Mirtazapine

From Wikipedia, the free encyclopedia

Mirtazapine
Systematic (IUPAC) name
1,2,3,4,10,14b-Hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3-c]benzazepine
Identifiers
CAS number	61337-67-5
ATC code	N06AX11
PubChem	4205
Chemical data
Formula	C17H19N3
Mol. mass	265.36
Pharmacokinetic data
Bioavailability	50%
Metabolism	Liver
Half life	37 hours (females), 26 hours (males)
Excretion	75% urine 15% feces
Therapeutic considerations
Pregnancy cat.	C
Legal status	Prescription only
Routes	Oral tablet, Solulable tablet

Mirtazapine is an antidepressant introduced by Organon International in 1996 used for the treatment of mild to severe depression. Although Mirtazapine has a tetracyclic chemical structure the pharmaceutical company have chosen to promote the drug using the acronym noradrenergic and specific serotonergic antidepressant (NaSSA), although there is only modest evidence from their research department to support its claimed effects. Indeed, recent work by researchers independent of Organon International has failed to replicate much of the original data. The difference in receptor profile from the 'parent' drug, mianserin, appears to be non-existent, at least with respect to those properties that are hypothesised to be relevant.^[1] Because of its unique pharmacologic profile, mirtazapine is virtually devoid of anticholinergic effects, serotonin-related side effects,^[2] and adrenolytic effects (orthostatic hypotension and sexual dysfunction). As such it may be preferable to SSRIs in some patients. Mirtazapine is relatively safe if an overdose is taken.^[3]

Contents 1 Trade Names 2 Indications 2.1 Approved 2.2 Unapproved/Off-label/Investigational 3 Mechanism of action 4 Side effects 4.1 Side effects occurring commonly: 4.2 Side effects occurring rarely: 4.3 Dangerous side effects 5 Dosage 6 Pregnancy and Lactation 7 Drug-Drug Interactions 8 External links 9 References

[edit] Trade Names

Mirtazapine is marketed under the tradenames Remeron® in the U.S., Canada, Brazil, Israel ,Finland , Netherlands and Switzerland, Avanza® and Axit® in Australia, Zispin® in the UK & Ireland, Norset® in France, Remergon® in Belgium, Remergil® in Germany, Mirtabene® in Austria, Mirtaz® in India and Srilanka, Rexer® in Spain and Promyrtil in Chile.

[edit] Indications

[edit] Approved

Mirtazapine is primarily used to treat the symptoms of mild to severe depression.^[4]

[edit] Unapproved/Off-label/Investigational

There is also evidence that mirtazapine can be used to treat panic disorder (PD),^[5] generalized anxiety disorder (GAD),^[6] obsessive-compulsive disorder (OCD),^[7] post traumatic stress disorder (PTSD)^[8] and pruritus.^[9] Mirtazapine has not been reported to be effective in the prophylactic treatment of chronic tension headache.^[10]

[edit] Mechanism of action

It is thought to work by blocking presynaptic alpha-2 adrenergic receptors that normally inhibit the release of the neurotransmitters norepinephrine (noradrenaline) and serotonin, thereby increasing active levels in the synapse.Mirtazapine also blocks post-synaptic 5-HT₂ and 5-HT₃ receptors—an action which is thought to enhance serotonergic neurotransmission while causing a low incidence of side effects.^{[citation needed]}

[edit] Side effects

Interestingly, its side effect profile can be used for benefit in certain clinical situations. The drowsiness, increased appetite, and weight gain it causes are useful in patients with depressive disorders with prominent sleep and appetite disturbances. In addition, it is quite useful in patient situations in which patients suffer from nausea since it also antagonizes the 5-HT₃ receptor, the target of the popular anti-emetic ondansetron (Zofran®).

At lower dosages, such as 7.5 mg, mirtazapine is primarily antihistaminergic, causing sedation, which can be beneficial in depressed patients who have difficulty falling asleep. At doses higher than 15 mg, its effect is primarily in inducing the release of norepinephrine, and is thus less sedating.^{[citation needed]}

[edit] Side effects occurring commonly:

• Increased appetite
• Weight gain
• Increase in cholesterol, independent of weight gain
• Drowsiness, especially at lower doses and during the first few weeks of treatment
• Dizziness
• Headache
• General or local swelling
• Visual hallucinations (when taken during the day)

[edit] Side effects occurring rarely:

• Mania
• Nightmares and vivid dreams
• Seizures
• Tremor
• Muscle twitching and Restless Legs Syndrome
• Pins and needles
• Rash and skin eruptions
• Pain in the joints or muscles
• Low blood pressure
• Higher blood pressure
• Causes obesity

[edit] Dangerous side effects

If you experience any of these, tell your doctor immediately. You will need to consult your doctor for taper-off instructions. Sudden withdrawal from antidepressants can cause serious symptoms.

• An allergic reaction; signs of swelling of the lips, face and tongue, difficulty in breathing, rash or itching (especially affecting the whole body) or feeling faint.
• Signs of infection such as fever, sore throat, mouth ulcers or stomach upset.
• Jaundice (yellowing of the skin and/or eyes).
• Agranulocytosis

[edit] Dosage

The usual starting dose for mirtazapine is 7.5 - 15 mg once daily, usually at bedtime (because of its sedative nature and the possibility of disturbed visual perception). Doses may be increased, following medical advice, every 1-2 weeks up to a dose of 45 mg; the maximum daily dose is 90 mg. It may be taken with or without food. Dissolving tablets (SolTab® orally disintegrating tablets) can even be taken without water.

[edit] Pregnancy and Lactation

• Pregnancy : Sufficient data in humans is lacking. The use should be justified by the severity of the condition to be treated.
• Lactation : Sufficient data in humans is also lacking. Additionally, Mirtazapine may be found in the maternal milk in significant concentrations. The use in breastfeeding women should be carefully weighed against possible risks.

[edit] Drug-Drug Interactions

Because of the sedative effects of Mirtazapine, excessive sedation may result when it is used with other sedating substances, such as alcohol or benzodiazepines. According to official prescribing information from Organon, mirtazapine should not be used within 14 days of the use of an MAOI because of the risk of serious effects such as hypertensive emergency and hyperthermia. However, MAOi experts generally consider them safe to use with mirtazapine, with proper monitoring.

[edit] External links

• Patient Information Leaflet (pdf)
• Official site of Remeron

[edit] References

1. ↑  Gillman, PK (2006). "A systematic review of the serotonergic effects of mirtazapine: implications for its dual action status". Human Psychopharmacology Clinical and Experimental 21 (2): 117-25. PMID 16342227. 
2. ↑  Burrows GD, Kremer CM. (1997). "Mirtazapine: clinical advantages in the treatment of depression.". Journal of Clinical Psychopharmacology 17 (2S): 34S-39S. PMID 9090576. 
3. ↑  Velazquez C, Carlson A, Stokes KA, Leikin JB. (2001). "Relative safety of mirtazapine overdose.". Veterinary and Human Toxicology 43 (6): 342-344. PMID 11757992. 
4. ↑  Gorman JM (1999). "Mirtazapine: clinical overview.". Journal of Clinical Psychiatry 60 (17): 9-13. PMID 10446735. 
5. ↑  Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU (2005). "Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology.". Journal of Psychopharmacology 19 (6): 567-596. PMID 16272179. 
6. ↑  Goodnick PJ, Puig A, DeVane CL, Freund BV (1999). "Mirtazapine in major depression with comorbid generalized anxiety disorder". Journal of Clinical Psychiatry 60 (7): 446-448. PMID 10453798. 
7. ↑  Koran LM, Gamel NN, Choung HW, Smith EH, Aboujaoude EN (2005). "Mirtazapine for obsessive-compulsive disorder: an open trial followed by double-blind discontinuation". Journal of Clinical Psychiatry 66 (4): 515-520. PMID 15816795. 
8. ↑  Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU (2005). "Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology.". Journal of Psychopharmacology 19 (6): 567-596. PMID 16272179. 
9. ↑  Davis MP, Frandsen JL, Walsh D, Andresen S, Taylor S. (2003). "Mirtazapine for pruritus.". Journal of pain and symptom management 25 (3): 288-291. PMID 12614964. 
10. ↑  Bendtsen L, Jensen R (2004). "Mirtazapine is effective in the prophylactic treatment of chronic tension-type headache.". Neurology 62 (10): 1706-1711. PMID 15159466. 
11. ↑  Gillman, PK (2006). "A systematic review of the serotonergic effects of mirtazapine: implications for its dual action status". Human Psychopharmacology Clinical and Experimental 21 (2): 117-25. PMID 16342227. 

v • d • e Antidepressants (ATC N06A)
Monoamine oxidase inhibitors (MAOI)	Harmaline, Iproniazid, Isocarboxazid, Nialamide, Pargyline, Phenelzine, Selegiline, Toloxatone, Tranylcypromine RIMAs: Brofaromine, Moclobemide
Dopamine reuptake inhibitor (DARI)	Amineptine, Phenmetrazine, Vanoxerine
Norepinephrine-dopamine reuptake inhibitors (NDRI)	Bupropion
Norepinephrine reuptake inhibitor (NRI) or (NARI)	Atomoxetine, Maprotiline, Reboxetine, Viloxazine
Serotonin-norepinephrine reuptake inhibitor (SNRI)	Duloxetine, Milnacipran, Nefazodone , Venlafaxine
Selective serotonin reuptake inhibitor (SSRI)	Alaproclate, Citalopram, Escitalopram, Etoperidone, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Zimelidine
Selective serotonin reuptake enhancer (SSRE)	Tianeptine
Noradrenergic and specific serotonergic antidepressant (NaSSA)	Mirtazapine
Tricyclic antidepressants (TCA)	Amitriptyline, Amoxapine, Butriptyline, Clomipramine, Desipramine, Dibenzepin, Dothiepin, Doxepin, Imipramine, Iprindole, Lofepramine, Melitracen, Nortriptyline, Opipramol, Protriptyline, Trimipramine
Tetracyclic antidepressants	Maprotiline, Mianserin, Nefazodone, Trazodone