Article: Mirtazapine

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. weight	265.36
Pharmacokinetic data
Bioavailability	50%
Metabolism	Liver
Half life	37 hours (females), 26 hours (males)
Excretion	?
Therapeutic considerations
Pregnancy cat.	C
Legal status	?
Routes	?

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 it is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA). Mirtazapine may be used in preference to an SSRI due to the fact that it causes fewer sexual dsyfunction problems. Due to its unique pharmacologic profile, mirtazapine is virtually devoid of anticholinergic, adrenolytic, and serotonin-related side effects^[1].

Trade Names

Mirtazapine is marketed under the tradenames Remeron® in the U.S. and Finland, Avanza® in Australia, Zispin® in the UK & Ireland, Norset® in France, Remergon® in Belgium, Remergil® in Germany and Mirtabene® in Austria).

Indications

Mirtazapine is primarily used to treat the symptoms of depression. It can also be used to treat panic disorder^[2], generalized anxiety disorder^[3], obsessive-compulsive disorder (OCD)^[4] and post traumatic stress disorder (PTSD)^[5].

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.

Side effects

The side effects that do occur are thought to be primarily related to the blockage of histamine receptors, which decreases with higher dosages.

Side effects occurring commonly:

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

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
• Agranulocytosis

Side effects to tell your doctor about and stop taking mirtazapine immediately

• 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).

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 inpatient situations in which patients suffer from nausea since it also antagonizes the 5-HT₃ receptor, the target of the popular anti-emetic ondansetron (Zofran®).

Dosage

The usual starting dose for mirtazapine is 15 mg once daily, usually at bedtime (Due to the sedative nature and disturbed visual perception). Doses may be increased every 1-2 weeks up to a maximum dose of 45 mg daily. It may be taken with or without food. Dissolving tablets can even be taken without water.

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.

Drug-Drug Interactions

Due to the sedative effects of Mirtazapine, alcohol should not be taken. Excessive sedation may result when it is used with other sedating drugs, such as benzodiazepines. Mirtazapine should not be used within 14 days of the use of a monoamine oxidase inhibitor because of the possibility that a hypertensive emergency will be triggered.