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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 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.
Indications of Mirtazapine
- Major Depressive Disorder
- Depression
- Diabetic neuropathies
- Migraines
- Sleep disorders and disturbances
- Sleeplessness
- Chronic pain
- Paresthesia ,itching ,numbness
- Anxiety and stress
- Chronic myofascial pain
- Burning mouth syndrome
- Insomnia
- Cyclic vomiting syndrome
- Fibromyalgia
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
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.
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.
References
