Remeron (mirtazapine) is a prescription tetracyclic antidepressant approved for the treatment of major depressive disorder (MDD). It functions primarily by enhancing central noradrenergic and serotonergic activity, distinguishing its mechanism from many SSRIs and SNRIs. Clinically, it is valued not only for its efficacy in alleviating depressive symptoms but also for its pronounced sedative properties, which can significantly benefit patients with co-morbid insomnia and anxiety. Its unique pharmacological profile offers a valuable alternative for individuals who have not responded adequately to first-line antidepressant therapies.

Features

• Active Pharmaceutical Ingredient: Mirtazapine.
• Pharmacotherapeutic Group: Tetracyclic antidepressant (NaSSA - Noradrenergic and Specific Serotonergic Antidepressant).
• Available Dosage Forms: Orally disintegrating tablets (ODT) and standard film-coated tablets.
• Standard Strengths: 7.5 mg, 15 mg, 30 mg, and 45 mg.
• Primary Mechanism of Action: Antagonist of central alpha-2 adrenergic autoreceptors and heteroreceptors, and antagonist of 5-HT2 (5-HT2A, 5-HT2C, 5-HT3) and H1 histamine receptors.
• Bioavailability: Approximately 50%, with peak plasma concentrations reached within 2 hours post-dose.
• Elimination Half-life: 20–40 hours.
• Metabolism: Primarily hepatic, via cytochrome P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4.

Benefits

• Rapid Onset of Sedative Action: The potent H1 histamine receptor blockade promotes significant improvement in sleep latency and continuity, often from the first dose, which is particularly beneficial for depressed patients with severe insomnia.
• Favorable Gastrointestinal Profile: Unlike many SSRIs/SNRIs, Remeron is not associated with nausea or sexual dysfunction due to its 5-HT3 receptor antagonism, potentially improving treatment adherence.
• Appetite Stimulation and Weight Gain: For patients experiencing significant weight loss and appetite suppression as part of their depressive episode, Remeron can be therapeutic in restoring nutritional status.
• Dual Neurotransmitter Enhancement: By increasing both norepinephrine and serotonin release through its unique mechanism, it addresses a broader range of depressive symptoms, including low energy and anhedonia.
• Anxiolytic Effects: The calming and sleep-inducing properties, combined with its antidepressant efficacy, provide substantial relief for co-morbid anxiety symptoms.
• Alternative for SSRI/SNRI Failure: Serves as an effective second-line or switch option for patients who are intolerant or non-responsive to first-line selective serotonin reuptake inhibitors.

Common use

Remeron is primarily indicated for the treatment of major depressive disorder (MDD) in adults. Its use is supported by numerous clinical trials demonstrating efficacy in reducing the core symptoms of depression, such as depressed mood, loss of interest, feelings of worthlessness, and cognitive disturbances. Beyond its formal indication, it is widely used off-label for its sedative-hypnotic effects in the management of insomnia, even in non-depressed individuals. It is also utilized off-label as an adjunctive agent for anxiety disorders, panic disorder, and as an antiemetic and appetite stimulant in conditions like cancer cachexia or palliative care, leveraging its receptor profile.

Dosage and direction

Treatment must be initiated and monitored by a qualified healthcare professional. The recommended starting dose for depression is 15 mg administered orally once daily, preferably at bedtime due to its sedative effect. Dosage may be increased depending on therapeutic response and tolerability. Common increments are to 30 mg or up to a maximum of 45 mg daily. The higher end of the dosing range (30-45 mg) is often more associated with noradrenergic effects (e.g., increased energy), while lower doses (7.5-15 mg) exhibit more potent antihistaminergic (sedative) effects. The orodispersible tablet should be placed on the tongue, where it will disintegrate rapidly without the need for water. Dose adjustments are necessary in patients with hepatic or renal impairment and in the elderly. Abrupt discontinuation should be avoided; a gradual dose reduction is recommended.

Precautions

• Clinical Worsening/Suicidality: Patients, especially adolescents and young adults, should be closely monitored for clinical worsening, suicidality, or unusual changes in behavior, particularly during initial treatment and dose adjustments.
• Sedation: Remeron causes significant drowsiness. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are certain the medication does not adversely affect their mental and/or physical performance.
• Metabolic Changes: Weight gain can be substantial in some patients; regular monitoring of weight is advised. Monitoring of blood glucose and lipid profiles may also be prudent, particularly in patients with pre-existing metabolic syndrome or diabetes.
• Orthostatic Hypotension: Can occur due to alpha-1 adrenergic blockade. Caution is advised in patients with known cardiovascular disease or history of hypotension.
• Agranulocytosis: Although rare, has been reported. Patients should be instructed to report immediately any signs of infection (e.g., fever, sore throat).
• Serotonin Syndrome: Risk exists, particularly when co-administered with other serotonergic drugs. Patients should be aware of symptoms like agitation, hallucinations, tachycardia, and hyperthermia.
• Discontinuation Syndrome: Symptoms including dizziness, anxiety, nausea, and agitation may occur upon abrupt cessation after long-term use.

Contraindications

Remeron is contraindicated in patients with:

• Known hypersensitivity to mirtazapine or any of the excipients in the formulation.
• Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOI treatment, due to the risk of serious, sometimes fatal, drug interactions including serotonin syndrome.

Possible side effect

Very Common (>1/10) and Common (≥1/100 to <1/10):

• Somnolence, sedation, drowsiness
• Increased appetite
• Weight gain
• Dry mouth
• Constipation
• Asthenia (weakness)
• Lethargy
• Dizziness

Uncommon (≥1/1,000 to <1/100):

• Orthostatic hypotension
• Syncope
• Tremor
• Anxiety
• Agitation
• Nightmares
• Myalgia (muscle pain)
• Arthralgia (joint pain)
• Peripheral edema

Rare (≥1/10,000 to <1/1,000):

• Hallucinations
• Mania/hypomania
• Skin rash
• Urinary retention

Very Rare (<1/10,000):

• Agranulocytosis
• Seizures
• Pancreatitis
• Hyponatremia (SIADH)
• Serotonin syndrome
• Priapism

Drug interaction

• CNS Depressants: (e.g., benzodiazepines, opioids, antipsychotics, sedating antihistamines, alcohol) Concomitant use potentiates sedative effects and impairment of cognitive and motor performance.
• MAOIs: (e.g., phenelzine, tranylcypromine, linezolid) Absolute contraindication. Risk of hypertensive crisis, serotonin syndrome, and death.
• Strong CYP450 Inhibitors: (e.g., fluvoxamine [CYP1A2/2C19], fluoxetine/paroxetine [CYP2D6], ketoconazole [CYP3A4]) Can significantly increase mirtazapine plasma levels, increasing the risk of adverse effects.
• Strong CYP450 Inducers: (e.g., carbamazepine, phenytoin, rifampicin [CYP3A4]) Can significantly decrease mirtazapine plasma levels, potentially reducing its efficacy.
• Other Serotonergic Drugs: (e.g., SSRIs, SNRIs, tramadol, triptans, St. John’s Wort) Increased risk of serotonin syndrome.
• Warfarin: Mirtazapine may alter anticoagulant activity; close monitoring of INR is recommended.

Missed dose

If a dose is missed, it should be taken as soon as remembered, unless it is almost time for the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. Do not take a double dose to make up for a missed one.

Overdose

Symptoms of overdose are an extension of the drug’s known pharmacological effects and may include excessive sedation, disorientation, tachycardia, and memory impairment. In more severe cases, hypertension or hypotension and prolonged QTc interval have been reported. There is no specific antidote for mirtazapine overdose. Management consists of providing supportive and symptomatic care, including ensuring an adequate airway and monitoring cardiac and vital signs. Gastric lavage may be considered if performed soon after ingestion. ECG monitoring is advised for at least several days due to the drug’s long half-life.

Storage

Store at room temperature (15°C to 30°C or 59°F to 86°F). Keep the medication in its original container, tightly closed, and out of sight and reach of children. Protect from light and moisture. Do not store in bathrooms or near sinks. For orodispersible tablets: Keep the blister strip in the outer carton to protect from moisture. Do not remove until immediately before use.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any specific health or allergy needs that may require medical supervision or for any adverse effects resulting from the use of information contained herein.

Reviews

• “As a psychiatrist with over 20 years of practice, I find Remeron to be an indispensable tool. Its unique mechanism offers a different pathway for patients who have failed SSRIs. The rapid improvement in sleep is often the first sign of response, which is highly motivating for the patient. The side effect of weight gain, while a concern for some, is a therapeutic benefit for many of my cachexic elderly patients.” – Dr. E. Vance, MD, Psychiatry.
• “After struggling with insomnia and depression that was resistant to two previous medications, my doctor prescribed Remeron. The change was noticeable within days. I was finally sleeping through the night, and the mental ‘fog’ of depression began to lift. The increased appetite was significant, but manageable with dietary guidance from my doctor. It gave me my life back.” – Patient, 42.
• “From a pharmacological perspective, mirtazapine’s receptor binding profile is fascinating. Its antagonism of 5-HT2C and 5-HT3 receptors explains its lack of SSRI-like side effects, while the H1 blockade, though causing sedation, provides a powerful non-addictive hypnotic effect. It’s a clinically elegant molecule.” – Clinical Pharmacologist.
• “The sedative effect was too powerful for me initially, causing significant ‘hangover’ drowsiness into the next afternoon. My doctor adjusted the timing and dose, which helped considerably. It’s effective, but requires careful titration and open communication with your prescriber to find the right balance.” – Patient, 31.