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Mirtazapine; Uses, Dosage, Side Effects, Interactions

Mirtazapine is a synthetic tetracyclic derivative of the piperazine-azepines with antidepressant activity. Although its mechanism of action is unknown, mirtazapine enhances central adrenergic and serotonergic transmission, possibly by acting as an antagonist at central presynaptic alpha 2 adrenergic inhibitory autoreceptors and heteroreceptors. This agent is a potent antagonist of 5-hydroxytryptamine type 2 (5-HT2), 5-HT3, and histamine 1 (H1) receptors, and a moderate antagonist of peripheral alpha 1 adrenergic and muscarinic receptors.

Mirtazapine is a tetracyclic antidepressant with a somewhat unique mechanism of action. Mirtazapine therapy can be associated with transient asymptomatic elevations in serum aminotransferase levels and has been linked to rare instances of clinically apparent acute liver injury.

Mirtazapine has a tetracyclic chemical structure and belongs to the piperazine-azepine group of compounds. It is designated 1,2,3,4,10,14b-hexahydro-2-methylpyrazino [2,1-a] pyrido [2,3-c] benzazepine and has the empirical formula of C17H19N3.Primarily in the treatment of depression. In addition to its antidepressant properties, mirtazapine has anxiolytic, sedative, antiemetic, and appetite stimulant effects and is sometimes used in the treatment of anxiety disorders, insomnia, nausea and vomiting, and to produce weight gain when desirable. It is taken by mouth. The drug acts as an antagonist of certain adrenergic and serotonin receptors and is also a strong antihistamine. It is sometimes described as a noradrenergic and specific serotonergic antidepressant (NaSSA), although the actual evidence in support of this label has been regarded as poor.

Mechanism of Action of Mirtazapine

Mirtazapine acts as an antagonist at central pre-synaptic alpha(2)-receptors, inhibiting negative feedback to the presynaptic nerve and causing an increase in NE release. Blockade of heteroreceptors, alpha(2)-receptors contained in serotonergic neurons, enhances the release of 5-HT, increasing the interactions between 5-HT and 5-HT₁ receptors and contributing to the anxiolytic effects of mirtazapine. Mirtazapine also acts as a weak antagonist at 5-HT₁ receptors and as a potent antagonist at 5-HT₂ (particularly subtypes 2A and 2C) and 5-HT₃ receptors. Blockade of these receptors may explain the lower incidence of adverse effects such as anxiety, insomnia, and nausea. Mirtazapine also exhibits significant antagonism at H1-receptors, resulting in sedation. Mirtazapine has no effects on the reuptake of either NE or 5-HT and has only minimal activity at dopaminergic and muscarinic receptors.

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Indications of Mirtazapine

Contra-Indications of Mirtazapine

High cholesterol
The high amount of triglyceride in the blood
Low amount of sodium in the blood
Extreme loss of body Water
Behaving with excessive cheerfulness and activity
A mild degree of mania
Having thoughts of suicide
Neuroleptic malignant syndrome
Closed angle glaucoma
Heart attack
Angina
Very rapid heartbeat
Prolonged QT interval on EKG
Abnormal EKG with QT changes from birth
stroke
Disorder of the blood vessels of the brain
Blood pressure drop upon standing
Abnormally low blood pressure
Liver problems

Dosage of Mirtazapine

Strengths: 7.5mg; 15 mg; 30 mg; 45 mg;

Depression

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

Side Effects

The most common

Constipation
dizziness
drowsiness
dry mouth
chest pain
headache
joint painPain
dizziness
nausea and vomiting
Severe stomach ache
epigastric pain,
diarrhoea,
anorexia,
flatulence,
headache,
fainting, fast or pounding heartbeats.

More common

Fast or irregular heartbeat
fever
Back pain
dizziness
a headache
increased cough
Acid or sour stomach
decreased appetite
Agitation
chest congestion
chest pain
cold sweats
confusion
decreased sexual ability or desire
diarrhea or loose stools
heartburn
sleepiness or unusual drowsiness
stomach or abdominal cramps, gas, or pain
trouble sleeping

Less common

Abnormal dreams
change in sense of taste
congestion
discouragement, feeling sad, or empty
Suicide attempts
Acting on dangerous impulses
Aggressive or violent behavior
Thoughts about suicide or dying
New or worse depression
New or worse anxiety or panic attacks
Agitation, restlessness, anger, or irritability
Trouble sleeping
An increase in activity or talking more than normal

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Drug Interactions of Mirtazapine

Mirtazapine may interact with following drugs, supplements & may decrease the efficacy of the drug

alpha blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin)
amphetamines (e.g., dextroamphetamine, lisdexamphetamine)
antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
“azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
baclofen
barbiturates (e.g., butalbital, pentobarbital phenobarbital)
benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)
beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
bupropion
calcitriol
calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
carbamazepine
carvedilol
celecoxib
ciprofloxacin
clobazam
oral corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
cyclosporine
doxycycline
folic acid
gabapentin
“gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
lansoprazole
loperamide
losartan
macrolide antibiotics (e.g., clarithromycin, erythromycin)
methylphenidate
multivitamins
montelukast
ondansetron
phenytoin
progestins (e.g., dienogest, levonorgestrel, medroxyprogesterone, norethindrone)
proton pump inhibitors (e.g., lansoprazole, omeprazole)
ranitidine
selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine,paroxetine, sertraline)
sildenafil
“statin” anti-cholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
thiazide diuretics (e.g., chlorothiazide, hydrochlorothiazide)
tramadol
tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
valproic acid
warfarin

Pregnancy & Lactation of Mirtazapine

FDA Pregnancy Category C

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. It has been reported that babies born to women who have taken mirtazapine during the last trimester of pregnancy may experience complications that result in an increase in the length of their hospital stay. If you become pregnant while taking this medication, contact your doctor immediately.

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Breastfeeding

It is not known if mirtazapine passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding.