting, diarrhea
• Rare (0.01% to 0.1%): Abdomen enlarged, eructation, glossitis, nausea and vomiting, gum hemorrhage, stomatitis, colitis, oral hypoesthesia
• Very rare (less than 0.01%): Tongue discoloration, ulcerative stomatitis, salivary gland enlargement, increased salivation, intestinal obstruction, pancreatitis, aphthous stomatitis, gastritis, gastroenteritis, oral moniliasis, tongue edema
• Frequency not reported: Dyspepsia, flatulence, oral paresthesia, mouth edema

Metabolic

• Very common (10% or more): Increased appetite (up to 17%), weight gain (up to 12%)
• Uncommon (0.1% to 1%): Anorexia
• Rare (0.01% to 0.1%): Dehydration, weight loss
• Very rare (less than 0.01%): Gout, acid phosphatase increased, diabetes mellitus, hyponatremia
• Frequency not reported: Hypertriglyceridemia
• Postmarketing reports: Hypercholesterolemia, hyperlipidemia

Psychiatric

• Common (1% to 10%): Abnormal dreams, thinking abnormal, confusion
• Uncommon (0.1% to 1%): Apathy, depression, agitation, anxiety, insomnia
• Rare (0.01% to 0.1%): Delirium, delusions, depersonalization, increased libido, hallucinations, manic reaction/mania, neurosis, hostility, emotional lability, euphoria, paranoid reaction, nightmares/vivid dreams
• Very rare (less than 0.01%): Drug dependence, psychotic depression, withdrawal syndrome, serotonin syndrome, aggression
• Frequency not reported: Nervousness, decreased libido, suicidal ideation, suicidal behavior, somnambulism
• Postmarketing reports: Psychomotor restlessness, drug withdrawal symptoms, paroniria

Cardiovascular

• Common (1% to 10%): Peripheral edema, edema
• Uncommon (0.1% to 1%): Hypertension, vasodilation, orthostatic hypotension
• Rare (0.01% to 0.1%): Angina pectoris, myocardial infarction, bradycardia, ventricular extrasystoles, hypotension
• Very rare (less than 0.01%): Chest pain substernal, atrial arrhythmia, bigeminy, cardiomegaly, phlebitis, left heart failure
• Frequency not reported: Chest pain, palpitation, tachycardia, postural hypotension, ECG changes
• Postmarketing reports: Ventricular arrhythmia, Torsades de pointes, generalized edema, localized edema
• There was a mean increase in heart rate observed in patients given this drug compared to placebo (3.4 bpm versus 0.8 bpm, respectively); however, the clinical significance of this difference is unknown.

Musculoskeletal

• Common (1% to 10%): Back pain, myalgia
• Uncommon (0.1% to 1%): Myasthenia, arthralgia, twitching
• Rare (0.01% to 0.1%): Neck rigidity, neck pain, arthritis, tenosynovitis
• Very rare (less than 0.01%): Pathologic fracture, osteoporosis fracture, bone pain, myositis, tendon rupture, arthrosis, bursitis
• Postmarketing reports: Increased creatine kinase blood levels, rhabdomyolysis

Respiratory

• Common (1% to 10%): Dyspnea
• Uncommon (0.1% to 1%): Cough increased, sinusitis
• Rare (0.01% to 0.1%): Epistaxis, bronchitis, asthma, pneumonia
• Very rare (less than 0.01%): Respiratory/pulmonary embolus, asphyxia, laryngitis, pneumothorax, hiccup
• Frequency not reported: Pharyngitis, rhinitis
• Postmarketing reports: Pulmonary embolism

Genitourinary

• Common (1% to 10%): Urinary frequency
• Uncommon (0.1% to 1%): Urinary tract infection
• Rare (0.01% to 0.1%): Dysuria, urinary incontinence, urinary retention, vaginitis, hematuria, breast pain, amenorrhea, dysmenorrhea, leukorrhea, impotence
• Very rare (less than 0.01%): Polyuria, urethritis, metrorrhagia, abnormal ejaculation, breast engorgement, breast enlargement, urinary urgency, menorrhagia

Other

• Common (1% to 10%): Asthenia
• Uncommon (0.1% to 1%): Malaise, thirst, fatigue
• Rare (0.01% to 0.1%): Chills, fever, face edema, ulcer, ear pain, deafness, hyperacusis
• Very rare (less than 0.01%): Healing abnormal, partial transitory deafness, otitis media
• Frequency not reported: Pain, tinnitus

Immunologic

• Common (1% to 10%): Influenza/flu syndrome
• Frequency not reported: Infection

Dermatologic

• Uncommon (0.1% to 1%): Pruritus, rash, exanthema
• Rare (0.01% to 0.1%): Photosensitivity reaction, acne, exfoliative dermatitis, dry skin, herpes simplex, alopecia
• Very rare (less than 0.01%): Cellulitis, petechia, urticaria, herpes zoster, skin hypertrophy, skin ulcer, seborrhea
• Frequency not reported: Sweating
• Postmarketing reports: Stevens-Johnson Syndrome, bullous dermatitis, erythema multiforme, toxic epidermal necrolysis, rash (including erythematous and maculopapular)

Ocular

• Rare (0.01% to 0.1%): Eye pain, abnormality of accommodation, conjunctivitis, keratoconjunctivitis, lacrimation disorder, angle-closure glaucoma
• Very rare (less than 0.01%): Diplopia, blepharitis
• Frequency not reported: Amblyopia
• Postmarketing reports: Glaucoma

Hepatic

• Rare (0.01% to 0.1%): Cholecystitis, liver function tests abnormal
• Very rare (less than 0.01%): Cirrhosis of the liver, AST increased, ALT increased
• Postmarketing reports: Jaundice, hepatitis

Renal

• Rare (0.01% to 0.1%): Kidney calculus, cystitis

Hematologic

• Very rare (less than 0.01%): Lymphadenopathy, leukopenia, anemia, thrombocytopenia, lymphocytosis, pancytopenia
• Frequency not reported: Bone marrow depression (granulocytopenia, agranulocytosis, aplastic anemia, thrombocytopenia), eosinophilia
• Postmarketing reports: Thromboembolic disorder, coagulation disorder

Endocrine

• Very rare (less than 0.01%): Goiter, hypothyroidism
• Frequency not reported: Inappropriate antidiuretic hormone secretion.

Mirtazapine overdose

There is very limited experience with mirtazapine tablets overdose. In premarketing clinical studies, there were eight reports of mirtazapine tablets overdose alone or in combination with other pharmacological agents. The only drug overdose death reported while taking mirtazapine tablets was in combination with amitriptyline and chlorprothixene in a non-US clinical study. Based on plasma levels, the mirtazapine tablets dose taken was 30 to 45 mg, while plasma levels of amitriptyline and chlorprothixene were found to be at toxic levels. All other premarketing overdose cases resulted in full recovery. Signs and symptoms reported in association with overdose included disorientation, drowsiness, impaired memory, and tachycardia. There were no reports of ECG abnormalities, coma or convulsions following overdose with mirtazapine tablets alone.

Overdose management

Treatment should consist of those general measures employed in the management of overdose with any drug effective in the treatment of major depressive disorder. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients.

Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion or exchange transfusion in the treatment of mirtazapine overdosage. No specific antidotes for mirtazapine are known.