Mirtazapine (Adverse Reactions)

Mirtazapine is a noradrenergic and serotonergic antidepressant used in the treatment of depression and other mood disorders. Although further studies are needed to elucidate the impact of mirtazapine pharmacogenetics, polymorphisms have been identified that could influence treatment response and risk of adverse effects.

Mirtazapine is a tetracyclic antidepressant analogous to mianserin. It belongs to the group of the atypical antidepressants and is classified as a specific noradrenergic and serotonergic antidepressant (NaSSA). Its mechanism of action is to increase noradrenergic and serotonergic neurotransmission at the level of the central nervous system (CNS).

CONTRAINDICATIONS

Hypersensitivity Contraindicated in concomitant use with IMAO antidepressants

CAUTIONS

Precautions should be taken when prescribing mirtazapine to patients with epilepsy and organic affective syndrome. Caution in patients with hepatic insufficiency, renal insufficiency, conduction disturbances, angina pectoris and recent myocardial infarction, hypotension, prostatic hypertrophy, acute narrow-angle glaucoma and diabetes mellitus.

Extreme precautions in the prescription and dosage of mirtazapine in patients with schizophrenia or other psychotic disorders, history of mania / hypomania.

Caution in individuals with known cardiovascular disease or family history of prolonged QT cardiac interval and even more extreme precautions if prescribed concomitantly with drugs that prolong the QTc interval and in patients at risk of hyponatremia (elderly or treated with drugs that cause hyponatremia) .

Stop treatment if jaundice, fever, sore throat, stomatitis or other signs of infection occur.

A gradual suspension of treatment should be performed to avoid withdrawal syndrome.

Do not use in children under 18 years old since in these individuals are more frequent suicidal behavior and hostility.

There is a risk of suicide, therefore regular monitoring of the patient should be carried out until improvement is detected, especially in patients with a history of suicidal episode or showing a significant degree of suicidal ideation before starting treatment.

There is a risk of serotonin syndrome in concomitant use with SSRI antidepressants.

Akathisia may appear in the first weeks of treatment.

SIDE EFFECTS

Weight gain, drowsiness, sedation, headache, lethargy, dizziness, tremor, dry mouth, nausea, diarrhea, vomiting, constipation, rash, arthralgia, myalgia, back pain, increased appetite, orthostatic hypotension, peripheral edema, fatigue; abnormal dreams, confusion, anxiety, insomnia.

PHARMACOLOGIC INTERACTIONS

Mirtazapine potentiates the sedative effect of benzodiazepines and other anxiolytics.

Decrease the dose of mirtazapine when taken concomitantly with: potent inhibitors of CYP3A4, HIV protease inhibitors, azole antifungals, erythromycin, cimetidine, nefazodone.

The plasma levels of mirtazapine are diminished by: carbamazepine, rifampicin or phenytoin.

Do not administer mirtazapine together with MAOI antidepressants or within 2 weeks after cessation of treatment.

There is a risk of serotonergic syndrome if mirtazapine is taken together with: L-tryptophan, triptans, tramadol, linezolid, SSRI antidepressants, lithium, St. John's wort.

Monitor the INR (""International Normalized Ratio"", parameter to monitor the prothrombin time, clotting time) if mirtazapine is taken together with warfarin or other anticoagulants.

There is a risk of prolonged QT cardiac interval and/or ventricular arrhythmias in concomitance of mirtazapine with substances that prolong the QTc interval, such as some antipsychotics and antibiotics.

BRAND NAMES:

  • Afloyan ®
  • Mirtamylan ®
  • Myrtazapina ®
  • Rexer ®

Genes analyzed

CYP2D6

Bibliography

Lind AB, Reis M, Bengtsson F, et al.Steady-state concentrations of mirtazapine, N-desmethylmirtazapine, 8-hydroxymirtazapine and their enantiomers in relation to cytochrome P450 2D6 genotype, age and smoking behaviour. Clin Pharmacokinet. 2009;48(1):63-70.

Paulzen M, Gründer G, et al . Distribution pattern of mirtazapine and normirtazapine in blood and CSF. Psychopharmacology (Berl). 2015 Feb;232(4):807-13.

Zastrozhin MS, Skryabin VY, Smirnov VV, et al.Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder. Can J Physiol Pharmacol. 2019 Aug;97(8):781-785.

Zastrozhin, Smirnov, Petukhov, et al.The Influence of Concentration of Micro-RNA hsa-miR-370-3p and CYP2D6*4 on Equilibrium Concentration of Mirtazapine in Patients With Major Depressive Disorder. Psychopharmacol Bull. 2020 Jul 23;50(3):58-75.

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